HCV eradication in recurrent hepatitis C after liver transplantation normalizes enhanced endothelial activation

Abstract

Summary The increased risk of cardiovascular disease (CVD) conferred by hepatitis C virus (HCV) is especially relevant after liver transplantation (LT), but its mechanism is still not well defined. This study aimed to evaluate the influence of HCV eradication in inflammatory and endothelial activation markers after LT. We evaluated inflammatory (TNF‐alfa, IL‐6, IL‐8, and MCP‐1) and endothelial activation (E‐selectin, ICAM‐1, VCAM‐1, and MMP‐9) markers before and after eradication in 45 LT recipients with HCV infection (LT+/HCV+) and 44 non‐transplanted HCV‐infected patients (LT‐/HCV+). We also considered an additional group of 40 LT recipients without HCV infection (LT+/HCV‐). LT+/HCV+ patients presented a higher endothelial activation status before eradication compared with LT+/HCV‐ patients. However, levels of E‐selectin, ICAM‐1, VCAM‐1, and MMP‐9 were comparable between LT+/HCV+ and LT‐/HCV+ patients before eradication. HCV eradication decreased ICAM‐1 (5466.55 pg/ml vs. 3354.88 pg/ml, P < 0.001) and VCAM‐1 (10456.52 pg/ml vs. 6658.85 pg/ml, P < 0.001) levels in LT+/HCV+ and LT‐/HCV+ patients. Remarkably, HCV eradication restored levels of endothelial activation markers of LT+/HCV+ patients compared with that of LT+/HCV‐ patients. HCV plays a major role in endothelial dysfunction after LT. Furthermore, HCV eradication restores endothelial activation despite the exposure to immunosuppressive therapy.

Significance of Vascular Cell Adhesion Molecule-1 and Tumor Necrosis Factor-Alpha in HIV-Infected Patients

“…This correlation between HIV, HCV, and pro-inflammatory processes has very important clinical relevance, because it may be linked with the degree of liver fibrosis in HIV/HCV co-infected patients [13]. Recently, it has been shown that HCV eradication after effective treatment with direct acting antivirals (DAAs) or after liver transplantation diminished significantly, and even often normalized serum markers' levels of endothelial activation [14,15]. However, in HIV/HCV co-infected patients the situation is more complex, and even successful HCV eradication does not always lead to the normalization of systemic inflammation and endothelial dysfunction conditions, especially in persons with already-increased liver fibrosis.…”