J Korean Med Sci.  2017 Nov;32(11):1857-1860. 10.3346/jkms.2017.32.11.1857.

Clevudine Induced Mitochondrial Myopathy

• Park SH
• Park KS
• Kim NH
• Cho JY
• Koh MS
• Lee JH

• KMID: 2390315
• DOI: http://doi.org/10.3346/jkms.2017.32.11.1857

Abstract

Clevudine was approved as an antiviral agent for hepatitis B virus, which showed marked, rapid inhibition of virus replication without significant toxicity. However, several studies have reported myopathy associated with clevudine therapy. Also, we experienced seven patients who suffered from myopathy during clevudine therapy. To characterize clevudine-induced myopathy, we collected previously reported cases of clevudine myopathy and analyzed all the cases including our cases. We searched electronic databases that were published in English or Korean using PubMed and KoreaMed. Ninety-five cases with clevudine myopathy, including our seven cases, were selected and analyzed for the demographic data, clinical features, and pathologic findings. The 95 patients with clevudine-induced myopathy comprised 52 women and 43 men aged 48.9 years (27-76 years). The patients received clevudine therapy for about 14.2 months (5-24 months) before the development of symptoms. Weakness mainly involved proximal extremities, especially in the lower extremities, and bulbar and neck weakness were observed in some cases (13.7%). Creatine kinase was elevated in the majority of patients (97.9%). Myopathic patterns on electromyography were observed in most patients examined (98.1%). Muscle biopsy presented patterns compatible with mitochondrial myopathy in the majority (90.2%). The weakness usually improved within about 3 months after the discontinuation of clevudine. Though clevudine has been known to be safe in a 6-month clinical trial, longer clevudine therapy for about 14 months may cause reversible mitochondrial myopathy. Careful clinical attention should be paid to patients with long-term clevudine therapy.

Keyword

Clevudine; Antiviral Agent; Hepatitis B; Mitochondrial Myopathy; Myopathy

MeSH Terms

Biopsy
Creatine Kinase
Electromyography
Extremities
Female
Hepatitis B
Hepatitis B virus
Humans
Lower Extremity
Male
Mitochondrial Myopathies*
Muscular Diseases
Neck
Virus Replication
Creatine Kinase

Figure

• 

  Fig. 1 Typical findings of mitochondrial myopathy from one of clevudine-induced mitochondrial myopathy. (A) Marked muscle fiber necrosis with degenerative muscle fibers (white asterisk) in hematoxylin and eosin stain. (B) Ragged-red fibers with red rim and speckled sarcoplasm (white asterisk) in modified Gomori trichrome stain. (C) Many cytochrome c oxidase-negative fibers (black asterisk) in cytochrome c oxidase stain. (D) Darkly stained type 1 fiber predominance and light stained type 2 fiber atrophy (black asterisk) in adenosine triphosphatase stain at pH 4.3. (E) Darkly stained muscle fibers with mitochondrial proliferation (white asterisk) in succinic dehydrogenase stain. (F) Enlarged mitochondria with blunting and focal clumping of cristae (black asterisk) in electron microscopic examination. Bar: (A-E) 100 μm and (F) 0.5 nm.

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