Liver cancer risk is increased in patients with porphyria cutanea tarda in comparison to matched control patients with chronic liver disease.
ABSTRACT Patients with porphyria and chronic liver disease could be at high risk of developing hepatocellular carcinoma. To define the incidence of primary liver cancer and identify variables associated with the risk of cancer in patients with porphyria cutanea tarda in comparison to control patients.
Fifty-three patients with porphyria cutanea tarda were enrolled in a prospective study (median follow-up 72 +/- 54.1 months; range 12-216) and matched individually to a control case according to age (+/-5 years), sex, duration of follow up (+/- 5 years), severity of liver disease, and hepatitis C virus infection.
During follow-up hepatocellular carcinoma developed in 18 patients with porphyria and in four control patients. Incidence of primary liver cancer was 4.8 and 1.3 x 100 patients/year in the overall series of patients and of controls, respectively. The cumulative probability of being tumor free was significantly lower in porphyria cutanea tarda than in matched controls (75 vs 95%). Variables independently associated with the risk of liver cancer were the presence of porphyria and cirrhosis at enrollment (Odds ratios: 5.3, 95% CI 1.4-19.3 and 3.0, 95% CI 1.2-7.6, respectively).
Patients with porphyria are at higher risk of developing liver cancer than matched control patients.
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ABSTRACT: Chronic hepatitis C virus (HCV) infection is associated with a spectrum of liver diseases and a proportion of chronic cases progress through cirrhosis to hepatocellular carcinoma (HCC). The viral and host factors that are important in the clinical and histological progression of HCV infection are unclear. We investigated the effect of moderate (<80 g/day) and heavy (>80 g/day) alcohol intake on the histological and clinical progression of HCV infection and their associated risk of hepatic cancer in a group of Japanese patients. A number of other variables were assessed to evaluate their impact on disease progression. We recruited 120 patients with HCV infection and categorized them into four groups, based on alcohol consumption pattern. All clinical and biochemical profiles were collected from recorded files. Liver biopsies were analysed for the degree of fibrosis, presence of cirrhosis and histological activity of necroinflammation. Hepatic tumours were detected by the follow-up imaging analysis. There was no difference in the age, length of exposure to HCV infection and HCV RNA serum levels in the alcohol and alcohol-free groups. The histological grading of necroinflammation, serum levels of alanine aminotransferase and HCV RNA did not have any correlation with each other in the alcohol and alcohol-free group. There was a 1.5-2. 5-fold greater risk of liver cirrhosis and hepatocellular carcinoma in the alcohol intake group compared to the alcohol-free group. Kruskal-Wallis analysis among four groups demonstrated a significant transition to fibrosis (P < 0.05) for alcoholics with HCV infection. The increased risk of liver cancer in the alcohol group is independent of size and growth of tumours. The clinical manifestations of gastro-oesophageal variceal bleeding, ascites, and encephalopathy were also higher in the alcohol intake group. Alcohol consumption is an important risk factor in the histological and clinical progression of HCV infection and has no relation with HCV replication. Chronic HCV carriers should avoid excessive alcohol intake to reduce the acceleration of liver disease and risk of liver cancer.Alcohol and Alcoholism 01/2000; 35(3):286-95. · 1.96 Impact Factor
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ABSTRACT: Previous retrospective studies have suggested an association between hepatocellular carcinoma and acute hepatic porphyrias. The incidence, the relative risk, the characteristics and the outcome of primary liver cancer were prospectively evaluated in patients with acute hepatic porphyrias; the molecular mechanism of carcinogenesis in these patients was also pointed out. A cohort of 650 patients with acute hepatic porphyria was followed over 7 years. Standardized rate ratio was used to measure the relative risk of primary liver cancer after indirect standardization. Morphological and clinical aspects of primary liver cancer were investigated, and survival rates were calculated using the Kaplan-Meier method. Common etiological factors involved in liver carcinogenesis were screened. Excretion rates of porphyrin precursors, serum melatonin levels and mutations in the genes encoding for heme biosynthetic enzymes were studied. Hepatocellular carcinoma was found in four symptomatic and three asymptomatic patients (four female, three male). The overall standardized rate ratio was 36 (95% CI: 14-74). The 5-year disease-free survival was 43% in patients with hepatocellular carcinoma. Usual risk factors for primary liver cancer were not confounding factors. Hepatocellular carcinoma was not related to specific heme biosynthesis gene mutations. Heme precursors were significantly increased in porphyric patients with hepatocellular carcinoma, and serum melatonin levels were low. Acute hepatic porphyrias are risk factors for hepatocellular carcinoma. Hepatic porphyrias should be sought in patients with hepatocellular cancer without obvious etiology, and a periodic screening for hepatocellular carcinoma should be evaluated in these patients. Genes encoding for heme biosynthetic pathway may not act as tumor suppressor genes. Chronic increased levels of delta aminolevulinic acid could lead to the generation of free radicals and subsequently to hepatic carcinogenesis.Journal of Hepatology 07/2000; 32(6):933-9. · 9.86 Impact Factor
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ABSTRACT: Hepatocellular carcinoma (HCC) occurs more frequently in patients with hepatitis C virus (HCV)-related chronic liver disease than those with hepatitis B virus-related disease. It is important to assess the factors affecting the development of HCC. A long term follow-up study involving patients with chronic HCV was performed retrospectively. A total of 153 patients diagnosed between June 1981 and November 1990 with chronic HCV with or without cirrhosis by liver biopsy were enrolled in a long term follow-up study (average, 99.4 months) and the cumulative incidence rate of HCC and factors affecting the appearance of HCC were examined. The 5-year cumulative incidence rate was 9%, the 10-year cumulative incidence rate was 23%, and the 15-year cumulative incidence rate was 42%. The annual rate of incidence increased as the follow-up period progressed. The authors selected ten variables and investigated their effect on the incidence rate of HCC, including age, gender, habitual heavy drinking, positivity of antibody against hepatitis B virus surface antigen, treatment with interferon (IFN) during the follow-up period, maximum and minimum serum alanine aminotransferase levels during the follow-up period, histologic staging, grading, and irregular regeneration of hepatocytes. Of the 10 variables, age (> 50 years), habitual heavy drinking, and histologic staging were determined to be independent risk factors according to multivariate Cox proportional hazards regression analysis. IFN therapy by itself was not found to be an independent factor affecting the appearance of HCC. In patients with chronic HCV, the annual incidence rate of HCC appeared to increase as the follow-up period progressed. According to the results of the current study, the factors that independently affected the development of HCC were age, habitual heavy drinking, and histologic staging.Cancer 07/2000; 89(1):53-9. · 5.20 Impact Factor