Metabolic significance of hepatic steatosis in non alcoholic fatty liver disease and HCV chronic hepatitis

Background: Steatosis, the hallmark of Non Alcoholic Fatty Liver Disease (NAFLD), is a common histological finding also in patients with chronic HCV hepatitis, but the mechanism(s) of fat accumulation might be differ- ent. Aims: To compare insulin sensitivity, glucose and lipid metabolism in HCV and NAFLD patients with similar degree of liver steatosis and fibrosis. Methods: Insulin sensitivity, glucose and glycerol turnover were evalu- ated by euglycemic clamp technique (insulin infusion rate:1 mU/kg · min) combined with tracers infusion (2H2glucose and 2H5glycerol) in 4 lean, non-diabetic HCV patients, 5 matched NAFLD patients and 4 healthy con- trols. Results: Insulin stimulated glucose disposal was markedly reduced in NAFLD compared with HCV patients (M=2.96 ± 1.62 mg/kg · min vs 6.10 ± 1.80 mg/kg · min, P=0.017) and controls (M=7.91 ± 0.34 mg/kg · min, P=0,00001). Hepatic glucose production (HGP) was similar in the three groups in the basal state, but less efficiently inhibited by insulin both in HCV and NAFLD (HGP during clamp=0.31 ± 0.36 and 0.29 ± 0.15 mg/kg · min vs 0.09 ± 0.03 in controls;P=0,06). In the basal state, glyc- erol Ra was increased in NAFLD compared with both HCV and controls (2.58 ± 0.48 vs 1.77 ± 0.76 and 1.50 ± 0.23 respectively, P=0.05) and less suppressed by insulin. The amount of hepatic steatosis was directly related to basal glycerol turnover in NAFLD (r=0.63) and inversely in HCV (r= -0.60). Conclusions: Liver steatosis a)in NAFLD is associated with peripheral insulin resistance and increased systemic lipolysis, b)in HCV with normal peripheral insulin sensitivity and reduced lipid turnover. These findings suggest that fat accumulation is secondary to increased lipid delivery to the liver in NAFLD, to reduced lipid dismission from the liver in HCV.