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Thromboembolic Events Among Patients with Hepatitis C Virus Infection and Cirrhosis: A Matched-Cohort Study

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Abstract

Introduction

Portal vein thrombosis is a known risk among patients with cirrhosis, but the incidence of other thromboembolic events among patients with liver disease is inadequately delineated. This study examined the incidence of venous and arterial thromboembolic events in patients with cirrhosis and hepatitis C virus (HCV) infection and matched comparators.

Methods

Patients diagnosed with HCV or cirrhosis of various etiologies were identified from a large medical claims database and matched by age and sex to comparator cohorts. New-onset diagnoses of venous and arterial thromboembolic events were determined. The incidence rate of each event was calculated and rate ratios computed using Poisson regression models, adjusting for baseline factors.

Results

The study included 22,733 HCV-infected patients and 68,198 comparators, and 15,158 cirrhosis patients and 45,473 comparators. The incidence of any thromboembolic event was 233.4 events per 10,000 person-years for the HCV cohort and 138.5 per 10,000 person-years for the comparators; the adjusted incidence rate ratio for any thromboembolic event was 1.62 (95% confidence interval [CI]: 1.48–1.77). For the cirrhosis patients and comparators, the crude rates of any thromboembolic event were 561.1 and 249.7 per 10,000 person-years, respectively. The adjusted incidence rate ratio was 2.28 (95% CI: 2.11–2.47). Arterial events, especially unstable angina and transient ischemic attack, were the most frequent events seen in both the HCV and cirrhosis cohorts, but venous events, especially portal vein thrombosis, showed a more pronounced elevation in patients with liver disease.

Conclusions

Patients with HCV and cirrhosis of various etiologies are at increased risk of several types of thromboembolic events. Physicians should consider this increased risk when managing patients with liver disease.

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References

  1. Miniño AM, Heron MP, Murphy SL, Kochankek KD. Deaths: final data for 2004. National vital statistics reports. Hyattsville: National Center for Health Statistics. 2007;55(19).

  2. Saadatmand F, Stinson FS, Grant BF, Dufour MC. Surveillance report #48: liver cirrhosis mortality in the United States, 1970–1995. Rockville: National Institute on Alcohol Abuse and Alcoholism, Division of Biometry and Epidemiology; 1998.

    Google Scholar 

  3. National Digestive Diseases Information Clearinghouse. http://digestive.niddk.nih.gov/.

  4. Lisman T, Leebeek FW. Hemostatic alterations in liver disease: a review on pathophysiology, clinical consequences, and treatment. Dig Surg. 2007;24:250–8.

    Article  PubMed  Google Scholar 

  5. Northup PG, Sundaram V, Fallon MB, et al. Hypercoagulation and thrombophilia in liver disease. J Thromb Haemost. 2008;6:2–9.

    CAS  PubMed  Google Scholar 

  6. Peck-Radosavljevic M. Review article: coagulation disorders in chronic liver disease. Aliment Pharmacol Ther. 2007;26(Suppl 1):21–8.

    Article  CAS  PubMed  Google Scholar 

  7. Amitrano L, Guardascione MA, Brancaccio V, et al. Risk factors and clinical presentation of portal vein thrombosis in patients with liver cirrhosis. J Hepatol. 2004;40:736–41.

    Article  PubMed  Google Scholar 

  8. Amitrano L, Guardascione MA, Ames PR. Coagulation abnormalities in cirrhotic patients with portal vein thrombosis. Clin Lab. 2007;53:583–9.

    PubMed  Google Scholar 

  9. Senzolo M, Sartori MT, Lisman T. Should we give thromboprophylaxis to patients with liver cirrhosis and coagulopathy? HPB (Oxford). 2009;11:459–64.

    Article  PubMed Central  PubMed  Google Scholar 

  10. Gulley D, Teal E, Suvannasankha A, Chalasani N, Liangpunsakul S. Deep vein thrombosis and pulmonary embolism in cirrhosis patients. Dig Dis Sci. 2008;53:3012–7.

    Article  PubMed  Google Scholar 

  11. Lesmana CR, Inggriani S, Cahyadinata L, Lesmana LA. Deep vein thrombosis in patients with advanced liver cirrhosis: a rare condition? Hepatol Int. 2010;4:433–8.

