Transforming growth factor-beta(1) in chronic hepatitis C

Transforming growth factor-beta(1) (TGF-beta(1)) has been implicated in mediating hepatic fibrogenesis and is known to have negative regulatory effects on the immune system. To analyse the effects of TGF-beta(1) in chronic HCV, serum samples were prospectively collected from 88 chronic hepatitis C virus (HCV) patients and 34 healthy controls. Total and biologically active TGF-beta(1), interleukin (IL)-4 and IL-10 were measured by enzyme-linked immunosorbent assay (ELISA). HCV RNA levels were quantified by branched DNA signal amplification pathway (bDNA), and HCV genotypes were determined by restriction fragment length polymorphism (RFLP) based on the 5'-untranslated region (UTR). Histological diagnosis was available in 87 patients, and liver sections from 80 other HCV patients were evaluated for hepatic expression of TGF-beta(1) using immunohistochemistry. Patients with chronic HCV infection had a higher level of TGF-beta(1), both total (817 +/- 464 ng ml(-1)) and biologically active forms (520+/-370 pg ml(-1)), compared with controls (total TGF-beta(1) 183+/-105 ng ml(-1), P<0.001; active TGF-beta(1) 290+/-140 pg ml(-1), P<0.01). There was no correlation between either total or biologically active TGF-beta(1) and clinical variables (age; gender, duration), liver biochemistry (serum alanine aminotransferase) or virological (HCV RNA level, genotype) parameters but there was a correlation between total TGF-beta(1) and Knodell scores (P = 0.03, n = 54), However, when individual histological parameters were analysed, only the fibrosis score showed significant correlation (P = 0.04, n = 54). Immunohistochemistry revealed that 62% of HCV patients had TGF-beta(1) present in sinusoidal cells. No correlation existed between hepatic expression of TGF-beta(1) and any histological parameters. A trend existed towards a correlation between total TGF-beta(1) and IL-4 (P = 0.059, n = 74) but not with IL-10. Therefore, the TGF-beta(1) system is activated in chronic HCV infection and may contribute towards hepatic fibrogenesis; in addition, the TGF-beta(1) system may interact with IL-4.