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<!DOCTYPE html> <html xmlns="http://www.w3.org/1999/xhtml" lang="en" xml:lang="en"> <head>  <script async src="https://www.googletagmanager.com/gtag/js?id=G-WVK41JBQ8K"></script> <script> window.dataLayer = window.dataLayer || []; function gtag(){dataLayer.push(arguments);} gtag('js', new Date()); gtag('config', 'G-WVK41JBQ8K'); </script> <meta http-equiv="Content-Type" content="text/html;charset=utf-8" /> <title>Core Concepts - Evaluation and Staging of Liver Fibrosis - Evaluation, Staging, and Monitoring of Chronic Hepatitis C - Hepatitis C Online</title>  <link href="https://fonts.googleapis.com/css?family=Open+Sans:400,400i,600,600i,700,700i&subset=latin-ext" rel="stylesheet"> <link rel="stylesheet" href="//cdn.hepatitisc.uw.edu/css/vendors.css?v=bmhjdmMtbWFzdGVyLWM4ODQzNjczLTIwMjQtMTEtMTMtMjA1NjI0Cg" type="text/css" media="screen,print" /> <link rel="stylesheet" href="//cdn.hepatitisc.uw.edu/css/dynamic.css.php?v=bmhjdmMtbWFzdGVyLWM4ODQzNjczLTIwMjQtMTEtMTMtMjA1NjI0Cg" 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class="menu-close glyphicon glyphicon-remove" aria-hidden="true"></span> <span class="hidden">Site Navigation</span></div></li><li class="section home-section"><a href="/" title="Hepatitis C Online" class=" link"></a></li><li class="section biology"><a href="/page/hcv/biology" class="link ">HCV <br />Biology</a></li><li class="section treatments nhcvc-medications has-submenu"><a href="/page/treatment/drugs" class=" link ">HCV <br />Medications<span class="submenu-trigger"></span></a><div class="submenu medications"><div class="description description-default">Listed in <strong>alphabetical</strong> order.</div><ul><li class="treatment treatment-7"><a href="/page/treatment/drugs/elbasvir-grazoprevir"><img class="drug-preview" src="//cdn.hepatitisc.uw.edu/css/images/drugs/7.png" alt="Elbasvir-Grazoprevir (Zepatier) Pill Preview" />Elbasvir-Grazoprevir <em>Zepatier</em></a></li><li class="treatment treatment-22"><a href="/page/treatment/drugs/glecaprevir-pibrentasvir"><img class="drug-preview" src="//cdn.hepatitisc.uw.edu/css/images/drugs/22.png" alt="Glecaprevir-Pibrentasvir (Mavyret) Pill Preview" />Glecaprevir-Pibrentasvir <em>Mavyret</em></a></li><li class="treatment treatment-11"><a href="/page/treatment/drugs/ledipasvir-sofosbuvir"><img class="drug-preview" src="//cdn.hepatitisc.uw.edu/css/images/drugs/11.png" alt="Ledipasvir-Sofosbuvir (Harvoni) Pill Preview" />Ledipasvir-Sofosbuvir <em>Harvoni</em></a></li><li class="treatment treatment-3"><a href="/page/treatment/drugs/ribavirin-drug"><img class="drug-preview" src="//cdn.hepatitisc.uw.edu/css/images/drugs/3.png" alt="Ribavirin (Copegus, Rebetol, Ribasphere) Pill Preview" />Ribavirin <em>Copegus, Rebetol, Ribasphere</em></a></li><li class="treatment treatment-1"><a href="/page/treatment/drugs/sofosbuvir-drug"><img class="drug-preview" src="//cdn.hepatitisc.uw.edu/css/images/drugs/1.png" alt="Sofosbuvir (Sovaldi) Pill Preview" />Sofosbuvir <em>Sovaldi</em></a></li><li class="treatment treatment-20"><a href="/page/treatment/drugs/epclusa"><img class="drug-preview" src="//cdn.hepatitisc.uw.edu/css/images/drugs/20.png" alt="Sofosbuvir-Velpatasvir (Epclusa) Pill Preview" />Sofosbuvir-Velpatasvir <em>Epclusa</em></a></li><li class="treatment treatment-21"><a href="/page/treatment/drugs/sofosbuvir-velpatasvir-voxilaprevir"><img class="drug-preview" src="//cdn.hepatitisc.uw.edu/css/images/drugs/21.png" alt="Sofosbuvir-Velpatasvir-Voxilaprevir (Vosevi) Pill Preview" />Sofosbuvir-Velpatasvir-Voxilaprevir <em>Vosevi</em></a></li></ul></div></li><li class="section modules active-trail has-submenu"><a href="/alternate" class="link active-trail">Course <br /> Modules<span class="submenu-trigger"></span></a><div class="submenu modules"><ul><li class="level1 level1-all "><a href="/alternate"><span class="caption">View all Course Modules</span></a></li><li class="level1 level1-31 has-subsubmenu"><a href="/go/screening-diagnosis"><span class="num">1</span><span class="caption">Screening and Diagnosis of Hepatitis C Infection</span><span class="submenu-trigger"></span></a><div class="subsubmenu custom"><a class="description" href="/custom/screening-diagnosis"><h3>Self-Study Module<span class="edition-tag edition-tag-4">4th Edition</span><span class="cme-tag cme-tag-available">CNE/CME Available</span></h3> Track your progress and receive CE credit</a><ul><li><a href="/custom/screening-diagnosis">Screening and Diagnosis: Self-Study <span class="cme-tag cme-tag-available">CNE/CME</span></a></li></ul><h4>Lessons</h4><ol><li class="level2 level2-108"><a href="/custom/screening-diagnosis/epidemiology-us"><span class="caption">HCV Epidemiology in the United States</span></a></li><li class="level2 level2-109"><a href="/custom/screening-diagnosis/recommendations-screening"><span class="caption">Recommendations for Hepatitis C Screening</span></a></li><li class="level2 level2-110"><a href="/custom/screening-diagnosis/diagnostic-testing"><span class="caption">Hepatitis C Diagnostic Testing</span></a></li><li class="level2 level2-111"><a href="/custom/screening-diagnosis/counseling-prevention"><span class="caption">Counseling for Prevention of HCV Transmission</span></a></li><li class="level2 level2-112"><a href="/custom/screening-diagnosis/acute-diagnosis"><span class="caption">Diagnosis of Acute HCV Infection</span></a></li></ol><ul><li><a href="/custom/screening-diagnosis/certificate">Certificate Requirements <span class="cme-tag cme-tag-available">CNE/CME</span></a></li></ul></div><div class="subsubmenu level2s"><a class="description" href="/go/screening-diagnosis"><h3>Quick Reference<span class="edition-tag edition-tag-4">4th Edition</span></h3> Rapidly access information in this module</a><ul><li><a href="/go/screening-diagnosis">Screening and Diagnosis of Hepatitis C Infection: Overview</a></li></ul><h4>Lessons</h4><ol><li class="level2 level2-153"><a href="/go/screening-diagnosis/epidemiology-us/core-concept/all"><span class="caption">HCV Epidemiology in the United States</span></a></li><li class="level2 level2-157"><a href="/go/screening-diagnosis/recommendations-screening/core-concept/all"><span class="caption">Recommendations for Hepatitis C Screening</span></a></li><li class="level2 level2-154"><a href="/go/screening-diagnosis/diagnostic-testing/core-concept/all"><span class="caption">Hepatitis C Diagnostic Testing</span></a></li><li class="level2 level2-155"><a href="/go/screening-diagnosis/counseling-prevention/core-concept/all"><span class="caption">Counseling for Prevention of HCV Transmission</span></a></li><li class="level2 level2-156"><a href="/go/screening-diagnosis/acute-diagnosis/core-concept/all"><span class="caption">Diagnosis of Acute HCV Infection</span></a></li></ol></div></li><li class="level1 level1-34 has-subsubmenu hovered active-trail"><a href="/go/evaluation-staging-monitoring" class="active-trail"><span class="num">2</span><span class="caption">Evaluation, Staging, and Monitoring of Chronic Hepatitis C</span><span class="submenu-trigger"></span></a><div class="subsubmenu custom"><a class="description" href="/custom/evaluation-staging-monitoring"><h3>Self-Study Module<span class="edition-tag edition-tag-4">4th Edition</span><span class="cme-tag cme-tag-available">CNE/CME Available</span></h3> Track your progress and receive CE credit</a><ul><li><a href="/custom/evaluation-staging-monitoring">Evaluation, Staging, and Monitoring: Self-Study <span class="cme-tag cme-tag-available">CNE/CME</span></a></li></ul><h4>Lessons</h4><ol><li class="level2 level2-124"><a href="/custom/evaluation-staging-monitoring/initial-evaluation-chronic"><span class="caption">Initial Evaluation of Persons with Chronic HCV</span></a></li><li class="level2 level2-125"><a href="/custom/evaluation-staging-monitoring/natural-history"><span class="caption">Natural History of HCV Infection</span></a></li><li class="level2 level2-126"><a href="/custom/evaluation-staging-monitoring/counseling-liver-health"><span class="caption">Counseling Persons with Chronic HCV Infection</span></a></li><li class="level2 level2-127"><a href="/custom/evaluation-staging-monitoring/evaluation-staging"><span class="caption">Evaluation and Staging of Liver Fibrosis</span></a></li><li class="level2 level2-128"><a href="/custom/evaluation-staging-monitoring/evaluation-prognosis-cirrhosis"><span class="caption">Evaluation and Prognosis of Persons with Cirrhosis</span></a></li><li class="level2 level2-129"><a href="/custom/evaluation-staging-monitoring/surveillance-hepatocellular-carcinoma"><span class="caption">Surveillance for Hepatocellular Carcinoma</span></a></li><li class="level2 level2-130"><a href="/custom/evaluation-staging-monitoring/extrahepatic-conditions"><span class="caption">Extrahepatic Conditions Related to HCV Infection</span></a></li></ol><ul><li><a href="/custom/evaluation-staging-monitoring/certificate">Certificate Requirements <span class="cme-tag cme-tag-available">CNE/CME</span></a></li></ul></div><div class="subsubmenu level2s"><a class="description" href="/go/evaluation-staging-monitoring"><h3>Quick Reference<span class="edition-tag edition-tag-4">4th Edition</span></h3> Rapidly access information in this module</a><ul><li><a href="/go/evaluation-staging-monitoring">Evaluation, Staging, and Monitoring of Chronic Hepatitis C: Overview</a></li></ul><h4>Lessons</h4><ol><li class="level2 level2-169"><a href="/go/evaluation-staging-monitoring/initial-evaluation-chronic/core-concept/all"><span class="caption">Initial Evaluation of Persons with Chronic HCV</span></a></li><li class="level2 level2-170"><a href="/go/evaluation-staging-monitoring/natural-history/core-concept/all"><span class="caption">Natural History of HCV Infection</span></a></li><li class="level2 level2-171"><a href="/go/evaluation-staging-monitoring/counseling-liver-health/core-concept/all"><span class="caption">Counseling Persons with Chronic HCV Infection</span></a></li><li class="level2 level2-172 class="active-trail hovered""><a href="/go/evaluation-staging-monitoring/evaluation-staging/core-concept/all" active-trail hovered><span class="caption">Evaluation and Staging of Liver Fibrosis</span></a></li><li class="level2 level2-175"><a href="/go/evaluation-staging-monitoring/evaluation-prognosis-cirrhosis/core-concept/all"><span class="caption">Evaluation and Prognosis of Persons with Cirrhosis</span></a></li><li class="level2 level2-173"><a href="/go/evaluation-staging-monitoring/surveillance-hepatocellular-carcinoma/core-concept/all"><span class="caption">Surveillance for Hepatocellular Carcinoma</span></a></li><li class="level2 level2-174"><a href="/go/evaluation-staging-monitoring/extrahepatic-conditions/core-concept/all"><span class="caption">Extrahepatic Conditions Related to HCV Infection</span></a></li></ol></div></li><li class="level1 level1-33 has-subsubmenu"><a href="/go/management-cirrhosis-related-complications"><span class="num">3</span><span class="caption">Management of Cirrhosis-Related Complications</span><span class="submenu-trigger"></span></a><div class="subsubmenu custom"><a class="description" href="/custom/management-cirrhosis-related-complications"><h3>Self-Study Module<span class="edition-tag edition-tag-4">4th Edition</span><span class="cme-tag cme-tag-available">CNE/CME Available</span></h3> Track your progress and receive CE credit</a><ul><li><a href="/custom/management-cirrhosis-related-complications">Management of Cirrhosis-Related Complications: Self-Study <span class="cme-tag cme-tag-available">CNE/CME</span></a></li></ul><h4>Lessons</h4><ol><li class="level2 level2-119"><a href="/custom/management-cirrhosis-related-complications/ascites-diagnosis-management"><span class="caption">Diagnosis and Management of Ascites</span></a></li><li class="level2 level2-120"><a href="/custom/management-cirrhosis-related-complications/spontaneous-bacterial-peritonitis-recognition-management"><span class="caption">Recognition and Management of Spontaneous Bacterial Peritonitis</span></a></li><li class="level2 level2-121"><a href="/custom/management-cirrhosis-related-complications/varices-screening-prevention-bleeding"><span class="caption">Screening for Varices and Prevention of Bleeding</span></a></li><li class="level2 level2-122"><a href="/custom/management-cirrhosis-related-complications/hepatic-encephalopathy-diagnosis-management"><span class="caption">Diagnosis and Management of Hepatic Encephalopathy</span></a></li><li class="level2 level2-123"><a href="/custom/management-cirrhosis-related-complications/liver-transplantation-referral"><span class="caption">Referral for Liver Transplantation</span></a></li></ol><ul><li><a href="/custom/management-cirrhosis-related-complications/certificate">Certificate Requirements <span class="cme-tag cme-tag-available">CNE/CME</span></a></li></ul></div><div class="subsubmenu level2s"><a class="description" href="/go/management-cirrhosis-related-complications"><h3>Quick Reference<span class="edition-tag edition-tag-4">4th Edition</span></h3> Rapidly access information in this module</a><ul><li><a href="/go/management-cirrhosis-related-complications">Management of Cirrhosis-Related Complications: Overview</a></li></ul><h4>Lessons</h4><ol><li class="level2 level2-164"><a href="/go/management-cirrhosis-related-complications/ascites-diagnosis-management/core-concept/all"><span class="caption">Diagnosis and Management of Ascites</span></a></li><li class="level2 level2-165"><a href="/go/management-cirrhosis-related-complications/spontaneous-bacterial-peritonitis-recognition-management/core-concept/all"><span class="caption">Recognition and Management of Spontaneous Bacterial Peritonitis</span></a></li><li class="level2 level2-166"><a href="/go/management-cirrhosis-related-complications/varices-screening-prevention-bleeding/core-concept/all"><span class="caption">Screening for Varices and Prevention of Bleeding</span></a></li><li class="level2 level2-167"><a href="/go/management-cirrhosis-related-complications/hepatic-encephalopathy-diagnosis-management/core-concept/all"><span class="caption">Diagnosis and Management of Hepatic Encephalopathy</span></a></li><li class="level2 level2-168"><a href="/go/management-cirrhosis-related-complications/liver-transplantation-referral/core-concept/all"><span class="caption">Referral for Liver Transplantation</span></a></li></ol></div></li><li class="level1 level1-35 has-subsubmenu"><a href="/go/evaluation-treatment"><span class="num">4</span><span class="caption">Evaluation and Preparation for Hepatitis C Treatment</span><span class="submenu-trigger"></span></a><div class="subsubmenu custom"><a class="description" href="/custom/evaluation-treatment"><h3>Self-Study Module<span class="edition-tag edition-tag-4">4th Edition</span><span class="cme-tag cme-tag-available">CNE/CME Available</span></h3> Track your progress and receive CE credit</a><ul><li><a href="/custom/evaluation-treatment">Evaluation and Preparation for Treatment: Self-Study <span class="cme-tag cme-tag-available">CNE/CME</span></a></li></ul><h4>Lessons</h4><ol><li class="level2 level2-131"><a href="/custom/evaluation-treatment/treatment-goals-predicting-response"><span class="caption">Goals and Benefits with HCV Treatment</span></a></li><li class="level2 level2-132"><a href="/custom/evaluation-treatment/treatment-initiation-decision"><span class="caption">Making a Decision on When to Initiate HCV Therapy</span></a></li><li class="level2 level2-133"><a