793 HEPATOCELLULAR CARCINOMA IN AUTOIMMUNE HEPATITIS

April 25 cells increases greatly following hepatic injury.The present study was aimed to provide data to support this hypothesis in humans.Methods: The study included 219 consecutive patients (154 males), median age 55 years (range, 22-68), who underwent liver transplantation for end stage liver disease; 236 blood donors (164 males), served as controls.Genotyping for the IL-6 -174 G>C polymorphism, that is associated with high IL-6 production, was performed on whole blood samples by a PCRrestriction fragment length polymorphism assay.All total hepatectomy specimens were sectioned at intervals of approximately 1 cm in search for suspicious focal hepatic lesions.Results: HCC foci were identified in the native livers of 66/219 patients undergoing liver transplantation.IL-6 -174 G>C allelic frequencies in patients and controls were G = 0.650 and 0.689, C = 0.350 and 0.311, respectively (p = ns).In both groups, no departure from the Hardy-Weinberg distribution was observed for each allele.A higher prevalence of the G/G + G/C genotypes was detected in patients with HCC (65/66) in comparison to the remaining patients without HCC (135/153) (p < 0.02).A highly significant linear trend was observed for increasing frequencies of HCC stratifying the patients as follows: males and females carrying the IL6 -174 C/C genotype (1/19), female patients with the G/G + G/C genotypes (9/60) and finally male patients with the G/G + G/C genotypes (56/140) (p < 0.0001).At multivariate analysis, detection of HCC foci in the explanted liver was independently associated with age at operation >50 years (p < 0.001), male gender (p = 0.001) and carriage of the IL-6 high producer genotypes (-174 G/G + G/C) (p = 0.001).Conclusions: The IL6 -174 G>C polymorphism may play a role in HCC development among patients with end stage liver disease.The protective effect of female gender against the occurrence of liver cancer is mainly effective among carriers of high IL-6 producer (IL6 -174 G/G + G/C) phenotype.