Heterozygous MZ Alpha1-Antitrypsin Deficiency in Adults with Chronic Active Hepatitis and Cryptogenic Cirrhosis

Abstract

To determine the prevalence of alpha 1-antitrypsin deficiency in patients with cirrhosis or chronic active hepatitis, we performed a five-year prospective study of liver-biopsy specimens from 1055 adults. Thirty-four patients whose specimens contained hepatocyte inclusions characteristic of the deficiency were phenotyped, and 25 had phenotype MZ (2.4 per cent). The distribution of patients with this phenotype among the 185 patients with cirrhosis diagnosed histologically was three of 84 patients with alcoholic cirrhosis (3.5 per cent), seven of 34 with non-B chronic active hepatitis (20.5 per cent), six of 28 with cryptogenic cirrhosis (21 per cent), and one of 39 with other kinds of cirrhosis (2.6 per cent). The increased prevalence of MZ in patients with cryptogenic cirrhosis and with chronic active hepatitis is highly significant (P < 0.001). Because serum levels of alpha 1-antitrypsin may be unreliable for identification of the subgroup of patients with chronic active hepatitis or cryptogenic cirrhosis, analysis of serum for the MZ phenotype and meticulous examination of biopsy specimens may be necessary.

SlimQuick™ - associated hepatotoxicity in a woman with alpha-1 antitrypsin heterozygosity

“…Besides taking a hepatotoxic weight-loss supplement, our patient was also heterozygous for alpha-1 antitrypsin deficiency. There remains considerable debate regarding the importance of the alpha-1 antitrypsin MZ phenotype [11,[17][18][19][20][21] . Graziadei et al [17] suggested that the alpha-1 antitrypsin MZ phenotype might be a risk factor for chronic liver disease or liver failure.…”

End‐stage liver disease developing with the use of methotrexate in heterozygous α1‐antitrypsin deficiency

“…There is no increased risk of emphysema. However, there is evidence linking these heterozygous states to cryptogenic cirrhosis (11)(12)(13). In one study, 2.4% of 1,055 adults who were undergoing liver biopsy had the MZ phenotype (12).…”

Intracellular and extracellular serpins modulate lung disease

“…Accordingly, a1AT*ZZ individuals who smoke exhibit a rapid onset of emphysema, often by 30 years of age, and death by the age of 50. 15 However, most a1AT*ZZ individuals who avoid smoking live normal length lives with minimal complications. Replacement therapy for a1AT deficiency, with intravenous a1AT from pooled human plasma, results in longer survival.…”