href="/custom/evaluation-treatment/addressing-structural-barriers-to-treatment"><span class="caption">Addressing Structural Barriers to HCV Treatment</span></a></li></ol><ul><li><a href="/custom/evaluation-treatment/certificate">Certificate Requirements <span class="cme-tag cme-tag-available">CNE/CME</span></a></li></ul></div><div class="subsubmenu level2s"><a class="description" href="/go/evaluation-treatment"><h3>Quick Reference<span class="edition-tag edition-tag-4">4th Edition</span></h3> Rapidly access information in this module</a><ul><li><a href="/go/evaluation-treatment">Evaluation and Preparation for Hepatitis C Treatment: Overview</a></li></ul><h4>Lessons</h4><ol><li class="level2 level2-176"><a href="/go/evaluation-treatment/treatment-goals-predicting-response/core-concept/all"><span class="caption">Goals and Benefits with HCV Treatment</span></a></li><li class="level2 level2-177"><a href="/go/evaluation-treatment/treatment-initiation-decision/core-concept/all"><span class="caption">Making a Decision on When to Initiate HCV Therapy</span></a></li><li class="level2 level2-178"><a href="/go/evaluation-treatment/addressing-structural-barriers-to-treatment/core-concept/all"><span class="caption">Addressing Structural Barriers to HCV Treatment</span></a></li></ol></div></li><li class="level1 level1-30 has-subsubmenu"><a href="/go/treatment-infection"><span class="num">5</span><span class="caption">Treatment of Hepatitis C Infection</span><span class="submenu-trigger"></span></a><div class="subsubmenu custom"><a class="description" href="/custom/treatment"><h3>Self-Study Module<span class="edition-tag edition-tag-4">4th Edition</span><span class="cme-tag cme-tag-available">CNE/CME Available</span></h3> Track your progress and receive CE credit</a><ul><li><a href="/custom/treatment">Treatment of HCV: Self-Study <span class="cme-tag cme-tag-available">CNE/CME</span></a></li></ul><h4>Lessons</h4><ol><li class="level2 level2-102"><a href="/custom/treatment/multi-genotype-treatment-new-lesson"><span class="caption">Simplified HCV Treatment for All HCV Genotypes</span></a></li><li class="level2 level2-103"><a href="/custom/treatment/retreatment-patients-prior-treatment-experience"><span class="caption">Retreatment of Patients with Prior HCV Treatment Experience</span></a></li><li class="level2 level2-101"><a href="/custom/treatment/monitoring"><span class="caption">Monitoring During and After HCV Treatment</span></a></li><li class="level2 level2-105"><a href="/custom/treatment/treatment-cirrhosis"><span class="caption">Treatment of HCV in Persons with Cirrhosis</span></a></li><li class="level2 level2-104"><a href="/custom/treatment/treatment-acute-infection"><span class="caption">Treatment of Acute HCV Infection</span></a></li></ol><ul><li><a href="/custom/treatment/certificate">Certificate Requirements <span class="cme-tag cme-tag-available">CNE/CME</span></a></li></ul></div><div class="subsubmenu level2s"><a class="description" href="/go/treatment-infection"><h3>Quick Reference<span class="edition-tag edition-tag-4">4th Edition</span></h3> Rapidly access information in this module</a><ul><li><a href="/go/treatment-infection">Treatment of Hepatitis C Infection: Overview</a></li></ul><h4>Lessons</h4><ol><li class="level2 level2-149"><a href="/go/treatment-infection/multi-genotype-treatment-new-lesson/core-concept/all"><span class="caption">Simplified HCV Treatment for All HCV Genotypes</span></a></li><li class="level2 level2-150"><a href="/go/treatment-infection/retreatment-patients-prior-treatment-experience/core-concept/all"><span class="caption">Retreatment of Patients with Prior HCV Treatment Experience</span></a></li><li class="level2 level2-143"><a href="/go/treatment-infection/monitoring/core-concept/all"><span class="caption">Monitoring During and After HCV Treatment</span></a></li><li class="level2 level2-152"><a href="/go/treatment-infection/treatment-cirrhosis/core-concept/all"><span class="caption">Treatment of HCV in Persons with Cirrhosis</span></a></li><li class="level2 level2-151"><a href="/go/treatment-infection/treatment-acute-infection/core-concept/all"><span class="caption">Treatment of Acute HCV Infection</span></a></li></ol></div></li><li class="level1 level1-32 has-subsubmenu"><a href="/go/key-populations-situations"><span class="num">6</span><span class="caption">Treatment of Key Populations and Unique Situations</span><span class="submenu-trigger"></span></a><div class="subsubmenu custom"><a class="description" href="/custom/key-populations-unique-situations"><h3>Self-Study Module<span class="edition-tag edition-tag-4">4th Edition</span><span class="cme-tag cme-tag-available">CNE/CME Available</span></h3> Track your progress and receive CE credit</a><ul><li><a href="/custom/key-populations-unique-situations">Treatment of Key Populations and Unique Situations: Self-Study <span class="cme-tag cme-tag-available">CNE/CME</span></a></li></ul><h4>Lessons</h4><ol><li class="level2 level2-113"><a href="/custom/key-populations-unique-situations/treatment-hiv-coinfection"><span class="caption">Treatment of HCV in Persons with HIV Coinfection</span></a></li><li class="level2 level2-114"><a href="/custom/key-populations-unique-situations/treament-renal-impairment"><span class="caption">Treatment of HCV in Persons with Renal Impairment</span></a></li><li class="level2 level2-115"><a href="/custom/key-populations-unique-situations/treatment-substance-use"><span class="caption">Treatment of HCV in Persons with Substance Use</span></a></li><li class="level2 level2-116"><a href="/custom/key-populations-unique-situations/treatment-corrections"><span class="caption">Treatment of HCV in a Correctional Setting</span></a></li><li class="level2 level2-117"><a href="/custom/key-populations-unique-situations/management-health-care-workers-potentially-exposed-to-hcv"><span class="caption">Management of Health Care Personnel Exposed to HCV</span></a></li><li class="level2 level2-118"><a href="/custom/key-populations-unique-situations/perinatal-hcv-transmission"><span class="caption">Perinatal HCV Transmission</span></a></li></ol><ul><li><a href="/custom/key-populations-unique-situations/certificate">Certificate Requirements <span class="cme-tag cme-tag-available">CNE/CME</span></a></li></ul></div><div class="subsubmenu level2s"><a class="description" href="/go/key-populations-situations"><h3>Quick Reference<span class="edition-tag edition-tag-4">4th Edition</span></h3> Rapidly access information in this module</a><ul><li><a href="/go/key-populations-situations">Treatment of Key Populations and Unique Situations: Overview</a></li></ul><h4>Lessons</h4><ol><li class="level2 level2-158"><a href="/go/key-populations-situations/treatment-hiv-coinfection/core-concept/all"><span class="caption">Treatment of HCV in Persons with HIV Coinfection</span></a></li><li class="level2 level2-159"><a href="/go/key-populations-situations/treament-renal-impairment/core-concept/all"><span class="caption">Treatment of HCV in Persons with Renal Impairment</span></a></li><li class="level2 level2-160"><a href="/go/key-populations-situations/treatment-substance-use/core-concept/all"><span class="caption">Treatment of HCV in Persons with Substance Use</span></a></li><li class="level2 level2-161"><a href="/go/key-populations-situations/treatment-corrections/core-concept/all"><span class="caption">Treatment of HCV in a Correctional Setting</span></a></li><li class="level2 level2-162"><a href="/go/key-populations-situations/management-health-care-workers-potentially-exposed-to-hcv/core-concept/all"><span class="caption">Management of Health Care Personnel Exposed to HCV</span></a></li><li class="level2 level2-163"><a href="/go/key-populations-situations/perinatal-hcv-transmission/core-concept/all"><span class="caption">Perinatal HCV Transmission</span></a></li></ol></div></li></ul></div></li><li class="section tools has-submenu"><a href="/page/clinical-calculators/apri" class="link ">Tools &<br /> Calculators<span class="submenu-trigger"></span></a><div class="submenu tools"><ul><li 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concepts, etc..." /></div><div class="search-results-container"></div><div class="search-notice"><strong>Use this Search to quickly find items or navigate the site.</strong></div></div></li></ul><div class="user-status"><a class="loggedout" href="https://www.hepatitisC.uw.edu/alternate" title="Sign In for registered users"><span class="glyphicon glyphicon-log-in"></span><span class="label-text"> Sign In</span></a><span class="hidden-xs"> or <a class="loggedout" href="https://www.hepatitisC.uw.edu/page/account/register" title="Create an account">Register</a></span></div></div></div></div></section><div id="wrap" class="content-wrap"> <div id="content"> <div id="notifications"></div><div class="page-titles"><h2 class="main-title level134"><a href="/go/evaluation-staging-monitoring"><span class="heading">Evaluation, Staging, and Monitoring of Chronic Hepatitis C</span></a></h2><h2 class="main-subtitle level134"><a href="/go/evaluation-staging-monitoring/evaluation-staging"><span class="heading">Evaluation and Staging of Liver Fibrosis</span></a></h2></div><div id="page" class="levels level134 menu-closed-forced menu-closed level4"><div class="inner"><div id="sidebar" class=""><span class="menu-toggle"><span class="icon_open glyphicon glyphicon-menu-hamburger title-extra" title="Open the navigation menu"></span><span class="icon_closed glyphicon glyphicon-remove" title="Hide the navigation menu"></span><span class="button-description">Section Navigation</span></span><div class="header">Section Navigation</div><div class="inner"><ul class="overview"><li class="page page-overview level1 first not-started"><a href="/go/evaluation-staging-monitoring" class="title-extra level1 " title="Evaluation, Staging, and Monitoring of Chronic Hepatitis C"><span class="type">Module 2 Overview</span><br /><span class="title">Evaluation, Staging, and Monitoring of Chronic Hepatitis C</span></a></li><li class="level2 not-started"><a href="/go/evaluation-staging-monitoring/initial-evaluation-chronic" title="Initial Evaluation of Persons with Chronic HCV" class="title-extra level2"><span class="progress-container level134" title="Progress of this Lessons"><span class="progress-bar progress-bar-0" style="width: 0%"><span class="percent less">0%</span></span></span><span class="type">Lesson 1</span><br /><span class="title">Initial Evaluation of Persons with Chronic HCV</span></a><div class="level3s" ><span class="title">Activities</span><ol><li class="level3 active-trail"><a href="/go/evaluation-staging-monitoring/initial-evaluation-chronic/core-concept/all" class="title-extra active-trail" title="Core Concepts"><span class="ui-icon ui-icon-note"></span><span class="num">1A.</span>Core Concepts</a></li><li class="level3"><a href="/go/evaluation-staging-monitoring/initial-evaluation-chronic/calculating-bmi" title="Calculating Body Mass Index (BMI)" class="title-extra"><span class="ui-icon ui-icon-calculator"></span><span class="num">1B.</span>Calculating Body Mass Index (BMI)</a></li><li class="level3"><a href="/go/evaluation-staging-monitoring/initial-evaluation-chronic/determining-audit-c" title="Determining AUDIT-C Score" class="title-extra"><span class="ui-icon ui-icon-calculator"></span><span class="num">1C.</span>Determining AUDIT-C Score</a></li></ol><li class="level2 not-started"><a href="/go/evaluation-staging-monitoring/natural-history" title="Natural History of HCV Infection" class="title-extra level2"><span class="progress-container level134" title="Progress of this Lessons"><span class="progress-bar progress-bar-0" style="width: 0%"><span class="percent less">0%</span></span></span><span class="type">Lesson 2</span><br /><span class="title">Natural History of HCV Infection</span></a><div class="level3s" ><span class="title">Activities</span><ol><li class="level3 active-trail"><a href="/go/evaluation-staging-monitoring/natural-history/core-concept/all" class="title-extra active-trail" title="Core Concepts"><span class="ui-icon ui-icon-note"></span><span class="num">2A.</span>Core Concepts</a></li></ol><li class="level2 not-started"><a href="/go/evaluation-staging-monitoring/counseling-liver-health" title="Counseling Persons with Chronic HCV Infection" class="title-extra level2"><span class="progress-container level134" title="Progress of this Lessons"><span class="progress-bar progress-bar-0" style="width: 0%"><span class="percent less">0%</span></span></span><span class="type">Lesson 3</span><br /><span class="title">Counseling Persons with Chronic HCV Infection</span></a><div class="level3s" ><span class="title">Activities</span><ol><li class="level3 active-trail"><a href="/go/evaluation-staging-monitoring/counseling-liver-health/core-concept/all" class="title-extra active-trail" title="Core Concepts"><span class="ui-icon ui-icon-note"></span><span class="num">3A.</span>Core Concepts</a></li></ol><li class="level2 active-trail expanded not-started"><a href="/go/evaluation-staging-monitoring/evaluation-staging" title="Evaluation and Staging of Liver Fibrosis" class="title-extra level2 active-trail expanded"><span class="progress-container level134" title="Progress of this Lessons"><span class="progress-bar progress-bar-0" style="width: 0%"><span class="percent less">0%</span></span></span><span class="type">Lesson 4</span><br /><span class="title">Evaluation and Staging of Liver Fibrosis</span></a><span class="active-trail-indicator"></span><div class="level3s" ><span class="title">Activities</span><ol><li class="level3 active-trail"><a href="/go/evaluation-staging-monitoring/evaluation-staging/core-concept/all" class="title-extra active-trail" title="Core Concepts"><span class="ui-icon ui-icon-note"></span><span class="num">4A.</span>Core Concepts</a></li><li class="level3"><a href="/go/evaluation-staging-monitoring/evaluation-staging/calculating-apri" title="Calculating APRI" class="title-extra"><span class="ui-icon ui-icon-calculator"></span><span class="num">4B.</span>Calculating APRI</a></li></ol><li class="level2 not-started"><a href="/go/evaluation-staging-monitoring/evaluation-prognosis-cirrhosis" title="Evaluation and Prognosis of Persons with Cirrhosis" class="title-extra level2"><span class="progress-container level134" title="Progress of this Lessons"><span class="progress-bar progress-bar-0" style="width: 0%"><span class="percent less">0%</span></span></span><span class="type">Lesson 5</span><br /><span class="title">Evaluation and Prognosis of Persons with Cirrhosis</span></a><div class="level3s" ><span class="title">Activities</span><ol><li class="level3 active-trail"><a href="/go/evaluation-staging-monitoring/evaluation-prognosis-cirrhosis/core-concept/all" class="title-extra active-trail" title="Core Concepts"><span class="ui-icon ui-icon-note"></span><span class="num">5A.</span>Core Concepts</a></li></ol><li class="level2 not-started"><a href="/go/evaluation-staging-monitoring/surveillance-hepatocellular-carcinoma" title="Surveillance for Hepatocellular Carcinoma" class="title-extra level2"><span class="progress-container level134" title="Progress of this Lessons"><span class="progress-bar progress-bar-0" style="width: 0%"><span class="percent less">0%</span></span></span><span class="type">Lesson 6</span><br /><span class="title">Surveillance for Hepatocellular Carcinoma</span></a><div class="level3s" ><span class="title">Activities</span><ol><li class="level3 active-trail"><a href="/go/evaluation-staging-monitoring/surveillance-hepatocellular-carcinoma/core-concept/all" class="title-extra active-trail" title="Core Concepts"><span class="ui-icon ui-icon-note"></span><span class="num">6A.