Hepatitis B virus genotype A2 harbours an L217R polymorphism which may account for a lower response to adefovir.

Sir, Hepatitis B virus (HBV) infection is a major health problem worldwide. The World Health Organization estimates that more than 400 million people are affected. Chronic hepatitis B frequently leads to end-stage liver disease and is the leading cause of liver cancer worldwide. Current HBV therapies are inadequate to eradicate chronic infection. However, anti-HBV drugs may ameliorate liver disease progression in the short term (with normalization of transaminases, reduction in serum HBV-DNA levels and/or HBeAg seroreversion) and in the long term (with prevention of liver cirrhosis and/or hepatocellular carcinoma). After many years of lamivudine being the only oral drug to treat chronic hepatitis B, marketing of adefovir was very welcome. Moreover, this nucleotide analogue was shown to be also effective in lamivudine-experienced patients, with a relatively low incidence of resistance, at least within the first 2 years of therapy but increasing to � 30% at 5 years. 1 Suboptimal response to adefovir, and subsequent selection of resistance mutations, has been associated with pharmacological issues, mainly derived from the low dose (10 mg daily) approved in an attempt to minimize renal toxicity. Adefovir resistance has been classically linked to a single mutation (rtN236T) within the D domain of the HBV polymerase gene. 2 A number of other mutations, such as V84M and S85A (A domain), A181T/V (B