1. Association of Alpha-1 Antitrypsin Pi*Z Allele Frequency and Progressive Liver Fibrosis in Two Chronic Hepatitis C Cohorts.
- Author
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Mücke, Victoria Therese, Fischer, Janett, Mücke, Marcus Maximilian, Teumer, Alexander, Koch, Alexander, Vermehren, Johannes, Fromme, Malin, Zeuzem, Stefan, Trautwein, Christian, Sarrazin, Christoph, Berg, Thomas, Zhou, Biaohuan, and Hamesch, Karim more...
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HEPATIC fibrosis ,CHRONIC hepatitis C ,GENE frequency ,TRYPSIN inhibitors ,ALPHA 1-antitrypsin deficiency ,DISEASE risk factors - Abstract
(1) Background: The inherited alpha-1 antitrypsin (A1AT) deficiency variant 'Pi*Z' emerged as a genetic modifier of chronic liver disease. Controversial data exist on the relevance of heterozygous Pi*Z carriage ('Pi*MZ' genotype) as an additional risk factor in patients with chronic viral hepatitis C to develop progressive liver fibrosis. (2) Methods: Two prospectively recruited cohorts totaling 572 patients with therapy-naïve chronic viral hepatitis C (HCV) were analyzed. The Frankfurt cohort included 337 patients and a second cohort from Leipzig included 235 patients. The stage of liver fibrosis was assessed by liver biopsy, AST-to-platelet ratio index (APRI) score and Fibrosis-4 (FIB-4) score (Frankfurt) as well as liver stiffness measurement (LSM) via transient elastography (Leipzig). All patients were genotyped for the Pi*Z variant (rs28929474) of the SERPINA1 gene. (3) Results: In the Frankfurt cohort, 16/337 (4.7%) patients carried the heterozygous Pi*Z allele while 10/235 (4.3%) in the Leipzig cohort were Pi*Z carriers. In both cohorts, there was no higher proportion of Pi*Z heterozygosity in patients with cirrhosis compared to patients without cirrhosis or patients with cirrhosis vs. no liver fibrosis. Accordingly, Pi*Z frequency was not different in histological or serological stages of liver fibrosis (F0–F4) and showed no clear association with LSM. (4) Conclusions: Evaluation in two representative HCV cohorts does not indicate Pi*Z heterozygosity as a clinically relevant disease modifier in chronic HCV infection. However, validation in even larger cohorts with longitudinal follow-up is warranted. [ABSTRACT FROM AUTHOR] more...
- Published
- 2023
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