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-Positive Chronic Hepatitis B

The loss of immune tolerance with upregulation of immune response can lead to the immune-active, HBeAg-positive stage of chronic hepatitis B. For persons who acquired chronic hepatitis B as a neonate, this may occur between the age of 20 and 50 years.[23] For those with HBV infection in later childhood or adulthood, the immune-tolerant phase will be shorter.

Immune-active chronic hepatitis B is characterized by elevation of the circulating HBV DNA level (>20,000 IU/mL), positive serum HBeAg, and twofold or greater ALT levels. Liver histology may identify hepatic inflammation with or without significant fibrosis. Up to 20% of these patients will clear circulating HBeAg and develop anti-HBe within 1 year of entering the immune-active phase.[24] This is often followed by transition to inactive chronic hepatitis B.


The AASLD recommends antiviral therapy for adults with immune-active chronic hepatitis B (HBeAg-negative or HBeAg-positive) to decrease the risk for liver-related complications. Immune-active chronic hepatitis B is defined by an elevation of ALT to more than twice the upper limit of normal or evidence of significant histologic disease, coupled with elevated HBV DNA levels > 2000 IU/mL (HBeAg-negative) or > 20,000 IU/mL (HBeAg-positive).[9] ALT levels are often > 60 U/mL in men and > 38 U/mL in women. In addition, the presence of cirrhosis in persons with immune-active chronic hepatitis B coupled with an HBV DNA level > 2000 IU/mL is an indication for antiviral therapy regardless of circulating ALT levels.[9]

The AASLD recommends pegylated interferon, entecavir, or tenofovir as the preferred initial therapy for adults with immune-active chronic hepatitis B.[9] These drugs have a lower rate of viral resistance after long-term use. The duration of therapy with pegylated interferon is generally 48 weeks.[25] The duration of therapy when nucleoside/nucleotide analogues are used varies on the basis of the continuous presence of HBeAg and adequacy of suppression of HBV DNA levels. Although the AASLD guideline does not recommend combining pegylated interferon with nucleoside/nucleotide analogues, a recent study has suggested that 48 weeks of pegylated interferon plus tenofovir will result in a greater loss of HBsAg than treatment with either drug alone.[26] Treatment with pegylated interferon is associated with a higher likelihood of HBeAg and HBsAg clearance than is treatment with nucleosides/nucleotide analogues.[27]

The AASLD suggests that HBeAg-positive adults without cirrhosis with chronic hepatitis B who seroconvert to anti-HBe on therapy discontinue nucleoside/nucleotide analogues after a period of treatment consolidation. Consolidation therapy generally involves treatment for at least 12 months of persistently normal ALT levels and undetectable HBV DNA levels.[9] Studies have shown that prolonged suppression of HBV DNA will reduce relapse rates.[28]

The alternative to stopping nucleoside/nucleotide analogue treatment with seroconversion to anti-HBe is to continue treatment until there is loss of circulating HBsAg. When treatment is stopped, the patient should be followed with measurement of ALT levels and evaluation for recurrent viremia or clinical worsening every 3 months for at least 1 year.

The AASLD suggests indefinite antiviral therapy for HBeAg-positive adults with cirrhosis and chronic hepatitis B who seroconvert to anti-HBe on nucleoside/nucleotide analogue therapy.[9] Discontinuation of therapy can be considered for patients with cirrhosis who clear HBsAg, followed by periodic measurement of ALT levels.


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