Treatment of patients with lamivudine-resistant and adefovir dipivoxil-resistant chronic hepatitis B virus infection: is tenofovir the answer?

We read with great interest the article by Yeon et al , reporting resistance rates to adefovir dipivoxil (ADV) in 25% of patients with lamivudine-resistant hepatitis B virus (HBV) after 24 months of ADV treatment ( Gut 2006; 55 :1488–95). How should we deal with these new important data on ADV resistance? The acyclic nucleotide analogue tenofovir disoproxil fumarate (TDF) was recently shown to be effective in patients with lamivudine-resistant HBV, with incomplete virological response to ADV.1 However, little is known about the efficacy of TDF in patients with lamivudine-resistant and ADV-resistant HBV as described by Yeon et al . We report data on six male patients (median age 48 years, range 34–64 years), who have been treated with TDF for at least 6 months. Five out of six patients were hepatitis B e (Hbe) antigen negative, and documented cirrhosis (Child–Pugh stage A) was present in two of them. Earlier treatments included lamivudine (median treatment duration 45 months, range 16–72 months), followed by ADV (median treatment duration 24 months, range 11–45). ADV resistance was suspected when virological breakthrough (HBV DNA ⩾4 log10 copies/ml; COBAS TaqMan, Roche, Grenzach-Whylen, Germany; lower limit of quantification 1.85 log10 copies/ml) occurred. In four of six patients, the typical HBV polymerase mutations rtA181V, rtA181T or rtN236T were shown (table 1). At that time, HBV DNA considerably increased in all patients (median HBV DNA …