To identify factors that might be useful as prognostic indexes for the risk of hepatocellular carcinoma in Italian patients with genetic hemochromatosis, 152 homozygotes were studied prospectively for 1 to 229 mo. Factors that were considered in estimating the risk of developing hepatocellular carcinoma were age, sex, cirrhosis (Child class), HBsAg, antibodies to HBsAg, antibodies to HBcAg, hepatitis C antibodies, alcohol abuse and the amount of iron removed during therapeutic phlebotomy to produce iron depletion. At diagnosis, cirrhosis was present in 97 patients and absent in 55. During follow-up, hepatocellular carcinoma developed in 28 of the 97 patients with cirrhosis but in none of those without. Among patients with cirrhosis, the cumulative probability of being free of hepatocellular carcinoma at 10 yr was 70%. For patients with and without HBsAg the probabilities of being free of liver cancer at 10 yr were, respectively, 54% and 75%; for those with and without history of alcoholism, 58% and 78%; and for those younger and older than 55 yr, 90% and 54%. In patients with cirrhosis, multivariate analysis using proportional-hazards (Cox) regression found that the only factors contributing significantly to the estimation of a prognostic index were age, presence of HBsAg and alcohol abuse. Age over 55 yr increased the relative risk of hepatocellular carcinoma 13.3-fold (p < 0.001), the presence of HBsAg increased it 4.9-fold (p < 0.02) and alcohol abuse increased it 2.3-fold (p < 0.04).(ABSTRACT TRUNCATED AT 250 WORDS)

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We studied 81 patients with chronic hepatitis C to investigate the relationship between iron and α‐interferon response. Sixty‐one patients (group A) were given α‐interferon irrespective of iron status, whereas 20 (group B) with iron overload, were iron depleted before α‐interferon therapy. In group A, 21 patients responded to α‐interferon and 40 were non‐responders. Increased iron indices were significantly more frequent in non‐responders than responders. Multivariate analysis showed that among the independent variables evaluated, only γ‐GT and liver iron concentration predicted therapy outcome. After phlebotomy treatment, serum alanine aminotransferase fell significantly both in patients of group B (196±122 IU/1 vs 82±37 IU/1, p<10‐6) and in 12 non‐responders of group A (198±89 IU/1 vs 107±81 IU/1, p<10‐6). In 16 iron depleted patients, eight from each group, subsequent treatment with α‐interferon produced a response in only one patient. These results suggest that increased liver iron is a negative prognostic factor for a‐interferon response in chronic hepatitis C. Iron depletion had a beneficial effect on serum alanine aminotransferase in all the patients treated, but did not improve the response to α‐interferon.