RELATIONSHIP BETWEEN HEPATOCYTE PROLIFERATIVE ACTIVITY AND LIVER FUNCTIONAL RESERVE IN HUMAN CIRRHOSIS

Hepatocyte proliferative activity is elevated in cirrhotic patients wh o develop hepatocellular carcinoma (HCC) and decreased in alcohol-indu ced hepatitis patients with poor outcome. Hepatocyte proliferative act ivity has not been evaluated in an unselected population of cirrhotic patients regarding the severity of the disease. Forty-six cirrhotic pa tients (21 alcoholic, 20 viral, and 5 other) were prospectively analyz ed by proliferating cell nuclear antigen (PCNA) immunostaining on meth anol-fixed, paraffin-embedded liver biopsy specimens. In these conditi ons, the PCNA-labeling index (PCNA-LI) measures the number of cells in the S-phase and assesses tissue proliferation. The median value of th e PCNA-LI for all samples was 4.3% (range, 0%-20.2%). It declined with worsening Child-Pugh score: 9.15% (range, 3.3%-20.2%), 5.3% (range, 1 .2%-18%), and 2.4% (range, 0%-4.4%) in Child classes A, B, and C, resp ectively (P < .05), Using the best cutoff PCNA-LI value to divide cirr hosis into slowly and rapidly proliferating tissue subsets, the PCNA i ndex was independently associated with serum albumin. The probability of survival in patients with a high PCNA-LP (>4.4%) was significantly higher than in those with a lower PCNA-LI (0.93 vs. 0.53, at a median follow-up of 153 days; P = .01). In all 6 patients undergoing placemen t of a transjugular intrahepatic portosystemic shunt (TIPS), the PCNA- LI decreased after the procedure. This early impairment of hepatocyte proliferative activity after TIPS placement might reflect the function al alterations induced by this treatment, In conclusion, hepatocyte pr oliferative activity assessed by PCNA-LI is increased in cirrhotic pat ients and decreases with worsening of the disease.