</span>Core Concepts</a></li></ol><li class="level2 not-started"><a href="/go/evaluation-staging-monitoring/extrahepatic-conditions" title="Extrahepatic Conditions Related to HCV Infection" class="title-extra level2"><span class="progress-container level134" title="Progress of this Lessons"><span class="progress-bar progress-bar-0" style="width: 0%"><span class="percent less">0%</span></span></span><span class="type">Lesson 7</span><br /><span class="title">Extrahepatic Conditions Related to HCV Infection</span></a><div class="level3s" ><span class="title">Activities</span><ol><li class="level3 active-trail"><a href="/go/evaluation-staging-monitoring/extrahepatic-conditions/core-concept/all" class="title-extra active-trail" title="Core Concepts"><span class="ui-icon ui-icon-note"></span><span class="num">7A.</span>Core Concepts</a></li></ol></div></li></ul><ul class="progress-tracker"><li class="progress-tracker last"><a href="javascript:void(0)" onclick="progressTracker()" class="progress-tracker title-extra" title="Progress Tracker"><i class="glyph-tasks"></i> Progress Tracker</a></li></ul></div></div><div id="page-content"><h1 class="title" id="page-title"><span class="type">Lesson 4.</span> Evaluation and Staging of Liver Fibrosis</h1><div id="page-navigation-top" class="page-navigation "><div class="content"><span class="left"><a class="button button-instructions left" alt="Self-Study Module" title="Evaluation, Staging, and Monitoring of Chronic Hepatitis C" href="https://www.hepatitisC.uw.edu/custom/evaluation-staging-monitoring/evaluation-staging"><span class="cme-tag cme-tag-available">CME/CNE</span> Earn CE credit for this module</a> </span><span class="reading-pane"><a class="button button-print left" title="PDF" href="//cdn.hepatitisc.uw.edu/pdf/evaluation-staging-monitoring/evaluation-staging/core-concept/all" target="_blank"><span class="glyphicon glyphicon-print"></span> PDF</a><a class="button button-share left" title="Share page" href="https://www.hepatitisC.uw.edu/go/evaluation-staging-monitoring/evaluation-staging/core-concept/all" onclick="return sharePage()" target="_blank"><span class="glyphicon glyphicon-envelope"></span> Share</a></span><span class="right next"></div></div><div class="section section-popup section-instructions-popup"><a class="close" onclick="toggleInstructions()"></a><div class="section section-objectives"><h3 class="title" id="objectives">Learning Objective Performance Indicators</h3><div class="content"><ul> <li>Discuss noninvasive indirect markers used for estimating liver fibrosis</li> <li>Describe noninvasive direct markers used for estimating liver fibrosis</li> <li>Summarize key radiologic methods that can estimate hepatic fibrosis</li> <li>List the transient elastography cutoff that is used to estimate cirrhosis in persons with chronic HCV</li> <li>Explain the indications, risks, and histologic assessment for liver biopsy in persons with chronic HCV</li> </ul></div></div></div><div class="inner"><div class="major-section major-section-core-concepts"><div class="section section-core-concepts"><div class="content"><div class="core-concepts-info"><div class="last-updated"><strong>Last Updated:</strong> <span class="date">March 16th, 2024</span></div><div class="contributor-blurbs speaker-info-level1"><strong>Authors:</strong> <div class="contributor-blurb"><a href="javascript:void(0)">H. Nina Kim, MD, MSc</a><div class="data-content"><strong>H. Nina Kim, MD, MSc</strong><br /> Professor of Medicine<br /> Division of Allergy & Infectious Diseases<br /> University of Washington<div class="disclosures"><em>Disclosures</em>: None</div></div></div>, <div class="contributor-blurb"><a href="javascript:void(0)">Maria A. Corcorran, MD, MPH</a><div class="data-content"><strong>Maria A. Corcorran, MD, MPH</strong><br /> Assistant Professor<br /> Division of Allergy & Infectious Diseases<br /> University of Washington<div class="disclosures"><em>Disclosures</em>: None</div></div></div></div><div class="contributor-blurbs speaker-info-level1 count-one"><strong>Reviewer:</strong> <div class="contributor-blurb"><a href="javascript:void(0)">David H. Spach, MD</a><div class="data-content"><strong>David H. Spach, MD</strong><br /> Professor of Medicine<br /> Division of Allergy & Infectious Diseases<br /> University of Washington<div class="disclosures"><em>Disclosures</em>: None</div></div></div></div></div></div></div><div id="page-toc" class="page-toc"><div class="header" title="Click to Pin/Unpin"><span class="heading">Table of Contents</span></div><ul class="nav nav-tabs"><li class="page-title nav-item"><a class="nav-link" href="#page-title">Evaluation and Staging of Liver Fibrosis</a></li><li class="nav-item"><a class="nav-link" href="#background">Background</a><ul class="subtoc"><li><a href="#background-pathogenesis-fibrosis-chronic-hcv-infection">Pathogenesis of Fibrosis with Chronic HCV Infection</a></li><li><a href="#background-general-approach-to-evaluating-liver-fibrosis">General Approach to Evaluating Liver Fibrosis</a></li></ul></li><li class="nav-item"><a class="nav-link" href="#indirect-markers-estimating-hepatic-fibrosis">Indirect Markers for Estimating Hepatic Fibrosis</a><ul class="subtoc"><li><a href="#indirect-markers-estimating-hepatic-fibrosis-commonly-used-indirect-markers-hepatic-fibrosis">Commonly Used Indirect Markers for Hepatic Fibrosis</a></li><li><a href="#indirect-markers-estimating-hepatic-fibrosis-less-commonly-used-markers-hepatic-fibrosis">Less Commonly Used Markers for Hepatic Fibrosis</a></li></ul></li><li class="nav-item"><a class="nav-link" href="#direct-markers-fibrosis">Direct Markers of Fibrosis</a><ul class="subtoc"><li><a href="#direct-markers-fibrosis-fibrospect-ii">FIBROSpect II</a></li></ul></li><li class="nav-item"><a class="nav-link" href="#radiologic-modalities-to-estimate-fibrosis">Radiologic Modalities to Estimate Fibrosis</a><ul class="subtoc"><li><a href="#radiologic-modalities-to-estimate-fibrosis-transient-elastography">Transient Elastography</a></li><li><a href="#radiologic-modalities-to-estimate-fibrosis-shear-wave-elastography">Shear Wave Elastography</a></li><li><a href="#radiologic-modalities-to-estimate-fibrosis-hepatic-ultrasound">Hepatic Ultrasound</a></li><li><a href="#radiologic-modalities-to-estimate-fibrosis-magnetic-resonance-elastography">Magnetic Resonance Elastography</a></li><li><a href="#radiologic-modalities-to-estimate-fibrosis-computed-tomography">Computed Tomography</a></li></ul></li><li class="nav-item"><a class="nav-link" href="#liver-biopsy-histologic-assessment-liver">Liver Biopsy and Histologic Assessment of the Liver</a><ul class="subtoc"><li><a href="#liver-biopsy-histologic-assessment-liver-liver-biopsy">Liver Biopsy</a></li><li><a href="#liver-biopsy-histologic-assessment-liver-indications-liver-biopsy">Indications for Liver Biopsy</a></li><li><a href="#liver-biopsy-histologic-assessment-liver-approaches-to-liver-biopsy">Approaches to Liver Biopsy</a></li><li><a href="#liver-biopsy-histologic-assessment-liver-classification-liver-histology">Classification of Liver Histology</a></li></ul></li><li class="nav-item"><a class="nav-link" href="#summary-points">Summary Points</a></li><li role="separator" class="divider"></li><li class="nav-item"><a class="nav-link" href="#citations">Citations</a></li><li class="nav-item"><a class="nav-link" href="#references-unassigned">Additional References</a></li><li class="nav-item"><a class="nav-link" href="#figures">Figures</a></li></ul></div><div class="core-concepts-text"><div class="content"><div class="core-concept-subsection"><h2 class="section-title" id="background">Background</h2><div class="level4s level4s-full-text section-content"><!DOCTYPE html PUBLIC "-//W3C//DTD HTML 4.0 Transitional//EN" "http://www.w3.org/TR/REC-html40/loose.dtd"> <html><body><h3 id="background-pathogenesis-fibrosis-chronic-hcv-infection">Pathogenesis of Fibrosis with Chronic HCV Infection</h3> <p>Hepatic fibrosis is a dynamic scarring process in which chronic inflammation stimulates production and accumulation of collagen and extracellular matrix proteins.<span class="reference-group reference-inline">[<a href="#reference-984" class="ref no-popup">1</a>,<a href="#reference-2442" class="ref no-popup">2</a>]</span> The hepatic stellate cells are the primary cells responsible for producing these extracellular matrix proteins. Over time, with chronic hepatitis C virus (HCV) infection, the total extracellular matrix protein content increases, and fibrosis can develop, with potential progression to cirrhosis.<span class="reference-group reference-inline">[<a href="#reference-2443" class="ref no-popup">3</a>]</span> This dynamic process can also involve remodeling and regression of the fibrous tissue via breakdown of the matrix proteins by the protease enzymes matrix metalloproteinases (MMP).<span class="reference-group reference-inline">[<a href="#reference-2442" class="ref no-popup">2</a>,<a href="#reference-2441" class="ref no-popup">4</a>]</span> </p> <h3 id="background-general-approach-to-evaluating-liver-fibrosis">General Approach to Evaluating Liver Fibrosis</h3> <p>Fibrosis is a precursor to cirrhosis, and establishing the severity of liver fibrosis helps predict liver-related morbidity and mortality, as well as to inform the need for hepatocellular carcinoma (HCC) screening in persons with chronic HCV. Noninvasive methods to estimate hepatic fibrosis are commonly used in clinical practice as a safer, more accessible, and less costly strategy than liver biopsy for stratifying persons according to risk.<span class="reference-group reference-inline">[<a href="#reference-2421" class="ref no-popup">5</a>,<a href="#reference-1622" class="ref no-popup">6</a>,<a href="#reference-2431" class="ref no-popup">7</a>]</span> These methods include indirect biomarkers, direct biomarkers, and elastography.<span class="reference-group reference-inline">[<a href="#reference-2431" class="ref no-popup">7</a>,<a href="#reference-2756" class="ref no-popup">8</a>,<a href="#reference-2757" class="ref no-popup">9</a>]</span> If a combination of noninvasive methods provides a clear-cut assessment of hepatic fibrosis, further assessment with liver biopsy is generally not needed.<span class="reference-group reference-inline">[<a href="#reference-1735" class="ref no-popup">10</a>,<a href="#reference-911" class="ref no-popup">11</a>]</span> Although liver biopsy with histologic analysis has long been considered the gold standard evaluation of hepatic fibrosis, it is now infrequently used for evaluation of liver fibrosis in persons with chronic HCV.<span class="reference-group reference-inline">[<a href="#reference-907" class="ref no-popup">12</a>]</span> In the current era, the optimal approach to fibrosis assessment is to use noninvasive serum markers/tests in conjunction with transient elastography. If transient elastography is not available, two different noninvasive serum markers/tests should be used.</p></body></html> </div></div><div class="core-concept-subsection"><h2 class="section-title" id="indirect-markers-estimating-hepatic-fibrosis">Indirect Markers for Estimating Hepatic Fibrosis</h2><div class="level4s level4s-full-text section-content"><!DOCTYPE html PUBLIC "-//W3C//DTD HTML 4.0 Transitional//EN" "http://www.w3.org/TR/REC-html40/loose.dtd"> <html><body><p>In recent years, the use of noninvasive (both indirect and direct) measures of fibrosis has become commonplace in clinical practice. Initial screening with simple laboratory tests, such as platelet count, prothrombin time, albumin, total bilirubin, and serum aminotransferase levels, are commonly performed to estimate fibrosis and identify cirrhosis. Different combinations of these measures have been used to estimate the degree of hepatic fibrosis in persons with chronic HCV. Additional serum markers of fibrosis, such as hyaluronic acid (HA) and alpha-2-macroglobulin, are less readily available and have been utilized primarily in tests that include panels of such markers, often combined with standard clinical liver tests.</p> <h3 id="indirect-markers-estimating-hepatic-fibrosis-commonly-used-indirect-markers-hepatic-fibrosis">Commonly Used Indirect Markers for Hepatic Fibrosis</h3> <h4>Aspartate Aminotransferase-to-Platelet Ratio Index (APRI)</h4> <p>The APRI model was developed as a simple, easily calculated method to predict significant, severe fibrosis (or cirrhosis) and has been tested in persons with HCV monoinfection and those with HCV and HIV coinfection.<span class="reference-group reference-inline">[<a href="#reference-405" class="ref no-popup">13</a>,<a href="#reference-2423" class="ref no-popup">14</a>]</span> The APRI is calculated using the individual’s aspartate aminotransferase (AST) level, corrected for the upper limit of normal, and platelet count (<a title="Figure 1 - Aspartate Aminotransferase-to-Platelet-Ratio Index (APRI)" data-doc-scroll="0" data-doc-source-format="0" data-doc-id="96" data-doc-weight="1" data-doc-source="png" data-doc-info-width="1278" data-doc-info-height="532" alt="Abbreviations: AST = aspartate aminotransferase<br /> The AST upper limit of normal should be the upper limit of normal established by the laboratory that performed the test. Most laboratories use an AST upper limit of 40 IU/mL.<div></div>" class="linked-doc-1 style-text-width-below document has-link-relation link-relation-below" href="//cdn.hepatitisc.uw.edu/doc/96-2/aspartate-aminotransferase-to-platelet-ratio-index-apri.jpg">Figure 1</a>). A meta-analysis of 40 studies found that an APRI cutoff of greater than or equal to 0.7 had an estimated sensitivity of 77% and specificity of 72% for detection of significant hepatic fibrosis (greater than or equal to F2 by Metavir) in persons with chronic HCV.<span class="reference-group reference-inline">[<a href="#reference-915" class="ref no-popup">15</a>]</span> A cutoff score of at least 1.0 has an estimated sensitivity of 61 to 76% and specificity of 64 to 72% for detection of severe fibrosis/cirrhosis (F3 to F4 by Metavir). For detection of cirrhosis, a cutoff score of at least 2.0 was more specific (91%) but less sensitive (46%). Overall, APRI has good diagnostic utility for predicting severe fibrosis/cirrhosis or low risk of significant fibrosis, but does not accurately differentiate intermediate stages of fibrosis from mild or severe fibrosis. Thus, clinicians should use APRI in combination with other noninvasive markers of fibrosis, rather than as the sole method of staging.<span class="reference-group reference-inline">[<a href="#reference-3421" class="ref no-popup">16</a>]</span></p> <h4>FIB-4</h4> <p>The FIB-4 is a widely used index based on readily available routine laboratory values and has been shown to have good performance characteristics for estimating hepatic fibrosis in large observational cohorts, including in persons with HCV and HIV coinfection.<span class="reference-group reference-inline">[<a href="#reference-913" class="ref no-popup">17</a>,<a href="#reference-918" class="ref no-popup">18</a>,<a href="#reference-3286" class="ref no-popup">19</a>]</span> Results are generated utilizing age, AST, alanine aminotransferase (ALT), and platelet count (<a title="Figure 2 - FIB-4" data-doc-scroll="0" data-doc-source-format="0" data-doc-id="97" data-doc-weight="2" data-doc-source="png" data-doc-info-width="1182" data-doc-info-height="509" alt="Abbreviations: AST = aspartate aminotransferase; ALT = alanine aminotransferase<div>Source: Vallet-Pichard A, Mallet V, Nalpas B, et al. FIB-4: an inexpensive and accurate marker of fibrosis in HCV infection. comparison with liver biopsy and fibrotest. Hepatology. 