Chronic hepatitis C and the risk for atherosclerotic and cardiomyopathic heart disease

Table 1 Overview of the cell types, cytokines with their actions on target cells

Cytokine	T helper cell type	Target cell	Action	Net effect on plague formation
TNF-α	Th1	Macrophages, endothelial cells	Promotes atherogenesis by increasing the expression of adhesion molecules on endothelial cells, leading to the recruitment of inflammatory cells into the arterial wall	Proatherogenic
IFN-γ	Th1	Macrophages, CD8, T cells, NK cells	Despite its antiviral effects, it increases adhesion molecules expression	Proatherogenic
IL-2	Th1	T cell	B cell clonal expansion and T cell development	Proatherogenic (less well-established)
IL-4	Th2	T and B cells	Promotes T cell development, upregulate pro-inflammatory mediators	Antiatherogenic (less well-established)
IL-5	Th2	B cell	B cell activation and production of protective natural immunoglobulin M antibodies against oxidation-specific antigens	Antiatherogenic (less well-established)
IL-6	Macrophages	Macrophages, Th1	Increase adhesion molecule expression	Proatherogenic
IL-8	Th2	Neutrophils	Releasing reactive oxygen species and promoting inflammation	Proatherogenic
IL-10	T reg cell	Macrophages, B cells	Suppresses activation of Th1 cells and macrophages	Antiatherogenic

TNF-α: Tumor necrosis factor-alpha; IL: Interleukin-6; IFN-γ: Interferon-gamma; NK: Natural killer.

Table 2 A summary table for key studies and their conclusions

Ref.	Year	Study design	Findings	Limitations
Wang et al[74]	2024	Cross-sectional study	HCV group without metabolic syndrome had higher odds ratio of 2.75	While CT is a widely used method, it primarily detects advanced atherosclerosis (calcified plaques) and may miss earlier stages of the disease
Chang et al[56]	2022	Population-based cohort	HCV patients have a high incidence of CVD, though it is lower than that of ALD and NAFLD	The findings may not be directly generalizable
Petta et al[9]	2011	Case-control	Severe hepatic fibrosis is associated with a high risk of early carotid atherosclerosis in G1 CHC patients	Selection bias in the recruitment of the control population and limited generalizability
Lee et al[72]	2019	Systematic review and meta-analysis	Patients with HCV had 28% higher risk compared to those without HCV infection	Limited generalizability on global scale, and significant heterogeneity
Wen et al[75]	2019	Systematic review and meta-analysis	The overall RR of 1.25 in the cohort studies, higher OR of 1.94 in these studies suggests a stronger association between HCV and CAD compared to the cohort studies	Small sample size between studies and different criteria for diagnosing CHC
Badawi et al[76]	2018	Survey analysis	HCV infection was significantly associated with a 25%-3.5% absolute risk increases of 10-year CVD after adjusting for sociodemographic and cardiometabolic risk factors	Confounding variables such as alcohol use, and drug use were not controlled
Roed et al[65]	2014	Cross-sectional study	Higher carotid intima media thickness in CHC patients with small difference of means	Confounding variables such as physical activity, diet, medication use, family history of CAD, and genetic predisposition were not controlled

HCV: Hepatitis C virus; CHC: Chronic hepatitis C; CAD: Coronary artery disease; NAFLD: Non-alcoholic fatty liver disease; ALD: Alcoholic liver disease; CT: Computed tomography.