Mitochondrial abnormalities in non-alcoholic steatohepatitis.
OBJECTIVE
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.
Caldwell
S H
SH
Department of Internal Medicine, University of Virginia, Charlottesville, USA.
Swerdlow
R H
RH
Khan
E M
EM
Iezzoni
J C
JC
Hespenheide
E E
EE
Parks
J K
JK
Parker
W D
WD
D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D005234:Fatty Liver / Q000235:genetics / Q000473:pathology*; D005260:Female; D017353:Gene Deletion; D006521:Hepatitis, Chronic / Q000235:genetics / Q000473:pathology*; D006801:Humans; D008107:Liver Diseases / Q000473:pathology; D008108:Liver Diseases, Alcoholic / Q000473:pathology; D008297:Male; D008854:Microscopy, Electron; D008875:Middle Aged; D008930:Mitochondria, Liver / Q000235:genetics / Q000648:ultrastructure*; D016133:Polymerase Chain Reaction