    Article  PubMed Central  PubMed  Google Scholar 

  12. Northup PG, McMahon MM, Ruhl AP, et al. Coagulopathy does not fully protect hospitalized cirrhosis patients from peripheral venous thromboembolism. Am J Gastroenterol. 2006;101:1524–8.

    Article  PubMed  Google Scholar 

  13. Berzigotti A, Bonfiglioli A, Muscari A, et al. Reduced prevalence of ischemic events and abnormal supraortic flow patterns in patients with liver cirrhosis. Liver Int. 2005;25:331–6.

    Article  PubMed  Google Scholar 

  14. Heit JA, Silverstein MD, Mohr DN, Petterson TM, O’Fallon WM, Melton LJ 3rd. Risk factors for deep vein thrombosis and pulmonary embolism: a population-based case–control study. Arch Intern Med. 2000;160:809–15.

    Article  CAS  PubMed  Google Scholar 

  15. Huerta C, Johansson S, Wallander MA, Garcia Rodriguez LA. Risk factors and short-term mortality of venous thromboembolism diagnosed in the primary care setting in the United Kingdom. Arch Intern Med. 2007;167:935–43.

    Article  PubMed  Google Scholar 

  16. Sogaard KK, Horvath-Puho E, Gronbaek H, Jepsen P, Vilstrup H, Sorensen HT. Risk of venous thromboembolism in patients with liver disease: a nationwide population-based case–control study. Am J Gastroenterol. 2009;104:96–101.

    Article  PubMed  Google Scholar 

  17. Forde KA, Haynes K, Troxel AB, et al. Risk of myocardial infarction associated with chronic hepatitis C virus infection: a population-based cohort study. J Viral Hepat. 2012;19:271–7.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  18. Alyan O, Kacmaz F, Ozdemir O, et al. Hepatitis C infection is associated with increased coronary artery atherosclerosis defined by modified Reardon severity score system. Circ J. 2008;72:1960–5.

    Article  PubMed  Google Scholar 

  19. Butt AA, Xiaoqiang W, Budoff M, Leaf D, Kuller LH, Justice AC. Hepatitis C virus infection and the risk of coronary disease. Clin Infect Dis. 2009;49:225–32.

    Article  PubMed Central  PubMed  Google Scholar 

  20. Adinolfi LE, Restivo L, Zampino R, et al. Chronic HCV infection is a risk of atherosclerosis. Role of HCV and HCV-related steatosis. Atherosclerosis. 2012;221:496–502.

    Article  CAS  PubMed  Google Scholar 

  21. Kakinami L, Block RC, Adams MJ, Cohn SE, Maliakkal B, Fisher SG. Risk of cardiovascular disease in HIV, hepatitis C, or HIV/hepatitis C patients compared to the general population. Int J Clin Pract. 2013;67:6–13.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  22. Maruyama S, Koda M, Oyake N, et al. Myocardial injury in patients with chronic hepatitis C infection. J Hepatol. 2013;58:11–5.

    Article  CAS  PubMed  Google Scholar 

  23. Lin MS, Guo SE, Chen MY, et al. The impact of hepatitis C infection on ischemic heart disease via ischemic electrocardiogram. Am J Med Sci. 2014;347:478–84.

    PubMed  Google Scholar 

  24. Arcari CM, Nelson KE, Netski DM, Nieto FJ, Gaydos CA. No association between hepatitis C virus seropositivity and acute myocardial infarction. Clin Infect Dis. 2006;43:e53–6.

    Article  PubMed  Google Scholar 

  25. Younossi ZM, Stepanova M, Nader F, Younossi Z, Elsheikh E. Associations of chronic hepatitis C with metabolic and cardiac outcomes. Aliment Pharmacol Ther. 2013;37:647–52.

    Article  CAS  PubMed  Google Scholar 

  26. Adinolfi LE, Restivo L, Guerrera B, et al. Chronic HCV infection is a risk factor of ischemic stroke. Atherosclerosis. 2013;231:22–6.

