Retrospective Cohort Study
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Aug 21, 2018; 24(31): 3547-3555
Published online Aug 21, 2018. doi: 10.3748/wjg.v24.i31.3547
Favorable clinical outcome of nonalcoholic liver cirrhosis patients with coronary artery disease: A population-based study
Ming-Chang Tsai, Tzu-Wei Yang, Chi-Chih Wang, Yao-Tung Wang, Wen-Wei Sung, Ming-Hseng Tseng, Chun-Che Lin
Ming-Chang Tsai, Tzu-Wei Yang, Chi-Chih Wang, Chun-Che Lin, Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung 402, Taiwan
Ming-Chang Tsai, Chi-Chih Wang, Yao-Tung Wang, Wen-Wei Sung, Chun-Che Lin, Institute of Medicine, Chung Shan Medical University, Taichung 402, Taiwan
Ming-Chang Tsai, Tzu-Wei Yang, Chi-Chih Wang, Wen-Wei Sung, Ming-Hseng Tseng, Chun-Che Lin, School of Medicine, Chung Shan Medical University, Taichung 402, Taiwan
Tzu-Wei Yang, Institute and Department of Biological Science and Technology, National Chiao Tung University, Hsinchu 300, Taiwan
Yao-Tung Wang, Division of Pulmonary Medicine, Chung Shan Medical University Hospital, Taichung 402, Taiwan
Wen-Wei Sung, Department of Urology, Chung Shan Medical University Hospital, Taichung 402, Taiwan
Ming-Hseng Tseng, Department of Medical Informatics, Chung Shan Medical University, Taichung 402, Taiwan
Author contributions: All authors reviewed the manuscript and completed final approval; Tsai MC, Yang TW, Tseng MH and Lin CC contributed to study concept and design; Tsai MC, Yang TW and Tseng MH acquired the data; Tsai MC, Yang TW, Wang YT, Sung WW, Tseng MH and Lin CC analyzed and interpreted the data; Tsai MC and Yang TW wrote the manuscript daft; Tsai MC, Yang TW, Wang CC, Wang YT, Sung WW, Tseng MH and Lin CC made critical revision on the manuscript for important intellectual content; Tsai MC, Yang TW and Tseng MH performed statistical analysis; Lin CC obtained funding; Tseng MH and Lin CC contributed to study supervision.
Supported by Chung Shan Medical University Hospital, Taichung, Taiwan, No. CSH- 2013-C-032.
Institutional review board statement: This study was approved by the Institutional Review Board (IRB) of Chung Shan Medical University Hospital, Taiwan.
Informed consent statement: The IRB waived the need of informed consent for this retrospective study based on an encrypted National Health Insurance Research Database (NHIRD).
Conflict-of-interest statement: The authors declare that they have no competing interests.
Data sharing statement: The data of our study were retrieved from the National Health Insurance Research Database (NHIRD) in Taiwan. The application for the data was reviewed and approved by the National Health Insurance (NHI). NHIRD are available via http://nhird.nhri.org.tw/.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
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: Chun-Che Lin, MD, PhD, Professor, Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chung Shan Medical University Hospital, No.110, Sec. 1, Jianguo N. Rd., South Dist., Taichung 402, Taiwan. forest65@csmu.edu.tw
Telephone: +886-4-24739595 Fax: +886-4-24739220
Received: April 19, 2018
Peer-review started: April 19, 2018
First decision: June 6, 2018
Revised: July 11, 2018
Accepted: July 16, 2018
Article in press: July 16, 2018
Published online: August 21, 2018
ARTICLE HIGHLIGHTS
Research background

The risk of mortality in nonalcoholic liver cirrhosis (LC) patients with coronary artery disease (CAD) is unclear. Previous case-control studies demonstrated conflicting results potentially due to the different etiologies of LC. LC patients with alcoholic and nonalcoholic fatty liver disease-related metabolic disorders exhibit an increased risk of CAD. In contrast, hemostatic defects that occur in LC, such as thrombocytopenia, coagulopathy, and low blood pressure, are not considered as potential protective factors of cirrhosis against atherosclerotic events.

Research motivation

The results of CAD risk in LC patients are controversial. In contrast to the present study, previous works using alcoholic LC-based cohorts may have been confounded by the increased risk of metabolic syndrome in heavy drinkers. To the best of our knowledge, the risk of CAD in nonalcoholic cirrhotic patients is not well established.

Research objectives

The aim of the study was to elucidate the prevalence and risk of mortality in nonalcoholic cirrhotic patients. The comorbidities and LC-related complications were also important prognostic factors among cirrhotic patients. The result of this study can provide a better understanding of CAD risk in LC patients.

Research methods

We collected 10142 LC patients diagnosed from 2004 to 2011 using the Taiwanese National Health Insurance research database. After exclusion of subjects who were treated before the end of 2005, had alcoholic or biliary cirrhosis, had LC occurring after CAD, and were younger than 40 years old, a total of 3409 LC patients were enrolled in the study. The comorbidities and complications of LC were collected. The first-time diagnosis of CAD was identified as the primary end point, and the death of the subject served as the secondary end point. All-cause mortality was analyzed in both the study and control cohorts. A Cox proportional hazards model was developed to calculate the overall mortality hazard ratios of all comorbidities and complications in cirrhotic patients. The six-year cumulative survival and survival curve were calculated using the Cox regression method and the Kaplan-Meier method.

Research results

CAD was less prevalent in nonalcoholic LC patients than in controls. Nonalcoholic LC patients with CAD were associated with a reduced risk of mortality. The six-year survival rates were increased in patients with CAD compared to patients without CAD in the nonalcoholic LC cohort. As this is a retrospective cohort study, further prospective studies are needed to confirm this finding.

Research conclusions

In this study, we demonstrate that CAD is less prevalent and associated with a reduced risk for mortality in nonalcoholic LC patients. This result confirms previous studies regarding the lower risk for atherosclerotic events (i.e. ischemic stroke and coronary artery disease) in alcohol-related and nonalcohol-related LC cohorts. Although viral hepatitis can cause endothelial dysfunction, which correlates with atherosclerotic disease progression, we propose that LC has a more powerful protective effect against atherosclerotic events based on the favorable cardiovascular risk profiles, such as thrombocytopenia, coagulopathy, and low blood pressure. The strengths of the study include the large sample size cohort and risk adjustments for comorbidities and complications. Finally, we conclude that nonalcoholic LC patients with CAD exhibit a favorable outcome.

Research perspectives

Future prospective research should focus on the advantages and disadvantages of antiplatelet therapy in the prevention of CAD in nonalcoholic LC patients. Additionally, it is advised that future studies should compare alcoholic and nonalcoholic LC cohorts and evaluate the effect of viral treatment.