Mitochondrial abnormalities in non-alcoholic steatohepatitis

doi:10.1016/S0168-8278(99)80033-6

Journal of Hepatology

Volume 31, Issue 3, September 1999, Pages 430-434

https://doi.org/10.1016/S0168-8278(99)80033-6 Get rights and content

Abstract

Background/Aims: We assessed mitochondrial morphology by electron microscopy and the prevalence of a mitochondrial gene deletion in patients with nonalcoholic 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.

Section snippets

Patients and Methods

The initial study group consisted of 30 patients: 10 with NASH, 10 with alcohol-related liver disease and 10 with other forms of liver disease (Table 1). The diagnosis of NASH was made if the liver biopsy revealed steatosis, inflammation and fibrosis in the absence of clinical, serologic or histologic findings of viral hepatitis, autoimmune hepatitis or other identifiable etiologies and in the absence of significant alcohol ingestion as assessed by interviews with the patient and family by

Results

Megamitochondria containing linear crystalline inclusions Fig. 1, Fig. 2 were evident in eight of ten NASH patients, one of seven patients with ALD and two of nine patients with other types of liver disease (p≤0.05 comparing NASH to either of the other two groups, Table 1). Among the NASH patients, two of four with cirrhosis had no evidence of inclusions, while inclusions were evident in all others (including two with cirrhosis and six without cirrhosis). Two of three non-NASH patients with

Discussion

In past studies, intramitochondrial crystalline inclusions have been observed primarily in early alcoholrelated liver disease 16., 17., 18.. These structures have also been observed in experimental conditions of alcoholinduced liver injury (36). The relative paucity of crystalline inclusions and megamitochondria in our patients with alcohol-related liver disease could represent loss of such structures in advanced disease, as has been previously suggested 16., 18.. In contrast, the NASH group

Acknowledgements

The authors thank Dr G. A. Cortopassi for supervision of the gene deletion work performed in his laboratory, Bonnie Sheppard and Jan Redick for their assistance in specimen preparation for electron microscopy, Dr Theo Wallimann for review of the EM results, and Dr Carl Berg for assistance with the manuscript.

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Mitochondrial abnormalities in non-alcoholic steatohepatitis

Abstract

Section snippets

Patients and Methods

Results

Discussion

Acknowledgements

Gastroenterology

Gastroenterol

J Hepatol

Hepatology

J Hepatol

Gastroenterology

Gastroenterology

Gastroenterology

Gastroenterology

Gastroenterology

Biochem Biophys Acta

Nonalcoholic steatohepatitis

Mayo Clin Proc

Comparison between nonalcoholic steatohepatitis and alcoholic hepatitis

Am J Gastroenterol

Nonalcoholic steatohepatitis

Ann Intern Med

Does a linear pattern of sinusoidal IgA deposition distinguish between alcoholic and diabetic liver disease?

Liver

Hepatic cytochrome P450 2E1 is increased in patients with nonalcoholic steatohepatitis

Hepatology

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Hepatology

Increased ethane exhalation, an in vivo index of lipid peroxidation, in alcohol-abusers

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Lab Invest