Angiogenesis, Inflammation & Therapeutics | Online ISSN  2207-872X
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Hepatitis C and Atherosclerosis: Inflammatory Interplay

Anastasia V. Poznyak 1*, Ludmila V Nedosugova 2, Vasily N. Sukhorukov 3, Alexandra A. Melnichenko 3, Elizaveta M. Pleshko 3 and Alexander N. Orekhov 3

+ Author Affiliations

Journal of Angiotherapy 7(1) 1-10 https://doi.org/10.25163/angiotherapy.719361

Submitted: 18 October 2023  Revised: 20 November 2023  Published: 24 November 2023 

A review of the relationship between HCV infection, inflammation, and cardiovascular pathologies.

Abstract


Atherosclerosis along with viral hepatitis C are major health problems. Despite the fact that atherosclerosis is usually associated only with blood vessels, and hepatitis C with the liver, these diseases have a number of common features. The pathogenesis of atherosclerosis includes many different mechanisms, one of the central roles among which is inflammation. The importance of inflammation for the development of hepatitis is also difficult to overestimate. The precise mechanisms of action by which HCV stimulates development of atherosclerosis are still being investigated. Both direct and indirect consequences of HCV infection, such as persistent inflammation and impairments in glucose and lipid metabolism, are well known atherogenic conditions. In this review, we have tried to describe the interaction between hepatitis C and atherosclerosis, with a particular focus on inflammation.

Keywords: atherosclerosis; hepatitis C; HCV; liver disease.

References


Adinolfi LE, Petta S, Fracanzani AL, Coppola C, Narciso V, Nevola R, Rinaldi L, Calvaruso V, Staiano L, Di Marco V, Marrone A, Pafundi PC, Solano A, Lombardi R, Sasso FC, Saturnino M, Rini F, Guerrera B, Troina G, Giordano M, Craxì A. Impact of hepatitis C virus clearance by direct-acting antiviral treatment on the incidence of major cardiovascular events: A prospective multicentre study. Atherosclerosis. 2020 Mar;296:40-47. doi: 10.1016/j.atherosclerosis.2020.01.010. Epub 2020 Jan 21. PMID: 32005004.

Adinolfi LE, Restivo L, Zampino R, Guerrera B, Lonardo A, Ruggiero L, Riello F, Loria P, Florio A. Chronic HCV infection is a risk of atherosclerosis. Role of HCV and HCV-related steatosis. Atherosclerosis. 2012;221:496–502.

Arida A, Protogerou AD, Kitas GD, Sfikakis PP. Systemic Inflammatory Response and Atherosclerosis: The Paradigm of Chronic Inflammatory Rheumatic Diseases. Int J Mol Sci. 2018 Jun 27;19(7):1890. doi: 10.3390/ijms19071890. PMID: 29954107; PMCID: PMC6073407.

Asada, Y., Yamashita, A., Sato, Y., & Hatakeyama, K. (2020). Pathophysiology of atherothrombosis: Mechanisms of thrombus formation on disrupted atherosclerotic plaques. Pathology international, 70(6), 309–322. https://doi.org/10.1111/pin.12921

Ashraf MA, Nookala V. Biochemistry of Platelet Activating Factor. [Updated 2022 Apr 14]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK557392/

Babiker, A., Hassan, M., Muhammed, S., Taylor, G., Poonia, B., Shah, A., & Bagchi, S. (2020). Inflammatory and cardiovascular diseases biomarkers in chronic hepatitis C virus infection: A review. Clinical cardiology, 43(3), 222–234. https://doi.org/10.1002/clc.23299

Babiker, A., Jeudy, J., Kligerman, S., Khambaty, M., Shah, A., & Bagchi, S. (2017). Risk of Cardiovascular Disease Due to Chronic Hepatitis C Infection: A Review. Journal of clinical and translational hepatology, 5(4), 343–362. https://doi.org/10.14218/JCTH.2017.00021

Bilora F, Campagnolo E, Rinaldi R, Rossato A, Arzenton M, Petrobelli F. Carotid and femoral atherosclerosis in chronic hepatitis C: a 5-year follow-up. Angiology. 2008;59:717–720.

