Hepatitis C virus and metabolic disorder interactions towards liver damage and atherosclerosis

Table 1 Overview of the main studies assessing the association between hepatitis C virus infection and the prevalence or incidence of cardio-cerebrovascular disease

Ref.	Study design	Country-setting	Total patients (%HCV+)	Main results
Prevalence of cardio- or cerebrovascular disease
Ishizaka et al[94], 2002	Cross-sectional	Japan-general health screening	4784 (2.1)	HCV+ independently associated with increased IMT [OR = 2.9 (2.3-3.6)] and CP [OR = 1.9 (1.6-2.4)]
Bilora et al[121], 2002	Case-control	Italy-hepatitis outpatient clinic	98 (49)	HCV+ have lower prevalence of CP, no significant difference of FP
Ishizaka et al[95], 2003	Cross-sectional	Japan-general health screening	1992 (1.3)	HCV+ associated with CP [OR = 5.5 (2.4-12.8)] and IMT [OR = NA]
				HCV+ independently associated with CP [OR = 5.6 (2.1-15.3)], but not with IMT
Fukui et al[96], 2003	Cross-sectional	Japan-ultrasound carotid screening	210 (14.8)	HCV+ have higher prevalence of increased IMT and CP. HCV+ is independently associated with CP [OR = NA]
Volzke et al[107], 2004	Cross-sectional	Germany-population registry data	4266 (5.5)	HCV+ or HBV+ not associated with IMT, CP, MI or S
Vassalle et al[102], 2004	Case-control	Not specified	686 (5.1)	HCV+ independently associated with CAD [OR = 4.2 (1.4-13)]
Arcari et al[108], 2006	Case-control	United States-United States army	582 (8.9)	HCV+ not associated with MI
Targher et al[97], 2007	Cross-sectional	United Kingdom-outpatient clinic	120 (50)	HCV+ independently associated with IMT [OR = 1.6 (1.1-2.5)]
Boddi et al[98], 2007	Cross-sectional	Italy-cardiovascular risk factor centre	151 (20.5)	HCV+ independently associated with IMT [OR = 4.4 (1.4-13.9)] , but not with CP
Alyan et al[103], 2008	Case-control	Turkey-cardiology unit	364 (38.2)	HCV+ independently associated with CAD [OR = 2.0 (1.6-2.6)]
Tien et al[119], 20095	Cross-sectional	United States-women’s interagency HIV study	503 (10.5)	HCV+ not associated with IMT or CP
Mostafa et al[120], 2010	Cross-sectional	Egypt-village metabolic study	494 (37.9)	IMT and CP not different in HCV+; HCV+ independently associated with IMT and CP [OR = 3.5 (1.2-9.9)]
Adinolfi et al[100], 2012	Case-control	Italy-liver outpatient clinic and general population screening	803 (40.6)	Increased IMT and CP more prevalent in HCV+; HCV-RNA independently associated with CP [OR = 5.2 (2.6-10.5)]
Petta et al[99], 2012	Case-control	Italy-liver and cardiology outpatient unit	348 (50)	Increased IMT and CP more prevalent in HCV+; HCV+ independently associated with IMT [OR = NA]. In HCV patient, older age [OR = 1.04 (1.01-1.08)] and severe fibrosis [OR = 2.18 (1.04-4.54)] are independently associated with CP
Younossi et al[125], 2013	Cross-sectional	United States-NHANES database	19741 (0.9)	HCV+ independently associated with CHF [OR = 2.5 (1.1-6)], but not with CHD
Miyajima et al[123], 2013	Cross-sectional	Japan-seven country study	1908 (2.1)	IMT significantly reduced in HCV+
Incidence of cardio- or cerebrovascular disease
Younossi et al[116], 19996	Retrospective 24.6 yr FU	United States-transplant centre	54 (22.2)	HCV+ associated with CHD mortality [HR NA], but not with CHD
Haji et al[104], 20047	Retrospective 4.2 yr FU	United States-transplant centre	417 (8.2)	HCV+ independently associated with increased mortality [HR 2.8 (1.3-5.7)] and CAD [HR 3.1 (1.5-6.2)]
