한빛사 논문
Abstract
1Department of Neurology, School of Medicine, Catholic University of Daegu, Daegu, South Korea
2Department of Internal Medicine, School of Medicine, Catholic University of Daegu, Daegu, South Korea
3Yeungnam University College of Medicine, Daegu, South Korea
4Kyungbook National University Hospital, Daegu, South Korea
5Department of Neurology, Medical Research Institute, Pusan National University School of Medicine, Pusan, South Korea
6Pathology, Medical Research Institute, Pusan National University School of Medicine, Pusan, South Korea
*Correspondence to Dae-Seong Kim, Department of Neurology, Pusan National University Yangsan Hospital, Beomo-ri, Mulgum-eup, Yangsan, 626-770 Gyeongsangnam-do, Korea
Potential conflict of interest: Nothing to report.
fax: +82-51-245-2783
Funded by:
Medical Research Institute Grant; Grant Number: 2006-38
Pusan National University
Abstract
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: To the best of our knowledge, this is the first report of myopathy associated with clevudine therapy. This study has clearly shown that long-term clevudine therapy can induce the depletion of mitochondrial DNA and lead to mitochondrial myopathy associated with myonecrosis. Careful clinical and laboratory attention should be paid to patients on long-term clevudine therapy for this skeletal muscle dysfunction.Received: 5 December 2008; Accepted: 19 February 2009
Digital Object Identifier (DOI)
10.1002/hep.22959 About DOI
논문정보
관련 링크
연구자 키워드
연구자 ID
관련분야 연구자보기
소속기관 논문보기
관련분야 논문보기
해당논문 저자보기