Retrospective Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Jun 8, 2015; 7(10): 1427-1432
Published online Jun 8, 2015. doi: 10.4254/wjh.v7.i10.1427
Alpha-1 antitrypsin deficiency and the risk of hepatocellular carcinoma in end-stage liver disease
Clara Antoury, Rocio Lopez, Nizar Zein, James K Stoller, Naim Alkhouri
Clara Antoury, Department of Internal Medicine, Cleveland Clinic Foundation, Cleveland, OH 44195, United States
Rocio Lopez, Department of Quantitative Health Sciences, Cleveland Clinic Foundation, Cleveland, OH 44195, United States
Nizar Zein, Naim Alkhouri, Department of Gastroenterology and Hepatology and Digestive Disease Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, United States
James K Stoller, Departments of Pulmonary and Critical Care, Respiratory Institute and Education Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, United States
Author contributions: Antoury C contributed to study concept and design, acquisition of data, analysis and interpretation of data, drafting of the manuscript and critical revision of the manuscript for important intellectual content; Lopez R contributed to analysis and interpretation of data, statistical analysis and critical revision of the manuscript for important intellectual content; Zein N contributed to analysis and interpretation of data; critical revision of the manuscript for important intellectual content; Stoller JK and Alkhouri N contributed to analysis and interpretation of data and critical revision of the manuscript for important intellectual content.
Ethics approval: The study was reviewed and approved by the Cleveland Clinic Institutional review board.
Informed consent: This is a minimal risk study using data collected for routine clinical practice. A waiver of Informed Consent and waiver of HIPAA authorization were approved by IRB. The presented data are anonymized and risk of identification is low.
Conflict-of-interest: None of the authors received any fees, research funding, own any stocks or shares or made any profit as a result of this study. None of the authors have any conflicting interests including but not limited to commercial, personal, political, intellectual or religious interests that are related to this work.
Data sharing: No additional data available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Clara Antoury, MD, Department of Internal Medicine, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, United States. antourc@ccf.org
Telephone: +1-440-3643714
Received: December 24, 2014
Peer-review started: December 26, 2014
First decision: January 20, 2015
Revised: March 9, 2015
Accepted: April 10, 2015
Article in press: April 14, 2015
Published online: June 8, 2015
Processing time: 161 Days and 9 Hours
Abstract

AIM: To evaluate the association between alpha-1 antitrypsin deficiency (A1ATD) and hepatocellular carcinoma (HCC) in patients with end-stage liver disease (ESLD).

METHODS: Patients with cirrhosis and ESLD referred to the Cleveland Clinic Foundation for liver transplantation between 2003 and 2014 were included in the study (N = 675). ESLD was defined as having histological features of cirrhosis and/or radiological evidence of cirrhosis in the context of portal hypertension (ascites, variceal bleeding, thrombocytopenia, or hepatic encephalopathy). A1ATD was diagnosed using phenotype characterization (MZ or ZZ), liver biopsy detection of PAS-positive diastase-resistant (PAS+) globules, or both. Patients with other causes of liver diseases such as hepatitis C virus (HCV), alcoholic liver disease and non-alcoholic steatohepatitis (NASH) or NASH were also included in the study. HCC was diagnosed by using imaging modalities, biopsy findings, or explanted liver inspection. Follow-up time was defined as the number of years from the diagnosis of cirrhosis to the diagnosis of hepatocellular carcinoma, or from the diagnosis of cirrhosis to the last follow up visit. The rate of HCC was assessed using time-to-interval analysis for interval censored data.

RESULTS: This study included 675 patients. 7% of subjects had A1ATD (n = 47). Out of all subjects who did not have A1ATD, 46% had HCV, 17% had alcoholic liver disease, 19% had NASH and 18% had another primary diagnosis. Of the 47 subjects with A1ATD, 15 had a primary diagnosis of A1ATD (PI*ZZ phenotype and PAS+ globules), 8 had a PI*MZ phenotype alone, 14 had PAS+ alone, and 10 had both the PI*MZ phenotype and PAS+. Median follow-up time was 3.4 (25th, 75th percentiles: 1, 5.2) years. The overall rate of hepatocellular carcinoma in all subjects was 29% (n = 199). In the A1ATD group, the incidence rate of HCC was 8.5% compared to 31% in the group of patients with other causes of cirrhosis (P = 0.001). Patients with ESLD due to A1ATD had the lowest yearly cumulative rate of hepatocellular carcinoma at 0.88% per year compared to 2.7% for those with HCV cirrhosis, 1.5% in patients with NASH and 0.9% in alcohol-induced liver disease (P < 0.001).

CONCLUSION: Within this group of patients with ESLD, there was no significant association between A1ATD and increased risk of HCC.

Keywords: Hepatocellular carcinoma; Liver cirrhosis; End-stage liver disease; Hepatitis C virus; Alpha-1 antitrypsin deficiency

Core tip: It’s been postulated that alpha-1 antitrypsin deficiency (A1ATD) and the presence of the Z allele increase the risk of hepatocellular carcinoma (HCC) above that attributable to cirrhosis alone. Our study showed that the occurrence of HCC in subjects with cirrhosis due to A1ATD was 0.88%/year. This incidence rate was considerably lower than that among patients with other causes of liver disease including hepatitis C, alcoholic liver disease and non-alcoholic liver steatohepatitis. This challenges the view that A1ATD confers a disproportionate risk of HCC.