Hepatitis C virus infection and risk of stroke: a systematic review and meta-analysis

He Huang, Rongyan Kang, Zhendong Zhao, He Huang, Rongyan Kang, Zhendong Zhao

Abstract

Background/aims: Several studies analyzed the association between hepatitis C virus (HCV) infection and the risk of stroke or cerebrovascular death, but their findings were inconsistent. Up to date, no systematic review about the association between HCV infection and stroke was performed. We conducted a meta-analysis to examine whether HCV infection dose increase stroke risk in comparison to the population without HCV infection.

Methods: We followed standard guidelines for performance of meta-analysis. Two independent investigators identified eligible studies through structured keyword searches in several databases. Random-effects and fixed-effects models were used to synthesize the data. Heterogeneity between studies and publication bias were also accessed.

Results: Combining the data from the eligible studies, we calculated the pooled multi-factor adjusted Odds Ratio (OR) with 95% confidence interval (CI). Upon the heterogeneity found between studies, the result was 1.58 (0.86, 2.30) by random-effects model. However, after omitting the study which induced heterogeneity, the pooled OR with 95% CI was 1.97 (1.64, 2.30).

Conclusions: This meta-analysis suggested that HCV infection increased the risk of stroke. More prospective cohort studies will be needed to confirm this association with underlying biological mechanisms in the future.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1. Flow diagram of study identification.
Figure 1. Flow diagram of study identification.
Figure 2. Forest plot for meta-analysis comparing…
Figure 2. Forest plot for meta-analysis comparing risk of stroke in HCV infected patients compared to that in non-infected controls.
Four studies reporting ORs and RR were included. Adjusted ORs from included studies and the pooled OR was shown. Dimension of shaded OR for individual studies is proportional to their total weight in calculation of the pooled estimator.
Figure 3. Begg’s funnel plot (with pseudo…
Figure 3. Begg’s funnel plot (with pseudo 95% confidence intervals) to detect any publication bias.
Figure 4. Forest plot for meta-analysis comparing…
Figure 4. Forest plot for meta-analysis comparing risk of stroke in HCV infected patients compared to that in non-infected controls.
After omitting the study which induced heterogeneity, adjusted ORs from the other three studies and the pooled OR was shown. Dimension of shaded OR for individual studies is proportional to their total weight in calculation of the pooled estimator.

