Clevudine (Revovir), a
pyrimidine nucleoside analogue, is a recently introduced
antiviral drug. Clinical trials have demonstrated potent, sustained
antiviral activity against hepatitis B virus without specific adverse events. The lack of cytotoxicity and absence of an effect on mitochondrial function have been considered the reasons for the fewer adverse events. However, it came to our attention that several
hepatitis B patients developed
myopathy during
clevudine therapy. Our study was aimed to analyze the clinical and pathological features of patients with
clevudine-induced
myopathy with some consideration of its pathogenetic mechanism. Seven
hepatitis B patients who developed severe skeletal
myopathy during
clevudine therapy were examined in this study. The demographic data, clinical features, pathological findings, and molecular studies of these patients were analyzed with speculation about the underlying pathogenic mechanisms. All seven patients were treated with
clevudine for more than 8 months (8-13 months). In all, the main symptom was slowly progressive proximal
muscular weakness over several months. A markedly elevated
creatine kinase level and myopathic patterns on electromyography were found. Muscle biopsies revealed severe myonecrosis associated with numerous ragged red fibers,
cytochrome c oxidase-negative fibers, and predominant type II fiber
atrophy. Molecular studies using quantitative polymerase chain reaction showed a depletion of the
mitochondrial DNA in the patients' skeletal muscle.
CONCLUSION: