The risk of venous thromboembolism in patients with hepatitis C

Pasquale Ambrosino; Luciano Tarantino; Livio Criscuolo; Aurelio Nasto; Aldo Celentano; Matteo Nicola Dario Di Minno

doi:10.1160/TH16-03-0185

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2016; 116(05): 958-966
DOI: 10.1160/TH16-03-0185

Stroke, Systemic or Venous Thromboembolism

Schattauer GmbH

The risk of venous thromboembolism in patients with hepatitis C

A systematic review and meta-analysis

Pasquale Ambrosino

¹Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy

,

Luciano Tarantino

²Department of Surgery, Interventional Hepatology Unit, Andrea Tortora Hospital, Pagani, Italy

,

Livio Criscuolo

¹Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy

,

Aurelio Nasto

³Department of Surgery, Unit of General Surgery and Oncology, Andrea Tortora Hospital, Pagani, Italy

,

Aldo Celentano

¹Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy

,

Matteo Nicola Dario Di Minno

⁴Department of Advanced Biomedical Sciences, Division of Cardiology, Federico II University, Naples, Italy

⁵Centro Cardiologico Monzino, IRCCS, Milan, Italy

› Author Affiliations

Abstract

Summary

Some studies suggest that patients with hepatitis C virus (HCV) infection have an increased risk of deep venous thrombosis (DVT) and pulmonary embolism (PE). Unfortunately, available data on this association are contrasting. A systematic review and meta-analysis of literature studies was performed to evaluate the risk of venous thromboembolism (VTE) associated with HCV. Studies reporting on VTE risk associated with HCV were systematically searched in the PubMed, Web of Science, Scopus and EMBASE databases. Six studies (10 data-sets) showed a significantly increased VTE risk in 100,364 HCV patients as compared with 8,471,176 uninfected controls (odds ratio [OR]: 1.900; 95 % confidence interval [CI]: 1.406, 2.570; p<0.0001). These results were confirmed when specifically considering the risk of DVT (6 studies, OR: 1.918; 95 %CI: 1.351, 2.723; p<0.0001), whereas a trend towards an increased risk of PE was documented in HCV patients (4 studies, OR: 1.811; 95 %CI: 0.895, 3.663; p=0.099). The increased VTE risk associated with HCV infection was consistently confirmed when analysing four studies reporting adjusted risk estimates (OR: 1.876; 95 %CI: 1.326, 2.654; P<0.0001), and after excluding studies specifically enrolling populations exposed to transient risk factors for VTE (4 studies, OR: 1.493; 95 %CI: 1.167, 1.910; p=0.001). Meta-regression models suggested that age and male gender may significantly impact on the risk of VTE associated with HCV-positivity. Results of our metaanalysis suggest that HCV-infected subjects may exhibit an increased risk of VTE. However, further high quality studies are needed to extend and confirm our findings.

Supplementary Material to this article is available online at www.thrombosis-online.com.

Keywords

Hepatitis C - viral hepatitis - deep venous thrombosis - pulmonary embolism - venous thromboembolism

