1. Fibrosis: The primary statistical analysis will compare the PPC and placebo groups with regard to changes in fibrosis score from baseline to the value after 36 months of treatment. The primary fibrosis end point is histological with degrees of fibrosis graded on liver biopsy according to Ishak et al (1995). Furthermore, we count the number of α-smooth muscle actin (SMA) expressing stellate cells (Reeves et al, 1996), the principal collagen producing cells. Activation of stellate cells and their transformation to myofibroblast-like cells has been demonstrated in experimental fibrosis (Mak et al, 1984, 1994). Smooth muscle actin α is an actin isoform typical of smooth muscle cells (Skalli et al, 1986), that may be localized in stellate cells of the human liver. Its expression in the stellate cells has been considered an indication of phenotypic modulation of stellate cells to myofibroblasts. In the human liver the appearance of smooth muscle actin α was closely related to the process of hepatic fibrosis (Reeves et al, 1996) and the formation of cirrhotic nodules (Nouchi et al, 1991). In addition, circulating break-down products of collagen or other components of the extracellular matrix (ECM) are being used as markers of liver pathology. These include laminin, the major noncollagenous glycoprotein of basement membranes. Indeed, extracellular basement membranes undergo a continuous turnover and elevation of laminin has been described in the sera of patients with alcoholic liver disease (Niemelä et al. 1988; Sato et al. 1986). Tenascin, a molecule expressed in proliferating ECM, TIMP-1 an inhibitor of the matrix degrading metalloproteinases (MMPs), collagen IV, collagen VI, a molecule that forms filaments between large collagen fibrils, the N-terminal propeptide of procollagen type III (PIIINP), considered a marker of fibrogenesis, hyaluronic acid (HA), an ubiquitous glycosaminoglycan with high extraction by the liver sinusoidal endothelium, and MMP-2. All these have been assessed before as markers of fibrosis, some specifically in patients with chronic hepatitis C (Kasahara et al, 1997; McHutchison et al, 2000; Kojima et la, 2001; Murawaki et al, 2001) but not in subjects who were also drinkers.