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Why and How I Assess Liver Disease Severity in Patients With Hepatitis B

Grace LH Wong, MD

Director, Medical Data Analytics Centre (MDAC)
Deputy Director, Center for Liver Health
Assistant Dean (Learning Experience), Faculty of Medicine
The Chinese University of Hong Kong
Honorary Consultant
Division of Gastroenterology and Hepatology
Department of Medicine and Therapeutics
Prince of Wales Hospital
Hong Kong

Grace LH Wong, MD, has disclosed that she has received funds for research support from AbbVie and Gilead Sciences, consulting fees from Gilead Sciences and Janssen, and fees for non-CME/CE services from Abbott, AbbVie, Bristol-Myers Squibb, Echosens, Furul, Gilead Sciences, Janssen, and Roche.

View ClinicalThoughts from this Author

Released: March 17, 2021

International treatment guidelines provide important guidance to physicians who care for patients with hepatitis B virus (HBV) infection. This guidance is particularly relevant when we are determining when to start antiviral treatment, as treatment indications have been evolving over the past 2 decades. Current treatment criteria are based primarily on the combination of 3 key factors: serum HBV DNA levels, serum alanine aminotransferase (ALT) levels, and severity of liver disease. The first 2 laboratory parameters are routinely checked at almost every clinic visit, but information about the severity of liver disease may be missing.

Severity of Liver Disease
Liver disease severity can be assessed by clinical evaluation, liver biopsy, or other noninvasive methods. Unless patients have obvious symptoms and signs of hepatic decompensation, advanced liver fibrosis and early cirrhosis are difficult to discern by routine clinical and laboratory assessments. From data collected via Hep B Consult, the point-of-care decision support tool that provides guideline recommendations on treating HBV infection, a significant percentage of users did not know the extent of liver fibrosis and inflammation for the patient case they entered. If such important information is missing, a recommendation on treatment candidacy cannot be made. For example, if a patient has normal or mildly elevated ALT (> upper limit of normal but <2 x upper limit of normal) and HBV DNA >2000 IU/mL without significant fibrosis or inflammation, the Asian Pacific Association for the Study of the Liver guidelines recommend monitoring every 3 months. By contrast, if the patient has significant fibrosis, these guidelines recommend initiating antiviral treatment instead.

Noninvasive Assessment of Liver Fibrosis: Current Standard of Care
Noninvasive assessment of liver fibrosis has become part of the current standard of care for patients with HBV infection. Liver stiffness measurement (LSM) with transient elastography (FibroScan) is one of the most widely validated noninvasive assessments for liver fibrosis. It is an accurate and reproducible method to predict advanced fibrosis in HBV. Using transient elastography, it is possible to perform repeated liver fibrosis assessments on asymptomatic patients. The key challenge of this tool is the confounding effect of ALT levels. Studies have demonstrated a correlation between LSM and ALT levels, and a decrease in LSM may only reflect ALT normalization. Hence, transient elastography is not accurate enough to indicate regression of liver fibrosis. This limitation may be partially addressed by combining LSM with a serum measurement–based formula that is independent of ALT. Examples include the Forns index and Enhanced Liver Fibrosis test. In regions where transient elastography is not readily accessible, serum test formulas based on common laboratory parameters have the advantage of high applicability. Examples include the aspartate aminotransferase to platelet ratio index, Forns index, and Fibrosis-4. As the parameters are readily available in routine liver biochemistry panels, these serum test formulas would be applicable to most patients with minimal interobserver variations.

Your Thoughts
Which noninvasive assessments of liver fibrosis do you commonly use in your management of patients with HBV infection? Please answer the polling question and share your thoughts in the comments section.

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