Hepatocyte proliferative activity in human liver cirrhosis

Background/Aims: The objective of this study was to validate, with an indep endent prospective cohort of patients, our previous data indicating that th e proliferating cell nuclear antigen-labeling index (PCNA-LI) reflects the liver functional reserve in human cirrhosis and might have prognostic signi ficance for patient survival. We also examined how this proliferative index is related to the expression of transforming growth factor beta 1 (TGF bet a 1) as a possible correlate of hepatocyte proliferative activity. Methods: The present group (n=70 patients) was similar in composition to ou r previous group regarding age, sex and severity of liver cirrhosis, PCNA a nd TGF beta 1 immunostaining were analyzed on methanol-fixed, paraffin-embe dded liver biopsies. Results: Our data show that PCNA-LI declined significantly with worsening C hild class and was negatively correlated with the Pugh score, Twenty-five p atients died and 10 underwent liver transplantation during the observation period. Liver function, hepatic venous pressure gradient and hepatocyte PCN A-LI were significantly different in survivors and non-survivors. At a mean follow-up of 356 days, the patients with a PCNA-LI higher than 4.4% (the p reviously determined best cut-off value) had a significantly higher probabi lity of survival than those with a PCNA-LI less than or equal to 4.4% (0.87 vs 0.48, p=0.0009), TGF beta 1 expression in liver parenchyma correlated n egatively with PCNA-LI, suggesting that this cytokine could be involved in the impaired regeneration observed in worsened liver cirrhosis. Conclusions: This prospective study strengthens our previous observation th at, in cirrhosis, hepatocyte proliferative activity, as evaluated by the PC NA-LI, provides information on liver functional reserve as well as on the p atient's prognosis.