Homozygous α1-antitrypsin deficiency (PiZZ phenotype) is known to be associated with increased risk of cirrhosis and primary liver cancer. Although a relationship between heterozygous α1-antitrypsin deficiency and chronic liver disease was suggested recently, it is still a matter of controversy whether such patients are at increased risk of liver cancer. The goal of this study was to determine the prevalence of heterozygous α1-antitrypsin deficiency of different phenotypes among patients with primary hepatobiliary cancers.
We studied 82 patients with primary hepatobiliary cancer; 59 had hepatocellular carcinoma and 23 had bile duct carcinoma. α1-Antitrypsin quantitation and phenotyping were performed in each patient using standard methods. The distribution of the various Pi phenotypes was compared with that found in a normal population and reported elsewhere. Odds-ratio and X2 tests were used to measure the relative risk and the significance of association, respectively, between primary hepatobiliary cancers and heterozygous α1-antitrypsin deficiency.
Four patients in each of the cancer groups were heterozygous. Among the hepatocellular carcinoma patients, three had the PiMS phenotype and one had the PiMZ phenotype. Of these four heterozygous patients, only two had cirrhosis; one had cryptogenic cirrhosis and the other had hepatitis B virus–related cirrhosis. One noncirrhotic patient with a PiMZ phenotype had a fibrolamellar carcinoma. Of the four patients with bile duct carcinoma, three had the PiMS phenotype and one had the PiMZ phenotype. Of the four heterozygous patients, two had primary sclerosing cholangitis without associated inflammatory bowel disease and one patient had had previous biliary operations. Heterozygosity of α1-antitrypsin Pi types (non-PiMM) does not mark an increased estimated risk for hepatocellular carcinoma (odds ratio = 0.78; 95% confidence index = 0.28, 2.16; p = not significant), or bile duct carcinoma (odds ratio = 2.27; 95% confidence index = 0.77, 6.70; p = not significant). Based on these results, we conclude that heterozygous α1-antitrypsin deficiency is not associated with hepatocellular carcinoma or bile duct carcinoma. (Hepatology 1992;15:407–410).