2007;46:32-6.</div>" class="linked-doc-2 style-text-width-below document has-link-relation link-relation-below" href="//cdn.hepatitisc.uw.edu/doc/97-3/fib-4.jpg">Figure 2</a>). A threshold value of less than 1.45 has a sensitivity of 74% and a negative predictive value of 95% for excluding advanced fibrosis (F3-F4).<span class="reference-group reference-inline">[<a href="#reference-919" class="ref no-popup">20</a>]</span> A threshold value greater than 3.25 has a positive predictive value for advanced fibrosis of 65 to 82%, with a specificity of 98% in confirming cirrhosis.<span class="reference-group reference-inline">[<a href="#reference-918" class="ref no-popup">18</a>,<a href="#reference-919" class="ref no-popup">20</a>]</span> This model was good at excluding or confirming cirrhosis, but values between 1.45 and 3.25 did not fully discriminate fibrosis and would need an additional method to predict liver fibrosis.<span class="reference-group reference-inline">[<a href="#reference-3421" class="ref no-popup">16</a>]</span> The <span class="guideline layout-inline" id="guideline-1"><span class="inline-guidelines inline-highlight guideline-1" title="American Association for the Study of Liver Diseases (AASLD)-Infectious Diseases Society of America (IDSA) HCV Guidance" data-guideline-id="1"><span class="field field-title">AASLD-IDSA HCV Guidance</span></span></span> considers a patient with chronic HCV is presumed to have cirrhosis if they have a FIB-4 score of greater than 3.25.<span class="reference-group reference-inline">[<a href="#reference-3125" class="ref no-popup">21</a>,<a href="#reference-3124" class="ref no-popup">22</a>,<a href="#reference-3295" class="ref no-popup">23</a>]</span></p> <h4>FibroTest and ActiTest</h4> <p>The HCV FibroTest and ActiTest are used for the assessment of liver fibrosis and inflammation, respectively.</p> <ul> <li><strong>FibroTest</strong>: The FibroTest uses a proprietary algorithm that includes the individual’s age and gender, along with a composite of five biochemical markers associated with hepatic fibrosis: alpha-2-macroglobulin, haptoglobin, gamma-glutamyltransferase (GGT), apolipoprotein A1, and total bilirubin. The FibroTest estimates hepatic fibrosis. In one meta-analysis of 30 studies with over 2,400 individual-level data, the FibroTest was found to be a reasonable alternative to biopsy for distinguishing moderate to higher fibrosis stages (F2-F4) from mild disease stages, with a mean standardized area under the receiver-operating characteristics (AUROC) curve of 85% for chronic HCV.<span class="reference-group reference-inline">[<a href="#reference-2427" class="ref no-popup">24</a>]</span></li> <li><strong>ActiTest</strong>: The ActiTest uses a second algorithm that adds a direct marker for inflammatory activity (the ALT value) to the same five parameters in the FibroTest. The ActiTest estimates hepatic inflammation (necroinflammation activity grade).<span class="reference-group reference-inline">[<a href="#reference-2439" class="ref no-popup">25</a>]</span></li> <li><strong>FibroSure Test/FibroTest-ActiTest</strong>: Commercially, the FibroTest and ActiTest are typically obtained as a combination test and referred to as the FibroSure Test or the FibroTest-ActiTest. Like other biomarkers, this test is indeterminate for discriminating the middle ranges, and an adjunct marker of fibrosis would be needed in those situations. Contraindications or cautions for use of these methods for fibrosis staging include the presence of any of the following: Gilbert’s disease, acute hemolysis, acute liver inflammation, extrahepatic cholestasis, renal insufficiency, posttransplantation, or receipt of medications that may cause unconjugated hyperbilirubinemia. All of these conditions may lead to inaccurate quantitative predictions. The HCV FibroTest-ActiTest is not approved by the Food and Drug Administration (FDA), but is available through LabCorp and the Mayo Clinic.</li> </ul> <h3 id="indirect-markers-estimating-hepatic-fibrosis-less-commonly-used-markers-hepatic-fibrosis">Less Commonly Used Markers for Hepatic Fibrosis</h3> <h4>FibroIndex</h4> <p>The FibroIndex is a simple scoring method consisting of three biochemical markers: AST, platelet count, and gamma globulin (<a title="Figure 3 - FibroIndex" data-doc-scroll="0" data-doc-source-format="0" data-doc-id="98" data-doc-weight="3" data-doc-source="png" data-doc-info-width="1304" data-doc-info-height="566" alt="Abbreviations: AST = aspartate aminotransferase<div>Source: Koda M, Matunaga Y, Kawakami M, Kishimoto Y, Suou T, Murawaki Y. FibroIndex, a practical index for predicting significant fibrosis in patients with chronic hepatitis C. Hepatology. 2007;45:297-306.</div>" class="linked-doc-3 style-text-width-below document has-link-relation link-relation-below" href="//cdn.hepatitisc.uw.edu/doc/98-3/fibroindex.jpg">Figure 3</a>).<span class="reference-group reference-inline">[<a href="#reference-914" class="ref no-popup">26</a>]</span> When a cutoff of less than or equal to 1.25 was used, the sensitivity was 40% and specificity 94% for mild fibrosis (F0 or F1 by Metavir). When a cutoff of greater than or equal to 2.25, the sensitivity was 36% and specificity 97% for significant fibrosis (F2 or F3 by Metavir). Persons with F4 fibrosis were not included in the validation study. The FibroIndex has good specificity but low sensitivity for determining mild or significant fibrosis. Because of this low sensitivity, the FibroIndex is not an adequate tool to be used alone but may serve as an adjunct along with other fibrosis markers.</p> <h4>Forns Index</h4> <p>The Forns Index uses simply obtained parameters—age, GGT, cholesterol, and platelet count—but requires a relatively complicated calculation (<a title="Figure 4 - Forns Index" data-doc-scroll="0" data-doc-source-format="0" data-doc-id="99" data-doc-weight="4" data-doc-source="png" data-doc-info-width="1364" data-doc-info-height="578" alt="<div>Forns X, Ampurdanès S, Llovet JM, et al. Identification of chronic hepatitis C patients without hepatic fibrosis by a simple predictive model. Hepatology. 2002;36(4 Pt 1):986-92.</div>" class="linked-doc-4 style-text-width-below document has-link-relation link-relation-below" href="//cdn.hepatitisc.uw.edu/doc/99-3/forns-index.jpg">Figure 4</a>).<span class="reference-group reference-inline">[<a href="#reference-912" class="ref no-popup">27</a>]</span> A cutoff score of less than 4.25 had a negative predictive value of 96% for excluding significant fibrosis (F2, F3, or F4). At a cutoff of greater than 6.9, the positive predictive value was 66% for significant fibrosis (F2, F3, or F4). This tool is useful and has good predictive value in identifying those with a low risk of significant fibrosis, but it does not reliably predict more advanced fibrosis or cirrhosis. Due to varying cholesterol levels that occur in persons with HCV genotype 3, this method should not be used in these individuals.<span class="reference-group reference-inline">[<a href="#reference-3166" class="ref no-popup">28</a>]</span> This method, along with other serum biomarkers, has also been studied as a predictive tool to evaluate fibrosis regression in response to HCV therapy, and for fibrosis assessment in persons with HIV and HCV coinfection, with comparable predictive value to persons with HCV monoinfection.<span class="reference-group reference-inline">[<a href="#reference-2425" class="ref no-popup">29</a>,<a href="#reference-2426" class="ref no-popup">30</a>]</span></p> <h4>HepaScore</h4> <p>The HepaScore was designed to improve upon nonspecific marker indices in fibrosis models by adding fibrosis-specific markers (age, sex, total bilirubin, GGT, alpha-2-macroglobulin, and hyaluronic acid levels).<span class="reference-group reference-inline">[<a href="#reference-909" class="ref no-popup">31</a>]</span> The HepaScore algorithm is more complicated than other indirect markers, and the laboratory performing the test utilizes a complex modeling equation to generate the result (<a title="Figure 5 - HepaScore (FibroScore)" data-doc-scroll="0" data-doc-source-format="0" data-doc-id="100" data-doc-weight="5" data-doc-source="png" data-doc-info-width="1381" data-doc-info-height="574" alt="<div>Becker L, Salameh W, Sferruzza A, et al. Validation of hepascore, compared with simple indices of fibrosis, in patients with chronic hepatitis C virus infection in United States. Clin Gastroenterol Hepatol. 2009;7:696-701.</div>" class="linked-doc-5 style-text-width-below document has-link-relation link-relation-below" href="//cdn.hepatitisc.uw.edu/doc/100-3/hepascore-fibroscore.jpg">Figure 5</a>). At values less than or equal to 0.2, the negative predictive value to exclude fibrosis is 98%. At values greater than or equal to 0.8, the positive predictive value for predicting cirrhosis is 62%. Given the good negative predictive value with a low HepaScore, this method is reliable for excluding significant fibrosis but not as good at predicting cirrhosis. For a HepaScore of greater than 0.2, an adjunct marker of fibrosis should be used to predict cirrhosis.</p></body></html> </div></div><div class="core-concept-subsection"><h2 class="section-title" id="direct-markers-fibrosis">Direct Markers of Fibrosis</h2><div class="level4s level4s-full-text section-content"><!DOCTYPE html PUBLIC "-//W3C//DTD HTML 4.0 Transitional//EN" "http://www.w3.org/TR/REC-html40/loose.dtd"> <html><body><p>Direct markers of fibrosis include procollagen type (I, III, IV), matrix metalloproteinases, cytokines, and chemokines. The direct markers have shown variable effectiveness in predicting liver fibrosis. Among these markers, those currently used involve matrix metalloproteinases. Liver fibrosis/cirrhosis is characterized by enhanced extracellular matrix synthesis by activated stellate cells.<span class="reference-group reference-inline">[<a href="#reference-984" class="ref no-popup">1</a>,<a href="#reference-2442" class="ref no-popup">2</a>]</span> Matrix metalloproteinases are endopeptidases that can degrade collagen and are involved in the tissue remodeling process that takes place with fibrosis.<span class="reference-group reference-inline">[<a href="#reference-984" class="ref no-popup">1</a>]</span> Levels of matrix metalloproteinases are regulated by specific tissue inhibitors of metalloproteinase (TIMPs) and a mismatch between these inhibitors is associated with extracellular matrix deposition and breakdown. Levels of TIMP-1 significantly correlate with fibrosis, with a sensitivity of 100% in diagnosing cirrhosis, but these tests have low specificity. Hyaluronic acid is a glycosaminoglycan secreted by hepatic stellate cells and is one of the chief components of the extracellular matrix. Extensive fibrosis/cirrhosis has been found to be associated with increased serum levels of hyaluronic acid.<span class="reference-group reference-inline">[<a href="#reference-3423" class="ref no-popup">32</a>]</span></p> <h3 id="direct-markers-fibrosis-fibrospect-ii">FIBROSpect II</h3> <p>The FIBROSpect II is a commercially available test that combines hyaluronic acid, tissue inhibitor of a metalloproteinase-1 (TIMP-1), and alpha-2-macroglobulin in a predictive algorithm for fibrosis stages F2 to F4. An index score of greater than 0.42 correlates with the presence of stage F2 to F4 fibrosis. Based on data from the test manufacturer involving 696 persons with chronic HCV infection, the overall sensitivity at this cutoff is 80.6% and the specificity 71.4%.<span class="reference-group reference-inline">[<a href="#reference-406" class="ref no-popup">33</a>]</span> Overall, similar to the noninvasive serum markers of fibrosis, the FIBROSpect II test is good for determining the presence or absence of significant fibrosis, but not useful in differentiating among intermediate stages of fibrosis.<span class="reference-group reference-inline">[<a href="#reference-620" class="ref no-popup">34</a>]</span> The HCV FIBROSpect II is not approved by the Food and Drug Administration.</p></body></html> </div></div><div class="core-concept-subsection"><h2 class="section-title" id="radiologic-modalities-to-estimate-fibrosis">Radiologic Modalities to Estimate Fibrosis</h2><div class="level4s level4s-full-text section-content"><!DOCTYPE html PUBLIC "-//W3C//DTD HTML 4.0 Transitional//EN" "http://www.w3.org/TR/REC-html40/loose.dtd"> <html><body><h3 id="radiologic-modalities-to-estimate-fibrosis-transient-elastography">Transient Elastography</h3> <p>Transient elastography (FibroScan) is a noninvasive, easy-to-perform office-based test that takes about 5 to 10 minutes; this test can be done in the clinic or office-based setting.<span class="reference-group reference-inline">[<a href="#reference-920" class="ref no-popup">35</a>]</span> Transient elastography examines a larger area of liver tissue (1 cm diameter by 5 cm in length) than liver biopsy and thus may provide a more representative assessment of the entire hepatic parenchyma. The test is performed using an ultrasound transducer probe that measures the shear wave velocity, which correlates directly with liver stiffness. Transient elastography was approved by the United States FDA in 2013 and has largely replaced liver biopsy as the preferred method for liver fibrosis staging in chronic HCV.</p> <ul> <li><strong>Transient Elastography Cutoff Values</strong>: In 2005, Castera published findings for optimal transient elastography cutoff values that correlate with Metavir fibrosis scores (<a title="Figure 6 - Correlation of Cutoffs and Metavir Fibrosis Scores" data-doc-scroll="0" data-doc-source-format="0" data-doc-id="315" data-doc-weight="6" data-doc-source="png" data-doc-info-width="1333" data-doc-info-height="555" alt="<div>Source: Castera L, Vergniol J, Foucher J, et al. Prospective comparison of transient elastography, Fibrotest, APRI, and liver biopsy for the assessment of fibrosis in chronic hepatitis C. Gastroenterology. 2005;128:343-50.</div>" class="linked-doc-6 style-text-width-split document document-series has-link-relation link-relation-below" href="//cdn.hepatitisc.uw.edu/doc/315-2/correlation-cutoffs-metavir-fibrosis-scores.jpg" onclick="return openFigure(6,this)">Figure 6</a>).<span class="reference-group reference-inline">[<a href="#reference-910" class="ref no-popup">36</a>,<a href="#reference-407" class="ref no-popup">37</a>,<a href="#reference-927" class="ref no-popup">38</a>]</span> This study of transient elastography found when liver stiffness values range between 2.5 and 7 kPa, mild or absent fibrosis is likely (F0-F1), scores between 7.1-9.5 correlated with significant fibrosis , scores between 9.6-12.5 indicated severe fibrosis (F3), whereas liver stiffness values above 12.5 kPa indicated cirrhosis (F4) is likely. Using a Castera study, a cutoff of 12.5 kPa (transient elastography score greater than 12.5 kPa), the diagnostic performance for cirrhosis in persons with chronic HCV was high, with a sensitivity of 87%, specificity of 91%, positive predictive value of 0.77, and a negative predictive value of 0.95. The <span class="guideline layout-inline" id="guideline-1"><span class="inline-guidelines inline-highlight guideline-1" title="American Association for the Study of Liver Diseases (AASLD)-Infectious Diseases Society of America (IDSA) HCV Guidance" data-guideline-id="1"><span class="field field-title">AASLD-IDSA HCV Guidance</span></span></span> considers a transient elastography score greater than 12.5 kPa as indicative of cirrhosis in patients with chronic HCV.