Chronic hepatitis B virus (HBV) infection, which can lead to cirrhosis and hepatocellular carcinoma, is a major health threat worldwide. Classic patients with chronic hepatitis B are positive for hepatitis Be-antigen (HBeAg) and HBV-DNA. In the Mediterranean basin, 30–80% of patients with chronic hepatitis B (CHB) are HBeAg-negative, in contrast to Northern European countries and the US, where only 10–40% of CHB patients are lacking HbeAg. HBeAg-negative CHB usually runs a progressive course. The greatest problem with the treatment of HBeAg-negative CHB is the high relapse rate. Their end treatment response rates are similar to those of classic CHB patients, but after discontinuation of treatment most of them relapse. All the data available in the literature show that more than 80% of patients with HBeAg-negative CHB do not respond to the current approved therapies. A literature review and our experience with thymosin indicate that the combination of IFN alfa2b and T-alfa1 is better tolerated and more likely to induce a sustained response in HbeAg-negative chronic hepatitis B patients when compared to other currently available therapies. As thymosin-alfa1 treatment is relatively free from adverse effects, future controlled trials are needed, with a longer follow-up, in order to fully evaluate the role of the combination therapy of thymosin-alfa1 with other emerging therapeutic agents.

Keywords: 2-Aminopurine - analogs & derivatives, 2-Aminopurine - therapeutic use, Antiviral Agents - therapeutic use, Drug Therapy, Combination, Hepatitis B e Antigens, Hepatitis B, Chronic - drug therapy, Interferons - therapeutic use, Lamivudine - therapeutic use, Reverse Transcriptase Inhibitors - therapeutic use, Thymosin - therapeutic use