Treatment of Hepatitis B e Antigen-negative Patients.

Hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB) occurs at the late phase in hepatitis B virus (HBV) infection's natural history. The disease is characterized by progressive liver damage due to variants with mutations in the precore/core promoter region that reduce or abolish HBeAg expression. Chronic HBeAg-negative disease's prognosis is poor, with only rare incidences of spontaneous remission. Recent studies in Europe, Asia, and the United States all have reported an increased prevalence of HBeAg-negative and a decreased prevalence of HBeAg-positive chronic hepatitis; this may be related to increased awareness, decrease in new HBV infections, and aging of existing carriers. The end point of therapy for HBeAg-negative CHB patients is difficult to assess. In most studies, HBV DNA suppression and normalization of serum alanine aminotransaminase levels have been used to indicate therapeutic response. Six drugs currently are licensed for the treatment of CHB infection. These are the immunomodulatory agents (conventional interferon-alpha-2b and pegylated interferon-alpha-2a) and the nucleoside/nucleotide analogues (lamivudine, adefovir dipivoxil, entecavir, and telbivudine). Sustained treatment response rates generally are poor due to the high probability of relapse, particularly following nucleoside/nucleotide analogue therapy. As not all patients can tolerate or will respond to interferon-based therapy, maintenance therapy with nucleoside/nucleotide therapy is the alternative. However, this latter approach can lead to development of viral resistance and long-term safety concerns.