Virological Response and Muscular Adverse Events during Long-Term Clevudine Therapy in Chronic Hepatitis B Patients

Abstract

BackgroundRecently, several reports issued clevudine induced myopathy in the long term use.ObjectivesThe aim of this study was to investigate antiviral effects and adverse events of clevudine monotherapy in patients with chronic hepatitis B (CHB).Patients and MethodsThe subjects were 110 treatment-naïve CHB patients. They were treated with 30 mg clevudine/day for more than six months. Virological and biochemical tests, including that for serum creatine kinase (CK), were monitored at baseline and at 3-month intervals during treatment period.ResultsIn HBeAg-positive patients, the cumulative rates of virological response were 74.0 %, 68.5 %, and 67.3 % after one, two, and three years of clevudine treatment, respectively. Cumulative rates of HBeAg loss or seroconversion were 17.8 %, 30 %, and 31.5 % after one, two and, three years of clevudine treatment, respectively. In HBeAg-negative patients, the cumulative rates of virological response were 97.3 %, 100 %, and 94.6 %, respectively. Virological breakthrough occurred in 27 patients. The rtM204I mutation in HBV polymerase was predominantly detected. Muscular adverse events were observed in 15 patients. All patients with myopathy recovered after the cessation of clevudine monotherapy. Fluctuations in CK level during the clevudine treatment period were frequently observed irrespective of development of myopathy. Multiple episodes of CK elevation were significantly related to the development of myopathy.ConclusionsLong-term clevudine monotherapy is effective for suppression of serum HBV DNA level and normalization of serum alanine amino transaminase levels, but associated with occurrence of rtM204I mutation. Clevudine-induced muscular adverse events are not uncommon, although they are totally reversible after cessation of the treatment. Muscular adverse events and serum CK level should be carefully monitored during long-term treatment with clevudine.

Asian-Pacific clinical practice guidelines on the management of hepatitis B: a 2015 update

“…Clevudine is an l -nucleoside pyrimidine analogue with potent antiviral activity against HBV. With clevudine 30 mg daily, the cumulative rate of undetectable HBV DNA is 67–83 % and HBeAg seroconversion is 23–31 % after 2–3 years [ 226 , 227 ]. Virological breakthrough occurs in approximately 25 % of patients, and is primarily related to rtM204I ± rtL180M mutants.…”

“…Virological breakthrough occurs in approximately 25 % of patients, and is primarily related to rtM204I ± rtL180M mutants. Myopathy was reported in up to 13 % of patients after being treated for a mean of 14 (range 9.3–23.5) months, but it was resolved spontaneously after stopping clevudine [ 226 ]. The global development of clevudine was terminated in 2009 because of case reports of serious myopathy related to myonecrosis.…”