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Comparison of cardiovascular outcomes and all-cause mortality in patients with chronic hepatitis B and C: A 13-year nationwide population-based study in Asia

      Highlights

      • Viral infections have been linked to atherosclerosis and cardiovascular events.
      • Inconsistent study results reported regarding the atherosclerotic potential by viral hepatitis B and C.
      • There exist no direct comparison for the effect of viral hepatitis B and C on atherosclerosis.
      • Patients with HCV had significantly increased risks in cardiovascular events compared to patients with HBV.

      Abstract

      Background and aims

      Viral hepatitis infection has been linked to increased atherosclerosis. We therefore investigated cardiovascular outcomes in patients with hepatitis B virus (HBV) and hepatitis C virus (HCV) infection.

      Methods

      Electronic medical records during 2000–2012 were retrieved from the Taiwan National Health Insurance Research Database. Exclusion criteria were age <18, history of coexisting HBV and HCV infection, acute coronary syndrome, coronary intervention, venous thromboembolism, peripheral artery disease, stroke, major or gastrointestinal bleeding, malignancy, and a follow-up period <180 days. Patients with HBV and HCV infection were propensity-matched then compared for outcomes. Primary outcomes were cardiovascular events at the 1-year follow-up, 3-year follow-up, 5-year follow-up, and at the end of follow-up.

      Results

      41,554 patients with diagnosis of HBV or HCV were retrieved from 2000 to 2012. After exclusion criteria, 31,943 patients were eligible for analysis and propensity score matched. The study population consisted of 6030 patients with HBV infection and 6030 patients with HCV infection. Risk of composite arterial events (acute coronary syndrome, peripheral artery disease, and acute ischemic stroke) was significantly higher in patients with HCV infection compared with patients with HBV infection (p = 0.012 at 5-year follow-up and p = 0.003 at the end of follow-up). All-cause mortality was significantly higher in patients with HCV infection compared with patients with HBV infection (p < 0.001 at 3-year follow-up, 5-year follow-up, and at the end of follow-up).

      Conclusions

      In patients with chronic viral hepatitis, subjects with HCV infection had a significantly higher risk of composite arterial events and all-cause mortality compared with those with HBV infection.

      Keywords

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      References

        • Epstein S.E.
        • Zhou Y.F.
        • Zhu J.
        Infection and atherosclerosis: emerging mechanistic paradigms.
        Circulation. 1999; 100: e20-e28
        • Rosenfeld M.E.
        • Campbell
        Pathogens and atherosclerosis - update on the potential contribution of multiple infectious organisms to the pathogenesis of atherosclerosis.
        Thromb. Haemostasis. 2011; 106: 858-867
        • Voorend M.
        • Faber C.G.
        • van der Ven A.J.
        • Kessels F.
        • Bruggeman C.A.
        • Lodder J.
        Chlamydia pneumoniae is likely a risk factor for ischemic stroke in young patients.
        J. Stroke Cerebrovasc. Dis. 2004; 13: 85-91
        • Tabib A.
        • Leroux C.
        • Mornex J.F.
        • Loire R.
        Accelerated coronary atherosclerosis and arteriosclerosis in young human-immunodeficiency-virus-positive patients.
        Coron. Artery Dis. 2000; 11: 41-46
        • Boehme A.K.
        • Ranawat P.
        • Luna J.
        • Kamel H.
        • Elkind M.S.
        Risk of acute stroke after hospitalization for sepsis: a case-crossover study.
        Stroke. 2017; 48: 574-580
        • Wang H.E.
        • Moore J.X.
        • Donnelly J.P.
        • Levitan E.B.
        • Safford M.M.
        Risk of acute coronary heart disease after sepsis hospitalization in the reasons for geographic and racial differences in stroke cohort.
        Clin. Infect. Dis. 2017 Mar 23; ([Epub ahead of print])https://doi.org/10.1093/cid/cix248
        • Zhou Y.F.
        • Shou M.
        • Guetta E.
        • Guzman R.
        • Unger E.F.
        • Yu Z.X.
        • Zhang J.
        • Finkel T.
        • Epstein S.E.
        Cytomegalovirus infection of rats increases the neointimal response to vascular injury without consistent evidence of direct infection of the vascular wall.
        Circulation. 1999; 100: 1569-1575
        • Tanaka K.
        • Zou J.P.
        • Takeda K.
        • Ferrans V.G.
        • Sandford G.R.
        • Johnson T.M.
        • Finkel T.
        • Epstein S.E.
        Effects of human cytomegalovirus immediate-early proteins on p53-mediated apoptosis in coronary artery smooth muscle cells.
        Circulation. 1999; 99: 1656-1659
        • Chuib B.
        • Viira E.
        • Tucker W.
        • Fong I.W.
        Chlamydia pneumoniae, cytomegalovirus, and herpes simplex virus in atherosclerosis of the carotid artery.
        Circulation. 1997; 96: 2144-2148
        • Nicholson A.C.
        • Hajjar D.P.
        Herpesvirus in atherosclerosis and thrombosis: etiologic agents or ubiquitous bystanders?.
        Arterioscler. Thromb. Vasc. Biol. 1998; 18: 339-348
        • Zhu J.
        • Quyyumi A.A.
        • Norman J.E.
        • Costello R.
        • Csako G.
        • Epstein S.E.
        The possible role of hepatitis A virus in the pathogenesis of atherosclerosis.
        J. Infect. Dis. 2000; 182: 1583-1587
        • Ishizaka N.
        • Ishizaka Y.
        • Takahashi E.
        • et al.
        Increased prevalence of carotid atherosclerosis in hepatitis B virus carriers.
        Circulation. 2002; 105: 1028-1030
        • Ishizaka N.
        • Ishizaka Y.
        • Takahashi E.
        • et al.
        Association between hepatitis C virus seropositivity, carotid-artery plaque, and intima-media thickening.
        Lancet. 2002; 359: 133-135
        • Sung J.
        • Song Y.M.
        • Choi Y.H.
        • et al.
        Hepatitis B virus seropositivity and the risk of stroke and myocardial infarction.
        Stroke. 2007; 38: 1436-1441
        • Butt A.A.
        • Xiaoqiang W.
        • Budoff M.
        • Leaf D.
        • Kuller L.H.
        • Justice A.C.
        Hepatitis C virus infection and the risk of coronary disease.
        Clin. Infect. Dis. 2009; 49: 225-232
        • Vӧlzke H.
        • Schwahn C.
        • Wolff B.
        • Mentel R.
        • Robinson D.M.
        • Kleine V.
        • Felix S.B.
        • John U.
        Hepatitis B and C virus infection and the risk of atherosclerosis in a general population.
        Atherosclerosis. 2014; 174: 99-103
      1. National Health Insurance Research Database, Taiwan. https://nhird.nhri.org.tw/en/Data_Subsets.html.

