Efficacy of tenofovir disoproxil fumarate switch therapy in chronic hepatitis B patients with suboptimal response to adefovir-based combination therapy

摘要

In the present study, the efficacy and safety of tenofovir disoproxil fumarate (TDF) switch therapy were assessed in patients with chronic hepatitis B exhibiting a suboptimal response to adefovir (ADV)-based combination therapy. First, the efficacy of the TDF switch therapy was retrospectively evaluated in 50 patients with chronic hepatitis B who failed to respond to ADV-based combination treatment. Among those, 48 patients with a median age of 35 years were hepatitis B e antigen (HBeAg)-positive and 17, 14 and 19 patients were previously treated with lamivudine (LAM) plus ADV, telbivudine plus ADV and entecavir (ETV) plus ADV, respectively. A total of 41 patients were treated with TDF alone and 9 with TDF plus ETV. The median time of follow-up was 102 weeks. The primary end-point was the cumulative probability of achieving a complete virologic response (CVR). The secondary end-points were the rate of alanine aminotransferase (ALT) normalization, HBeAg seroconversion in HBeAg-positive patients, and the plasma levels of creatinine and creatine kinase. The mean serum hepatitis B virus DNA levels prior to initiation of the TDF switch therapy were 4.8±1.6 log10IU/ml. The cumulative probability of achieving a VR at 24, 48, 96 and 108 weeks was 52.0, 76.0, 89.8 and 94.9%, respectively. The cumulative probability of normalization of ALT at 12, 24, 36, 48, 60,72, 84, 96, 108, 120 and 132 weeks was 34, 44, 50, 58, 66, 70, 74, 80, 90, 92 and 94%, respectively. HBeAg seroconversion was achieved in 5 patients. During the follow-up, 6 patients suffered from a virologic breakthrough, 3 patients failed to respond to the TDF treatment and the remaining patients were able to obtain VR following the continuation of TDF treatment. Slightly elevated serum levels of creatinine were observed in one patient, whereas creatine kinase activity did not increase in any of the subjects. In conclusion, TDF switch therapy is efficient and safe for patients with chronic hepatitis B with a suboptimal response to ADV-based combination therapy.