In the United Kingdom’s National Health somehow Service, interferon-�� and ribavirin treatment for chronic hepatitis C is only recommended for patients who show significant histological fibrosis or necroinflammation (National Institute for Clinical Excellence 2000). Interobserver variation in Knodell scoring has been shown to be only fair to moderate (Gr?nb?k et al. 2002); immunohistochemistry for activated caspase-3 could therefore provide a more reproducible method of measuring disease activity, making such treatment decisions more robust and the monitoring of treatment effects more accurate. Acknowledgments We thank Angela Gillies and Linda Potter for technical assistance and Dr Angus McGregor for helpful comments on the manuscript.

The hepatic parenchyma is composed of epithelial (hepatocytes) and endothelial cells, macrophages and perisinusoidal, mesenchymal cells called stellate cells (fat-storing cells), which are considered to be the major cell type responsible for fibrosis (Burt 1999). In a normal liver, these components are organized within the hepatic acini, where hepatocytes are separated from sinusoidal endothelium by the space of Disse. This space contains low amounts of extracellular matrix (ECM) components that maintain all the cell types of the liver under a functional state. However, once the liver becomes fibrotic, the ECM undergoes important quantitative and qualitative changes in its composition. The total content of collagens increases many fold, and the ECM becomes much more dense with fibril-forming collagens (Gressner 1998; Burt 1999).

Liver fibrosis is a defence mechanism of adult liver in response to injury that results in the encapsulation of the damaged tissue and stabilization of the remaining structure. Hepatic fibrogenesis represents the first step in how wound healing reverses tissue damage and can be induced by several conditions including viral hepatitis, alcohol abuse, metabolic disorders, auto immune hepatic disease or genetically inherited abnormalities (Friedman 2000). The development of fibrosis usually takes months and often will only develop when a significant amount of damaged tissue accumulates. Once fibrosis is established, the hepatic tissue can either revert to its previous status, or evolve to liver cirrhosis, which is the final, irreversible, consequence of chronic fibrosis.

Thus, comprehension of the molecular mechanisms underlying hepatic fibrosis is a major objective in finding therapies that could prevent or modulate its development. Transforming growth factor-�� (TGF-��) is a major profibrogenic molecule (Sanderson et al. 1995; Kanzler et al. 1999; Bauer & Schuppan 2001). TGF-�� overexpression induces fibrosis, and treatment with Drug_discovery TGF-��-specific antibodies reverts the fibrotic lesion (George et al. 1999; Qi et al. 1999).