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Does the heterozygous state of alpha-1 antitrypsin deficiency have a role in chronic liver diseases? Interim results of a large case-control study.
J Pediatr Gastroenterol Nutr. 2006 Jul; 43 Suppl 1:S30-5.JP

Abstract

BACKGROUND

The role of the heterozygous PiZ state of alpha-1 antitrypsin deficiency (alpha1ATD) in the pathogenesis of chronic liver disease (LD) is still a matter of controversy.

AIM

To determine the prevalence of alpha1ATD 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 alpha1AT levels and alpha1AT 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 alpha1ATD 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 alpha1ATD heterozygous state may have a role in worsening LD due to HCV or NAFLD.

Authors+Show Affiliations

Division of Hepatology, Center for Liver Diseases, University of Miami, Leonard M. Miller School of Medicine, FL 33136, USA. aregev@med.miami.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16819398

Citation

Regev, Arie, et al. "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, vol. 43 Suppl 1, 2006, pp. S30-5.
Regev A, Guaqueta C, Molina EG, et al. Does the heterozygous state of alpha-1 antitrypsin deficiency have a role in chronic liver diseases? Interim results of a large case-control study. J Pediatr Gastroenterol Nutr. 2006;43 Suppl 1:S30-5.
Regev, A., Guaqueta, C., Molina, E. G., Conrad, A., Mishra, V., Brantly, M. L., Torres, M., De Medina, M., Tzakis, A. G., & Schiff, E. R. (2006). 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, 43 Suppl 1, S30-5.
Regev A, et al. Does the Heterozygous State of Alpha-1 Antitrypsin Deficiency Have a Role in Chronic Liver Diseases? Interim Results of a Large Case-control Study. J Pediatr Gastroenterol Nutr. 2006;43 Suppl 1:S30-5. PubMed PMID: 16819398.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Does the heterozygous state of alpha-1 antitrypsin deficiency have a role in chronic liver diseases? Interim results of a large case-control study. AU - Regev,Arie, AU - Guaqueta,Constanza, AU - Molina,Enrique G, AU - Conrad,Andrew, AU - Mishra,Vishnu, AU - Brantly,Mark L, AU - Torres,Maria, AU - De Medina,Maria, AU - Tzakis,Andreas G, AU - Schiff,Eugene R, PY - 2006/7/5/pubmed PY - 2007/1/24/medline PY - 2006/7/5/entrez SP - S30 EP - 5 JF - Journal of pediatric gastroenterology and nutrition JO - J Pediatr Gastroenterol Nutr VL - 43 Suppl 1 N2 - BACKGROUND: The role of the heterozygous PiZ state of alpha-1 antitrypsin deficiency (alpha1ATD) in the pathogenesis of chronic liver disease (LD) is still a matter of controversy. AIM: To determine the prevalence of alpha1ATD 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 alpha1AT levels and alpha1AT 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 alpha1ATD 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 alpha1ATD heterozygous state may have a role in worsening LD due to HCV or NAFLD. SN - 0277-2116 UR - https://www.unboundmedicine.com/medline/citation/16819398/Does_the_heterozygous_state_of_alpha_1_antitrypsin_deficiency_have_a_role_in_chronic_liver_diseases_Interim_results_of_a_large_case_control_study_ L2 - https://doi.org/10.1097/01.mpg.0000226387.56612.1e DB - PRIME DP - Unbound Medicine ER -