Does the Heterozygous State of Alpha‐1 Antitrypsin Deficiency Have a Role in Chronic Liver Diseases? Interim Results of a Large Case‐Control Study

Journal of Pediatric Gastroenterology and Nutrition - Tập 43 Số S1 - 2006
Arie Regev1, Constanza Guaqueta1, Enrique Molina1, Andrew Conrad2, Vishnu S. Mishra3, Mark Brantly3, M. Torres1, Maria De Medina1, Andreas G. Tzakis4, Eugene R. Schiff1
1Center for Liver Diseases, Division of Hepatology University of Miami Leonard M. Miller School of Medicine Miami FL
2National Genetics Institute, Los Angeles, CA
3University of Florida College of Medicine, Gainesville, FL
4Division of Liver/Gastrointestinal Transplantation University of Miami Leonard M. Miller School of Medicine Miami FL

Tóm tắt

ABSTRACTBackground:The role of the heterozygous PiZ state of alpha‐1 antitrypsin deficiency (α1ATD) in the pathogenesis of chronic liver disease (LD) is still a matter of controversy.Aim:To determine the prevalence of α1ATD heterozygote states in a large population of patients with established LD compared with individuals with no LD, and to determine whether the prevalence of PiZ is increased in patients with more severe LD.Methods:A cross sectional case‐control study among patients with and without LD. Blood samples were tested for α1AT levels and α1AT phenotype. The severity of LD was determined by clinical evaluation, lab tests, imaging studies and histopathology.Results:In total, 1405 patients were enrolled; 651 with, and 754 without LD. Out of them, 173 patients had decompensated cirrhosis requiring liver transplantation. PiMZ was significantly more prevalent in White patients (3.5%) compared with Hispanics (1.7%; P = 0.029). There was no difference in PiMZ prevalence between the total LD group and the group with no LD (2.1% vs. 1.7%; P = 0.64). Within the LD group, 5.7% of 173 patients with decompensated LD, listed for liver transplantation, had PiMZ, compared with 2.1% of 478 patients with less severe LD (P = 0.016). Similarly, there was a disproportionately higher prevalence of PiZ among hepatitis C virus (HCV) patients (5.6%) and patients with nonalcoholic fatty liver disease (NAFLD) (5.0%) with decompensated LD, compared with HCV patients (1.2%) and NAFLD patients (1.9%) with less severe LD (P = 0.044 and 0.017, respectively). Patients with cryptogenic cirrhosis, who were not considered NAFLD patients, did not have a higher prevalence of PiMZ compared with patients with LD of known etiologies (1.9% vs. 2.3%; P = 0.12).Conclusions:We found no association between the heterozygous PiZ state of α1ATD and the presence of chronic LD in‐general or the presence of cryptogenic cirrhosis. In contrast, patients with decompensated LD of any etiology had a significantly higher prevalence of PiMZ compared with patients with compensated LD. Furthermore, in patients with chronic LD due to HCV or NAFLD there was a significant association between the PiMZ heterozygous state and increased severity of LD and the need for liver transplantation. These interim results suggest that the PiMZ α1ATD heterozygous state may have a role in worsening LD due to HCV or NAFLD.

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Tài liệu tham khảo

Perlmutter D, 2003, Schiff's Diseases of the Liver, 9th, 1207

10.1016/S0016-5085(76)80558-6

10.1016/S0140-6736(75)91143-5

Theodoropoulos G, 1976, Alpha 1‐antitrypsin phenotypes in cirrhosis and hepatoma, Acta Hepatogastroenterol (Stuttg), 23, 114

10.1159/000198937

Eigenbrodt ML, 1997, Heterozygous alpha 1‐antitrypsin phenotypes in patients with end stage liver disease, Am J Gastroenterol, 92, 602

10.1016/S0168-8278(00)80119-1

10.1002/hep.510280421

10.1056/NEJM198103053041001

10.3109/00365528509088831

10.3109/00365529008999216

10.1097/00007890-199605270-00014

Bruce RM, 1984, Collaborative study to assess risk of lung disease in Pi MZ phenotype subjects, Am Rev Respir Dis, 130, 386

Buist AS, 1979, Pulmonary function in heterozygotes for alpha,‐antitrypsin deficiency: a case‐control study, Am Rev Respir Dis, 120, 759

10.1016/0002-9343(77)90354-0

10.1378/chest.77.2.261b

10.1056/NEJM197705262962102

Brantly M, 1995, Alpha‐1 Antitrypsin Deficiency, 45

Brantly M, 1995, Alpha‐1 Antitrypsin Deficiency, 211

10.1378/chest.100.3.703

10.1164/rccm.168.7.818

10.1378/chest.122.5.1818

10.1183/09031936.94.07122199

Klayton R, 1975, Determinants of chronic obstructive pulmonary disease in patients with intermediate levels of alpha‐antitrypsin, Am Rev Respir Dis, 112, 71

10.1165/ajrcmb.20.2.3177

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Journal of Pediatric Gastroenterology and Nutrition

Tập 43 Số S1

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