Background and Aim: Studies have shown monounsaturated oleic acid to be less toxic than palmitic acid and to prevent/attenuate palmitic acid hepatocites toxicity in steatosis models in vitro. However, to what degree these effects are mediated by steatosis extent is unknown. Methods: We evaluated whether steatosis per se is associated with hepatocytes apoptosis and determined the role of oleic and palmitic acid, the most abundant fatty acids in western diets, on triglyceride accumulation and apoptosis in an in vitro model of steatosis induced in three hepatocytic cell lines (HepG2, HuH7, WRL68). The impact of incubation for 24 h with oleic (0.66 and 1.32 mM) and palmitic acid (0.33 and 0.66 mM), alone or combined (molar ratio 2 : 1) on steatosis, apoptosis, and insulin signalling, was evaluated. Results: Concurrent with PPARg and SREBP-1 gene activation, steatosis extent was larger when cells were treated with oleic than with palmitic acid; the latter fatty acid was associated with increased PPARa expression. Cell apoptosis was inversely proportional to steatosis deposition. Moreover, palmitic, but not oleic acid, impaired insulin signalling. Despite the higher amount of fat resulting from incubation of the two fatty acids combined, the apoptosis rate and impaired insulin signalling were lower than in cells treated with palmitic acid alone, indicating a protective effect of oleic acid. Conclusions: Oleic acid is more steatogenic but less apoptotic than palmitic acid in hepatocityc cell cultures. These data may provide a biological basis for clinical findings on dietary patterns and pathogenetic models of nonalcoholic fatty liver disease.

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This study was designed to obtain a general overview of gallstone disease in Italy. A total of 18 cohorts in 10 Italian regions were enrolled in this survey. Four cohorts were excluded from analysis because of a participation rate of less than 50 percent. Field activities started in December 1984 and terminated in April 1987. A precoded questionnaire was administered to each subject by a trained member of the medical staff. Participants underwent an ultrasonographic examination of the upper abdomen and blood sampling. Each research group was provided with an identical ultrasonographic machine. Standardized criteria were established for both the examination and diagnosis. The inter- and intraobserver variation in the ultrasonographic procedure was assessed using a reliability study. The overall kappa score for interobserver agreement was good (0.649), while intraobserver agreement was good or excellent (kappa scores > 0.60) in 75 percent of the observers. A total of 29,739 of the 46,139 (64.4 percent) enrolled subjects were examined. Among those with a clear-cut definition of the gallbladder status, 6.5 percent of the males and 10.5 percent of the females had gallstones. Additional 3.0 and 8.4 percents, respectively, had already undergone cholecystectomy. Prevalence of gallstone disease (gallstones plus cholecystectomy) increased linearly with age in both sexes. Among subjects with gallstones, 76.7 percent of men and 72 percent of women were not aware of having gallstones; 87.0 percent of men and 84.9 percent of women were asymptomatic. This study confirms that gallstone disease is a highly prevalent condition. Gallstones rarely cause symptoms, and subjects are mostly unaware of their presence.

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The overall prevalence of steatosis in patients with Hepatitis C virus (HCV) chronic infection is 55.5% (range 34.8-81.2%). This is a two to threefold increase compared with the prevalence of steatosis in chronic hepatitides because of other aetiologies and of the figures expected on the grounds of a steatosis-HCV chance association. HCV genotype 3 (HCV-3) has specific epidemiological features; furthermore, as compared with HCV-non-3 genotypes, it is associated with a higher prevalence (74.1%vs 47.9%, P < 0.01) and with more severe grades of steatosis (prevalence of grade 3 steatosis 29.6 vs 5.5 P < 0.01). Host and viral factors play a role, although to a variable extent, in the pathogenesis of HCV-3 and non-3 steatosis. HCV load and body mass index are associated with steatosis in HCV-3 and in HCV-non-3 patients respectively. Serum cholesterol levels and liver steatosis at baseline follow an inverse relationship in HCV infection. As hypocholesterolaemia corrects only in those sustained responders to antiviral treatment both in genotype 3 and in non-3 genotypes, the occurrence of a virally induced, acquired and reversible hypobetalipoproteinaemia seems plausible. Steatosis affects the natural course of HCV infection: it is associated with fibrosis, a possible mediator of increased risk to develop type 2 diabetes, it impairs the response to antiviral treatment in HCV-3 patients and might constitute a risk factor for the development of hepatocellular carcinoma. These observations indicate the need to evaluate the efficacy of combined antiviral and 'metabolic' approaches vs standard antiviral regimes in patients with steatosis and HCV chronic infection.

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Eighty-four consecutive subjects with nonalcoholic fatty liver disease (NAFLD) were tested for non-organ-specific autoantibodies (NOSA) by indirect immunoflorescence. Indices of insulin resistance and biochemical and anthropometric parameters were assessed. The overall prevalence of anti-nuclear-antibodies (ANA), smooth muscle antibodies (SMA) and anti-mitochondrial-antibodies (AMA) was 35.7% (30/84), 18 subjects (21.4%) being positive for ANA, 4 (4.7%) for SMA, 6 for ANA and SMA, and 2 for AMA. NOSA-positive subjects were older (P < 0.01) and mostly females (63.3%). No significant difference was found in the age-corrected parameters studied, except for copper and ceruloplasmin, which was more elevated in NOSA-positive patients. The subset of high titer (>1:100) ANA-positive patients had significantly (P < 0.05) greater insulin resistance than ANA-negative patients. In contrast, SMA-positive patients had higher gammaglobulin and significantly lower insulin resistance as compared to high-titer ANA-positive patients. In 3 NOSA-positive but not in NOSA-negative patients, liver biopsy disclosed features of overlapping NASH with autoimmune hepatitis, partially responding to diet combined with steroid treatment. In conclusion, NOSA positivity in NAFLD is more prevalent than in the general population. High-titre ANA but not SMA positivity is associated with insulin resistance.

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