<span class="reference-group reference-inline">[<a href="#reference-3125" class="ref no-popup">21</a>,<a href="#reference-3124" class="ref no-popup">22</a>,<a href="#reference-3295" class="ref no-popup">23</a>]</span></li> <li><strong>Factors that Impact Transient Elastography</strong>: It is important to note that in clinical practice, multiple factors, such as hepatic inflammation, obesity, ingestion of a meal within 2 hours of the test, ascites, and elevated central venous pressure, can influence the transient elastography result. In addition, use of transient elastography is not advised to stage fibrosis in pregnant women since pregnancy can be associated with a reversible increase in liver stiffness.<span class="reference-group reference-inline">[<a href="#reference-3168" class="ref no-popup">39</a>]</span></li> <li><strong>Contraindications for Transient Elastography</strong>: Transient elastography is contraindicated in those with pacemakers and implantable defibrillators.</li> <li><strong>Performance of Transient Elastography</strong>: Studies evaluating transient elastography have demonstrated reproducible performance across a variety of patient populations, including in persons with chronic HCV.<span class="reference-group reference-inline">[<a href="#reference-1734" class="ref no-popup">40</a>,<a href="#reference-924" class="ref no-popup">41</a>,<a href="#reference-922" class="ref no-popup">42</a>]</span> Most experts consider transient elastography as the most accurate noninvasive test for identifying Metavir Stage F3 fibrosis or cirrhosis, but in clinical practice, it is typically used in conjunction with other indirect or direct measures of hepatic fibrosis.</li> </ul> <h3 id="radiologic-modalities-to-estimate-fibrosis-shear-wave-elastography">Shear Wave Elastography</h3> <p>Shear wave elastography (ShearWave Elastography), otherwise known as ultrasound elastography, is a noninvasive sonographic test that can estimate hepatic fibrosis. The test is performed by watching a real-time image with B-mode ultrasound, and then measuring liver stiffness based on anatomical information; the test also can assess liver homogeneity based on the color images it generates that correlates with varying degrees of liver stiffness.<span class="reference-group reference-inline">[<a href="#reference-2759" class="ref no-popup">43</a>,<a href="#reference-2760" class="ref no-popup">44</a>]</span> Based on limited data, shear wave elastography performs with similar accuracy as transient elastography in estimating hepatic fibrosis.<span class="reference-group reference-inline">[<a href="#reference-2759" class="ref no-popup">43</a>,<a href="#reference-2760" class="ref no-popup">44</a>]</span> In the United States, shear wave elastography is used much less frequently than transient elastography.</p> <h3 id="radiologic-modalities-to-estimate-fibrosis-hepatic-ultrasound">Hepatic Ultrasound</h3> <p>Hepatic ultrasound is a noninvasive and reproducible technique for determining focal and parenchymal disease of the liver. Ultrasound can potentially identify various factors that are useful in evaluating chronic liver disease: nodularity of the liver surface (which reflects the presence of regenerative nodules and fibrous septa often seen in cirrhosis), coarseness of the parenchyma, patency and flow of veins and arteries, spleen size (which, if enlarged, can suggest portal hypertension), hepatocellular carcinoma, and small volume ascites. The use of high-frequency ultrasound transducers is reported to be more reliable than low-frequency ultrasound in diagnosing cirrhosis.<span class="reference-group reference-inline">[<a href="#reference-921" class="ref no-popup">45</a>]</span> In general, though, a standard ultrasound has been shown to have low sensitivity (in the range of 40%) for the detection of cirrhosis.<span class="reference-group reference-inline">[<a href="#reference-932" class="ref no-popup">46</a>]</span> In addition, false-positive readings by radiologists can occur, particularly in the absence of more conclusive findings of portal hypertension (e.g., coarse echotexture without splenomegaly).<span class="reference-group reference-inline">[<a href="#reference-3167" class="ref no-popup">47</a>]</span> Given the limitations noted above, hepatic ultrasound is not recommended routinely for liver disease staging.</p> <h3 id="radiologic-modalities-to-estimate-fibrosis-magnetic-resonance-elastography">Magnetic Resonance Elastography</h3> <p>Magnetic resonance elastography involves applying a probe to a person’s back, emitting low-frequency vibrations through the liver, which then are measured through magnetic resonance imaging spin echo sequence. A meta-analysis of five trials comparing magnetic resonance elastography to liver biopsies showed a sensitivity of 94% and specificity of 95% in differentiating F0 to F1 from F2 to F4, as well as a sensitivity of 98% and specificity of 94% in differentiating F0 to F3 from F4.<span class="reference-group reference-inline">[<a href="#reference-926" class="ref no-popup">48</a>]</span> This technique shares the same limitations as transient elastography and is less widely available.<span class="reference-group reference-inline">[<a href="#reference-931" class="ref no-popup">49</a>,<a href="#reference-925" class="ref no-popup">50</a>]</span></p> <h3 id="radiologic-modalities-to-estimate-fibrosis-computed-tomography">Computed Tomography</h3> Morphologic changes related to cirrhosis to the liver can be detected on computed tomography (CT) scan at later stages, but CT, like ultrasound, is not considered sufficiently sensitive for detecting less advanced stages of fibrosis.<span class="reference-group reference-inline">[<a href="#reference-3424" class="ref no-popup">51</a>]</span> Newer modalities, such as perfusion CT and software using artificial intelligence, may offer alternative and more sensitive options for staging fibrosis in the future.</body></html> </div></div><div class="core-concept-subsection"><h2 class="section-title" id="liver-biopsy-histologic-assessment-liver">Liver Biopsy and Histologic Assessment of the Liver</h2><div class="level4s level4s-full-text section-content"><!DOCTYPE html PUBLIC "-//W3C//DTD HTML 4.0 Transitional//EN" "http://www.w3.org/TR/REC-html40/loose.dtd"> <html><body><h3 id="liver-biopsy-histologic-assessment-liver-liver-biopsy">Liver Biopsy</h3> <p>Liver biopsy is considered the gold standard for diagnosing and assessing liver fibrosis.<span class="reference-group reference-inline">[<a href="#reference-907" class="ref no-popup">12</a>,<a href="#reference-3420" class="ref no-popup">52</a>]</span> Although liver biopsy is infrequently used to stage fibrosis in clinical practice, there are several advantages to this modality for fibrosis staging when compared to non-invasive testing. For one, a liver biopsy provides information on both the grade (degree of inflammation that reflects ongoing liver disease injury) and the stage (amount of currently established fibrosis) of liver fibrosis. Second, liver biopsy can provide helpful diagnostic information when other factors, such as alcohol consumption, chronic hepatitis B virus (HBV) infection, increased iron stores, or metabolic dysfunction-associated steatotic liver disease (MASLD), may be contributing to accelerated fibrosis progression.<span class="reference-group reference-inline">[<a href="#reference-985" class="ref no-popup">53</a>]</span> Given that potential liver injury related to any of these factors is best assessed by histology, their presence may contribute to the clinical decision-making process regarding the need for liver biopsy. There are several limitations to the use of liver biopsy that have curtailed its use for assessing fibrosis: (1) persons undergoing liver biopsy may experience significant pain with the procedure, (2) it may be associated with risk of bleeding, and (3) even under ideal circumstances, liver biopsy may incorrectly stage fibrosis 20% of the time due to sampling error and/or interobserver variability.<span class="reference-group reference-inline">[<a href="#reference-909" class="ref no-popup">31</a>,<a href="#reference-903" class="ref no-popup">54</a>,<a href="#reference-982" class="ref no-popup">55</a>,<a href="#reference-930" class="ref no-popup">56</a>,<a href="#reference-906" class="ref no-popup">57</a>]</span> Noninvasive methods for assessing fibrosis have replaced liver biopsy for the routine assessment of fibrosis severity in persons with chronic HCV.<span class="reference-group reference-inline">[<a href="#reference-928" class="ref no-popup">58</a>]</span>&</p> <h3 id="liver-biopsy-histologic-assessment-liver-indications-liver-biopsy">Indications for Liver Biopsy</h3> <p>Prior to the development of widely used noninvasive tests that estimate hepatic fibrosis, such as aspartate aminotransferase-to-platelet ratio index (APRI), FibroSure, FibroTest, and transient elastography (FibroScan), liver biopsy was used to estimate liver fibrosis. Traditionally, the primary reasons for doing a liver biopsy have been to (1) provide information on fibrosis stage, which can help guide therapeutic HCV management decisions, (2) diagnose coexisting liver diseases, and (3) help identify cirrhosis (or advanced fibrosis) that would necessitate routine cancer surveillance. In the current era, liver biopsy is used less frequently. The following outlines certain circumstances that may warrant consideration of liver biopsy when evaluating a person with chronic HCV.</p> <ul> <li>Two indirect markers (such as FibroTest and APRI) show discordant results. For example, when an APRI score is in the 0.5 to 1.5 range, and the FibroSure/FibroTest is less than 0.48, then a liver biopsy may be warranted to determine the presence or absence of advanced fibrosis/cirrhosis and the need for routine hepatocellular cancer surveillance and follow-up. This is most relevant when there is no access to transient elastography.</li> <li>There is a second cause of liver disease suspected.</li> <li>Indirect, direct, and transient elastography tests are unavailable or not advisable for specific reasons.</li> </ul> <h3 id="liver-biopsy-histologic-assessment-liver-approaches-to-liver-biopsy">Approaches to Liver Biopsy</h3> <p>There are three ways to obtain a liver biopsy: (1) percutaneous (often with ultrasound guidance), (2) transjugular or transfemoral, and (3) laparoscopic. The percutaneous route is the most commonly performed biopsy method in most settings. Specimens are obtained either with a core aspiration needle or sheathed cutting needle that is at least 16-gauge in caliber. The optimum size of a specimen that offers the least risk of understaging fibrosis is 3 cm in length after formalin fixation, and the sample should include at least 11 portal tracts. The number of portal tracts is relative to biopsy size, and, generally, samples greater than 2 cm in length are acceptable.<span class="reference-group reference-inline">[<a href="#reference-986" class="ref no-popup">59</a>]</span> In most circumstances, liver biopsy can be done with minimal side effects, but pain and bleeding can occur.<span class="reference-group reference-inline">[<a href="#reference-905" class="ref no-popup">60</a>]</span></p> <h3 id="liver-biopsy-histologic-assessment-liver-classification-liver-histology">Classification of Liver Histology</h3> <p>Several histologic scoring systems have been developed to grade (inflammation) and stage (fibrosis) hepatic disease caused by hepatitis (<a title="Figure 7 - Scoring Systems for Histologic Grade (Inflammation)" data-doc-scroll="0" data-doc-source-format="0" data-doc-id="95" data-doc-weight="7" data-doc-source="png" data-doc-info-width="800" data-doc-info-height="377" alt="Abbreviation: IASL = International Association for Study of the Liver <div>Modified from: Ghany MG, Strader DB, Thomas DL, Seeff LB; American Association for the Study of Liver Diseases. Diagnosis, management, and treatment of hepatitis C: an update. Hepatology. 2009;49:1335-74.</div>" class="linked-doc-7 style-text-width-split document document-series has-link-relation link-relation-below" href="//cdn.hepatitisc.uw.edu/doc/95-3/scoring-systems-histologic-grade-inflammation.jpg" onclick="return openFigure(7,this)">Figure 7</a>).<span class="reference-group reference-inline">[<a href="#reference-986" class="ref no-popup">59</a>,<a href="#reference-987" class="ref no-popup">61</a>,<a href="#reference-3422" class="ref no-popup">62</a>]</span> More complex scoring systems, such as Knodell or Ishak, are generally limited to use in research, including clinical trials.<span class="reference-group reference-inline">[<a href="#reference-401" class="ref no-popup">63</a>,<a href="#reference-402" class="ref no-popup">64</a>]</span> For clinical purposes, scoring systems with fewer grade and stage categories are generally utilized; these include Batts and Ludwig, Metavir, and International Association for Study of the Liver (IASL).<span class="reference-group reference-inline">[<a href="#reference-903" class="ref no-popup">54</a>,<a href="#reference-902" class="ref no-popup">65</a>]</span> The main determinants of inflammatory activity are lymphocytic piecemeal necrosis, lobular necroinflammation, and portal inflammation, which are graded 0 to 4 in most classification systems. The main determinant of fibrosis is the degree of expansion of fibrotic areas between portal tracts, and these changes are staged 0 to 4 in the classification systems commonly used in clinical practice. Fragmentation of the biopsy sample, which can occur more extensively with advanced stages of fibrosis, may also suggest septal or bridging fibrosis (stage 3-4 disease).<span class="reference-group reference-inline">[<a href="#reference-3165" class="ref no-popup">66</a>]</span></p></body></html> </div></div><div class="core-concept-subsection"><h2 class="section-title" id="summary-points">Summary Points</h2><div class="level4s level4s-full-text section-content"><!DOCTYPE html PUBLIC "-//W3C//DTD HTML 4.0 Transitional//EN" "http://www.w3.org/TR/REC-html40/loose.dtd"> <html><body><ul> <li>HCV-related hepatic fibrosis is a dynamic scarring process in which chronic inflammation stimulates production and accumulation of collagen and extracellular matrix proteins.</li> <li> <p>Hepatic fibrosis is a precursor to cirrhosis and establishing the severity of liver fibrosis helps predict liver-related morbidity and mortality.</p> </li> <li>Simple laboratory tests should continue to be utilized to identify overt cirrhosis, in conjunction with abdominal imaging where appropriate.</li> <li>Liver biopsy remains the gold standard for diagnosing other causes of liver disease and for establishing the presence and severity of fibrosis.</li> <li>Noninvasive serum markers show clinical utility in predicting presence or absence of significant fibrosis/cirrhosis, but are not as useful in differentiating between intermediate stages of fibrosis.</li> <li>In general, the optimal approach to fibrosis assessment is to use noninvasive serum markers/tests in conjunction with transient elastography. If transient elastography is not available then two different noninvasive serum markers/tests should be used.