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Title: Risk of hepatobiliary disease in adults with severe alpha 1-antitrypsin deficiency (PiZZ): is chronic viral hepatitis B or C an additional risk factor for cirrhosis and hepatocellular carcinoma?
Author: Elzouki AN, Eriksson S.
Journal: Eur J Gastroenterol Hepatol; 1996 Oct; 8(10):989-94. PubMed ID: 8930564.
Abstract:
OBJECTIVES: To assess homozygous alpha 1-antitrypsin deficiency (PiZZ) as a risk factor for cirrhosis, hepatocellular carcinoma (HCC) and gallstone disease, and to analyse the respective interrelation-ships and those suggested to exist between PiZZ, alpha 1-antitrypsin and chronic hepatitis B and C. DESIGN/METHODS: This study was based on 31 autopsied adults with severe alpha 1-antitrypsin deficiency diagnosed during the period 1963-94, in the city of Malmö, Sweden. For each autopsied PiZZ individual, four age- and sex-matched controls were selected from the same autopsy register. The autopsy rate during the study period was 57.2% of all deaths in the city and 85% of deaths at the hospital. Relative risks were estimated in terms of Mantel-Haenszel odds ratios (ORmh). RESULTS: In the PiZZ group, we found 13 cases of cirrhosis (ORmh = 8.3; 95% CI, 3.8-18.3; P < 0.0001), 5 cases of HCC (ORmh = 5.0; 95% CI, 1.6-15.8; P = 0.008), and 8 cases of gallstone disease (ORmh = 1.0; 95% CI, 0.4-2.3; P = 0.924), compared with 7, 4 and 29 cases, respectively, in the control group. Stratification of the data by age and sex showed the difference in relative risk of cirrhosis between the PiZZ and control groups to be significant in both sexes, but that of HCC to be significant only in the male subgroup. There was no correlation between PiZZ state and gallstone disease in either sex. All PiZZ patients with cirrhosis and HCC had had negative tests for anti-hepatitis B core antigen and/or hepatitis B surface antigen. Of the homozygotes with cirrhosis or HCC for whom frozen sera were available (54% (7/13) and 60% (3/5), respectively), none had antihepatitis C antibodies, as tested both with ELISA-2 and RIBA-3. The prevalence of cirrhosis was higher in the PiZZ group than in controls for all ages above 50 years (P < 0.05). The occurrence of gallstone disease increased steadily with age in the two populations. CONCLUSIONS: Although males and females with severe alpha 1-antitrypsin deficiency are not at significantly greater risk of gallstone disease, they are at greater risk of cirrhosis and HCC, the risk of HCC being more manifest in males. The risk of cirrhosis or HCC was unrelated to the presence of hepatitis B or C infection.

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