Management of Chronic Hepatitis B Patients: Efficacy & Limitation of Nucleos(T)Ide Analogues (Commentary) (Report‪)‬

Hepatitis B virus (HBV) causes a spectrum of liver diseases including acute hepatitis, chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. HBV contains a circular, partially double-stranded DNA genome of 3.2 kb. This genome includes 4 partly overlapping open reading frames. One of these is the polymerase gene that encodes for the polymerase protein including the reverse transcriptase (RT) region. In the process of HBV replication, the pregenomic RNA, which is transcribed from covalently closed circular DNA (cccDNA), is reverse-transcribed by the polymerase protein of HBV. This step is mainly targeted by nucleos(t)ide analogues such as lamivudine, adefovir, entecavir, tenofovir, and telbivudine. Oral administration of these drugs results in virological, biochemical, and histological improvement in most patients (1), but the effect is often transient due to the emergence of drug-resistant mutants of HBV. In this issue, Kumar et al (2) performed a randomized pilot study to compare lamivudine and adefovir in terms of the HBV kinetics. To our knowledge, this is the first report of a randomized study comparing these drugs, and hence valuable. Based on several previous studies, it was thought that adefovir has weaker suppressive effect on serum HBV DNA than other nucleos(t)ide analogues including lamivudine (3,4): the virological response (undetectable HBV DNA) rate of adefovir at 1 year was 21 per cent, and that of lamivudine was 39-44 per cent. However, this 24-wk study showed no significant difference in virological, biological, and histological responses between adefovir and lamivudine. A recent meta-analysis, which compared 48-52-wk outcomes of several antiviral drugs to HBV, demonstrated that there was no significant difference in outcomes between adefovir and lamivudine in both HBeAg-positive and HBeAg-negative patients (5). Therefore, the results of Kumar et al (2) seem to be reasonable. The sample size however is small and the treatment duration was short, as they described. A larger samples is needed to reach a conclusion, and analyses should be performed in view of the HBeAg status and HBV genotypes, which are known to affect the efficacy of anti-viral drugs (6).