EARLY VIROLOGIC AND BIOCHEMICAL RESPONSE TO CLEVUDINE IN CIRRHOTIC PATIENTS WITH CHRONIC HBV INFECTION

Abstract

Backgound/Aim: Clevudine is a new nucleoside analogue with potent antiviral activity in chronic hepatitis B patients. However, the efficacy and safety of clevudine in cirrhotic patients are not well recognized. This study was conducted to evaluate the early virologic and biochemical response rate as well as safety of clevudine in cirrhotic patients with chronic HBV infection.

Methods: Forty-six patients with chronic HBV infection who visited Korea University Ansan Hospital and Guro Hospital between May 2007 and May 2008 were included. Twenty-four patients had chronic hepatitis B (group A) and twenty-two had liver cirrhosis (group B). Liver cirrhosis was diagnosed based on liver histopathology or abdominal sonographic findings combined with laboratory data and clinical manifestations. All patients with HBV DNA levels over 20,000 IU/mL were treated with clevudine for median of 25 weeks (range 12-38 weeks). Early virologic response was defined as HBV DNA less than 200 IU/mL at week 12. Early biochemical response was defined to be normalization of ALT (<45 IU/L) at week 12.

Results: The mean ages were 39.3 and 46.8 years-old in group A and group B, respectively (p=0.02). The proportions of male patients were not significantly different in both groups (58% vs 54.5%, p>0.05). Two patients (9%) had hepatic decompensation at baseline in group B. Pretreatment HBV DNA levels were higher in group A compared with group B (8.06 log IU/mL vs 7.09 log IU/mL, p=0.06). Pretreatment ALT levels were not significantly different between the 2 groups (166 IU/L vs 139 IU/L, p=0.725). The rate of early virologic response was significantly higher in group B compared with groups A (72.7% vs 33%, p=0.01). The rate of early biochemical response were not significantly different in both groups (75% vs 72.7%, p=0.725). ALT elevation in 12 weeks of treatment compared with baseline were noticed in 16.7% in group A, but 0% in group B (p=0.11). No new-onset hepatic decompensation was noticed during treatment in both groups.

Conclusion: Previously,episodes of ALT flare during the early treatment period have been reported in chronic hepatitis B patients treated with clevudine (Lee HS et al, Hepatology 2006). Such phenomenon could be associated with initial clinical deterioration if clevudine is administered in cirrhotic patients. However our study showed that such ALT elevation was not found in cirrhotic patients receiving clevudine and no hepatic decompensation was newly developed. Clevudine is considered to be safe and effective in cirrhotic patients with chronic HBV infection as well as chronic hepatitis B patients. Long term safety and efficacy need to be evaluated in the future.