Biomy R, Abdelshafy M, Abdelmonem A, Abu-Elenin H, Ghaly G. Effect of Chronic Hepatitis C Virus Treatment by Combination Therapy on Cardiovascular System. Clin Med Insights Cardiol. 2017 Jun 22;11:1179546817713204. doi: 10.1177/1179546817713204. PMID: 28804248; PMCID: PMC5484549.

Boddi M, Abbate R, Chellini B, Giusti B, Solazzo V, Soft F, Pratesi G, Pratesi C, Gensini G, Zignego AL. HCV infection facilitates asymptomatic carotid atherosclerosis: preliminary report of HCV RNA localization in human carotid plaques. Dig Liver Dis. 2007;39 Suppl 1:S55–S60.

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;49:225–232.

Butt AA, Yan P, Shuaib A, Abou-Samra AB, Shaikh OS, Freiberg MS. Direct-Acting Antiviral Therapy for HCV Infection Is Associated With a Reduced Risk of Cardiovascular Disease Events. Gastroenterology. 2019 Mar;156(4):987-996.e8. doi: 10.1053/j.gastro.2018.11.022. Epub 2018 Nov 13. PMID: 30445009.

Caliskan Y, Oflaz H, Pusuroglu H, Boz H, Yazici H, Tamer S, Karsidag K, Yildiz A. Hepatitis C virus infection in hemodialysis patients is not associated with insulin resistance, inflammation and atherosclerosis. Clin Nephrol. 2009;71:147–157.

Campo S, Sardo MA, Trimarchi G, Bonaiuto A, Saitta C, Bitto A, Castaldo M, Cinquegrani M, Bonaiuto M, Cristadoro S, Saitta A. Platelet activating factor-acetylhydrolase (PAF-AH) activity and HDL levels, but not PAF-AH gene polymorphisms, are associated with successful aging in Sicilian octogenarians. Aging Clin Exp Res. 2008 Apr;20(2):171-7. doi: 10.1007/BF03324764. PMID: 18431085.

Chang M. L. (2016). Metabolic alterations and hepatitis C: From bench to bedside. World journal of gastroenterology, 22(4), 1461–1476. https://doi.org/10.3748/wjg.v22.i4.1461

Daiber, A., Steven, S., Weber, A., Shuvaev, V. V., Muzykantov, V. R., Laher, I., Li, H., Lamas, S., & Münzel, T. (2017). Targeting vascular (endothelial) dysfunction. British journal of pharmacology, 174(12), 1591–1619. https://doi.org/10.1111/bph.13517

Di Minno MND, Ambrosino P, Buonomo AR, Pinchera B, Calcaterra I, Crispo M, Scotto R, Borgia F, Mattia C, Gentile I. Direct-acting antivirals improve endothelial function in patients with chronic hepatitis: a prospective cohort study. Intern Emerg Med. 2020 Mar;15(2):263-271. doi: 10.1007/s11739-019-02163-8. Epub 2019 Aug 8. PMID: 31396919.

Forde KA, Haynes K, Troxel AB, Trooskin S, Osterman MT, Kimmel SE, Lewis JD, Lo Re V. Risk of myocardial infarction associated with chronic hepatitis C virus infection: a population-based cohort study. J Viral Hepat. 2012;19:271–277.

Fukui M, Kitagawa Y, Nakamura N, Yoshikawa T. Hepatitis C virus and atherosclerosis in patients with type 2 diabetes. JAMA. 2003;289:1245–1246.

Goodkin, D. A., Bieber, B., Jadoul, M., Martin, P., Kanda, E., & Pisoni, R. L. (2017). Mortality, Hospitalization, and Quality of Life among Patients with Hepatitis C Infection on Hemodialysis. Clinical journal of the American Society of Nephrology : CJASN, 12(2), 287–297. https://doi.org/10.2215/CJN.07940716

Grundy, S. M., Stone, N. J., Bailey, A. L., Beam, C., Birtcher, K. K., Blumenthal, R. S., Braun, L. T., de Ferranti, S., Faiella-Tommasino, J., Forman, D. E., Goldberg, R., Heidenreich, P. A., Hlatky, M. A., Jones, D. W., Lloyd-Jones, D., Lopez-Pajares, N., Ndumele, C. E., Orringer, C. E., Peralta, C. A., Saseen, J. J., … Yeboah, J. (2019). 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation, 139(25), e1082–e1143. https://doi.org/10.1161/CIR.0000000000000625

Guiltinan AM, Kaidarova Z, Custer B, Orland J, Strollo A, Cyrus S, Busch MP, Murphy EL. Increased all-cause, liver, and cardiac mortality among hepatitis C virus-seropositive blood donors. Am J Epidemiol. 2008;167:743–750.

