Association between liver fibrosis and thrombotic or bleeding events in acute coronary syndrome patients

Thrombosis Journal
Yupeng Liu1, Jingjing Song2, Wenyao Wang3, Kuo Zhang2, Jie Yang2, Jun Wen2, Xiaoxue Meng3, Jun Gao3, Jingjia Wang3, Chunli Shao4, Yi‐Da Tang3
1Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
2Department of Cardiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
3Department of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital, Beijing, China
4Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, China

Tóm tắt

AbstractBackgroundThe prognostic implication of liver fibrosis in acute coronary syndrome (ACS) patients are scarce. We sought to evaluate whether liver fibrosis scores (LFS) were associated with thrombotic or bleeding events in patients with acute coronary syndrome.MethodsWe included 6386 ACS patients who underwent percutaneous coronary intervention (PCI). This study determined liver fibrosis with aspartate aminotransferase to platelet ratio index (APRI), aspartate aminotransferase to alanine aminotransferase ratio (AST/ALT ratio), Forns score, and nonalcoholic fatty liver disease fibrosis score (NFS). The primary endpoint was major adverse cardiac and cerebrovascular events (MACCE), a composite of all-cause mortality (ACM), myocardial infarction (MI), and ischemic stroke (IS).ResultsDuring the follow-up, 259 (4.06%) MACCE and 190 (2.98%) bleeding events were recorded. As a continuous variable or a categorical variable stratified by the literature-based cutoff, LFS was positively associated with MACCE (p > 0.05) but not with bleeding events. Compared with subjects with low APRI scores, AST/ALT ratio scores, Forns scores, and NFS scores, subjects with high scores had a 1.57- to 3.73-fold increase risk of MACCE after adjustment (allp < 0.05). The positive relationship between LFS and MACCE was consistent in different subgroups.ConclusionsIn ACS patients, increased LFS predicted an elevated risk of thrombotic events but not bleeding. LFS may contribute to thrombotic risk stratification after ACS.

Từ khóa


Tài liệu tham khảo

Neumann F-J, Sousa-Uva M, Ahlsson A, Alfonso F, Banning AP, Benedetto U, et al. 2018 ESC/EACTS Guidelines on myocardial revascularization. Eur Heart J. 2019;40:87–165.

Moon AM, Singal AG, Tapper EB. Contemporary epidemiology of chronic liver disease and cirrhosis. Clin Gastroenterol Hepatol. 2020;18:2650–66.

Karsdal MA, Manon-Jensen T, Genovese F, Kristensen JH, Nielsen MJ, Sand JMB, et al. Novel insights into the function and dynamics of extracellular matrix in liver fibrosis. Am J Physiol Gastrointest Liver Physiol. 2015;308:G807–30.

Caballería L, Pera G, Arteaga I, Rodríguez L, Alumà A, Morillas RM, et al. High prevalence of liver fibrosis among European adults with unknown liver disease: a population-based study. Clin Gastroenterol Hepatol. 2018;16:1138–1145.e5.

Ishiba H, Sumida Y, Kataoka S, Kuroda M, Akabame S, Tomiyasu K, et al. Association of coronary artery calcification with liver fibrosis in Japanese patients with non-alcoholic fatty liver disease. Hepatol Res. 2016;46:1107–17.

You SC, Kim KJ, Kim SU, Kim BK, Park JY, Kim DY, et al. Hepatic fibrosis assessed using transient elastography independently associated with coronary artery calcification: liver stiffness and coronary calcification. J Gastroenterol Hepatol. 2015;30:1536–42.

Jin J-L, Zhang H-W, Cao Y-X, Liu H-H, Hua Q, Li Y-F, et al. Liver fibrosis scores and coronary atherosclerosis: novel findings in patients with stable coronary artery disease. Hepatol Int. 2021;15:413–23.

Bravo AA, Sheth SG, Chopra S. Liver Biopsy. N Engl J Med. 2001;344:495–500.

Ratziu V, Charlotte F, Heurtier A, Gombert S, Giral P, Bruckert E, et al. Sampling variability of liver biopsy in nonalcoholic fatty liver disease. Gastroenterology. 2005;128:1898–906.

Hagström H, Talbäck M, Andreasson A, Walldius G, Hammar N. Ability of noninvasive scoring systems to identify individuals in the population at risk for severe liver disease. Gastroenterology. 2020;158:200–14.

Naveau S, Gaudé G, Asnacios A, Agostini H, Abella A, Barri-Ova N, et al. Diagnostic and prognostic values of noninvasive biomarkers of fibrosis in patients with alcoholic liver disease. Hepatology. 2009;49:97–105.

Wai C. A simple noninvasive index can predict both significant fibrosis and cirrhosis in patients with chronic hepatitis C. Hepatology. 2003;38:518–26.

Forns X, Ampurdanès S, Llovet JM, Aponte J, Quintó L, Martínez-Bauer E, et al. Identification of chronic hepatitis C patients without hepatic fibrosis by a simple predictive model: identification of chronic hepatitis C patients without hepatic fibrosis by a simple predictive model. Hepatology. 2002;36:986–92.

Sheth SG, Flamm SL, Gordon FD, Chopra S. AST/ALT ratio predicts cirrhosis in patients with chronic hepatitis C virus infection. Am J Gastroenterol. 1998;93:44–8.

