Subcellular shift of the hepatic growth hormone receptor with progression of hepatitis C virus-related chronic liver disease

Aims: To evaluate the cytoplasmic and nuclear expression of hepatic growth hormone receptor (GHR) in different stages (S-0, S-1, S-3 and S-4, according to Knodell's classification) of chronic liver disease (CLD) and in hepatocellular carcinoma (HCC). Methods and results: Liver specimens from 31 patients with hepatitis C virus-related CLD, five patients with HCC and nine controls were examined for expression of hepatic GHR by immunohistochemistry with MAb 263. Cytoplasmic and nuclear staining were evaluated as a percentage of positively stained cells. The cytoplasmic expression of GHR was comparable between normal liver and S-0 hepatitis, while it progressively decreased in S-1, S-3 and S-4 CLD (P < 0.01). Conversely, nuclear GHR showed increased expression in S-3 and S-4 CLD (P < 0.05). No differences were observed between HCC and normal liver in terms of GHR immunoreactivity. Conclusions: This is the first study to show that the subcellular expression of hepatic GHR changes with the progression of CLD. The increase in nuclear expression of GHR with advanced stages of CLD suggests that GH may act directly at the nuclear level to promote hepatocyte proliferation/regeneration.