Beneficial Effects of DAAs on Cardiac Function and Structure in Hepatitis C Patients With Low-moderate Liver Fibrosis

Andrea Dalbeni; Simone Romano; Michele Bevilacqua; Anna Piccoli; Egidio Imbalzano; Anna Mantovani; Marco Benati; Martina Montagnana; Angela Donato; Gioia Torin; Cinzia Monaco; Filippo Cattazzo; Angela Tagetti; Veronica Paon; Donatella Ieluzzi; Laura Iogna Prat; Davide Roccarina; Flavio Ribichini; Franco Capra; Pietro Minuz; Cristiano Fava

Disclosures

J Viral Hepat. 2020;27(11):1214-1221. 

In This Article

Abstract and Introduction

Abstract

Hepatitis C virus (HCV)-related chronic infection has been associated with a higher incidence of cardiovascular diseases. An altered morphology and function of both left and right heart have been described in HCV patients; however, the causality of the association is still debated. Ninety-eight nonobese and nondiabetic HCV patients (59.5 ± 12.0 years; males 52%) with Fibroscan-Transient Elastography assessed low-moderate liver fibrosis that achieved sustained viral response at 12 and 24 weeks after DAAs (direct-acting antivirals) participated. 56 were matched with 52 control subjects for age, sex and cardiovascular risk factors at baseline. A trans-thoracic echocardiography was performed in each subject at baseline (T0) and repeated in all HCV patients after eradication (6 months later eligibility, T1). TNF-α and IL-10 were measured at baseline and at T1. A concentric remodelling of the left heart in HCV participants was identified, whereas tricuspidal annular plane systolic excursion, right indexed atrial volume, right basal ventricular diameter, inferior vena cava diameter and pulmonary arterial pressure were higher in HCV participants compared to matched controls. After virus eradication, left indexed atrial volume and all right cardiac chambers measures were lower than baseline. A significant reduction of TNF-α was shown at T1, while IL-10 did not change. This study shows a concentric remodelling of the left ventricle and structural modifications in the right sections in HCV patients compared to controls. Virus eradication with DAAs was associated with a reduction of the main right atrioventricular parameters indicating a direct involvement of the HCV in cardiac changes.

Introduction

Hepatitis Virus C (HCV) infection is among the most common causes of chronic liver disease, liver cirrhosis and hepatocellular carcinoma (HCC).[1] It has been estimated that about 1.6% of the worldwide general population carries antibodies against HCV (anti-HCV positive) and 1.1% has detectable HCV-RNA levels in the blood.[2] In Italy, the rate of HCV infection is between 1.2% and 5.4%.[2]

In addition to the well-known deleterious effects on the liver structure and function, HCV-related chronic infection is associated with other serious extra-hepatic manifestations, such as mixed cryoglobulinemia, glomerulonephritis, pulmonary fibrosis, autoimmune diseases, dermatological and ocular involvement and non-Hodgkin B-cell lymphoma, whose pathogenetic mechanism is probably related to the persistent stimulation of the immune system and the tropism of the virus for other tissues.[3,4] Most recently, HCV infection has been even associated with metabolic effects, specially diabetes and insulin resistance,[5] atherosclerosis and cardiovascular disease (CVD).[6] A reduced insulin sensitivity and chronic hyperglycaemia were indicated as possible co-factors in determining liver steatosis, severity and progression of fibrosis, development and growth of HCC and reduced response to antiviral drugs.[7] Chronic hepatitis C has been also associated with higher risk of carotid intima-media thickening and carotid artery plaques,[8] increased incidence of coronary artery disease[9] (CAD), acute coronary syndromes[9] (ACS) and cerebrovascular events, such as stroke,[10] suggesting that HCV could be considered as a new cardiovascular risk factor.[11] In fact, some authors hypothesized that HCV infection might contribute to the atheromatous process[12] mainly through chronic inflammation, increased oxidative stress, insulin resistance[11] and virus replication on pre-existing plaques.[13] Moreover, there are few studies evaluating the possible deleterious effects of HCV infection on both the right and left heart, but the results are still contradictory.[14–16] Dilated and hypertrophic cardiomyopathy have been recently described as an extra-hepatic morbidity of HCV infection[17] but their real frequency is still not known.[18] The pathogenesis of this phenomenon is not completely understood, but HCV cardio-tropism,[19] the release of pro-inflammatory cytokines[20,21] and an abnormal immune response[17] were hypothesized as the main putative determinants. In study by Demir et al,[14] pulmonary arterial pressure (PAP) vascular resistance and right ventricular and atrial diameters were higher in HCV patients compared to controls, suggesting also the right side of the heart to be impaired. Furthermore, pegylated-interferon α plus ribavirin (Interferon-Based Therapy, IBT) and DAAs-based therapies were shown to significantly improve CVD outcomes.[22,23] However, few studies exist about the effects of the IBT and the new direct-acting antivirals (DAAs) on cardiovascular system after virus eradication. In fact, although HCV elimination has been associated with general improvement in extra-hepatic comorbidities, particularly in insulin sensitivity,[24] the real benefit of antivirals on cardiomyopathy, especially regarding DAAs, has not been clearly defined yet.

The aim of our study was to evaluate the effect of HCV infection on cardiac function and structure, evaluated by trans-thoracic echocardiography (TTE), and to assess the effect of DAAs on cardiac structure and function abnormalities.

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