title: Lamivudine/telbivudine-associated neuromyopathy: neurogenic damage, mitochondrial dysfunction and mitochondrial DNA depletion.
abstract: OBJECTIVE
  Myopathy or neuropathy has been associated with lamivudine/telbivudine therapy in hepatitis B patients. We aim to describe the pathological changes of lamivudine/telbivudine-associated neuromyopathy.
  
  
  METHODS
  We retrospectively recruited six patients who were diagnosed with nucleotide analogues-associated myopathy or neuropathy. Muscle and nerve biopsy were performed, and the specimens were prepared for the light microscopy and electron microscopy. Genomic DNA was extracted from frozen muscle specimens, and the mitochondrial DNA (mtDNA) content was quantified by real-time PCR.
  
  
  RESULTS
  Recovery of the myopathy can be achieved after the discontinuation or changing the drugs to entecavir. Muscle and nerve biopsy revealed similar changes under either the light or electronic microscopy in all the subjects. Quantitative real-time PCR revealed decrease of mtDNA content in the affected muscle.
  
  
  CONCLUSIONS
  MtDNA depletion results in mitochondrial dysfunction in the lamivudine/telbivudine-associated neuromyopathy. Myopathy was characterised by mitochondrial dysfunction accompanied with neurogenic damage due to axonal neuropathy. Ultrastructure changes of mitochondria included vacuolisation, simplification of the cristae and homogenised matrix.
authors.affiliation: Department of Neurology, Peking University First Hospital, Beijing, PR China.
authors.forename: Hongliang
authors.initials: H
authors.lastname: Xu
authors.affiliation: Department of Neurology, Peking University First Hospital, Beijing, PR China.
authors.forename: Zhaoxia
authors.initials: Z
authors.lastname: Wang
authors.affiliation: The Institute of Cardiovascular Sciences and Institute of Systems Biomedicine, School of Basic Medical Sciences, and Key Laboratory of Molecular Cardiovascular Sciences of Ministry of Education, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Lemin
authors.initials: L
authors.lastname: Zheng
authors.affiliation: Department of Neurology, Peking University First Hospital, Beijing, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Peking University First Hospital, Beijing, PR China.
authors.forename: He
authors.initials: H
authors.lastname: Lv
authors.affiliation: Department of Neurology, Peking University First Hospital, Beijing, PR China.
authors.forename: Suqin
authors.initials: S
authors.lastname: Jin
authors.affiliation: Department of Neurology, Peking University First Hospital, Beijing, PR China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Yuan
mesh_terms: D000328:Adult; D000369:Aged, 80 and over; D000998:Antiviral Agents / Q000009:adverse effects*; D001706:Biopsy; D004272:DNA, Mitochondrial / Q000378:metabolism*; D005260:Female; D006509:Hepatitis B / Q000188:drug therapy*; D006801:Humans; D019259:Lamivudine / Q000009:adverse effects*; D008297:Male; D008854:Microscopy, Electron; D008875:Middle Aged; D008931:Mitochondria, Muscle / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D009135:Muscular Diseases / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D010525:Peripheral Nerves / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D011237:Predictive Value of Tests; D060888:Real-Time Polymerase Chain Reaction; D012189:Retrospective Studies; D000077712:Telbivudine; D013936:Thymidine / Q000009:adverse effects / Q000031:analogs & derivatives*; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D004272:DNA, Mitochondrial; D000077712:Telbivudine; D019259:Lamivudine; D013936:Thymidine
keywords: NEUROPATHIES; NEUROPATHOLOGY; neuromuscular