Prognostic potential of hepatocyte volume and cytokine expression in cirrhotic portal hypertension

Background: Differentiating the prognosis of Child-Pugh A and B patients is difficult, particularly following an acute variceal hemorrhage. We have examined the prognostic significance of hepatocyte volume (HV) and the expression of selected cytokines controlling liver repair and regeneration. Methods: Forty Child-Pugh A and B cirrhotic patients surviving a first acute variceal hemorrhage were recruited prospectively. Hematological, biochemical, neurological, hemodynamic, radio-nuclear and histological assessments were carried out following recovery (at 3 weeks). Fibrosis (%) and HV were calculated using histological morphometry and radio-nuclear liver volume assessment. Immunohistochemistry was used in liver biopsy specimens to assess markers of proliferation (PCNA) and the expression of mitogens (TGF-alpha, TGF-beta(1)) or their receptors (C-met and EGFR). Results: In total, 27 patients died during the follow-up period. HV was predictive of survival in Child-Pugh grade A patients (chi(2) = 10.5, P = 0.0012), but percentage fibrosis and regeneration factor expression were not predictive in either Child-Pugh A or B patients. Cox regression modeling with Child-Pugh grade demonstrated HV to be an independent predictor of survival (chi(2) = 7.1, P = 0.02). Conclusions: HV predicts survival independently in cirrhotic portal hypertension, and may help to differentiate prognosis in those at the more favorable end of the disease spectrum. Liver cytokine expression 3 weeks following an acute variceal bleed did not appear useful in determining prognosis. (C) 2005 Blackwell Publishing Asia Pty Ltd.