Haberal, I., Yesiltas, M. A., Koyuncu, A. O., Batur, S., Ozsoy, S. D., Yilmaz, H., & Buge, A. (2020). Is it possible to predict atherosclerosis in the ascending aorta by the patient's lipid panel?. Archives of medical sciences. Atherosclerotic diseases, 5, e237–e244. https://doi.org/10.5114/amsad.2020.98940

Hanna, D. B., Lin, J., Post, W. S., Hodis, H. N., Xue, X., Anastos, K., Cohen, M. H., Gange, S. J., Haberlen, S. A., Heath, S. L., Lazar, J. M., Liu, C., Mack, W. J., Ofotokun, I., Palella, F. J., Tien, P. C., Witt, M. D., Landay, A. L., Kingsley, L. A., Tracy, R. P., … Kaplan, R. C. (2017). Association of Macrophage Inflammation Biomarkers With Progression of Subclinical Carotid Artery Atherosclerosis in HIV-Infected Women and Men. The Journal of infectious diseases, 215(9), 1352–1361. https://doi.org/10.1093/infdis/jix082

Hsu YC, Lin JT, Ho HJ, Kao YH, Huang YT, Hsiao NW, Wu MS, Liu YY, Wu CY. Antiviral treatment for hepatitis C virus infection is associated with improved renal and cardiovascular outcomes in diabetic patients. Hepatology. 2014;59:1293–1302.

Hsu YH, Muo CH, Liu CY, Tsai WC, Hsu CC, Sung FC, Kao CH. Hepatitis C virus infection increases the risk of developing peripheral arterial disease: a 9-year population-based cohort study. J Hepatol. 2015;62:519–525.

Iorga, R. A., Bacalbasa, N., Bratu, O. G., Ionita Radu, F., & Diaconu, C. C. (2020). The impact of infection with hepatitis C virus on cardiovascular risk. American journal of cardiovascular disease, 10(3), 201–206.

Ishizaka N, Ishizaka Y, Takahashi E, Tooda Ei, Hashimoto H, Nagai R, Yamakado M. Association between hepatitis C virus seropositivity, carotid-artery plaque, and intima-media thickening. Lancet. 2002;359:133–135.

Ishizaka N, Ishizaka Y, Yamkado M. Atherosclerosis as a possible extrahepatic manifestation of chronic hepatitis C virus infection. Clin Med Insights Cardiol. 2014 Nov 12;8(Suppl 3):1-5. doi: 10.4137/CMC.S17069. PMID: 25452704; PMCID: PMC4230236.

Ishizaka Y, Ishizaka N, Takahashi E, Unuma T, Tooda E, Hashimoto H, Nagai R, Yamakado M. Association between hepatitis C virus core protein and carotid atherosclerosis. Circ J. 2003;67:26–30.

Kang, H., Li, X., Xiong, K., Song, Z., Tian, J., Wen, Y., Sun, A., & Deng, X. (2021). The Entry and Egress of Monocytes in Atherosclerosis: A Biochemical and Biomechanical Driven Process. Cardiovascular therapeutics, 2021, 6642927. https://doi.org/10.1155/2021/6642927

Kany, S., Vollrath, J. T., & Relja, B. (2019). Cytokines in Inflammatory Disease. International journal of molecular sciences, 20(23), 6008. https://doi.org/10.3390/ijms20236008

Kralj, D., Virovic Jukic, L., Stojsavljevic, S., Duvnjak, M., Smolic, M., & Curcic, I. B. (2016). Hepatitis C Virus, Insulin Resistance, and Steatosis. Journal of clinical and translational hepatology, 4(1), 66–75. https://doi.org/10.14218/JCTH.2015.00051

 Lee MH, Yang HI, Lu SN, Jen CL, You SL, Wang LY, Wang CH, Chen WJ, Chen CJ. Chronic hepatitis C virus infection increases mortality from hepatic and extrahepatic diseases: a community-based long-term prospective study. J Infect Dis. 2012;206:469–477.

