Does the heterozygous state of alpha-1 antitrypsin deficiency have a role in chronic liver diseases? Interim results of a large case-control study

Arie Regev, Constanza Guaqueta, Enrique G. Molina, Andrew Conrad, Vishnu Mishra, Mark L. Brantly, Maria Torres, Maria De Medina, Andreas G. Tzakis, Eugene R Schiff

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Abstract

BACKGROUND: 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.

Original languageEnglish
JournalJournal of Pediatric Gastroenterology and Nutrition
Volume43
Issue number1 SUPPL. 1
DOIs
StatePublished - Jul 1 2006

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alpha 1-Antitrypsin Deficiency
liver diseases
case-control studies
Case-Control Studies
Liver Diseases
Chronic Disease
fatty liver
Hepatitis C virus
liver transplant
Hepacivirus
Autosomal Recessive alpha-1-Antitrypsin Deficiency
Liver Transplantation
etiology

Keywords

  • Alpha-1 antitrypsin deficiency
  • Chronic liver disease
  • Gene modifiers

ASJC Scopus subject areas

  • Gastroenterology
  • Histology
  • Medicine (miscellaneous)
  • Food Science
  • Pediatrics, Perinatology, and Child Health

Cite this

Does the heterozygous state of alpha-1 antitrypsin deficiency have a role in chronic liver diseases? Interim results of a large case-control study. / Regev, Arie; Guaqueta, Constanza; Molina, Enrique G.; Conrad, Andrew; Mishra, Vishnu; Brantly, Mark L.; Torres, Maria; De Medina, Maria; Tzakis, Andreas G.; Schiff, Eugene R.

In: Journal of Pediatric Gastroenterology and Nutrition, Vol. 43, No. 1 SUPPL. 1, 01.07.2006.

Research output: Contribution to journalArticle

Regev, Arie ; Guaqueta, Constanza ; Molina, Enrique G. ; Conrad, Andrew ; Mishra, Vishnu ; Brantly, Mark L. ; Torres, Maria ; De Medina, Maria ; Tzakis, Andreas G. ; Schiff, Eugene R. / Does the heterozygous state of alpha-1 antitrypsin deficiency have a role in chronic liver diseases? Interim results of a large case-control study. In: Journal of Pediatric Gastroenterology and Nutrition. 2006 ; Vol. 43, No. 1 SUPPL. 1.
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title = "Does the heterozygous state of alpha-1 antitrypsin deficiency have a role in chronic liver diseases? Interim results of a large case-control study",
abstract = "BACKGROUND: 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.",
keywords = "Alpha-1 antitrypsin deficiency, Chronic liver disease, Gene modifiers",
author = "Arie Regev and Constanza Guaqueta and Molina, {Enrique G.} and Andrew Conrad and Vishnu Mishra and Brantly, {Mark L.} and Maria Torres and {De Medina}, Maria and Tzakis, {Andreas G.} and Schiff, {Eugene R}",
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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 - 2006/7/1

Y1 - 2006/7/1

N2 - BACKGROUND: 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.

AB - BACKGROUND: 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.

KW - Alpha-1 antitrypsin deficiency

KW - Chronic liver disease

KW - Gene modifiers

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