SMAD3 and hepatocellular carcinoma: Interestingly, specimens from chronic hepatitis B patients who develop HCC show high levels of linker Smad3 phosphorylation, but low levels of C-terminal Smad3 phosphorylation in hepatocytic nuclei, whereas other patients with a high level of hepatocytic pSmad3C but a low level of pSmad3L do not develop HCC [43].