Clinical, biochemical, and pathological characteristics of clevudine-associated myopathy
Received 21 October 2009; received in revised form 4 March 2010; accepted 9 March 2010. published online 26 April 2010.
Background & Aims
The aim of this study was to define the clinical, biochemical, and pathological characteristics of myopathy developed during clevudine therapy.
Methods
We prospectively enrolled 36 consecutive myopathy patients who were receiving clevudine therapy for the treatment of chronic hepatitis B (CHB). We evaluated patients with a complete medical history, neurologic examination with a questionnaire on neuromuscular diseases, laboratory tests, electrophysiology studies, and muscle biopsies.
Results
The median duration of clevudine therapy was 18.0months (ranging from 9 to 24months). The chief complaint was weakness of the lower extremities in 30 patients (83.3%) and asthenia in five patients (13.9%). One patient (2.8%) had only persistently elevated serum muscle enzyme without any symptoms. Weakness of the lower extremity mainly involved proximal muscle group of the lower extremity, characterized by difficulty in climbing stairs (83.3%), a decrease in exercise capacity (75.0%) and difficulty in walking (55.6%). All patients showed an elevation of more than two of serum creatine kinase, lactate dehydrogenase, and lactate levels. Muscle biopsies performed in 23 patients revealed myopathic features with abnormal mitochondria in 21 patients, and nonspecific myositis in two patients. Motor weakness gradually improved after discontinuation of clevudine.
Conclusions
Myopathy associated with clevudine is characterized by a weakness in proximal muscles of the lower extremities with elevated muscle enzymes and presumably caused by mitochondrial toxicities. Careful medical and serologic examinations are essential for the early detection and management of this potential adverse reaction in CHB patients under clevudine therapy.
aDepartment of Internal Medicine, Liver Research Institute, Graduate School of Medicine, Kyungpook National University, Daegu, Republic of Korea
bDepartment of Pathology, Graduate School of Medicine, Kyungpook National University, Daegu, Republic of Korea
Corresponding author. Address: Department of Internal Medicine, Kyungpook National University Hospital, 200 Dongduk-Ro, Jung-Gu, Daegu 700-721, Republic of Korea. Tel.: +82 53 420 5519; fax: +82 53 426 8773.
1 Drs. Tak and Park share the first authorship of this article.
ABSTRACT