Lee, K. K., Stelzle, D., Bing, R., Anwar, M., Strachan, F., Bashir, S., Newby, D. E., Shah, J. S., Chung, M. H., Bloomfield, G. S., Longenecker, C. T., Bagchi, S., Kottilil, S., Blach, S., Razavi, H., Mills, P. R., Mills, N. L., McAllister, D. A., & Shah, A. (2019). Global burden of atherosclerotic cardiovascular disease in people with hepatitis C virus infection: a systematic review, meta-analysis, and modelling study. The lancet. Gastroenterology & hepatology, 4(10), 794–804. https://doi.org/10.1016/S2468-1253(19)30227-4

Lee, M. H., Yang, H. I., Yuan, Y., L'Italien, G., & Chen, C. J. (2014). Epidemiology and natural history of hepatitis C virus infection. World journal of gastroenterology, 20(28), 9270–9280. https://doi.org/10.3748/wjg.v20.i28.9270

Lei, Y., Yang, J., Li, H., Zhong, H., & Wan, Q. (2019). Changes in glucose-lipid metabolism, insulin resistance, and inflammatory factors in patients with autoimmune thyroid disease. Journal of clinical laboratory analysis, 33(7), e22929. https://doi.org/10.1002/jcla.22929

Lin MS, Guo SE, Chen MY, Huang TJ, Huang JC, Hu JH, Lin YS. The impact of hepatitis C infection on ischemic heart disease via ischemic electrocardiogram. Am J Med Sci. 2014;347:478–484.

Lorey, M. B., Öörni, K., & Kovanen, P. T. (2022). Modified Lipoproteins Induce Arterial Wall Inflammation During Atherogenesis. Frontiers in cardiovascular medicine, 9, 841545. https://doi.org/10.3389/fcvm.2022.841545

Lusis A. J. (2000). Atherosclerosis. Nature, 407(6801), 233–241. https://doi.org/10.1038/35025203

Ma, J., & Chen, X. (2021). Anti-inflammatory Therapy for Coronary Atherosclerotic Heart Disease: Unanswered Questions Behind Existing Successes. Frontiers in cardiovascular medicine, 7, 631398. https://doi.org/10.3389/fcvm.2020.631398

Masiá M, Padilla S, Robledano C, Ramos JM, Gutiérrez F. Evaluation of endothelial function and subclinical atherosclerosis in association with hepatitis C virus in HIV-infected patients: a cross-sectional study. BMC Infect Dis. 2011;11:265.

McGlynn EA, Adams JL, Kramer J, Sahota AK, Silverberg MJ, Shenkman E, Nelson DR. Assessing the Safety of Direct-Acting Antiviral Agents for Hepatitis C. JAMA Netw Open. 2019 Jun 5;2(6):e194765. doi: 10.1001/jamanetworkopen.2019.4765. PMID: 31173117; PMCID: PMC6563580.

Mostafa A, Mohamed MK, Saeed M, Hasan A, Fontanet A, Godsland I, Coady E, Esmat G, El-Hoseiny M, Abdul-Hamid M, et al. Hepatitis C infection and clearance: impact on atherosclerosis and cardiometabolic risk factors. Gut. 2010;59:1135–1140.

Petta S, Ciminnisi S, Di Marco V, Cabibi D, Cammà C, Licata A, Marchesini G, Craxì A. Sarcopenia is associated with severe liver fibrosis in patients with non-alcoholic fatty liver disease. Aliment Pharmacol Ther. 2017 Feb;45(4):510-518. doi: 10.1111/apt.13889. Epub 2016 Dec 27. PMID: 28028821.

Petta S, Torres D, Fazio G, Cammà C, Cabibi D, Di Marco V, Licata A, Marchesini G, Mazzola A, Parrinello G, et al. Carotid atherosclerosis and chronic hepatitis C: a prospective study of risk associations. Hepatology. 2012;55:1317–1323.

Pothineni NV, Delongchamp R, Vallurupalli S, Ding Z, Dai Y, Hagedorn CH, Mehta JL. Impact of hepatitis C seropositivity on the risk of coronary heart disease events. Am J Cardiol. 2014;114:1841–1845.

