A total of 84 patients with hepatocellular carcinoma and cirrhosis were analyzed retrospectively to investigate prognostic factors. All patients received transarterial oily chemoembolization as the only anticancer therapy. The follow-up range was 1 to 39 mo (median, 9.5 mo). The overall actuarial survival rates at 12, 24 and 30 mo were 62%, 31% and 24%, respectively. According to univariate analysis, variables significantly associated with survival were age, Child-Pugh grade, total serum bilirubin, Okuda stage, tumor size, degree of labeling of the tumor with Lipiodol, gelatin foam use, changes with treatment in tumor size and changes with treatment in alpha-fetoprotein concentration. Two multivariate analyses were performed. When pretreatment and treatment variables were considered, parameters with independent prognostic value were age, Child-Pugh grade, total serum bilirubin, tumor size and degree of Lipiodol labeling of the tumor. When follow-up variables were also considered, we (a) confirmed the prognostic significance of all these parameters (age, Child-Pugh grade, total serum bilirubin, tumor size) and (b) found the independent prognostic value of the change in tumor size (or change in alpha-fetoprotein concentration). Both models yielded different risk coefficients for each class of each variable. Two simple prognostic indexes, based on these coefficients, are proposed: an "initial" index (including pretreatment and treatment variables) and a "follow-up" index (also including follow-up variables). According to the two indexes, the patients were classified into three groups with different prognoses: good (93% and 100% actuarial survival at 1 yr for the initial and follow-up indexes, respectively), intermediate (65% and 53%, respectively) and poor (27% for both indexes).
Factors influencing the progression of liver disease and the development of hepatocellular carcinoma (HCC) in chronic hepatitis C virus (HCV) infection are poorly understood. Inherited variations of drug-metabolizing enzyme (DME) activities may affect liver damage and cancer risk by modifying individual susceptibility to endogenous or exogenous toxic compounds. We investigated the association of liver disease severity with common alleles of microsomal epoxide hydrolase (mEH), an enzyme involved in the metabolism of highly reactive epoxide intermediates. Three polymorphisms (Tyr113His, His139Arg, and ؊613C/T) were analyzed by polymerase chain reaction (PCR) restriction fragment length polymorphisms (RFLPs) in 394 patients at different stages of disease, including 92 asymptomatic carriers, 109 patients with chronic hepatitis, 100 patients with cirrhosis, and 93 patients with HCC. Reference allele frequencies were obtained from 99 healthy blood donors. Allele distributions between categories were compared using the 2 test; odds ratios (ORs) and 95% CI were calculated to express relative risks. Allele frequencies among 99 healthy controls were as follows: 15.1% for 113His/His, 4.0% for 139Arg/Arg, and 46.5% for ؊613C/T. mEH 113His/His homozygotes were overrepresented in advanced stages of disease, in particular among HCC patients (27.9%; P ؍ .03; OR, 2.2; 95% CI, 1.0-4.6). Differences were more pronounced among men and between extreme patient categories. When mEH genotypes were combined to express a metabolic phenotype, very slow metabolizers were highly prevalent among cirrhotic and HCC patients (18% vs. 3.3% in carriers; P < .001). In conclusion, mEH gene polymorphisms were significantly associated with HCV-related liver disease severity and HCC risk. Men were at higher risk than women; this might be explained by hormonal regulation of gene expression or by differential exposure to environmental toxins. (HEPATOLOGY 2002;36:195-201.) T he worldwide burden of deaths caused by liver diseases and liver cancer, which usually arises in the setting of cirrhosis and chronic viral hepatitis, is estimated to be approximately 1.3 million/yr. 1 Chronic hepatitis C virus (HCV) infections account for over 80% of cases of cirrhosis and hepatocellular carcinomas (HCC) in Italy, 2 for which over 2 million anti-HCV-positive cases are estimated. 3 HCV-related liver disease displays a multiplex phenotype in which environmental and viral factors are likely to act in concert with individual susceptibility to induce liver damage. Overall penetration of disease expression is low, because less than 20% of infected individuals will develop cirrhosis over a 20-to 30-year period. 4 Determinants of HCV pathogenesis are barely known and include age at infection, 5 disease duration, 4 sex, 6 modes of transmission, 7 immunogenetic variables, 8 and viral heterogeneity, 9 but these factors account for only a small part of the clinical variability of the disease. Dietary factors, inherited metabolic defects, such as hemochromatosis, 10 and alc...
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