Angulo P, Hui JM, Marchesini G, Bugianesi E, George J, Farrell GC, et al. The NAFLD fibrosis score: a noninvasive system that identifies liver fibrosis in patients with NAFLD. Hepatology. 2007;45:846–54.

McPherson S, Stewart SF, Henderson E, Burt AD, Day CP. Simple non-invasive fibrosis scoring systems can reliably exclude advanced fibrosis in patients with non-alcoholic fatty liver disease. Gut. 2010;59:1265–9.

AST/ALT Ratio [Internet]. Standard of Care. Available from: https://standardofcare.com/ast-alt-ratio/

Mehran R, Rao SV, Bhatt DL, Gibson CM, Caixeta A, Eikelboom J, et al. Standardized bleeding definitions for cardiovascular clinical trials: a consensus report from the bleeding academic research consortium. Circulation. 2011;123:2736–47.

Tamaki N, Kurosaki M, Takahashi Y, Itakura Y, Inada K, Kirino S, et al. Liver fibrosis and fatty liver as independent risk factors for cardiovascular disease. J Gastroenterol Hepatol. 2021;36:2960–6.

Angulo P, Kleiner DE, Dam-Larsen S, Adams LA, Bjornsson ES, Charatcharoenwitthaya P, et al. Liver fibrosis, but no other histologic features, is associated with long-term outcomes of patients with nonalcoholic fatty liver disease. Gastroenterology. 2015;149:389–397.e10.

Ekstedt M, Hagström H, Nasr P, Fredrikson M, Stål P, Kechagias S, et al. Fibrosis stage is the strongest predictor for disease-specific mortality in NAFLD after up to 33 years of follow-up. Hepatology. 2015;61:1547–54.

Siddiqui MS, Fuchs M, Idowu MO, Luketic VA, Boyett S, Sargeant C, et al. Severity of nonalcoholic fatty liver disease and progression to cirrhosis are associated with atherogenic lipoprotein profile. Clin Gastroenterol Hepatol. 2015;13:1000–1008.e3.

Villanova N, Moscatiello S, Ramilli S, Bugianesi E, Magalotti D, Vanni E, et al. Endothelial dysfunction and cardiovascular risk profile in nonalcoholic fatty liver disease. Hepatology. 2005;42:473–80.

Møller S, Bernardi M. Interactions of the heart and the liver. Eur Heart J. 2013;34:2804–11.

Lonardo A, Nascimbeni F, Mantovani A, Targher G. Hypertension, diabetes, atherosclerosis and NASH: cause or consequence? J Hepatol. 2018;68:335–52.

Henson JB, Simon TG, Kaplan A, Osganian S, Masia R, Corey KE. Advanced fibrosis is associated with incident cardiovascular disease in patients with non-alcoholic fatty liver disease. Aliment Pharmacol Ther. 2020;51:728–36.

Kim D, Kim WR, Kim HJ, Therneau TM. Association between noninvasive fibrosis markers and mortality among adults with nonalcoholic fatty liver disease in the United States. Hepatology. 2013;57:1357–65.

Unalp-Arida A, Ruhl CE. Liver fibrosis scores predict liver disease mortality in the United States population: Unalp-Arida and Ruhl. Hepatology. 2017;66:84–95.

Chun HS, Lee JS, Lee HW, Kim BK, Park JY, Kim DY, et al. Association between the severity of liver fibrosis and cardiovascular outcomes in patients with type 2 diabetes. J Gastroenterol Hepatol. 2021;36:1703–13.

Parikh NS, Kamel H, Navi BB, Iadecola C, Merkler AE, Jesudian A, et al. Liver fibrosis indices and outcomes after primary intracerebral hemorrhage. Stroke. 2020;51:830–7.

Fandler-Höfler S, Stauber RE, Kneihsl M, Wünsch G, Haidegger M, Poltrum B, et al. Non-invasive markers of liver fibrosis and outcome in large vessel occlusion stroke. Ther Adv Neurol Disord. 2021, 2022 Jan; http://journals.sagepub.com/doi/10.1177/17562864211037239.

Chang Y, Ryu S, Sung K-C, Cho YK, Sung E, Kim H-N, et al. Alcoholic and non-alcoholic fatty liver disease and associations with coronary artery calcification: evidence from the Kangbuk Samsung health study. Gut. 2019;68:1667–75.

Sigon G, D’Ambrosio R, Clerici M, Pisano G, Chantarangkul V, Sollazzi R, et al. Procoagulant imbalance influences cardiovascular and liver damage in chronic hepatitis C independently of steatosis. Liver Int. 2019;39:2309–16.

Tripodi A, Fracanzani AL, Primignani M, Chantarangkul V, Clerici M, Mannucci PM, et al. Procoagulant imbalance in patients with non-alcoholic fatty liver disease. J Hepatol. 2014;61:148–54.

Northup PG, Argo CK, Shah N, Caldwell SH. Hypercoagulation and thrombophilia in nonalcoholic fatty liver disease: mechanisms, human evidence, therapeutic implications, and preventive implications. Semin Liver Dis. 2012;32:39–48.

Northup PG, Sundaram V, Fallon MB, Reddy KR, Balogun RA, Sanyal AJ, et al. Hypercoagulation and thrombophilia in liver disease. J Thromb Haemost. 2008;6:2–9.

Thông tin
Thông tin xuất bản

Thrombosis Journal

Thông tin tác giả