Lamivudine/telbivudine-associated neuromyopathy: neurogenic damage, mitochondrial dysfunction and mitochondrial DNA depletion

J Clin Pathol. 2014 Nov;67(11):999-1005. doi: 10.1136/jclinpath-2013-202069. Epub 2014 Sep 4.

Abstract

Aims: 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.

Keywords: NEUROPATHIES; NEUROPATHOLOGY; neuromuscular.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged, 80 and over
  • Antiviral Agents / adverse effects*
  • Biopsy
  • DNA, Mitochondrial / metabolism*
  • Female
  • Hepatitis B / drug therapy*
  • Humans
  • Lamivudine / adverse effects*
  • Male
  • Microscopy, Electron
  • Middle Aged
  • Mitochondria, Muscle / drug effects*
  • Mitochondria, Muscle / metabolism
  • Mitochondria, Muscle / ultrastructure
  • Muscle, Skeletal / drug effects*
  • Muscle, Skeletal / metabolism
  • Muscle, Skeletal / ultrastructure
  • Muscular Diseases / chemically induced*
  • Muscular Diseases / metabolism
  • Muscular Diseases / pathology
  • Peripheral Nerves / drug effects*
  • Peripheral Nerves / metabolism
  • Peripheral Nerves / ultrastructure
  • Peripheral Nervous System Diseases / chemically induced*
  • Peripheral Nervous System Diseases / metabolism
  • Peripheral Nervous System Diseases / pathology
  • Predictive Value of Tests
  • Real-Time Polymerase Chain Reaction
  • Retrospective Studies
  • Telbivudine
  • Thymidine / adverse effects
  • Thymidine / analogs & derivatives*
  • Young Adult

Substances

  • Antiviral Agents
  • DNA, Mitochondrial
  • Telbivudine
  • Lamivudine
  • Thymidine