        • Wu C.Y.
        • Chen Y.J.
        • Ho H.J.
        • Hsu Y.C.
        • Kuo K.N.
        • Wu M.S.
        • Lin J.T.
        Association between nucleoside analogues and risk of hepatitis B virus-related hepatocellular carcinoma recurrence following liver resection.
        JAMA. 2012; 308: 1906-1914
        • Fine J.P.
        • Gray R.J.
        A proportional hazards model for the subdistribution of a competing risk.
        J. Am. Stat. Assoc. 1999; 94: 496-509
        • Frothingham C.
        The relationship between acute infectious diseases and arterial lesions.
        Arch. Intern. Med. 1911; 8: 153-162
        • Ophuls W.
        Arteriosclerosis and cardiovascular disease: their relation to infectious diseases.
        JAMA. 1921; 76: 700-701
        • Minick C.R.
        • Fabricant C.G.
        • Fabricant J.
        • Litrenta M.M.
        Atheroarteriosclerosis induced by infection with a herpesvirus.
        Am. J. Pathol. 1979; 96: 673-706
        • Fabricant C.G.
        • Hajjar D.P.
        • Minick C.R.
        • Fabricant J.
        Herpesvirus infection enhances cholesterol and cholesteryl ester accumulation in cultured arterial smooth muscle cells.
        Am. J. Pathol. 1981; 105: 176-184
        • Kleindienst R.
        • Xu Q.
        • Willeit J.
        • Waldenberger F.R.
        • Wimann S.
        • Wick G.
        Immunology of atherosclerosis demonstration of heat shock protein and T-lymphocytes bearing α/β or γ/δ receptor in human atherosclerotic lesions.
        Am. J. Pathol. 1993; 142: 1927-1937
        • Xu Q.
        • Luef G.
        • Weimann S.
        • Gupta R.S.
        • Wolf H.
        • Wick G.
        Staining of endothelial cells and macrophages in atherosclerotic lesions with human heat-shock protein-reactive antisera.
        Arterioscler. Thromb. 1993; 13: 1763-1769
        • Stemme S.
        • Faber B.
        • Holm J.
        • Wiklund O.
        • Witztum J.L.
        • Hansson G.K.
        T lymphocytes from human atherosclerotic plaques recognize oxidized LDL.
        Proc. Natl. Acad. Sci. U. S. A. 1995; 92: 3892-3897
        • Taylor-Wiedeman J.
        • Sissons J.P.
        • Sinclair J.H.
        Induction of endogenous cytomegalovirus gene expression after differentiation of monocytes from healthy carriers.
        J. Virol. 1994; 68: 1597-1604
        • Guetta E.
        • Guetta V.
        • Shibutani T.
        • Epstein S.E.
        Monocytes harboring cytomegalovirus: interactions with endothelial cells, smooth muscle cells and oxidized low density lipoprotein: possible mechanisms for activating virus delivered by monocytes to sites of vascular injury.
        Circ. Res. 1997; 81: 8-16
        • Epstein S.E.
        • Zhu J.
        • Najafi A.H.
        • Burnett M.S.
        Insights into the role of infection in plaque rupture.
        Circulation. 2009; 119: 3133-3141
        • Wang C.H.
        • Chen C.J.
        • Lee M.H.
        • Yang H.I.
        • Hsiao C.K.
        Chronic hepatitis B infection and risk of atherosclerosis-related mortality: a 17-year follow-up study based on 22,472 residents in Taiwan.
        Atherosclerosis. 2010; 211: 624-629
        • Yaqin Wang
        • Jianping Xiong
        • Xi Chen
        • Meng Niu
        • Xiaowei Chen
        • Yuheng Guan
        • Kechuang Zheng
        • Ke Xu
        Hepatitis virus infection and decreased risk of stroke: a meta-analysis.
        Oncotarget. 2017; 8: 59658-59665
        • Petta S.
        • Maida M.
        • Macaluso F.S.
        • Barbara M.
        • Licata A.
        • Craxì A.
        • Cammà C.
        Hepatitis C virus infection is associated with increased cardiovascular mortality: a meta-analysis of observational studies.
        Gastroeneterology. 2016; 150: 145-155

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