Risk of NASH and severe fibrosis in patients with NAFLD and low visceral adiposity

NAFLD, the hepatic expression of the metabolic syndrome. Insulin resistance is the underlying metabolic condition favouring the occurrence of NAFLD, a spectrum of liver conditions ranging from fatty liver, to steatohepatitis, fibrosis and cirrhosis. Waist circumference (WC), the simplest and most widely used surrogate marker of visceral adiposity is a clinical correlate of insulin resistance. In a small series of patients with NAFLD, it has recently been reported that metabolic and histological characteristics were similar in patients with or without diabetes and obesity. Aim To evaluate the clinical presentation and liver histological findings in patients with NAFLD according to the presence of visceral obesity estimated by WC. Methods We merged the databases of consecutive patients with liver biopsyconfirmed NAFLD observed in four Liver Units (427 cases) who underwent liver biopsy between January 2003 and June 2008. Patients were divided in two groups according to their WC (group A≥94 and ≥ 80 cm, group B < 94 cm and < 80 cm, in men and in women respectively). Patients in group A (273 cases) were significantly older (45 ± 10 vs 39 ± 11 years, p=0.01), had higher triglycerides (158 ± 80 vs 134 ±88 mg/dl, p=0.03), HOMA-IR (5 ± 4 vs 3.4 ± 2, p= 0.007), and a higher prevalence of females (22% vs 6%, p=0.001), diabetes or impaired glucose tolerance (27% vs 15%, p=0.01), arterial hypertension (44% vs 22%, p=0.001), metabolic syndrome (35% vs 8%, p=0.001) and NASH (47% vs 36%, p=0.03), with no significant differences in the prevalence of severe fibrosis (≥2) (31% and 27%) between groups. Serum ferritin, fasting glucose, diabetes and ALT were significantly associated with fibrosis ≥ 2 in the overall series and in the two groups evaluated separately. At multivariate logistic regression analysis in the overall series of patients and in the two groups analysed separately, ALT (p=0.02)and diabetes (p=0.0001) remained independently associated with fibrosis ≥ 2. Conclusion Patients with NAFLD and normal waist circumference, despite a milder metabolic involvement, may have NASH and are at high risk of developing severe liver fibrosis. These findings suggest that visceral obesity does not influence the severity of liver damage in patients with NAFLD, whereas diabetes is a risk factor, independent of obesity.