Chronic Hepatitis B

A Treatment Update

Vincent Wong, MD; Henry Chan, MD


Semin Liver Dis. 2013;33(2):122-129. 

In This Article

Goal of Treatment

Various antiviral therapies can lead to normalization of serum alanine aminotransferase (ALT), hepatitis B virus (HBV) DNA suppression, hepatitis B e antigen (HBeAg) seroconversion, hepatitis B surface antigen (HBsAg) seroclearance, and histological improvement. At the end of the day, however, these are all just surrogate markers. The most important goal of treatment is prevention of hepatic mortality and morbidity like hepatocellular carcinoma (HCC) and cirrhotic complications. The strongest evidence on the role of antiviral therapy in preventing clinical complications came from the Cirrhosis Asian Lamivudine Multicentre (CALM) Study.[1] In this placebo-controlled randomized trial, lamivudine treatment for around 3 years reduced the risk of a composite end point of progression in the Child-Pugh score of 2 points or more, cirrhotic complications, HCC, and liver-related deaths from 17.7% to 7.8%. Subsequent meta-analyses including the CALM Study and other observational studies showed that lamivudine treatment, compared with placebo or no treatment, is associated with lower risk of HCC.[2] Successful treatment with conventional interferon is also associated with reduced risk of HCC and cirrhotic complications.[3] Besides, patients with ALT normalization or histological improvement after antiviral therapy have lower incidence of hepatic events than nonresponders, again supporting the role of antiviral therapy in preventing adverse outcomes.[4]

For historic reasons, there are scarce data on the effect of new antiviral agents on hard clinical outcomes. When patients treated with peginterferon were followed for 5 to 8 years, liver fibrosis improved gradually and new cases of advanced fibrosis or cirrhosis only occurred rarely in nonresponders.[5] In an uncontrolled cohort study of 372 patients treated with entecavir, HCC, liver decompensation, and death were less frequent in those with on-treatment HBV DNA below 80 IU/mL, but the beneficial effect was only apparent in patients with cirrhosis.[6]