</li> <li>Relatively little experience exists with the use of direct serum markers and the clinical utility of these markers remains less well-defined when compared with other markers.</li> <li>Among the noninvasive tests used to evaluate liver fibrosis, transient elastography is one of the most accurate for identifying cirrhosis.</li> <li>Magnetic resonance elastography has also been shown to be highly accurate in estimating hepatic fibrosis, but this test is less widely available.</li> </ul></body></html> </div></div><div id="page-navigation-middle" class="page-navigation "><div class="content"><span class="left"> </span><span class="reading-pane"><a class="button button-print left" title="PDF" href="//cdn.hepatitisc.uw.edu/pdf/evaluation-staging-monitoring/evaluation-staging/core-concept/all" target="_blank"><span class="glyphicon glyphicon-print"></span> PDF</a><a class="button button-share left" title="Share page" href="https://www.hepatitisC.uw.edu/go/evaluation-staging-monitoring/evaluation-staging/core-concept/all" onclick="return sharePage()" target="_blank"><span class="glyphicon glyphicon-envelope"></span> Share</a></span><span class="right next"></div></div><div class="core-concept-subsection"><h2 class="section-title" id="citations">Citations</h2><ol class="refs section-content ref-citations" start="1"><li class="ref" id="reference-984"><span class="weight">1.</span>Friedman SL. Evolving challenges in hepatic fibrosis. Nat Rev Gastroenterol Hepatol. 2010;7:425-36.<div>[<a class="link" href="http://www.ncbi.nlm.nih.gov/pubmed/20585339">PubMed Abstract</a>]<span class="highlight-controls"> - </span></div></li><li class="ref" id="reference-2442"><span class="weight">2.</span>Hernandez-Gea V, Friedman SL. Pathogenesis of liver fibrosis. Annu Rev Pathol. 2011;6:425-56.<div>[<a class="link" href="http://www.ncbi.nlm.nih.gov/pubmed/21073339">PubMed Abstract</a>]<span class="highlight-controls"> - </span></div></li><li class="ref" id="reference-2443"><span class="weight">3.</span>Pinzani M. Pathophysiology of Liver Fibrosis. Dig Dis. 2015;33:492-7.<div>[<a class="link" href="http://www.ncbi.nlm.nih.gov/pubmed/26159264">PubMed Abstract</a>]<span class="highlight-controls"> - </span></div></li><li class="ref" id="reference-2441"><span class="weight">4.</span>Seki E, Brenner DA. Recent advancement of molecular mechanisms of liver fibrosis. J Hepatobiliary Pancreat Sci. 2015;22:512-8.<div>[<a class="link" href="http://www.ncbi.nlm.nih.gov/pubmed/25869468">PubMed Abstract</a>]<span class="highlight-controls"> - </span></div></li><li class="ref" id="reference-2421"><span class="weight">5.</span>Sharma S, Khalili K, Nguyen GC. Non-invasive diagnosis of advanced fibrosis and cirrhosis. World J Gastroenterol. 2014;20:16820-30.<div>[<a class="link" href="http://www.ncbi.nlm.nih.gov/pubmed/25492996">PubMed Abstract</a>]<span class="highlight-controls"> - </span></div></li><li class="ref" id="reference-1622"><span class="weight">6.</span>AASLD-IDSA. HCV Guidance: Recommendations for testing, management, and treating hepatitis C. When and in whom to initiate HCV therapy.<div>[<a class="link" href="https://www.hcvguidelines.org/evaluate/when-whom">AASLD-IDSA Hepatitis C Guidance</a>]<span class="highlight-controls"> - </span></div></li><li class="ref" id="reference-2431"><span class="weight">7.</span>Chou R, Wasson N. Blood tests to diagnose fibrosis or cirrhosis in patients with chronic hepatitis C virus infection: a systematic review. Ann Intern Med. 2013;158:807-20.<div>[<a class="link" href="http://www.ncbi.nlm.nih.gov/pubmed/23732714">PubMed Abstract</a>]<span class="highlight-controls"> - </span></div></li><li class="ref" id="reference-2756"><span class="weight">8.</span>van Katwyk S, Coyle D, Cooper C, et al. Transient elastography for the diagnosis of liver fibrosis: a systematic review of economic evaluations. Liver Int. 2017;37:851-861.<div>[<a class="link" href="http://www.ncbi.nlm.nih.gov/pubmed/27699993">PubMed Abstract</a>]<span class="highlight-controls"> - </span></div></li><li class="ref" id="reference-2757"><span class="weight">9.</span>Carlson JJ, Kowdley KV, Sullivan SD, Ramsey SD, Veenstra DL. An evaluation of the potential cost-effectiveness of non-invasive testing strategies in the diagnosis of significant liver fibrosis. J Gastroenterol Hepatol. 2009;24:786-91.<div>[<a class="link" href="http://www.ncbi.nlm.nih.gov/pubmed/19457153">PubMed Abstract</a>]<span class="highlight-controls"> - </span></div></li><li class="ref" id="reference-1735"><span class="weight">10.</span>Boursier J, de Ledinghen V, Zarski JP, et al. Comparison of eight diagnostic algorithms for liver fibrosis in hepatitis C: new algorithms are more precise and entirely noninvasive. Hepatology. 2012;55:58-67.<div>[<a class="link" href="http://www.ncbi.nlm.nih.gov/pubmed/21898504">PubMed Abstract</a>]<span class="highlight-controls"> - </span></div></li><li class="ref" id="reference-911"><span class="weight">11.</span>Duarte-Rojo A, Altamirano JT, Feld JJ. Noninvasive markers of fibrosis: key concepts for improving accuracy in daily clinical practice. Ann Hepatol. 2012;11:426-39.<div>[<a class="link" href="http://www.ncbi.nlm.nih.gov/pubmed/22700624">PubMed Abstract</a>]<span class="highlight-controls"> - </span></div></li><li class="ref" id="reference-907"><span class="weight">12.</span>Rockey DC, Caldwell SH, Goodman ZD, Nelson RC, Smith AD; American Association for the Study of Liver Diseases. Liver biopsy. Hepatology. 2009;49:1017-44.<div>[<a class="link" href="http://www.ncbi.nlm.nih.gov/pubmed/19243014">PubMed Abstract</a>]<span class="highlight-controls"> - </span></div></li><li class="ref" id="reference-405"><span class="weight">13.</span>Wai CT, Greenson JK, Fontana RJ, Kalbfleisch JD, Marrero JA, Conjeevaram HS, Lok AS. A simple noninvasive index can predict both significant fibrosis and cirrhosis in patients with chronic hepatitis C. Hepatology. 2003;38:518-26.<div>[<a class="link" href="http://www.ncbi.nlm.nih.gov/pubmed/12883497">PubMed Abstract</a>]<span class="highlight-controls"> - </span></div></li><li class="ref" id="reference-2423"><span class="weight">14.</span>Schmid P, Bregenzer A, Huber M, et al. Progression of Liver Fibrosis in HIV/HCV Co-Infection: A Comparison between Non-Invasive Assessment Methods and Liver Biopsy. PLoS One. 2015;10:e0138838.<div>[<a class="link" href="http://www.ncbi.nlm.nih.gov/pubmed/26418061">PubMed Abstract</a>]<span class="highlight-controls"> - </span></div></li><li class="ref" id="reference-915"><span class="weight">15.</span>Lin ZH, Xin YN, Dong QJ, et al. Performance of the aspartate aminotransferase-to-platelet ratio index for the staging of hepatitis C-related fibrosis: an updated meta-analysis. Hepatology. 2011;53:726-36.<div>[<a class="link" href="http://www.ncbi.nlm.nih.gov/pubmed/21319189">PubMed Abstract</a>]<span class="highlight-controls"> - </span></div></li><li class="ref" id="reference-3421"><span class="weight">16.</span>Suan MAM, Chan HK, Sem X, Shilton S, Hassan MRA. Diagnostic performance of two non-invasive biomarkers used individually and in sequential combination for cirrhosis associated with hepatitis C virus infection. Sci Rep. 2022;12:20153.<div>[<a class="link" href="http://www.ncbi.nlm.nih.gov/pubmed/36418369">PubMed Abstract</a>]<span class="highlight-controls"> - </span></div></li><li class="ref" id="reference-913"><span class="weight">17.</span>Holmberg SD, Lu M, Rupp LB, et al. Noninvasive serum fibrosis markers for screening and staging chronic hepatitis C virus patients in a large US cohort. Clin Infect Dis. 2013;57:240-6.<div>[<a class="link" href="http://www.ncbi.nlm.nih.gov/pubmed/23592832">PubMed Abstract</a>]<span class="highlight-controls"> - </span></div></li><li class="ref" id="reference-918"><span class="weight">18.</span>Sterling RK, Lissen E, Clumeck N, et al. Development of a simple noninvasive index to predict significant fibrosis in patients with HIV/HCV coinfection. Hepatology. 2006;43:1317–25.<div>[<a class="link" href="http://www.ncbi.nlm.nih.gov/pubmed/16729309">PubMed Abstract</a>]<span class="highlight-controls"> - </span></div></li><li class="ref" id="reference-3286"><span class="weight">19.</span>Sterling RK, Lissen E, Clumeck N, et al. Development of a simple noninvasive index to predict significant fibrosis in patients with HIV/HCV coinfection. Hepatology. 2006;43:1317-25.<div>[<a class="link" href="http://www.ncbi.nlm.nih.gov/pubmed/16729309">PubMed Abstract</a>]<span class="highlight-controls"> - </span></div></li><li class="ref" id="reference-919"><span class="weight">20.</span>Vallet-Pichard A, Mallet V, Nalpas B, et al. FIB-4: an inexpensive and accurate marker of fibrosis in HCV infection. comparison with liver biopsy and fibrotest. Hepatology. 2007;46:32-6.<div>[<a class="link" href="http://www.ncbi.nlm.nih.gov/pubmed/17567829">PubMed Abstract</a>]<span class="highlight-controls"> - </span></div></li><li class="ref" id="reference-3125"><span class="weight">21.</span>AASLD-IDSA. HCV Guidance: Recommendations for testing, management, and treating hepatitis C. Simplified HCV Treatment for Treatment-Naive Adults With Compensated Cirrhosis.<div>[<a class="link" href="https://www.hcvguidelines.org/treatment-naive/simplified-treatment-compensated-cirrhosis">AASLD-IDSA Hepatitis C Guidance</a>]<span class="highlight-controls"> - </span></div></li><li class="ref" id="reference-3124"><span class="weight">22.</span>AASLD-IDSA. HCV Guidance: Recommendations for testing, management, and treating hepatitis C. Simplified HCV Treatment for Treatment-Naive Adults Without Cirrhosis.<div>[<a class="link" href="https://www.hcvguidelines.org/treatment-naive/simplified-treatment">[AASLD-IDSA Hepatitis C Guidance</a>]<span class="highlight-controls"> - </span></div></li><li class="ref" id="reference-3295"><span class="weight">23.</span>Bhattacharya D, Aronsohn A, Price J, Lo Re V. Hepatitis C Guidance 2023 Update: AASLD-IDSA Recommendations for Testing, Managing, and Treating Hepatitis C Virus Infection. Clin Infect Dis. 2023 May 25;ciad319.<div>[<a class="link" href="http://www.ncbi.nlm.nih.gov/pubmed/37229695">PubMed Abstract</a>]<span class="highlight-controls"> - </span></div></li><li class="ref" id="reference-2427"><span class="weight">24.</span>Poynard T, Morra R, Halfon P, et al. Meta-analyses of FibroTest diagnostic value in chronic liver disease. BMC Gastroenterol. 2007;7:40.<div>[<a class="link" href="http://www.ncbi.nlm.nih.gov/pubmed/17937811">PubMed Abstract</a>]<span class="highlight-controls"> - </span></div></li><li class="ref" id="reference-2439"><span class="weight">25.</span>Poynard T, Imbert-Bismut F, Munteanu M, et al. Overview of the diagnostic value of biochemical markers of liver fibrosis (FibroTest, HCV FibroSure) and necrosis (ActiTest) in patients with chronic hepatitis C. Comp Hepatol. 2004;3:8.<div>[<a class="link" href="http://www.ncbi.nlm.nih.gov/pubmed/15387887">PubMed Abstract</a>]<span class="highlight-controls"> - </span></div></li><li class="ref" id="reference-914"><span class="weight">26.</span>Koda M, Matunaga Y, Kawakami M, Kishimoto Y, Suou T, Murawaki Y. FibroIndex, a practical index for predicting significant fibrosis in patients with chronic hepatitis C. Hepatology. 2007;45:297-306.<div>[<a class="link" href="http://www.ncbi.nlm.nih.gov/pubmed/17256741">PubMed Abstract</a>]<span class="highlight-controls"> - </span></div></li><li class="ref" id="reference-912"><span class="weight">27.</span>Forns X, Ampurdanès S, Llovet JM, et al. Identification of chronic hepatitis C patients without hepatic fibrosis by a simple predictive model. Hepatology. 2002;36(4 Pt 1):986-92.<div>[<a class="link" href="http://www.ncbi.nlm.nih.gov/pubmed/12297848">PubMed Abstract</a>]<span class="highlight-controls"> - </span></div></li><li class="ref" id="reference-3166"><span class="weight">28.</span>Thabut D, Simon M, Myers RP, et al. Noninvasive prediction of fibrosis in patients with chronic hepatitis C. Hepatology. 2003;37:1220-1.<div>[<a class="link" href="http://www.ncbi.nlm.nih.gov/pubmed/12717403">PubMed Abstract</a>]<span class="highlight-controls"> - </span></div></li><li class="ref" id="reference-2425"><span class="weight">29.</span>Haseltine EL, Penney MS, George S, Kieffer TL. Successful treatment with telaprevir-based regimens for chronic hepatitis C results in significant improvements to serum markers of liver fibrosis. J Viral Hepat. 2015;22:701-7.<div>[<a class="link" href="http://www.ncbi.nlm.nih.gov/pubmed/25582683">PubMed Abstract</a>]<span class="highlight-controls"> - </span></div></li><li class="ref" id="reference-2426"><span class="weight">30.</span>Tural C, Tor J, Sanvisens A, et al. Accuracy of simple biochemical tests in identifying liver fibrosis in patients co-infected with human immunodeficiency virus and hepatitis C virus. Clin Gastroenterol Hepatol. 2009;7:339-45.<div>[<a class="link" href="http://www.ncbi.nlm.nih.gov/pubmed/19171202">PubMed Abstract</a>]<span class="highlight-controls"> - </span></div></li><li class="ref" id="reference-909"><span class="weight">31.</span>Becker L, Salameh W, Sferruzza A, et al. Validation of hepascore, compared with simple indices of fibrosis, in patients with chronic hepatitis C virus infection in United States. Clin Gastroenterol Hepatol. 2009;7:696-701.<div>[<a class="link" href="http://www.ncbi.nlm.nih.gov/pubmed/19514117">PubMed Abstract</a>]<span class="highlight-controls"> - </span></div></li><li class="ref" id="reference-3423"><span class="weight">32.</span>Neuman MG, Cohen LB, Nanau RM. Hyaluronic acid as a non-invasive biomarker of liver fibrosis. Clin Biochem. 2016;49:302-15.<div>[<a class="link" href="http://www.ncbi.nlm.nih.gov/pubmed/26188920">PubMed Abstract</a>]<span class="highlight-controls"> - </span></div></li><li class="ref" id="reference-406"><span class="weight">33.</span>Patel K, Gordon SC, Jacobson I, et al. Evaluation of a panel of non-invasive serum markers to differentiate mild from moderate-to-advanced liver fibrosis in chronic hepatitis C patients. J Hepatol. 2004;41:935-42.<div>[<a class="link" href="http://www.ncbi.nlm.nih.gov/pubmed/15582126">PubMed Abstract</a>]<span class="highlight-controls"> - </span></div></li><li class="ref" id="reference-620"><span class="weight">34.</span>Zaman A, Rosen HR, Ingram K, Corless CL, Oh E, Smith K. Assessment of FIBROSpect II to detect hepatic fibrosis in chronic hepatitis C patients. Am J Med. 2007;120:280.e9-14.<div>[<a class="link" href="http://www.ncbi.nlm.nih.gov/pubmed/17349453">PubMed Abstract</a>]<span class="highlight-controls"> - </span></div></li><li class="ref" id="reference-920"><span class="weight">35.</span>Afdhal NH. Fibroscan (transient elastography) for the measurement of liver fibrosis. Gastroenterol Hepatol (N Y). 2012;8:605-7.<div>[<a class="link" href="http://www.ncbi.nlm.nih.gov/pubmed/23483859">PubMed Abstract</a>]<span class="highlight-controls"> - </span></div></li><li class="ref" id="reference-910"><span class="weight">36.</span>Castera L. Noninvasive methods to assess liver disease in patients with hepatitis B or C. Gastroenterology. 2012;142:1293-1302.e4.<div>[<a class="link" href="http://www.ncbi.nlm.nih.gov/pubmed/22537436">PubMed Abstract</a>]<span class="highlight-controls"> - </span></div></li><li class="ref" id="reference-407"><span class="weight">37.</span>Castera L, Vergniol J, Foucher J, et al. Prospective comparison of transient elastography, Fibrotest, APRI, and liver biopsy for the assessment of fibrosis in chronic hepatitis C. Gastroenterology. 