CLINICAL FEATURES AND RISK FACTORS FOR CLEVUDINE RESISTANCE IN TREATMENT-NAiVE CHRONIC HEPATITIS B PATIENTS

Abstract

Background and Aims: Clevudine is a potent antiviral agent for the treatment of chronic hepatitis B. The incidence of resistance to clevudine is increased in lamivudine-experienced patients. However, resistance rates, risk factors and mutational patterns are not well known in treatment naive patients. This study is aimed to analyze the factors related to development of clevudine resistance and mutational patterns.

Patients and methods: Medical records from 82 treatment-naive patients who visited Korea University Ansan Hospital and started to receive clevudine between May 2007 and November 2008 were reviewed. Sex, age, liver cirrhosis, HBeAg/Ab status, and HBV DNA(baseline and month 6) were compared between clevudine-resistance group and no resistance group. P-values<0.05 were considered significant.

Results: Median duration of treatment was 69.9 weeks (range 24-106 weeks). One patient non-compliant to treatment was excluded from analysis. A total of 12 out of 81 patients showed viral breakthrough. Antiviral resistance test showed rtM204I in 12 patients. rtL80I was detected in 6 patients. rtD131G, rtS213T, or rtF221Y were additionally detected in 3 patients. Median duration from the start of treatment to viral breakthrough was 60.3 weeks (range 24-78 weeks). HBeAg positive rate was higher in clevudine-resistance group (91.7% vs 47.8%, p=0.005). Baseline HBV DNA level was significantly higher in clevudine-resistance group (8.3 log copies/mL vs 7.4 log copies/mL, p=0.028) Virologic response rate (<2000 copies/mL) at month 6 was lower in clevudine-resistance group (50.0% vs 82.6%, p=0.021).

Conclusions: Although clevudine is a potent antiviral agent, the resistance rate was appreciably high. Attention needs to be paid for the development of resistance to clevudine in patients with positive HBeAg, high HBV DNA level at baseline, and incomplete virologic response at month 6.