Alpha-1 Antitrypsin Deficiency and the Risk of Hepatocellular Carcinoma in Patients With End-Stage Liver Disease

Abstract

Introduction: Based on limited studies, it has been proposed that alpha-1 antitrypsin deficiency (A1ATD) is associated with a risk of primary hepatocellular carcinoma (HCC) that exceeds that attributable to cirrhosis alone. Moreover, recent data suggest that PI*Z heterozygotes (e.g., PI*MZ) had an increased risk of HCC. The aim of this study was to evaluate the association between A1ATD/ Z allele and HCC in a cohort of patients with end stage liver disease (ESLD). Methods: Patients evaluated for orthotopic liver transplant at the Cleveland clinic between 2003 and 2014 were included in this retrospective study. Complete data was collected on 696 subjects. The diagnosis of A1ATD was based on phenotype abnormalities (ZZ or MZ), the presence of PAS-positive diastaseresistant (PAS+) globules on liver biopsy, or both. The diagnosis of HCC was based on imaging, biopsy, or examination of the explanted liver. All patients with A1ATD were identified and the prevalence of HCC in this population was calculated. Time-to-event analysis for interval censored data was performed to assess occurrence of HCC in patients with other causes of cirrhosis such as alcoholic liver disease, hepatitis C (HCV), or non-alcoholic steatohepatitis (NASH). Results: A total of 696 subjects were included in the analysis. Seven percent of these had A1ATD. Of subjects without A1ATD, 45% had HCV, 18% had alcoholic liver disease, 18% had NASH, and 18% had other primary diagnosis. Median follow-up time was 3.2 years (25th, 75th percentiles: 1, 5.2), during which time 29% of subjects developed HCC. Crude percentage of HCC was 8.5% in the A1ATD group compared to 30% in the no A1ATD group (p=0.004). Figure 1 presents the cumulative incidence plot for HCC. Subjects with A1ATD were found to have significantly lower HCC rates compared to subjects without A1ATD (p=0.002).Figure 1: Cumulative incidence of HCC in ESLD patients with and without A1ATD.Conclusion: A1ATD was not associated with an increased risk of HCC in a group of patients with ESLD. In fact, patients with cirrhosis and A1ATD were less likely to develop HCC compared to patients with other causes of cirrhosis.