Rafieian-Kopaei, M., Setorki, M., Doudi, M., Baradaran, A., & Nasri, H. (2014). Atherosclerosis: process, indicators, risk factors and new hopes. International journal of preventive medicine, 5(8), 927–946.

Roed, T., Kristoffersen, U. S., Knudsen, A., Wiinberg, N., Lebech, A. M., Almdal, T., Thomsen, R. W., Kjær, A., & Weis, N. (2014). Increased prevalence of coronary artery disease risk markers in patients with chronic hepatitis C--a cross-sectional study. Vascular health and risk management, 10, 55–62. https://doi.org/10.2147/VHRM.S53557

Sidorkiewicz M. (2021). Hepatitis C Virus Uses Host Lipids to Its Own Advantage. Metabolites, 11(5), 273. https://doi.org/10.3390/metabo11050273

Soehnlein, O., & Libby, P. (2021). Targeting inflammation in atherosclerosis - from experimental insights to the clinic. Nature reviews. Drug discovery, 20(8), 589–610. https://doi.org/10.1038/s41573-021-00198-1

Solbach, P., Westhaus, S., Deest, M., Herrmann, E., Berg, T., Manns, M. P., Ciesek, S., Sarrazin, C., & von Hahn, T. (2015). Oxidized Low-Density Lipoprotein Is a Novel Predictor of Interferon Responsiveness in Chronic Hepatitis C Infection. Cellular and molecular gastroenterology and hepatology, 1(3), 285–294.e1. https://doi.org/10.1016/j.jcmgh.2015.03.002

Sosner P, Wangermez M, Chagneau-Derrode C, Le Moal G, Silvain C. Atherosclerosis risk in HIV-infected patients: the influence of hepatitis C virus co-infection. Atherosclerosis. 2012;222:274–277.

Targher G, Bertolini L, Padovani R, Rodella S, Arcaro G, Day C. Differences and similarities in early atherosclerosis between patients with non-alcoholic steatohepatitis and chronic hepatitis B and C. J Hepatol. 2007;46:1126–1132.

Tien PC, Schneider MF, Cole SR, Cohen MH, Glesby MJ, Lazar J, Young M, Mack W, Hodis HN, Kaplan RC. Association of hepatitis C virus and HIV infection with subclinical atherosclerosis in the women’s interagency HIV study. AIDS. 2009;23:1781–1784.

Tomiyama H, Arai T, Hirose K, Hori S, Yamamoto Y, Yamashina A. Hepatitis C virus seropositivity, but not hepatitis B virus carrier or seropositivity, associated with increased pulse wave velocity. Atherosclerosis. 2003;166:401–403.

Tsui JI, Whooley MA, Monto A, Seal K, Tien PC, Shlipak M. Association of hepatitis C virus seropositivity with inflammatory markers and heart failure in persons with coronary heart disease: data from the Heart and Soul study. J Card Fail. 2009 Jun;15(5):451-6. doi: 10.1016/j.cardfail.2008.12.003. Epub 2009 Feb 10. PMID: 19477406; PMCID: PMC2782758.

Voulgaris, T., & Sevastianos, V. A. (2016). Atherosclerosis as Extrahepatic Manifestation of Chronic Infection with Hepatitis C Virus. Hepatitis research and treatment, 2016, 7629318. https://doi.org/10.1155/2016/7629318

Wang PC, Wu YF, Lin MS, Lin CL, Chang ML, Chang ST, Weng TC, Chen MY. The Impact of Hepatitis C Virus, Metabolic Disturbance, and Unhealthy Behavior on Chronic Kidney Disease: A Secondary Cross-Sectional Analysis. Int J Environ Res Public Health. 2022 Mar 17;19(6):3558. doi: 10.3390/ijerph19063558. PMID: 35329244; PMCID: PMC8952695.

Zampino, R., Marrone, A., Restivo, L., Guerrera, B., Sellitto, A., Rinaldi, L., Romano, C., & Adinolfi, L. E. (2013). Chronic HCV infection and inflammation: Clinical impact on hepatic and extra-hepatic manifestations. World journal of hepatology, 5(10), 528–540. https://doi.org/10.4254/wjh.v5.i10.528

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