Significance of pSmad2/3 and Smad4 in hepatitis C virus-related liver fibrosis and hepatocellular carcinoma.

Chronic hepatitis C (CHC) is a major public health problem, especially in Egypt. Risk of hepatocellular carcinoma (HCC) development increases as hepatitis C virus (HCV)-related liver diseases progress. Smads act as substrates for the transforming growth factor-beta (TGF-β) family of receptors. This study aims to assess hepatic expression of pSmad2/3 and Smad4 in CHC with different stages of fibrosis and grades of necro-inflammation as well as in HCC on top of CHC. This study was done on 33 core liver biopsies from patients with CHC (15 with early fibrosis and 18 with late fibrosis), 15 liver specimens from HCC cases on top of CHC, as well as five normal controls. pSmad2/3 and Smad4 show more immunopositivity, higher percentage of positive hepatocytes and stronger staining intensity in CHC with late fibrosis compared to early fibrosis. pSmad2/3 shows increase of the previous parameters in CHC with high grade activity than those with low activity. Smad4 shows increase of the previous parameters in HCC compared to CHC cases. pSmad2/3 and Smad4 can be used as diagnostic and/or prognostic markers for progression of HCV-related fibrosis to cirrhosis and further progression to HCC.