Background: Hepatitis B virus (HBV) infection is one of the major global health problems which can lead to cirrhosis and hepatocellular carcinoma. Currently, main treatment for chronic hepatitis B (CHB) is oral nucleos(t)ide analogues (NA) such as lamivudine, entecavir, tenofovir and tenofovir alafenamide. Lamivudine (LAM) is the first agent and still widely used especially in resource-limited countries. LAM is safe and affordable, but the only drawback is high rate of drug resistance which is roughly 20% during first year of treatment.
Objective: To assess the rate of sustained hepatitis B virological suppression during long-term treatment with LAM in NA naive CHB patients.
Materials and Methods: This is a retrospective, single center study of adult chronic hepatitis B patients who were eligible for treatment according to treatment guideline. LAM was prescribed as the first treatment and must continue for at least 1 year. The patients were excluded if there were co-infected with hepatitis C virus or HIV, underlying hepatocellular carcinoma. Patient demographic data, liver biochemistries and HBV viral load were collected.
Results: There were 547 patients, 403 (73.7%) were male and 111 (20.3%) patients had cirrhosis at baseline which mostly Child-Pugh A (92/111, 86%). Two hundred and seventy-six patients (50.5%) were HBeAg-positive with mean age of 46.8 years. Cumulative incidence of sustained virological suppression defined as HBV DNA below detection was 98.7%, 69.8%, 47.4%, 30.6%, and 18.2%, at year 1, 2, 3, 4, and 5, respectively. In addition, in HBeAg positive CHB patients, 111/276 (40.3%) achieved HBeAg seroconversion and 1 (0.18%) had HBsAg loss. Factors associated with virological breakthrough included HBeAg positive and age >50 years old, tenofovir was added to rescue the patients who had virological breakthrough. No serious adverse event was seen.
Conclusion: Long-term treatment of CHB patients with LAM was sub-optimal. Rate of virological suppression was less than 20% at year 5. These patients must be monitored regularly, and rescued treatment added to prevent biochemical breakthrough. Treatment with high genetic barrier NA from beginning is advised to avoid unnecessary monitoring and the risk of virological breakthrough.

Keywords: Chronic hepatitis B, HBeAg positive, HBeAg seroconversion, Lamivudine, Oral nucleos(t)ide, Virological breakthrough