Deciding on the Best Treatment in Patients With Various Types of Hepatitis B

Rowen K. Zetterman, MD


April 19, 2016

In This Article

Immune-Active, HBeAg-Negative Chronic Hepatitis B

Some patients develop recurrent viremia after cessation of antiviral therapy. Up to 20% of patients will develop increased levels of HBV DNA with abnormal aminotransferase values after seroconversion with loss of circulating HBeAg.[29] Some may be associated with circulating HBV mutation. Precore and basal core promoter mutations are the most frequent mutations and may be present in both HBeAg-positive and HBeAg-negative disease. There is a greater risk for development of cirrhosis and hepatocellular carcinoma in patients with sustained disease activity.[30]


The AASLD suggests indefinite antiviral therapy for adults with immune-active, HBeAg-negative chronic hepatitis B unless there is a competing rationale for treatment discontinuation.[9] Prolonged antiviral therapies may reduce the risk for viral recurrence.[30] Patients who clear circulating HBsAg can be considered for treatment cessation. Patients who stop treatment should be monitored every 3 months for reactivation of disease, as manifested by ALT elevation, recurrent viremia, or clinical symptoms and signs.

Patients with immune-active, HBeAg-negative chronic hepatitis B who have concomitant cirrhosis should receive indefinite nucleoside/nucleotide therapy. Although such treatment can reduce circulating HBV DNA levels, it may not eliminate viral DNA within hepatocytes or when integrated into the host genome. Long-term antiviral therapy may reduce viremia and the risk for progressive disease or hepatocellular carcinoma.[17]

Treatment in patients with low-level HBV viremia. The AASLD suggests that persons with persistent low-level viremia (< 2000 IU/mL) on entecavir or tenofovir monotherapy continue monotherapy, regardless of ALT level.

The AASLD suggests one of two strategies in persons with a virologic breakthrough on entecavir or tenofovir: Switch to another antiviral monotherapy with a high barrier to resistance, or add a second antiviral drug that lacks cross-resistance.[9] "Viral breakthrough" is defined as a > 1-log increase in HBV DNA compared with the lowest level or a continuing level of circulating HBV DNA > 100 IU/mL while on treatment. This includes patients with persistent viremia after 48 weeks of initial therapy.


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