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References

References
1 Wasley A, Alter MJ. Epidemiology of hepatitis C: geographic differences and temporal trends. Semin Liver Dis 2000; 20: 1e16.
2 Lauer GM, Walker BD. Hepatitis C virus infection. N Engl J Med 2001; 345: 41-52.
3 Conry-Cantilena C, VanRaden M, Gibble J. et al. Routes of infection, viremia, and liver disease in blood donors found to have hepatitis C virus infection. N Engl J Med 1996; 334: 1691-1696.
4 Seeff LB. Natural history of chronic hepatitis C. Hepatology 2002; 36: S35-S46.
5 Zignego AL, Craxi A. Extrahepatic manifestations of hepatitis C virus infection. Clin Liver Dis 2008; 12: 611-636.
6 Khattab MA, Eslam M, Alavian SM. Hepatitis C virus as a multifaceted disease: a simple and updated approach for extrahepatic manifestations of hepatitis C virus infection. Hepat Mon 2010; 10: 258e69.
7 Durante-Mangoni E, Iardino P, Resse M. et al. Silent celiac disease in chronic hepatitis C: impact of interferon treatment on the disease onset and clinical outcome. J Clin Gastroenterol 2004; 38: 901e5.
8 Goeijenbier M, van Wissen M, van de Weg C. et al. Review: Viral infections and mechanisms of thrombosis and bleeding. J Med Virol 2012; 84: 1680-1696.
9 Negro F. Facts and fictions of HCV and comorbidities: steatosis, diabetes mellitus, and cardiovascular diseases. J Hepatol 2014; 61: S69-78.
10 Enger C, Forssen UM, Bennett D. et al. Thromboembolic events among patients with hepatitis C virus infection and cirrhosis: a matched-cohort study. Adv Ther 2014; 31: 891-903.
11 Petta S, Macaluso FS, Craxì A. Cardiovascular diseases and HCV infection: a simple association or more?. Gut 2014; 63: 369-375.
12 Petta S, Maida M, Macaluso FS. et al. Hepatitis C Virus Infection Is Associated With Increased Cardiovascular Mortality: A Meta-Analysis of Observational Studies. Gastroenterology 2016; 150: 145-155 e4.
13 He Huang, Kang R, Zhao Z. Hepatitis C virus infection and risk of stroke: a systematic review and meta-analysis. PLoS One 2013; 08: e81305.
14 RostamiJalilian M, Omid Ghaemi M. et al. Relationship of hepatitis B and C with deep vein thrombosis in IV drug abusers. J Mil Med 2006; 08: 78-81.
15 Wang CC, Chang CT, Lin CL. et al. Hepatitis C virus infection associated with an increased risk of deep vein thrombosis: a population-based cohort study. Medicine 2015; 94: e1585.
16 Galli L, Gerdes VE, Guasti L. et al. Thrombosis Associated with Viral Hepatitis. J Clin Transl Hepatol 2014; 02: 234-239.
17 Moher D, Liberati A, Tetzlaff J. et al. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLOS Med 2009; 06: e1000097.
18 Juni P, Witschi A, Bloch R. et al. The hazards of scoring the quality of clinical trials for meta-analysis. J Am Med Assoc 1999; 282: 1054-1060.
19 Higgins JP, Thompson SG, Deeks JJ. et al. Measuring inconsistency in meta-analyses. Br Med J 2003; 327: 557-560.
20 Sterne JA, Egger M, Smith GD. Systematic reviews in health care: investigating and dealing with publication and other biases in meta-analysis. Br Med J 2001; 323: 101-105.
21 Duval S, Tweedie R. Trim and fill: A simple funnel-plot-based method of testing and adjusting for publication bias in meta-analysis. Biometrics 2000; 56: 455-463.
22 Ahmed S, Mehta V, Vendetti N. et al. Risk of venous thromboembolism (VTE) in patients with chronic hepatitis C (CHC). Pharmacoepidemiol Drug Saf 2012; 21: 1-481.
23 Best MJ, Buller LT, Klika AK. et al. Increase in perioperative complications following primary total hip and knee arthroplasty in patients with hepatitis C without cirrhosis. J Arthroplasty 2015; 30: 663-668.
24 El Bokl MA, Shawky A, Riad GS. Abdel et al. Procoagulant versus anticoagulant factors in cirrhotic patients. Arab J Gastroenterol 2014; 15: 123-129.
25 Qi X, Ren W, Guo X. et al. Epidemiology of venous thromboembolism in patients with liver diseases: a systematic review and meta-analysis. Intern Emerg Med 2015; 10: 205-217.
26 Ha NB, Regal RE. Anticoagulation in Patients With Cirrhosis: Caught Between a Rock-Liver and a Hard Place. Ann Pharmacother 2016; 50: 402-409.
27 Engbers MJ, van Hylckama Vlieg A. et al. Venous thrombosis in the elderly: incidence, risk factors and risk groups. J Thromb Haemost 2010; 08: 2105-2112.
28 Roach RE, Lijfering WM, Tait RC. et al. Sex difference in the risk of recurrent venous thrombosis: a detailed analysis in four European cohorts. J Thromb Haemost 2015; 13: 1815-1822.
29 Zampino R, Marrone A, Restivo L. et al. Chronic HCV infection and inflammation: clinical impact on hepatic and extra-hepatic manifestations. World J Hepatol 2013; 05: 528-540.
30 Lesmana CR, Inggriani S, Cahyadinata L. et al. Deep vein thrombosis in patients with advanced liver cirrhosis: a rare condition?. Hepatol Int 2010; 04: 433-438.
31 Tripodi A, Mannucci PM. The coagulopathy of chronic liver disease. N Engl J Med 2011; 365: 147-156.
32 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: 1524-1528.
33 Lisman T, Porte RJ. Rebalanced hemostasis in patients with liver disease: evidence and clinical consequences. Blood 2010; 116: 878-885.
34 Ambrosino P, Lupoli R, Tarantino P. et al. Viral hepatitis and anti-phospholipid antibodies positivity: A systematic review and meta-analysis. Dig Liver Dis 2015; 47: 478-487.
35 Ambrosino P, Lupoli R, Spadarella G. et al. Autoimmune liver diseases and antiphospholipid antibodies positivity: a meta-analysis of literature studies. J Gastrointestin Liver Dis 2015; 24: 25-34.
36 Yadav D, Hertan HI, Schweitzer P. et al. Serum and liver micronutrient antioxidants and serum oxidative stress in patients with chronic hepatitis C. Am J Gastroenterol 2002; 97: 2634-2639.
37 Jacobson Brown PM, Neuman MG. Immunopathogenesis of hepatitis C viral infection: Th1/Th2 responses and the role of cytokines. Clin Biochem 2001; 34: 167-171.
38 Oliveira CP, Kappel CR, Siqueira ER. et al. Effects of hepatitis C virus on cardiovascular risk in infected patients: a comparative study. Int J Cardiol 2013; 164: 221-226.
39 Opal SM. Interactions between coagulation and inflammation. Scand J Infect Dis 2003; 35: 545-554.
40 Tarantino L, Ambrosino P, Di Minno MN. Contrast-enhanced ultrasound in differentiating malignant from benign portal vein thrombosis in hepatocellular carcinoma. World J Gastroenterol 2015; 21: 9457-9460.
41 Kralj D, Virović Jukić L. et al. Hepatitis C Virus, Insulin Resistance, and Steatosis. J Clin Transl Hepatol 2016; 04: 66-75.

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