Increased Frequency of Heterozygous Alpha-1-Antitrypsin Deficiency in Liver Explants From Nonalcoholic Steatohepatitis Patients

Gregory Cheeney, Lincoln J. Pac, Purva Gopal, Charles S. Landis, Eric Q. Konnick, Paul E. Swanson, Dina N. Greene, Christina M. Lockwood, Maria Westerhoff

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

Cirrhotic explanted livers occasionally have unexpected periodic acid–Schiff-diastase (PASD)–positive globules within the hepatocyte cytoplasm. It is often unclear whether this finding is a nonspecific consequence of cirrhosis or is indicative of an underlying alpha-1-antitrypsin deficiency (A1ATD) contributing to the cirrhosis. In this study, explanted livers were retrospectively evaluated for histopathology (including PASD status with confirmatory alpha-1-antitrypsin [A1AT] immunohistochemistry [IHC]), and chart review provided etiology of liver failure and general clinical parameters. Real-time polymerase chain reaction was used to detect A1AT genotype (SERPINA1 S and Z alleles) by melting curve analysis on liver explant tissue from selected cases. Of 196 explanted livers, 21 (11%) had PASD+ globules, which were significantly enriched in patients with a clinical diagnosis of nonalcoholic steatohepatitis (NASH; 47%) compared with other causes (P < 0.001). IHC confirmed all PASD+ globules were A1AT+, with 20 of 21 cases demonstrating diffuse A1AT staining. In an expanded NASH cohort, 42% (14/33) of explants had PASD+ globules, 92% of which were homozygous (n = 1) or heterozygous (n = 11) for the SERPINA1 Z allele, corresponding to nearly 40% of all NASH patients. Overall, the Z allele was present in 10% of all tested liver explants, with 85% of PASD+ cases genotyping homozygous (n = 2) or heterozygous (n = 20), which is far in excess of the estimated 2% in the general population. These results indicate PASD+ A1AT globules (with confirmatory genotyping showing at least 1 Z allele) are commonly observed in NASH, suggesting a synergistic relationship toward liver fibrosis. In addition, the high frequency of SERPINA1 Z alleles in liver transplantation patients supports the utility of pretransplant genotyping.

Original languageEnglish (US)
Pages (from-to)17-24
Number of pages8
JournalLiver Transplantation
Volume26
Issue number1
DOIs
StatePublished - Jan 1 2020

ASJC Scopus subject areas

  • Surgery
  • Hepatology
  • Transplantation

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    Cheeney, G., Pac, L. J., Gopal, P., Landis, C. S., Konnick, E. Q., Swanson, P. E., Greene, D. N., Lockwood, C. M., & Westerhoff, M. (2020). Increased Frequency of Heterozygous Alpha-1-Antitrypsin Deficiency in Liver Explants From Nonalcoholic Steatohepatitis Patients. Liver Transplantation, 26(1), 17-24. https://doi.org/10.1002/lt.25652