2005;128:343-50.<div>[<a class="link" href="http://www.ncbi.nlm.nih.gov/pubmed/15685546">PubMed Abstract</a>]<span class="highlight-controls"> - </span></div></li><li class="ref" id="reference-927"><span class="weight">38.</span>Castera L, Forns X, Alberti A. Non-invasive evaluation of liver fibrosis using transient elastography. J Hepatol. 2008;48:835-47.<div>[<a class="link" href="http://www.ncbi.nlm.nih.gov/pubmed/18334275">PubMed Abstract</a>]<span class="highlight-controls"> - </span></div></li><li class="ref" id="reference-3168"><span class="weight">39.</span>Ammon FJ, Kohlhaas A, Elshaarawy O, et al. Liver stiffness reversibly increases during pregnancy and independently predicts preeclampsia. World J Gastroenterol. 2018;24:4393-402.<div>[<a class="link" href="http://www.ncbi.nlm.nih.gov/pubmed/30344423">PubMed Abstract</a>]<span class="highlight-controls"> - </span></div></li><li class="ref" id="reference-1734"><span class="weight">40.</span>Ziol M, Handra-Luca A, Kettaneh A, et al. Noninvasive assessment of liver fibrosis by measurement of stiffness in patients with chronic hepatitis C. Hepatology. 2005;41:48-54.<div>[<a class="link" href="http://www.ncbi.nlm.nih.gov/pubmed/15690481">PubMed Abstract</a>]<span class="highlight-controls"> - </span></div></li><li class="ref" id="reference-924"><span class="weight">41.</span>Steadman R, Myers RP, Leggett L, et al. A health technology assessment of transient elastography in adult liver disease. Can J Gastroenterol. 2013;27:149-58.<div>[<a class="link" href="http://www.ncbi.nlm.nih.gov/pubmed/23516679">PubMed Abstract</a>]<span class="highlight-controls"> - </span></div></li><li class="ref" id="reference-922"><span class="weight">42.</span>Kirk GD, Astemborski J, Mehta SH, et al. Assessment of liver fibrosis by transient elastography in persons with hepatitis C virus infection or HIV-hepatitis C virus coinfection. Clin Infect Dis. 2009;48:963-72.<div>[<a class="link" href="http://www.ncbi.nlm.nih.gov/pubmed/19236273">PubMed Abstract</a>]<span class="highlight-controls"> - </span></div></li><li class="ref" id="reference-2759"><span class="weight">43.</span>Kim HJ, Lee HK, Cho JH, Yang HJ. Quantitative comparison of transient elastography (TE), shear wave elastography (SWE) and liver biopsy results of patients with chronic liver disease. J Phys Ther Sci. 2015;27:2465-8.<div>[<a class="link" href="http://www.ncbi.nlm.nih.gov/pubmed/26357427">PubMed Abstract</a>]<span class="highlight-controls"> - </span></div></li><li class="ref" id="reference-2760"><span class="weight">44.</span>Verlinden W, Bourgeois S, Gigase P, et al. Liver Fibrosis Evaluation Using Real-time Shear Wave Elastography in Hepatitis C-Monoinfected and Human Immunodeficiency Virus/Hepatitis C-Coinfected Patients. J Ultrasound Med. 2016;35:1299-308.<div>[<a class="link" href="http://www.ncbi.nlm.nih.gov/pubmed/27151906">PubMed Abstract</a>]<span class="highlight-controls"> - </span></div></li><li class="ref" id="reference-921"><span class="weight">45.</span>Goyal N, Jain N, Rachapalli V, Cochlin DL, Robinson M. Non-invasive evaluation of liver cirrhosis using ultrasound. Clin Radiol. 2009;64:1056-66.<div>[<a class="link" href="http://www.ncbi.nlm.nih.gov/pubmed/19822238">PubMed Abstract</a>]<span class="highlight-controls"> - </span></div></li><li class="ref" id="reference-932"><span class="weight">46.</span>Bonekamp S, Kamel I, Solga S, Clark J. Can imaging modalities diagnose and stage hepatic fibrosis and cirrhosis accurately? J Hepatol. 2009;50:17-35.<div>[<a class="link" href="http://www.ncbi.nlm.nih.gov/pubmed/19022517">PubMed Abstract</a>]<span class="highlight-controls"> - </span></div></li><li class="ref" id="reference-3167"><span class="weight">47.</span>Kelly EMM, Feldstein VA, Parks M, Hudock R, Etheridge D, Peters MG. An Assessment of the Clinical Accuracy of Ultrasound in Diagnosing Cirrhosis in the Absence of Portal Hypertension. Gastroenterol Hepatol (N Y). 2018;14:367-73.<div>[<a class="link" href="http://www.ncbi.nlm.nih.gov/pubmed/30166950">PubMed Abstract</a>]<span class="highlight-controls"> - </span></div></li><li class="ref" id="reference-926"><span class="weight">48.</span>Wang QB, Zhu H, Liu HL, Zhang B. Performance of magnetic resonance elastography and diffusion-weighted imaging for the staging of hepatic fibrosis: A meta-analysis. Hepatology. 2012;56:239-47.<div>[<a class="link" href="http://www.ncbi.nlm.nih.gov/pubmed/22278368">PubMed Abstract</a>]<span class="highlight-controls"> - </span></div></li><li class="ref" id="reference-931"><span class="weight">49.</span>Talwalkar JA, Yin M, Fidler JL, Sanderson SO, Kamath PS, Ehman RL. Magnetic resonance imaging of hepatic fibrosis: emerging clinical applications. Hepatology. 2008;47:332-42.<div>[<a class="link" href="http://www.ncbi.nlm.nih.gov/pubmed/18161879">PubMed Abstract</a>]<span class="highlight-controls"> - </span></div></li><li class="ref" id="reference-925"><span class="weight">50.</span>Wang Y, Ganger DR, Levitsky J, et al. Assessment of chronic hepatitis and fibrosis: comparison of MR elastography and diffusion-weighted imaging. AJR Am J Roentgenol. 2011;196:553-61.<div>[<a class="link" href="http://www.ncbi.nlm.nih.gov/pubmed/21343496">PubMed Abstract</a>]<span class="highlight-controls"> - </span></div></li><li class="ref" id="reference-3424"><span class="weight">51.</span>Li S, Sun X, Chen M, et al. Liver Fibrosis Conventional and Molecular Imaging Diagnosis Update. J Liver. 2019;8:236.<div>[<a class="link" href="http://www.ncbi.nlm.nih.gov/pubmed/31341723">PubMed Abstract</a>]<span class="highlight-controls"> - </span></div></li><li class="ref" id="reference-3420"><span class="weight">52.</span>Ginès P, Krag A, Abraldes JG, Solà E, Fabrellas N, Kamath PS. Liver cirrhosis. Lancet. 2021;398:1359-76.<div>[<a class="link" href="http://www.ncbi.nlm.nih.gov/pubmed/34543610">PubMed Abstract</a>]<span class="highlight-controls"> - </span></div></li><li class="ref" id="reference-985"><span class="weight">53.</span>Theise ND. Liver biopsy assessment in chronic viral hepatitis: a personal, practical approach. Mod Pathol. 2007;20 Suppl 1:S3-14.<div>[<a class="link" href="http://www.ncbi.nlm.nih.gov/pubmed/17486049">PubMed Abstract</a>]<span class="highlight-controls"> - </span></div></li><li class="ref" id="reference-903"><span class="weight">54.</span>Bedossa P, Dargère D, Paradis V. Sampling variability of liver fibrosis in chronic hepatitis C. Hepatology. 2003;38:1449-57.<div>[<a class="link" href="http://www.ncbi.nlm.nih.gov/pubmed/14647056">PubMed Abstract</a>]<span class="highlight-controls"> - </span></div></li><li class="ref" id="reference-982"><span class="weight">55.</span>Gara N, Zhao X, Kleiner DE, Liang TJ, Hoofnagle JH, Ghany MG. Discordance among transient elastography, aspartate aminotransferase to platelet ratio index, and histologic assessments of liver fibrosis in patients with chronic hepatitis C. Clin Gastroenterol Hepatol. 2013;11:303-8.<div>[<a class="link" href="http://www.ncbi.nlm.nih.gov/pubmed/23142332">PubMed Abstract</a>]<span class="highlight-controls"> - </span></div></li><li class="ref" id="reference-930"><span class="weight">56.</span>Manning DS, Afdhal NH. Diagnosis and quantitation of fibrosis. Gastroenterology. 2008;134:1670-81.<div>[<a class="link" href="http://www.ncbi.nlm.nih.gov/pubmed/18471546">PubMed Abstract</a>]<span class="highlight-controls"> - </span></div></li><li class="ref" id="reference-906"><span class="weight">57.</span>Regev A, Berho M, Jeffers LJ, et al. Sampling error and intraobserver variation in liver biopsy in patients with chronic HCV infection. Am J Gastroenterol. 2002;97:2614-8.<div>[<a class="link" href="http://www.ncbi.nlm.nih.gov/pubmed/12385448">PubMed Abstract</a>]<span class="highlight-controls"> - </span></div></li><li class="ref" id="reference-928"><span class="weight">58.</span>Schmeltzer PA, Talwalkar JA. Noninvasive tools to assess hepatic fibrosis: ready for prime time? Gastroenterol Clin North Am. 2011;40:507-21.<div>[<a class="link" href="http://www.ncbi.nlm.nih.gov/pubmed/21893271">PubMed Abstract</a>]<span class="highlight-controls"> - </span></div></li><li class="ref" id="reference-986"><span class="weight">59.</span>Guido M, Mangia A, Faa G; Gruppo Italiano Patologi Apparato Digerente (GIPAD); Società Italiana di Anatomia Patologica e Citopatologia Diagnostica/International Academy of Pathology, Italian division (SIAPEC/IAP). Chronic viral hepatitis: the histology report. Dig Liver Dis. 2011;43 Suppl 4:S331-43.<div>[<a class="link" href="http://www.ncbi.nlm.nih.gov/pubmed/21459339">PubMed Abstract</a>]<span class="highlight-controls"> - </span></div></li><li class="ref" id="reference-905"><span class="weight">60.</span>Piccinino F, Sagnelli E, Pasquale G, Giusti G. Complications following percutaneous liver biopsy. A multicentre retrospective study on 68,276 biopsies. J Hepatol. 1986;2:165-73.<div>[<a class="link" href="http://www.ncbi.nlm.nih.gov/pubmed/3958472">PubMed Abstract</a>]<span class="highlight-controls"> - </span></div></li><li class="ref" id="reference-987"><span class="weight">61.</span>Lefkowitch JH.Arch Med Res. Liver biopsy assessment in chronic hepatitis. 2007;38:634-43.<div>[<a class="link" href="http://www.ncbi.nlm.nih.gov/pubmed/17613355">PubMed Abstract</a>]<span class="highlight-controls"> - </span></div></li><li class="ref" id="reference-3422"><span class="weight">62.</span>Chowdhury AB, Mehta KJ. Liver biopsy for assessment of chronic liver diseases: a synopsis. Clin Exp Med. 2023;23:273-85.<div>[<a class="link" href="http://www.ncbi.nlm.nih.gov/pubmed/35192111">PubMed Abstract</a>]<span class="highlight-controls"> - </span></div></li><li class="ref" id="reference-401"><span class="weight">63.</span>Knodell RG, Ishak KG, Black WC, et al. Formulation and application of a numerical scoring system for assessing histological activity in asymptomatic chronic active hepatitis. Hepatology. 1981;1:431-5. <div>[<a class="link" href="http://www.ncbi.nlm.nih.gov/pubmed/7308988">PubMed Abstract</a>]<span class="highlight-controls"> - </span></div></li><li class="ref" id="reference-402"><span class="weight">64.</span>Ishak K, Baptista A, Bianchi L, et al. Histological grading and staging of chronic hepatitis. J Hepatol. 1995;22:696-9.<div>[<a class="link" href="http://www.ncbi.nlm.nih.gov/pubmed/7560864">PubMed Abstract</a>]<span class="highlight-controls"> - </span></div></li><li class="ref" id="reference-902"><span class="weight">65.</span>Batts KP, Ludwig J. Chronic hepatitis. An update on terminology and reporting. Am J Surg Pathol. 1995;19:1409-17.<div>[<a class="link" href="http://www.ncbi.nlm.nih.gov/pubmed/7503362">PubMed Abstract</a>]<span class="highlight-controls"> - </span></div></li><li class="ref" id="reference-3165"><span class="weight">66.</span>Malik AH, Kumar KS, Malet PF, Jain R, Prasad P, Ostapowicz G. Correlation of percutaneous liver biopsy fragmentation with the degree of fibrosis. Aliment Pharmacol Ther. 2004;19:545-9.<div>[<a class="link" href="http://www.ncbi.nlm.nih.gov/pubmed/14987323">PubMed Abstract</a>]<span class="highlight-controls"> - </span></div></li></ol></div><div class="core-concept-subsection"><h2 class="section-title" id="references-unassigned">Additional References</h2><ul class="refs section-content"><li class="ref" id="reference-2430">Boursier J, Bacq Y, Halfon P, et al. Improved diagnostic accuracy of blood tests for severe fibrosis and cirrhosis in chronic hepatitis C. Eur J Gastroenterol Hepatol. 2009;21:28-38.<div>[<a class="link" href="http://www.ncbi.nlm.nih.gov/pubmed/19060630">PubMed Abstract</a>]<span class="highlight-controls"> - </span></div></li><li class="ref" id="reference-2434">Halfon P, Bacq Y, De Muret A, et al. Comparison of test performance profile for blood tests of liver fibrosis in chronic hepatitis C. J Hepatol. 2007;46:395-402.<div>[<a class="link" href="http://www.ncbi.nlm.nih.gov/pubmed/17156890">PubMed Abstract</a>]<span class="highlight-controls"> - </span></div></li><li class="ref" id="reference-2422">Harris R, Harman DJ, Card TR, Aithal GP, Guha IN. Prevalence of clinically significant liver disease within the general population, as defined by non-invasive markers of liver fibrosis: a systematic review. Lancet Gastroenterol Hepatol. 2017;2:288-297.<div>[<a class="link" href="http://www.ncbi.nlm.nih.gov/pubmed/28404158">PubMed Abstract</a>]<span class="highlight-controls"> - </span></div></li><li class="ref" id="reference-3169">Naganuma H, Ishida H, Uno A, Nagai H, Kuroda H, Ogawa M. Diagnostic problems in two-dimensional shear wave elastography of the liver. World J Radiol. 2020;12:76-86.<div>[<a class="link" href="http://www.ncbi.nlm.nih.gov/pubmed/32549956">PubMed Abstract</a>]<span class="highlight-controls"> - </span></div></li><li class="ref" id="reference-916">Nguyen D, Talwalkar JA. Noninvasive assessment of liver fibrosis. Hepatology. 2011;53:2107-10.<div>[<a class="link" href="http://www.ncbi.nlm.nih.gov/pubmed/21547935">PubMed Abstract</a>]<span class="highlight-controls"> - </span></div></li><li class="ref" id="reference-917">Patel K, Benhamou Y, Yoshida EM, et al. An independent and prospective comparison of two commercial fibrosis marker panels (HCV FibroSURE and FIBROSpect II) during albinterferon alfa-2b combination therapy for chronic hepatitis C. J Viral Hepat. 2009;16:178-86.<div>[<a class="link" href="http://www.ncbi.nlm.nih.gov/pubmed/19175870">PubMed Abstract</a>]<span class="highlight-controls"> - </span></div></li><li class="ref" id="reference-2437">Rossi E, Adams L, Prins A, et al. Validation of the FibroTest biochemical markers score in assessing liver fibrosis in hepatitis C patients. Clin Chem. 2003;49:450-4.<div>[<a class="link" href="http://www.ncbi.nlm.nih.gov/pubmed/12600957">PubMed Abstract</a>]<span class="highlight-controls"> - </span></div></li><li class="ref" id="reference-923">Shire NJ, Yin M, Chen J, et al. Test-retest repeatability of MR elastography for noninvasive liver fibrosis assessment in hepatitis C. J Magn Reson Imaging. 2011;34:947-55.<div>[<a class="link" href="http://www.ncbi.nlm.nih.gov/pubmed/21751289">PubMed Abstract</a>]<span class="highlight-controls"> - </span></div></li><li class="ref" id="reference-929">Talwalkar JA. Elastography for detecting hepatic fibrosis: options and considerations. Gastroenterology. 2008;135:299-302.<div>[<a class="link" href="http://www.ncbi.nlm.nih.gov/pubmed/18555023">PubMed Abstract</a>]<span class="highlight-controls"> - </span></div></li><li class="ref" id="reference-2433">Zarski JP, Sturm N, Guechot J, et al. Comparison of nine blood tests and transient elastography for liver fibrosis in chronic hepatitis C: the ANRS HCEP-23 study. J Hepatol. 2012;56:55-62.<div>[<a class="link" href="http://www.ncbi.nlm.nih.gov/pubmed/21781944">PubMed Abstract</a>]<span class="highlight-controls"> - </span></div></li></ul></div><div class="core-concept-subsection section section-figures "><h2 class="section-title" id="figures">Figures</h2><div class="content section-content"><div class="documents"><div data-doc-id="96" data-doc-scroll="0" data-doc-weight="1" data-doc-info-width="1278" data-doc-info-height="532" class="document doc-1"><div class="inner"><a target="_blank" rel="" alt="Abbreviations: AST = aspartate aminotransferase<br /> The AST upper limit of normal should be the upper limit of normal established by the laboratory that performed the test. Most laboratories use an AST upper limit of 40 IU/mL.