References

    1. Shepard CW, Finelli L, Alter MJ (2005) Global epidemiology of hepatitis C virus infection. Lancet Infect Dis 5: 558-567. doi:10.1016/S1473-3099(05)70216-4. PubMed: .
    1. Lauer GM, Walker BD (2001) Hepatitis C virus infection. N Engl J Med 345: 41-52. doi:10.1056/NEJM200107053450107. PubMed: .
    1. Raimondi S, Bruno S, Mondelli MU, Maisonneuve P (2009) Hepatitis C virus genotype 1b as a risk factor for hepatocellular carcinoma development: a meta-analysis. J Hepatol 50: 1142-1154. doi:10.1016/j.jhep.2009.01.019. PubMed: .
    1. White DL, Ratziu V, El-Serag HB (2008) Hepatitis C infection and risk of diabetes: a systematic review and meta-analysis. J Hepatol 49: 831-844. doi:10.1016/j.jhep.2008.08.006. PubMed: .
    1. Pereira AA, Jacobson IM (2009) New and experimental therapies for HCV. Nat. Rev Gastroenterol Hepatol 6: 403-411. doi:10.1038/nrgastro.2009.92.
    1. Feigin VL (2007) Stroke in developing countries: can the epidemic be stopped and outcomes improved? Lancet Neurol 6: 94-97. doi:10.1016/S1474-4422(07)70007-8. PubMed: .
    1. Strong K, Mathers C, Bonita R (2007) Preventing stroke: saving lives around the world. Lancet Neurol 6: 182-187. doi:10.1016/S1474-4422(07)70031-5. PubMed: .
    1. O'Donnell MJ, Xavier D, Liu L, Zhang H, Chin SL et al. (2010) Risk factors for ischaemic and intracerebral haemorrhagic stroke in 22 countries (the INTERSTROKE study): a case-control study. Lancet 376: 112-123. doi:10.1016/S0140-6736(10)60834-3. PubMed: .
    1. Grau AJ, Urbanek C, Palm F (2010) Common infections and the risk of stroke. Nat Rev Neurology 6: 681-694. doi:10.1038/nrneurol.2010.163. PubMed: .
    1. Forssen U, McAfee A, Enger C, Bennett D, Shantakumar S (2009) Risk of thromboembolic events (TEs) among patients infected with hepatitis C. Hepatology 50: 672A.
    1. Lee MH, Yang HI, Wang CH, Jen CL, Yeh SH et al. (2010) Hepatitis C virus infection and increased risk of cerebrovascular disease. Stroke 41: 2894-2900. doi:10.1161/STROKEAHA.110.598136. PubMed: .
    1. Hsu CS, Kao JH, Chao YC, Lin HH, Fan YC et al. (2013) Interferon-based therapy reduces risk of stroke in chronic hepatitis C patients: A population-based cohort study in Taiwan. Aliment Pharmacol Ther 38: 415-423. doi:10.1111/apt.12391. PubMed: .
    1. Adinolfi LE, Restivo L, Guerrera B, Sellitto A, Ciervo A et al. (2013) Chronic HCV infection is a risk factor of ischemic stroke. Atherosclerosis 231: 22-26. doi:10.1016/j.atherosclerosis.2013.08.003. PubMed: .
    1. Gutierrez J, Elkind MSV (2012) Chronic inflammatory diseases and stroke: Evidence for heterogeneous mechanisms. Ann Neurol 72: S6-S7. doi:10.1002/ana.23669.
    1. Liao CC, Su TC, Sung FC, Chou WH, Chen TL (2012) Does hepatitis C virus infection increase risk for stroke? A population-based cohort study. PLOS ONE 7: e31527. doi:10.1371/journal.pone.0031527. PubMed: .
    1. Younossi ZM, Stepanova M, Nader F, Younossi Z, Elsheikh E (2013) Associations of chronic hepatitis C with metabolic and cardiac outcomes. Aliment Pharmacol Ther 37: 647-652. doi:10.1111/apt.12234. PubMed: .
    1. Moher D, Liberati A, Tetzlaff J, Altman DG (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ 339: b2535. doi:10.1136/bmj.b2535. PubMed: .
    1. Wells GA SB, O’Connell D, Peterson J, Welch V (2012) The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses.
    1. Higgins JP, Thompson SG (2002) Quantifying heterogeneity in a meta-analysis. Stat Med 21: 1539-1558. doi:10.1002/sim.1186. PubMed: .
    1. Normand SL (1999) Meta-analysis: formulating, evaluating, combining, and reporting. Stat Med 18: 321-359. doi:10.1002/(SICI)1097-0258(19990215)18:3. PubMed: .
    1. Macaskill P, Walter SD, Irwig L (2001) A comparison of methods to detect publication bias in meta-analysis. Stat Med 20: 641-654. doi:10.1002/sim.698. PubMed: .
    1. Vinikoor MJ, Napravnik S, Floris-Moore M, Wilson S, Huang DY et al. (2013) Incidence and clinical features of cerebrovascular disease among HIV-infected adults in the southeastern United States. AIDS Res Hum Retrovir 29: 1068-1074. doi:10.1089/aid.2012.0334. PubMed: .
    1. Restivo L, Iuliano N, Nevola R, Amelia A, Fascione MC et al. (2013) Chronic HCV infection and extrahepatic diseases: Ischemic stroke and ischemic heart disease. Dig Liver Dis 45: S13. doi:10.1016/S1590-8658(13)60039-0.
    1. Greenland S (1987) Quantitative methods in the review of epidemiologic literature. Epidemiol Rev 9: 1-30. PubMed: .
    1. Fukui M, Kitagawa Y, Nakamura N, Yoshikawa T (2003) Hepatitis C virus and atherosclerosis in patients with type 2 diabetes. JAMA 289: 1245-1246. doi:10.1001/jama.289.10.1245-a. PubMed: .
    1. Ishizaka N, Ishizaka Y, Takahashi E, Toda E, Hashimoto H et al. (2002) Increased prevalence of carotid atherosclerosis in hepatitis B virus carriers. Circulation 105: 1028-1030. doi:10.1161/hc0902.105718. PubMed: .
    1. Ishizaka N, Ishizaka Y, Takahashi E, Tooda Ei, Hashimoto H et al. (2002) Association between hepatitis C virus seropositivity, carotid-artery plaque, and intima-media thickening. Lancet 359: 133-135. doi:10.1016/S0140-6736(02)07339-7. PubMed: .
    1. O'Leary DH, Polak JF, Kronmal RA, Manolio TA, Burke GL et al. (1999) Carotid-artery intima and media thickness as a risk factor for myocardial infarction and stroke in older adults. Cardiovascular Health Study Collaborative Research Group. N Engl J Med 340: 14-22. doi:10.1056/NEJM199901073400103. PubMed: .
    1. Libby P, Ridker PM, Maseri A (2002) Inflammation and atherosclerosis. Circulation 105: 1135-1143. doi:10.1161/hc0902.104353. PubMed: .
    1. Boddi M, Abbate R, Chellini B, Giusti B, Giannini C et al. (2010) Hepatitis C virus RNA localization in human carotid plaques. J Clin Virol 47: 72-75. doi:10.1016/j.jcv.2009.10.005. PubMed: .
    1. Patsopoulos NA, Evangelou E, Ioannidis JP (2008) Sensitivity of between-study heterogeneity in meta-analysis: proposed metrics and empirical evaluation. Int J Epidemiol 37: 1148-1157. doi:10.1093/ije/dyn065. PubMed: .
    1. Hartemink N, Boshuizen HC, Nagelkerke NJ, Jacobs MA, van Houwelingen HC (2006) Combining risk estimates from observational studies with different exposure cutpoints: a meta-analysis on body mass index and diabetes type 2. Am J Epidemiol 163: 1042-1052. doi:10.1093/aje/kwj141. PubMed: .

Source: PubMed

Sponsors en medewerkers

Medische omstandigheden

Geneesmiddelinterventies

3
Abonneren