Alpha-1 Antitrypsin Deficiency and Liver Disease

Abstract

We can hardly support 2 statements in the review by Köhnlein and Welte.1Köhnlein T. Welte T. Alpha-1 antitrypsin deficiency: pathogenesis, clinical presentation, diagnosis, and treatment.Am J Med. 2008; 121: 3-9Abstract Full Text Full Text PDF PubMed Scopus (100) Google Scholar“Jaundice from alpha-1 antitrypsin deficiency resolves spontaneously after a few weeks. Clinical signs in newborns are not necessarily associated with liver disease in adulthood.” In fact, the risk of developing cirrhosis among those with liver dysfunction is 50%; 25% die within the first decade of life, and 2% develop cirrhosis later in childhood.2Hussain M. Mieli-Vergani G. Mowat A.P. Alpha 1-antitrypsin deficiency and liver disease: clinical presentation, diagnosis and treatment.J Inherit Metab Dis. 1991; 14: 497-511Crossref PubMed Scopus (43) Google Scholar In 246 individuals with the Z mutation followed-up for up to 11 years, Larsson noted cirrhosis in 12%.3Larsson C. Natural history and life expectancy in severe alpha 1- antitrypsin deficiency, Pi Z.Acta Med Scand. 1978; 204: 345-351Crossref PubMed Scopus (396) Google Scholar“Alpha-1 antitrypsin deficiency is one of the most frequent reasons for liver cirrhosis, after viral hepatitis, alcohol abuse, and chronic cholangitis.” Nonalcoholic steatohepatitis and autoimmune hepatitis are missing; moreover, alpha-1 antitrypsin deficiency is only one of the inherited diseases causing liver disease, hemochromatosis being the most frequent. We can hardly support 2 statements in the review by Köhnlein and Welte.1Köhnlein T. Welte T. Alpha-1 antitrypsin deficiency: pathogenesis, clinical presentation, diagnosis, and treatment.Am J Med. 2008; 121: 3-9Abstract Full Text Full Text PDF PubMed Scopus (100) Google Scholar “Jaundice from alpha-1 antitrypsin deficiency resolves spontaneously after a few weeks. Clinical signs in newborns are not necessarily associated with liver disease in adulthood.” In fact, the risk of developing cirrhosis among those with liver dysfunction is 50%; 25% die within the first decade of life, and 2% develop cirrhosis later in childhood.2Hussain M. Mieli-Vergani G. Mowat A.P. Alpha 1-antitrypsin deficiency and liver disease: clinical presentation, diagnosis and treatment.J Inherit Metab Dis. 1991; 14: 497-511Crossref PubMed Scopus (43) Google Scholar In 246 individuals with the Z mutation followed-up for up to 11 years, Larsson noted cirrhosis in 12%.3Larsson C. Natural history and life expectancy in severe alpha 1- antitrypsin deficiency, Pi Z.Acta Med Scand. 1978; 204: 345-351Crossref PubMed Scopus (396) Google Scholar “Alpha-1 antitrypsin deficiency is one of the most frequent reasons for liver cirrhosis, after viral hepatitis, alcohol abuse, and chronic cholangitis.” Nonalcoholic steatohepatitis and autoimmune hepatitis are missing; moreover, alpha-1 antitrypsin deficiency is only one of the inherited diseases causing liver disease, hemochromatosis being the most frequent. The ReplyThe American Journal of MedicineVol. 121Issue 6PreviewWe are not ready to change our statements challenged by Braillon and Nguyen-Khac. The reference they cite1 describes the results from a highly selected cohort of a tertiary center in London. In addition, the same article reports the early phase of the largest prospective study about the clinical course of liver disease in alpha-1 antitrypsin deficiency. Today we have the follow-up results of 119 patients observed over 26 years,2 and in adulthood no elevated incidence of clinically relevant liver disease could be detected. Full-Text PDF