Mitochondrial abnormalities in non-alcoholic steatohepatitis

J Hepatol. 1999 Sep;31(3):430-4. doi: 10.1016/s0168-8278(99)80033-6.


Background/aims: We assessed mitochondrial morphology by electron microscopy and the prevalence of a mitochondrial gene deletion in patients with non-alcoholic steatohepatitis (NASH), alcohol-related liver disease and non-fatty liver diseases. Respiratory chain function using a cytoplasmic hybrid (cybrid) assay was further studied in NASH patients and healthy controls.

Methods: Electron microscopy was performed in 26 specimens. Fifteen patients were studied by polymerase chain reaction to detect a 520-bp deletion product of the mitochondrial genome (dmtDNA). Cybrids were created by fusion of platelets with anaerobic neuroblastoma cells in six NASH patients and 12 controls.

Results: Eight of ten NASH, one of seven alcoholics and two of nine other patients had linear crystalline inclusions in megamitochondria (p<0.05). Three of five patients with alcohol-related liver disease had dmtDNA compared to one of five NASH patients and one of five non-steatohepatitis controls. Cybrid respiratory chain function in platelets was not different from that of controls.

Conclusions: Respiratory chain dysfunction, if present in NASH, is not expressed in platelet-derived mitochondria. In contrast to alcohol-related liver disease with active drinking, NASH patients do not commonly express the 5-kb mitochondrial DNA gene deletion in liver tissue. As previously described in early alcohol-related liver disease, crystalline inclusions of unknown composition are seen in hepatic mitochondria in NASH. Their presence suggests either an adaptive process or mitochondrial injury.

MeSH terms

  • Adult
  • Aged
  • Case-Control Studies
  • Fatty Liver / genetics
  • Fatty Liver / pathology*
  • Female
  • Gene Deletion
  • Hepatitis, Chronic / genetics
  • Hepatitis, Chronic / pathology*
  • Humans
  • Liver Diseases / pathology
  • Liver Diseases, Alcoholic / pathology
  • Male
  • Microscopy, Electron
  • Middle Aged
  • Mitochondria, Liver / genetics
  • Mitochondria, Liver / ultrastructure*
  • Polymerase Chain Reaction