Efficacy and safety of tenofovir-based rescue therapy for multi-drug resistant hepatitis B

Abstract

Background: Persistent HBV replication with active hepatitis leads to disease progression. Antiviral agents effectively suppress the HBV replication. Antiviral agent contains a major problem in the management of patients, because of antiviral drug resistance. We evaluated the efficacy and safety of tenofovir (TDF) in Chronic hepatitis B (CHB) patients who had suboptimal response to previous antiviral therapy or multidrug resistant patients.

Design: An observational study TDF 300mg or TDF 300mg plus LMV 100mg daily. Methods: Sixteen patients with CHB who failed to achieve virologic response during lamivudine (LMV), adefovir (ADV), clevudine (CLV), entecavir (ETV) mono-therapy or treated with LMV-ADV or ADV-ETV combination therapy for at least 6 months were enrolled. The median age was 47.5 years (range 33-64). Twelve patients were male, and 13 patients were HBeAg positive. Quantitative HBV-DNA by real time PCR and alanine aminotransferase (ALT),presence of HBe Ag was measured every 3 or 6 months and serum creatinine was monitored. Genotypic multidrug-resistant mutations for antiviral agent were measured by RFMP method.

Results: The median duration of follow up was 42 months(range, 6-72) after the start of TDF. Before TDF therapy, LMV-resistant mutations at rt180M or rtM204I/V or ADV-resistant mutations at rt181T or rt236T were detected. Median ALT at baseline was 74IU/L and HBV DNA level was 6.9 log10 copies/mL. After TDF therapy, HBV DNA level was dropped from 6.9 log10 copies/mL to 3.54log10 and 3.38log10 at 12 and 24 months. The probability of HBV DNA ≤300 copies/mLwas overall 43% and 83% at 12 and 24 months. Four patients lost HBe Ag (after 3, 12, 27, and 48 months, respectively). ALT was dropped from 74IU/L to 45IU/L and 41IU/L at 12 and 24 months. Five patients showed virological breakthrough (defined as increased ≥1 log10 copies/mL). In four of five was incompliance with the TDF. No significant changes in serum creatinine were observed except chronic renal failure patient.

Conclusions: Our study demonstrated that TDF monotherapy orTDF plus LMV safely and effectively suppressed HBV replication in patients with resistance or suboptimal response to previous antiviral agent. TDF-based antiviral treatment could be an effective rescue therapy for multi-drug resistant hepatitis B.