Amin et al[111], 20061	Retrospective	Australia-Australian national death index	117547 (66.7)	HCV+ independently associated with cardiovascular mortality [HR 1.3 (1.2-1.5)]
Neal et al[117], 2007	Prospective 6.7 yr FU	United Kingdom-trent hepatitis C cohort	22858	HCV+ not associated with cardiovascular mortality
Bilora et al[122], 2008	Case-control prospective 5 yr FU	Italy-not specified	67 (50.7)	HCV+ have lower prevalence of CP, no difference in FP
Caliskan et al[133], 20092	Prospective 59 mo FU	Turkey-hemodialysis unit	72 (50)	HCV+ have lower increase of IMT, not significant difference in increase of CP and FP No differences in IMT, FMD and CP in HCV+
Butt et al[109], 2009	Prospective 5 yr FU	United States-ERCHIVES database	171665 (47.8)	HCV+ not associated with CHD in univariate analysis, but independently associated with CHD [HR 1.25 (1.2-1.3)], in adjusted models
Lee et al[113], 2010	Prospective 16.9 yr FU	Taiwan-general population	23665 (5.5)	HCV+ independently associated with CVD mortality [HR 2.2 (1.5-3.2)]. CVD risk increases with HCV-RNA
Bedimo et al[105], 20103	Retrospective 3.9 yr FU	United States-HIV infected United States veterans	19424 (31.6)	HCV+ independently associated with CVD [HR 1.2 (1.1-1.4)], but not MI
Ohsawa et al[114], 20112	Prospective 5 yr FU	Japan-KAREN Study	1077 (10.1)	HCV+ independently associated with cardiovascular mortality [HR 1.8 (1.1-3)]
Freiberg et al[106], 20114	Retrospective 7.5 yr FU	United States-veterans aging cohort study	8579 (16.8)	HCV+/HIV+ independently associated with incident CHD as compared with HCV-/HIV+ or controls. HCV+ not associated with incident CHD
Kristiansen et al[118], 2011	Prospective 7 yr FU	Norway-population registry data	10108	HCV+ not associated with increased risk of cardiovascular mortality
Forde et al[110], 2012	Retrospective 3.9 yr FU	United Kingdom-health improvement network	4809 (6.3)	HCV+ not associated with incident MI
Lee et al[115], 2012	Prospective 16.9 yr FU	Taiwan-general population	1095 (5.6)	HCV+ associated with vascular mortality [HR 1.5 (1.1-2)]
Hsu et al[124], 2013	Retrospective case-control 5 yr FU	Taiwan-Taiwan national health insurance program	3113 (20)	HCV+ independently associated with S [HR 1.2 (1.1-1.4)]

¹Carried out in hepatitis C virus (HCV) and/or hepatitis B virus patient;

²Carried out in patients in hemodialysis;

³Carried out in human immunodeficiency virus (HIV) mono-infected and HIV/HCV coinfected veterans;

⁴Carried out in HIV and/or HCV United States veterans (only males);

⁵Carried out in women HIV and/or HCV positive: 220 HCV⁺/HIV⁺; 53 HCV⁺; 950 HIV⁺; 452 controls;

⁶Carried out in kidney transplant recipients with allografts functioning over 20 years;

⁷Carried out in cardiac transplant recipients who received hearths from HCV+ or - donors;

⁸Carried out on HCV patients compared to their reference general population. IMT: Intima-media thickness; CP: Carotid plaques; FP: Femoral plaques; FMD: Flow-mediated-dilation; FU: Follow-up; CAD: Coronary artery disease, angiographically documented; MI: Myocardial infarction; S: Stroke; CHD: Coronary hearth disease (myocardial infarction, unstable angina, need for revascularization procedures); CHF: Congestive hearth failure; CVD: Cerebrovascular disease (transient ischemic attack or stroke); NA: Not available.