title: Non-alcoholic steatohepatitis: impaired antipyrine metabolism and hypertriglyceridaemia may be clues to its pathogenesis.
abstract: Non-alcoholic steatohepatitis resembles alcoholic liver disease in hepatic morphology but appears to have a different natural history. We sought to assess the nature of non-alcoholic steatohepatitis by a prospective study of its clinical progression and the relationship of biochemical abnormalities to changes in serum lipids among 15 patients with this disorder. In addition, antipyrine clearance (Cl-AP), which reflects hepatic microsomal oxidative capacity, was measured serially. Although initial liver histology included micronodular cirrhosis in five cases and bridging fibrosis in another three, only one patient developed a hepatic complication during 1-10 years (median: 3.7) of follow up. This confirms the relatively benign nature of non-alcoholic steatohepatitis. Moreover, Cl-AP, which was below the normal range in 13 patients, did not change significantly during 10-40 months of follow up. However, compared with other chronic liver diseases, the reduced Cl-AP was disproportionately low relative to the uniformly normal serum albumin concentration and other indices of hepatic metabolic function. This is consistent with selective impairment of endoplasmic reticular drug oxidizing enzymes. Hyperlipidaemia was present in 11 patients. In three of these, diet-induced correction of serum triglyceride elevation was associated with reduction of hepatocellular damage as indicated by serum enzyme levels. A hypothesis that unites these and earlier findings is that release of cytokines may occur in non-alcoholic steatohepatitis and produce accumulation of free fatty acids in the liver, leading to focal necro-inflammatory lesions and the destruction or down-regulation of cytochrome P450.
authors.affiliation: University of Sydney Department of Medicine, Westmead Hospital, New South Wales, Australia.
authors.forename: J R
authors.initials: JR
authors.lastname: Fiatarone
authors.forename: S A
authors.initials: SA
authors.lastname: Coverdale
authors.forename: R G
authors.initials: RG
authors.lastname: Batey
authors.forename: G C
authors.initials: GC
authors.lastname: Farrell
mesh_terms: D000328:Adult; D000368:Aged; D000983:Antipyrine / Q000493:pharmacokinetics*; D001663:Bilirubin / Q000097:blood; D005234:Fatty Liver / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D015228:Hypertriglyceridemia / Q000150:complications*; D008055:Lipids / Q000097:blood; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D012709:Serum Albumin / Q000032:analysis
chemical_list: D008055:Lipids; D012709:Serum Albumin; D001663:Bilirubin; D000983:Antipyrine