DOI QR코드

DOI QR Code

Mitochondrial myopathies caused by prolonged use of telbivudine

  • Lee, Jong-Mok (Department of Neurology, Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Pusan National University School of Medicine) ;
  • Shin, Jin-Hong (Department of Neurology, Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Pusan National University School of Medicine) ;
  • Park, Young-Eun (Department of Neurology, Pusan National University School of Medicine) ;
  • Kim, Dae-Seong (Department of Neurology, Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Pusan National University School of Medicine)
  • Received : 2016.10.13
  • Accepted : 2016.12.12
  • Published : 2017.01.31

Abstract

Background: Telbivudine is a nucleoside analogue used for the treatment of chronic hepatitis B, but it often develops mitochondrial toxicity leading to symptomatic myopathy. In this study, three patients with telbivudine induced myopathy were enrolled in order to investigate the nature and pathogenesis of mitochondrial toxicity caused by long-term use of telbivudine. Methods: Clinical features, laboratory findings, muscle pathology, and quantitation of mitochondrial DNA were studied in three patients. Results: Patients presented with progressive muscle weakness with high serum creatine kinase levels. Light microscopic findings of muscle pathology showed ragged red fibers that reacted strongly with succinate dehydrogenase stain, but negative for cytochrome c oxidase activities. Electron microscopy revealed abnormal mitochondrial accumulation with rod shaped inclusions. The quantitative peroxidase chain reaction showed a depletion of mitochondrial DNA in skeletal muscle of the patients. Conclusions: Nucleoside analogues including telbivudine are potent inhibitors of viral DNA polymerases. However, they are not specific for viral DNA and can disturb mitochondrial replication at the same time. All nucleotide analogues should be used with close clinical observation in order to avoid development of mitochondrial myopathy.

Keywords

References

  1. McMahon BJ. The natural history of chronic hepatitis B virus infection. Hepatology 2009;49(5 Suppl):S45-S55. https://doi.org/10.1002/hep.22898
  2. Fattovich G, Bortolotti F, Donato F. Natural history of chronic hepatitis B: special emphasis on disease progression and prognostic factors. J Hepatol 2008;48:335-352. https://doi.org/10.1016/j.jhep.2007.11.011
  3. Liaw YF, Gane E, Leung N, Zeuzem S, Wang Y, Lai CL, et al. 2-year GLOBE trial results: telbivudine is superior to lamivudine in patients with chronic hepatitis B. Gastroenterology 2009;136:486-495. https://doi.org/10.1053/j.gastro.2008.10.026
  4. Zou XJ, Jiang XQ, Tian DY. Clinical features and risk factors of creatine kinase elevations and myopathy associated with telbivudine. J Viral Hepat 2011;18:892-896. https://doi.org/10.1111/j.1365-2893.2010.01412.x
  5. Seok JI, Lee DK, Lee CH, Park MS, Kim SY, Kim HS, et al. Long-term therapy with clevudine for chronic hepatitis B can be associated with myopathy characterized by depletion of mitochondrial DNA. Hepatology 2009;49:2080-2086. https://doi.org/10.1002/hep.22959
  6. Masanes F, Barrientos A, Cebrian M, Pedrol E, Miro O, Casademont J, et al. Clinical, histological and molecular reversibility of zidovudine myopathy. J Neurol Sci 1998;159:226-228. https://doi.org/10.1016/S0022-510X(98)00151-8
  7. Kim EH, Park H, Lee KH, Ahn SH, Kim SM, Han KH. Two cases of telbivudine-induced myopathy in siblings with chronic hepatitis B. Clin Mol Hepatol 2013;19:82-86. https://doi.org/10.3350/cmh.2013.19.1.82
  8. Wang M, Da Y, Cai H, Lu Y, Wu L, Jia J. Telbivudine myopathy in a patient with chronic hepatitis B. Int J Clin Pharm 2012;34:422-425. https://doi.org/10.1007/s11096-012-9633-3
  9. Dalakas MC, Illa I, Pezeshkpour GH, Laukaitis JP, Cohen B, Griffin JL. Mitochondrial myopathy caused by long-term zidovudine therapy. N Engl J Med 1990;322:1098-1105. https://doi.org/10.1056/NEJM199004193221602
  10. Lo YL, See SJ, Tan CK. Continuous single motor unit electromyographic activity in adefovir associated myopathy. J Clin Neurosci. 2008;15:1073-1074. https://doi.org/10.1016/j.jocn.2007.09.009
  11. Ambang T, Tan JS, Ong S, Wong KT, Goh KJ. Clinicopathological features of telbivudine-associated myopathy. PLoS ONE 2016;11:e0162760. https://doi.org/10.1371/journal.pone.0162760
  12. Mazzucco CE, Hamatake RK, Colonno RJ, Tenney DJ. Entecavir for treatment of hepatitis B virus displays no in vitro mitochondrial toxicity or DNA polymerase gamma inhibition. Antimicrob Agents Chemother 2008;52:598-605. https://doi.org/10.1128/AAC.01122-07
  13. Yuan K, Guochun W, Huang Z, Lin B, Zhou H, Lu X. Entecavir-associated myopathy: a case report and literature review. Muscle Nerve 2014;49:610-614. https://doi.org/10.1002/mus.24118