Hepatocyte proliferative activity in human liver cirrhosis

Background/Aims: The objective of this study was to validate, with an independent prospective cohort of patients, our previous data indicating that the proliferating cell nuclear antigen-labeling index (PCNA-LI) reflects the liver functional reserve in human cirrhosis and might have prognostic significance for patient survival. We also examined how this proliferative index is related to the expression of transforming growth factor beta 1 (TGF beta 1) as a possible correlate of hepatocyte proliferative activity. Methods: The present group (n=70 patients) was similar in composition to our previous group regarding age, sex and severity of liver cirrhosis, PCNA and TGF beta 1 immunostaining were analyzed on methanol-fixed, paraffin-embedded liver biopsies. Results: Our data show that PCNA-LI declined significantly with worsening Child class and was negatively correlated with the Pugh score, Twenty-five patients died and 10 underwent liver transplantation during the observation period. Liver function, hepatic venous pressure gradient and hepatocyte PCNA-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 previously determined best cut-off value) had a significantly higher probability 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 negatively 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 that, in cirrhosis, hepatocyte proliferative activity, as evaluated by the PCNA-LI, provides information on liver functional reserve as well as on the patient's prognosis.