SMAD3 and hepatocellular carcinoma: Because extent of Smad3L phosphorylation increases as fibrotic stage progresses in chronic hepatitis C, Smad3L showed little phosphorylation in early chronic hepatitis C. In contrast, degree of linker phosphorylation of Smad3 in hepatocytic nuclei was high (staining scored as 3 or 4) in all patients with mildly fibrotic NASH livers (F1 to F2) that developed HCC.