<div></div>" title="Figure 1 - Aspartate Aminotransferase-to-Platelet-Ratio Index (APRI)" class="image" href="//cdn.hepatitisc.uw.edu/doc/96-2/aspartate-aminotransferase-to-platelet-ratio-index-apri.jpg"><img src="//cdn.hepatitisc.uw.edu/doc/96-2/thumb/aspartate-aminotransferase-to-platelet-ratio-index-apri.jpg" alt="Abbreviations: AST = aspartate aminotransferase<br /> The AST upper limit of normal should be the upper limit of normal established by the laboratory that performed the test. Most laboratories use an AST upper limit of 40 IU/mL." srcset="//cdn.hepatitisc.uw.edu/doc/96-2/thumb/aspartate-aminotransferase-to-platelet-ratio-index-apri.jpg 100w, //cdn.hepatitisc.uw.edu/doc/96-2/third/aspartate-aminotransferase-to-platelet-ratio-index-apri.png 320w, //cdn.hepatitisc.uw.edu/doc/96-2/text/aspartate-aminotransferase-to-platelet-ratio-index-apri.png 800w, //cdn.hepatitisc.uw.edu/doc/96-2/full/aspartate-aminotransferase-to-platelet-ratio-index-apri.png 1280w" sizes="(max-width: 200px) 100px, (max-width: 320px) 320px, (max-width: 800px) 800px, 1280px" /> <div class="field field-name"><span class="short">Figure 1.</span> <span class="long">Aspartate Aminotransferase-to-Platelet-Ratio Index (APRI)</span></div></a><div class="field field-caption">Abbreviations: AST = aspartate aminotransferase<br /> The AST upper limit of normal should be the upper limit of normal established by the laboratory that performed the test. Most laboratories use an AST upper limit of 40 IU/mL.</div><div style="clear: both;"></div></div></div><div data-doc-id="97" data-doc-scroll="0" data-doc-weight="2" data-doc-info-width="1182" data-doc-info-height="509" class="document doc-2"><div class="inner"><a target="_blank" rel="" alt="Abbreviations: AST = aspartate aminotransferase; ALT = alanine aminotransferase<div>Source: Vallet-Pichard A, Mallet V, Nalpas B, et al. FIB-4: an inexpensive and accurate marker of fibrosis in HCV infection. comparison with liver biopsy and fibrotest. Hepatology. 2007;46:32-6.</div>" title="Figure 2 - FIB-4" class="image" href="//cdn.hepatitisc.uw.edu/doc/97-3/fib-4.jpg"><img src="//cdn.hepatitisc.uw.edu/doc/97-3/thumb/fib-4.jpg" alt="Abbreviations: AST = aspartate aminotransferase; ALT = alanine aminotransferase" srcset="//cdn.hepatitisc.uw.edu/doc/97-3/thumb/fib-4.jpg 100w, //cdn.hepatitisc.uw.edu/doc/97-3/third/fib-4.png 320w, //cdn.hepatitisc.uw.edu/doc/97-3/text/fib-4.png 800w, //cdn.hepatitisc.uw.edu/doc/97-3/full/fib-4.png 1280w" sizes="(max-width: 200px) 100px, (max-width: 320px) 320px, (max-width: 800px) 800px, 1280px" /> <div class="field field-name"><span class="short">Figure 2.</span> <span class="long">FIB-4</span></div></a><div class="field field-caption">Abbreviations: AST = aspartate aminotransferase; ALT = alanine aminotransferase</div><div class="field field-source">Source: Vallet-Pichard A, Mallet V, Nalpas B, et al. FIB-4: an inexpensive and accurate marker of fibrosis in HCV infection. comparison with liver biopsy and fibrotest. Hepatology. 2007;46:32-6.</div><div style="clear: both;"></div></div></div><div data-doc-id="98" data-doc-scroll="0" data-doc-weight="3" data-doc-info-width="1304" data-doc-info-height="566" class="document doc-3"><div class="inner"><a target="_blank" rel="" alt="Abbreviations: AST = aspartate aminotransferase<div>Source: Koda M, Matunaga Y, Kawakami M, Kishimoto Y, Suou T, Murawaki Y. FibroIndex, a practical index for predicting significant fibrosis in patients with chronic hepatitis C. Hepatology. 2007;45:297-306.</div>" title="Figure 3 - FibroIndex" class="image" href="//cdn.hepatitisc.uw.edu/doc/98-3/fibroindex.jpg"><img src="//cdn.hepatitisc.uw.edu/doc/98-3/thumb/fibroindex.jpg" alt="Abbreviations: AST = aspartate aminotransferase" srcset="//cdn.hepatitisc.uw.edu/doc/98-3/thumb/fibroindex.jpg 100w, //cdn.hepatitisc.uw.edu/doc/98-3/third/fibroindex.png 320w, //cdn.hepatitisc.uw.edu/doc/98-3/text/fibroindex.png 800w, //cdn.hepatitisc.uw.edu/doc/98-3/full/fibroindex.png 1280w" sizes="(max-width: 200px) 100px, (max-width: 320px) 320px, (max-width: 800px) 800px, 1280px" /> <div class="field field-name"><span class="short">Figure 3.</span> <span class="long">FibroIndex</span></div></a><div class="field field-caption">Abbreviations: AST = aspartate aminotransferase</div><div class="field field-source">Source: Koda M, Matunaga Y, Kawakami M, Kishimoto Y, Suou T, Murawaki Y. FibroIndex, a practical index for predicting significant fibrosis in patients with chronic hepatitis C. Hepatology. 2007;45:297-306.</div><div style="clear: both;"></div></div></div><div data-doc-id="99" data-doc-scroll="0" data-doc-weight="4" data-doc-info-width="1364" data-doc-info-height="578" class="document doc-4"><div class="inner"><a target="_blank" rel="" alt="<div>Forns X, Ampurdanès S, Llovet JM, et al. Identification of chronic hepatitis C patients without hepatic fibrosis by a simple predictive model. Hepatology. 2002;36(4 Pt 1):986-92.</div>" title="Figure 4 - Forns Index" class="image" href="//cdn.hepatitisc.uw.edu/doc/99-3/forns-index.jpg"><img src="//cdn.hepatitisc.uw.edu/doc/99-3/thumb/forns-index.jpg" alt="" srcset="//cdn.hepatitisc.uw.edu/doc/99-3/thumb/forns-index.jpg 100w, //cdn.hepatitisc.uw.edu/doc/99-3/third/forns-index.png 320w, //cdn.hepatitisc.uw.edu/doc/99-3/text/forns-index.png 800w, //cdn.hepatitisc.uw.edu/doc/99-3/full/forns-index.png 1280w" sizes="(max-width: 200px) 100px, (max-width: 320px) 320px, (max-width: 800px) 800px, 1280px" /> <div class="field field-name"><span class="short">Figure 4.</span> <span class="long">Forns Index</span></div></a><div class="field field-source">Forns X, Ampurdanès S, Llovet JM, et al. Identification of chronic hepatitis C patients without hepatic fibrosis by a simple predictive model. Hepatology. 2002;36(4 Pt 1):986-92.</div><div style="clear: both;"></div></div></div><div data-doc-id="100" data-doc-scroll="0" data-doc-weight="5" data-doc-info-width="1381" data-doc-info-height="574" class="document doc-5"><div class="inner"><a target="_blank" rel="" alt="<div>Becker L, Salameh W, Sferruzza A, et al. Validation of hepascore, compared with simple indices of fibrosis, in patients with chronic hepatitis C virus infection in United States. Clin Gastroenterol Hepatol. 2009;7:696-701.</div>" title="Figure 5 - HepaScore (FibroScore)" class="image" href="//cdn.hepatitisc.uw.edu/doc/100-3/hepascore-fibroscore.jpg"><img src="//cdn.hepatitisc.uw.edu/doc/100-3/thumb/hepascore-fibroscore.jpg" alt="" srcset="//cdn.hepatitisc.uw.edu/doc/100-3/thumb/hepascore-fibroscore.jpg 100w, //cdn.hepatitisc.uw.edu/doc/100-3/third/hepascore-fibroscore.png 320w, //cdn.hepatitisc.uw.edu/doc/100-3/text/hepascore-fibroscore.png 800w, //cdn.hepatitisc.uw.edu/doc/100-3/full/hepascore-fibroscore.png 1280w" sizes="(max-width: 200px) 100px, (max-width: 320px) 320px, (max-width: 800px) 800px, 1280px" /> <div class="field field-name"><span class="short">Figure 5.</span> <span class="long">HepaScore (FibroScore)</span></div></a><div class="field field-source">Becker L, Salameh W, Sferruzza A, et al. Validation of hepascore, compared with simple indices of fibrosis, in patients with chronic hepatitis C virus infection in United States. Clin Gastroenterol Hepatol. 2009;7:696-701.</div><div style="clear: both;"></div></div></div><div data-doc-id="315" data-doc-scroll="0" data-doc-weight="6" data-doc-info-width="1333" data-doc-info-height="555" class="document doc-6"><div class="inner"><a target="_blank" rel="image-series-315" alt="<div>Source: Castera L, Vergniol J, Foucher J, et al. Prospective comparison of transient elastography, Fibrotest, APRI, and liver biopsy for the assessment of fibrosis in chronic hepatitis C. Gastroenterology. 2005;128:343-50.</div>" title="Figure 6 (Image Series) - Correlation of Cutoffs and Metavir Fibrosis Scores" class="image-series image-series-315" image-series-title="Figure 6 (Image Series) - Castera Transient Elastography Cutoffs" href="//cdn.hepatitisc.uw.edu/doc/315-2/correlation-cutoffs-metavir-fibrosis-scores.jpg"><img src="//cdn.hepatitisc.uw.edu/doc/315-2/thumb/correlation-cutoffs-metavir-fibrosis-scores.jpg" alt="" srcset="//cdn.hepatitisc.uw.edu/doc/315-2/thumb/correlation-cutoffs-metavir-fibrosis-scores.jpg 100w, //cdn.hepatitisc.uw.edu/doc/315-2/third/correlation-cutoffs-metavir-fibrosis-scores.png 320w, //cdn.hepatitisc.uw.edu/doc/315-2/text/correlation-cutoffs-metavir-fibrosis-scores.png 800w, //cdn.hepatitisc.uw.edu/doc/315-2/full/correlation-cutoffs-metavir-fibrosis-scores.png 1280w" sizes="(max-width: 200px) 100px, (max-width: 320px) 320px, (max-width: 800px) 800px, 1280px" /> <div class="field field-name"><span class="short">Figure 6 (Image Series).</span> <span class="long">Castera Transient Elastography Cutoffs</span></div></a><div class="field field-source">Source: Castera L, Vergniol J, Foucher J, et al. Prospective comparison of transient elastography, Fibrotest, APRI, and liver biopsy for the assessment of fibrosis in chronic hepatitis C. Gastroenterology. 2005;128:343-50.</div><div style="clear: both;"></div></div></div><div class="doc-series doc-series-315"><div data-doc-id="316" data-doc-scroll="0" data-doc-weight="6B" data-doc-info-width="1327" data-doc-info-height="586" class="document doc-315-6B"><div class="inner"><a target="_blank" rel="image-series-315" alt="<div>Source: Castera L, Forns X, Alberti A. Non-invasive evaluation of liver fibrosis using transient elastography. J Hepatol. 2008;48:835-47.</div>" title="Figure 6B - Diagnostic Performance in Persons with HCV Using Castera Cutoffs" class="image-series image-series-315" href="//cdn.hepatitisc.uw.edu/doc/316-2/diagnostic-performance-persons-hcv-using-castera-cutoffs.jpg"><img src="//cdn.hepatitisc.uw.edu/doc/316-2/thumb/diagnostic-performance-persons-hcv-using-castera-cutoffs.jpg" alt="" srcset="//cdn.hepatitisc.uw.edu/doc/316-2/thumb/diagnostic-performance-persons-hcv-using-castera-cutoffs.jpg 100w, //cdn.hepatitisc.uw.edu/doc/316-2/third/diagnostic-performance-persons-hcv-using-castera-cutoffs.png 320w, //cdn.hepatitisc.uw.edu/doc/316-2/text/diagnostic-performance-persons-hcv-using-castera-cutoffs.png 800w, //cdn.hepatitisc.uw.edu/doc/316-2/full/diagnostic-performance-persons-hcv-using-castera-cutoffs.png 1280w" sizes="(max-width: 200px) 100px, (max-width: 320px) 320px, (max-width: 800px) 800px, 1280px" /> <div class="field field-name"><span class="short">Figure 6B.</span> <span class="long">Diagnostic Performance in Persons with HCV Using Castera Cutoffs</span></div></a><div class="field field-source">Source: Castera L, Forns X, Alberti A. Non-invasive evaluation of liver fibrosis using transient elastography. J Hepatol. 2008;48:835-47.</div><div style="clear: both;"></div></div></div></div><script type="text/javascript">$("a.image-series-315").colorbox({ onComplete: function(){ $("#colorbox").addClass("series").addClass("series-315"); $("#cboxContent").addClass("series-315"); colorBoxSetup(); }, title: function(){ var desc = $(this).attr("alt"); var children = ""; var current = ""; var title = $(this).attr("title"); var parts = title.split(" - "); var letter = parts[0].slice(-1); if($(this).parents(".doc-series").length==0){ current = "A. "+parts[1]; children = $(this).attr("image-series-title")+"<br />"; }else{ children = $(this).parents(".doc-series").prev().find("a.image-series").attr("image-series-title")+"<br />"; current = letter+". "+parts[1]; } var title = children+current; return "<strong>"+title+"</strong><br />"+desc; }, onClosed: function() { $(this).find(".cboxSeriesList").remove(); $("#colorbox").attr("class",""); $("#cboxContent").attr("class","") }, rel: "image-series-315", current: "", maxWidth: colorbox_max_width, maxHeight: "100%"});</script><div data-doc-id="95" data-doc-scroll="0" data-doc-weight="7" data-doc-info-width="800" data-doc-info-height="377" class="document doc-7"><div class="inner"><a target="_blank" rel="image-series-95" alt="Abbreviation: IASL = International Association for Study of the Liver <div>Modified from: Ghany MG, Strader DB, Thomas DL, Seeff LB; American Association for the Study of Liver Diseases. Diagnosis, management, and treatment of hepatitis C: an update. Hepatology. 2009;49:1335-74.</div>" title="Figure 7 (Image Series) - Scoring Systems for Histologic Grade (Inflammation)" class="image-series image-series-95" image-series-title="Figure 7 (Image Series) - Classification of Liver Histology" href="//cdn.hepatitisc.uw.edu/doc/95-3/scoring-systems-histologic-grade-inflammation.jpg"><img src="//cdn.hepatitisc.uw.edu/doc/95-3/thumb/scoring-systems-histologic-grade-inflammation.jpg" alt="Abbreviation: IASL = International Association for Study of the Liver " srcset="//cdn.hepatitisc.uw.edu/doc/95-3/thumb/scoring-systems-histologic-grade-inflammation.jpg 100w, //cdn.hepatitisc.uw.edu/doc/95-3/third/scoring-systems-histologic-grade-inflammation.png 320w, //cdn.hepatitisc.uw.edu/doc/95-3/text/scoring-systems-histologic-grade-inflammation.png 800w, //cdn.hepatitisc.uw.edu/doc/95-3/full/scoring-systems-histologic-grade-inflammation.png 1280w" sizes="(max-width: 200px) 100px, (max-width: 320px) 320px, (max-width: 800px) 800px, 1280px" /> <div class="field field-name"><span class="short">Figure 7 (Image Series).</span> <span class="long">Classification of Liver Histology</span></div></a><div class="field field-caption">Abbreviation: IASL = International Association for Study of the Liver </div><div class="field field-source">Modified from: Ghany MG, Strader DB, Thomas DL, Seeff LB; American Association for the Study of Liver Diseases. Diagnosis, management, and treatment of hepatitis C: an update. Hepatology. 2009;49:1335-74.</div><div style="clear: both;"></div></div></div><div class="doc-series doc-series-95"><div data-doc-id="526" data-doc-scroll="0" data-doc-weight="7B" data-doc-info-width="800" data-doc-info-height="441" class="document doc-95-7B"><div class="inner"><a target="_blank" rel="image-series-95" alt="Abbreviation: International Association for Study of the Liver (IASL)<div>Modified from: Ghany MG, Strader DB, Thomas DL, Seeff LB; American Association for the Study of Liver Diseases. Diagnosis, management, and treatment of hepatitis C: an update. Hepatology. 2009;49:1335-74.</div>" title="Figure 7B - Scoring Systems for Histologic Stage (Fibrosis)" class="image-series image-series-95" href="//cdn.hepatitisc.uw.edu/doc/526-1/scoring-systems-histologic-stage-fibrosis.jpg"><img src="//cdn.hepatitisc.uw.edu/doc/526-1/thumb/scoring-systems-histologic-stage-fibrosis.jpg" alt="Abbreviation: International Association for Study of the Liver (IASL)" srcset="//cdn.hepatitisc.uw.edu/doc/526-1/thumb/scoring-systems-histologic-stage-fibrosis.jpg 100w, //cdn.hepatitisc.uw.edu/doc/526-1/third/scoring-systems-histologic-stage-fibrosis.png 320w, //cdn.hepatitisc.uw.edu/doc/526-1/text/scoring-systems-histologic-stage-fibrosis.png 800w, //cdn.hepatitisc.uw.edu/doc/526-1/full/scoring-systems-histologic-stage-fibrosis.png 1280w" sizes="(max-width: 200px) 100px, (max-width: 320px) 320px, (max-width: 800px) 800px, 1280px" /> <div class="field field-name"><span class="short">Figure 7B.</span> <span class="long">Scoring Systems for Histologic Stage (Fibrosis)</span></div></a><div class="field field-caption">Abbreviation: International Association for Study of the Liver (IASL)</div><div class="field field-source">Modified from: Ghany MG, Strader DB, Thomas DL, Seeff LB; American Association for the Study of Liver Diseases. 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