Hepatocellular carcinoma in patients with acute hepatic porphyria: frequency of occurrence and related factors

Background/Aims: Previous retrospective studies have suggested an associati on between hepatocellular carcinoma and acute hepatic porphyrias, The incid ence, the relative risk, the characteristics and the outcome of primary liv er cancer were prospectively evaluated in patients with acute hepatic porph yrias; the molecular mechanism of carcinogenesis in these patients was also pointed out. Methods: A cohort of 650 patients with acute hepatic porphyria was followed over 7 years. Standardized rate ratio was used to measure the relative ris k of primary liver cancer after indirect standardization. Morphological and clinical aspects of primary liver cancer were investigated, and survival r ates were calculated using the Kaplan-Meier method. Common etiological fact ors involved in liver carcinogenesis were screened. Excretion rates of porp hyrin precursors, serum melatonin levels and mutations in the genes encodin g for heme biosynthetic enzymes were studied, Results: Hepatocellular carcinoma was found in four symptomatic and three a symptomatic patients (four female, three male). The overall standardized ra te ratio was 36 (95% CI: 14-74), The 5-year disease-free survival was 43% i n patients with hepatocellular carcinoma. Usual risk factors for primary li ver cancer were not confounding factors. Hepatocellular carcinoma was not r elated to specific heme biosynthesis gene mutations. Heme precursors were s ignificantly increased in porphyric patients with hepatocellular carcinoma, and serum melatonin levels were low. Conclusions: Acute hepatic porphyrias are risk factors for hepatocellular c arcinoma. Hepatic porphyrias should be sought in patients with hepatocellul ar cancer without obvious etiology, and a periodic screening for hepatocell ular carcinoma should be evaluated in these patients. Genes encoding for he me biosynthetic pathway may not act as tumor suppressor genes. Chronic incr eased levels of delta aminolevulinic acid could lead to the generation of f ree radicals and subsequently to hepatic carcinogenesis.