Korean J Gastroenterol.  2013 Jan;61(1):30-36. 10.4166/kjg.2013.61.1.30.

Efficacy of Entecavir Switching Therapy in Chronic Hepatitis B Patients with Clevudine-induced Myopathy

• Lee JW
• Lee YJ
• Lee JJ
• Kim JH
• Jung YK
• Kwon OS
• Choi DJ
• Kim YS
• Kim JH

• KMID: 1775784
• DOI: http://doi.org/10.4166/kjg.2013.61.1.30

Abstract

BACKGROUND/AIMS
Clevudine is a potent antiviral agent against HBV. However, long-term clevudine therapy may cause myopathy. This study was carried out to identify the efficacy of entecavir switching therapy in chronic hepatitis B patients experiencing clevudine-induced myopathy.
METHODS
One hundred forty six patients with chronic hepatitis B treated with 30 mg of clevudine per day for 73 weeks (range, 36-132 weeks) were enrolled. Among them, clevudine-induced myopathy occurred in 21 patients (14.4%) which was diagnosed if the patients had symptoms related to myopathy with concurrent CK and AST elevation. All the patients who were diagnosed as clevudine-induced myopathy stopped the therapy, and 17 patients (81%) were switched to entecavir 0.5 mg.
RESULTS
The patients with clevudine-induced myopathy were switched to entecavir 0.5 mg for median 68 weeks, and all of them showed disappearance of clinical myopathic symptoms and normalization of CK and AST level within median 2.2 months. Eight patients (47%) were HBeAg positive before entecavir treatment, and HBeAg seroconversion was achieved in 2 patients (25%). HBV DNA level was elevated in 3 patients (17.6%) at the time when the patients were diagnosed as myopathy, all of them achieved virological response with entecavir switching therapy. ALT level was elevated in 3 patients (17.6%) before entecavir treatment, all of them showed normalization of ALT level. During entecavir therapy, genotypic resistance to entecavir or virological breakthrough was not noted.
CONCLUSIONS
In chronic hepatitis B patients experiencing clevudine-induced myopathy, switching to entecavir 0.5 mg per day showed a resolution of myopathy and adequate viral suppression.

Keyword

Clevudine; Entecavir; Chronic hepatitis B; Muscular diseases

MeSH Terms

Adult
Aged
Alanine Transaminase/analysis
Antiviral Agents/*adverse effects/therapeutic use
Arabinofuranosyluracil/adverse effects/*analogs & derivatives/therapeutic use
Creatine Kinase/analysis
DNA, Viral/blood
Drug Resistance, Viral
Female
Guanine/*analogs & derivatives/therapeutic use
Hepatitis B e Antigens/blood
Hepatitis B virus/genetics
Hepatitis B, Chronic/*drug therapy
Humans
Male
Middle Aged
Muscular Diseases/*chemically induced
Antiviral Agents
DNA, Viral
Hepatitis B e Antigens
Arabinofuranosyluracil
Guanine
Alanine Transaminase
Creatine Kinase

Figure

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  Fig. 1. Cumulative incidence of biochemical, virologic, serologic responses and drug resistance during clevudine therapy.

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  Fig. 2. Cumulative incidence of clevudine myopathy. Clevudine-induced myopathy occurred in 21 patients (14.4%) as early as 18 weeks and gradually increased during the treatment of 64 weeks.

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  Fig. 3. Screening and follow-up of patients diagnosed as clevudine-induced myopathy.

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  Fig. 4. Changes of HBV DNA (log10 IU/mL) with entecavir switching therapy in HBV DNA-positive and HBV DNA-negative patients. (A) In 3 patients who had detectable HBV DNA at time point of myopathy, virologic response after entecavir switching therapy were noted. (B) Also 14 patients with virologic response with clevudine therapy maintained HBV DNA negativity during switching to entecavir therapy.

Reference

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