Relationships of Hepatic Histology to Metabolic, Inflammatory and Viral Parameters in Chronic HCV Infection

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Purpose: Hepatic steatosis is commonly associated with chronic hepatitis C infection (HCV). The purpose of this study was to determine the associations between hepatic histology, and metabolic, inflammatory and viral parameters. Methods: This was a cross-sectional study of 31 hepatitis C infected subjects prior to HCV treatment, 21 male and 10 female, of whom 21 were HCV/HIV co-infected and 9 were HCV mono-infected. The infection was genotype I in 22 cases. Serum HCV RNA, soluble TNF receptors I and II (sTNFRI, II), fasting triglycerides, HDL-cholesterol, glucose and insulin levels were measured. Insulin resistance (IR) was calculated by HOMA. Body composition measures included BMI, body fat and fat free mass by bio-impedance analysis (BIA), and anthropometric measures of fat distribution. Liver biopsies were evaluated using a 4-point scale for disease activity (grade), and a 6-point scale for fibrosis (stage). Steatosis was measured using NIDDK 4-point scale plus a quantitative percent area estimate of macro and microvesicular fat. Data was analyzed by the general linear model method and by multiple regression, using steatosis, steatohepatitis, disease activity and fibrosis as dependent variables; and metabolic, inflammatory, HCV viral parameters and HIV as independent variables. Results: HIV infection was associated with greater area of steatosis (p = 0.07), greater waist:hip ratio (p = 0.04), thinner thigh skinfolds (p = 0.006). Steatosis was directly associated with serum insulin level (p = 0.04), HOMA (p = 0.05), sTNFR II (p = 0.02). Grade was related to HCV RNA (p = 0.04), AST (p = 0.004), total body fat (p = 0.07). Disease stage was associated directly with sTNFR II (p = 0.0001), and AST (p = 0.07), and inversely with HDL. By multiple regression steatosis was associated with increased sTNFR I and II, grade was related to IVDU, HCV viral load, gender, and stage was related to sTNFR II, HCV viral load, and glucose. Conclusions: Multiple factors affect hepatic histology in subjects with chronic HCV infection. While HCV viral load affects disease activity, the metabolic syndrome and TNF may be related to steatosis and fibrosis.