7. Bushby KM, Beckmann JS. The 105th ENMC sponsored workshop: pathogenesis in the non-sarcoglycan limb-girdle muscular dystrophies, Naarden, April 12–14, 2002. Neuromuscul Disord 2003;13:80–90. 8. Greenberg SA, Salajegheh M, Judge DP, Feldman MW, Kuncl RW, Waldon Z, et al. Etiology of limb girdle muscular dystrophy 1D/1E determined by laser capture microdissection proteomics. Ann Neurol 2012;71:141–145. 9. Sato T, Hayashi YK, Oya Y, Kondo T, Sugie K, Kaneda D, et al. DNAJB6 myopathy in an Asian cohort and cytoplasmic/nuclear inclusions. Neuromuscul Disord 2013;23:269–276. 10. Sandell SM, Mahjneh I, Palmio J, Tasca G, Ricci E, Udd BA. ’Pathognomonic’ muscle imaging findings in DNAJB6 mutated LGMD1D. Eur J Neurol 2013 Jul 19. [Epub ahead of print] 11. Stojkovic T, el Hammouda H, Richard P, Lopez de Munain A, Ruiz-Martinez J, Camano P, et al. Clinical outcome in 19 French and

Spanish patients with valosin-containing protein myopathy associated with Paget’s disease of bone and frontotemporal dementia. Neuromuscul Dis 2009;19:316–323. 12. Kimonis V, Donkervoort S, Watts G. Inclusion body myopathy with Paget disease of bone and/or frontotemporal dementia. In: Pagon RA, Adam MP, Bird TD, editors. GeneReviews. Seattle, WA: University of Washington; 1993. 13. Ma˚nsson C, Kakkar V, Monsellier E, Sourigues Y, Harmark J, Kampinga HH, et al. DNAJB6 is a peptide-binding chaperone which can suppress amyloid fibrillation of polyglutamine peptides at substoichiometric molar ratios. Cell Stress Chaperones 2013 Aug 1. [Epub ahead of print] 14. Kampinga HH, Craig EA. The HSP70 chaperone machinery: J proteins as drivers of functional specificity. Nature Rev Mol Cell Biol 2010;11:579–592.

ENTECAVIR-ASSOCIATED MYOPATHY: A CASE REPORT AND LITERATURE REVIEW KAI YUAN, MD,1 GUOCHUN WANG, MD, PhD,1 ZHENGUO HUANG, MD,2 BING LIN, MD,1 HUIQIONG ZHOU, MD, PhD,1 and XIN LU, MD1 1 2

Department of Rheumatology, China–Japan Friendship Hospital, Yinghua East Road, Chaoyang District, Beijing 100029, China Department of Radiology, China–Japan Friendship Hospital, Beijing, China

Accepted 6 November 2013 ABSTRACT: Introduction: Entecavir, a nucleoside analog (NA), is effective for treatment of chronic hepatitis B virus (HBV) infection. Methods: We report the case of a patient we encountered with entecavir-associated myopathy. We also performed a literature review of myopathies associated with nucleoside analogs. Results: A 44-year-old man presented with a 3-month history of myalgia and progressive weakness. He had HBV infection and had received entecavir antiviral treatment for 5 years. Laboratory tests showed that serum creatine kinase levels were significantly elevated. Muscle histopathology showed abundant T-lymphocyte infiltration of muscle fibers, and HBV surface antigen and HBV core antigen were not present in muscle fibers. Entecavir-associated myopathy was subsequently diagnosed. The patient’s symptoms eventually resolved, and serum CK levels decreased rapidly after he stopped receiving entecavir treatments. Conclusions: Patients who receive NA therapy should be closely monitored for myopathic side effects. Muscle Nerve 49:610–614, 2014

Chronic infection by hepatitis B virus (HBV) affects more than 350 million people worldwide and can have serious consequences, including cirrhosis, hepatic failure, and hepatocellular carcinoma.1 Nucleoside analogs (NAs) and interferons are the first-line treatments for HBV. NAs include entecavir, Additional Supporting Information may be found in the online version of this article. This work was supported by the Beijing Science and Technology Committee (Z111107058811084). Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; ATP, adenosine triphosphate; CK, creatine kinase; HBV, hepatitis B virus; MANA, myopathies associated with nucleoside analogs; MHC, major histocompatibility complex; MMT, manual muscle testing; MRC, Medical Research Council; MRI, magnetic resonance imaging; NA, nucleoside analog; PM, polymyositis; STIR, short time inversion recovery Key words: creatine kinase; entecavir; hepatitis B; myopathy; nucleoside analog Correspondence to: X. Lu; e-mail: [email protected] C 2013 Wiley Periodicals, Inc. V

Published online 12 November 2013 in Wiley Online Library (wileyonlinelibrary. com). DOI 10.1002/mus.24118

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Entecavir-Associated Myopathy

lamivudine, telbivudine, clevudine, and adefovir. The primary mechanism by which NAs act is to inhibit viral polymerase activity. Entecavir has proven to be effective and safe for HBV treatment, but the treatment has some side effects. Common adverse effects related to entecavir include headache, upper respiratory tract infection, upper abdominal pain, and flu-like symptoms. Most of these adverse effects are of mild-to-moderate severity.2 To our knowledge, entecavir-associated myopathy has not been reported. We describe a patient with entecavirassociated myopathy. We also review the literature regarding myopathies associated with nucleoside analogs (MANA) to find new information about their clinical and pathologic features, management, and prognosis. CASE REPORT

A 44-year-old man who had received entacavir therapy previously for chronic hepatitis B presented with a 3-month history of muscle pain and weakness in his lower extremities. He had a 20-year history of chronic hepatitis B infection and had been treated with entecavir for the HBV infection for the past 5 years on a stable dose of 0.5 mg/ day. He did not supplement the entecavir therapy with any other medication, and his blood HBV DNA levels had remained within the normal range (

Entecavir-associated myopathy: a case report and literature review.

Entecavir, a nucleoside analog (NA), is effective for treatment of chronic hepatitis B virus (HBV) infection...
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