    Article  CAS  PubMed  Google Scholar 

  27. Karibe H, Niizuma H, Ohyama H, Shirane R, Yoshimoto T. Hepatitis C virus (HCV) infection as a risk factor for spontaneous intracerebral hemorrhage: hospital based case–control study. J Clin Neurosci. 2001;8:423–5.

    Article  CAS  PubMed  Google Scholar 

  28. Harmsen P, Wilhelmsen L, Jacobsson A. Stroke incidence and mortality rates 1987–2006 related to secular trends of cardiovascular risk factors in Gothenburg, Sweden. Stroke. 2009;40:2691–7.

    Article  PubMed  Google Scholar 

  29. Parikh NI, Gona P, Larson MG, et al. Long-term trends in myocardial infarction incidence and case fatality in the National Heart, Lung, and Blood Institute’s Framingham Heart study. Circulation. 2009;119:1203–10.

    Article  PubMed Central  PubMed  Google Scholar 

  30. Wattanakit K, Cushman M. Chronic kidney disease and venous thromboembolism: epidemiology and mechanisms. Curr Opin Pulm Med. 2009;15:408–12.

    Article  PubMed Central  PubMed  Google Scholar 

  31. White RH, Keenan CR. Effects of race and ethnicity on the incidence of venous thromboembolism. Thromb Res. 2009;123(Suppl 4):S11–7.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

Sponsorship and article processing charges for this study were funded by a contract between Optum, Ann Arbor, MI and GlaxoSmithKline (GSK), Collegeville, PA. The contract granted Optum full control of the study conduct, reporting and interpretation, as well as the final wording of any resulting manuscript. All named authors meet the ICMJE criteria for authorship for this manuscript, take responsibility for the integrity of the work as a whole, and have given final approval for the version to be published. The authors wish to acknowledge Ms. Claire Chiang, M.S. at Optum (i3 Drug Safety at the time the work was performed) for her contribution to the data analysis. Medical writing assistance for this study, in the form of development of draft outline and draft manuscript, assembling of tables and figures and referencing, was provided by Dr. Beth Nordstrom, PhD at Evidera (formerly United BioSource Corporation) and funded by GlaxoSmithKline (Collegeville, PA).

Conflict of interest

Cheryl Enger reports that this work was conducted under a contract between GlaxoSmithKline and Cheryl Enger’s institution, Optum. Ulla Forssen was an employee of GSK and a GSK shareholder, now works for CSL Behring. Dimitri Bennett is an employee of GSK and is a GSK shareholder. Sumitra Shantakumar is an employee of GSK and is a GSK shareholder. Dickens Theodore is an employee of GSK and is a GSK shareholder.

Compliance with ethics guidelines

The analysis in this article is based on previously conducted studies and does not involve any new studies of human or animal subjects performed by any of the authors.

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Author notes

  1. Ulla M. Forssen

    Present address: CSL Behring, 1020 1st Ave, King of Prussia, PA, 19406, USA

Authors and Affiliations

  1. Optum, 315 E. Eisenhower Parkway, Suite 305, Ann Arbor, MI, 48108, USA

    Cheryl Enger

  2. WorldWide Epidemiology, Research and Development, GlaxoSmithKline, 1250 S. Collegeville Road, Collegeville, PA, 19426, USA

    Ulla M. Forssen & Dimitri Bennett

  3. Clinical Development, Research and Development, GlaxoSmithKline, 5 Moore Drive, Research Triangle Park, NC, 27709, USA

    Dickens Theodore & Sumitra Shantakumar

  4. WorldWide Epidemiology, Research and Development, GlaxoSmithKline, 5 Moore Drive, Research Triangle Park, NC, 27709, USA

    Sumitra Shantakumar

  5. Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

    Andrew McAfee

Authors
  1. Cheryl Enger
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Corresponding author

Correspondence to Dimitri Bennett.

Additional information

Deceased: A. McAfee

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Enger, C., Forssen, U.M., Bennett, D. et al. Thromboembolic Events Among Patients with Hepatitis C Virus Infection and Cirrhosis: A Matched-Cohort Study. Adv Ther 31, 891–903 (2014). https://doi.org/10.1007/s12325-014-0138-4

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  • DOI: https://doi.org/10.1007/s12325-014-0138-4

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