Mitochondrial abnormalities in non-alcoholic steatohepatitis
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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