Effect of Hepatitis C Treatment with Ombitasvir/Paritaprevir/R + Dasabuvir on Renal, Cardiovascular and Metabolic Extrahepatic Manifestations: A Post-Hoc Analysis of Phase 3 Clinical Trials

Abstract

IntroductionWe analyzed phase 3 trial data of ombitasvir/paritaprevir/ritonavir and dasabuvir (3D) ± ribavirin (RBV) in genotype 1 chronic hepatitis C patients to investigate the impact of 3D ± RBV on renal, cardiovascular and metabolic extrahepatic manifestations (EHMs), including persistency 52 weeks post treatment and differential impact by EHM disease severity.MethodsEstimated glomerular filtration rate (eGFR), fasting triglyceride and fasting glucose values from clinical trials were used to assess renal, cardiovascular and metabolic EHMs, respectively. Two placebo-controlled trials were used to study the effect of treatment, while the pooled sample of treated patients was used to study the persistency and differential effect of treatment by baseline EHM disease severity, as defined by baseline values of respective EHM biomarkers. Changes in EHM outcomes from baseline were assessed with mixed models adjusting for patient baseline demographic and clinical characteristics.ResultsTreatment with 3D ± RBV resulted in statistically significant declines from baseline of triglycerides and glucose and no statistical change in eGFR. By 52 weeks post treatment patients with elevated triglycerides (−35.3 mg/dl), pre-diabetes (−4.4 mg/dl), diabetes (−34.2 mg/dl) and CKD stage 3 (+1.6 ml/min/1.73 m2) at baseline experienced a statistically significant improvement in their respective EHM values. Patients with CKD stages 2, 4 and 5 experienced no statistically significant change in eGFR from baseline.ConclusionTreatment with 3D ± RBV resulted in improvement or no worsening of cardiovascular, metabolic and renal EHM markers, especially in patients with severe EHMs at baseline, which persisted until 52 weeks post treatment.FundingAbbvie Inc.Electronic supplementary materialThe online version of this article (doi:10.1007/s40121-017-0171-0) contains supplementary material, which is available to authorized users.

Impact of hepatitis C virus clearance by direct-acting antiviral treatment on the incidence of major cardiovascular events: A prospective multicentre study

“…There is a wide literature supporting that HCV infection increases the subclinical and clinical risk of CV diseases [2][3][4][5][6][7][8][9][10][11] through multiple direct and indirect proatherogenic immune and inflammatory mechanisms, metabolic alterations (insulin resistance, diabetes) and a direct cardiovascular tropism of HCV [27]. Some studies evaluated the effect of clearance of HCV by DAAs on pro-atherosclerosis metabolic alterations [20,28,29]. An analysis of a large population of HCV patients treated with DAAs showed that those who achieved SVR had a significant improvement in some CV risk biomarkers [28].…”

“…Some studies evaluated the effect of clearance of HCV by DAAs on pro-atherosclerosis metabolic alterations [20,28,29]. An analysis of a large population of HCV patients treated with DAAs showed that those who achieved SVR had a significant improvement in some CV risk biomarkers [28]. A prospective study evaluated IR changes after SVR in patients treated with DAAs [20] demonstrated a normalization or reduction of IR levels in 76% of cases and a significant improvement CV: cardiovascular; OR: odds ratio; CI: confidence interval; BMI: body mass index.…”

“…Our study did not investigate the mechanisms involved in reducing CV risk after HCV clearance. Literature data reported that the clearance of HCV by DAA improves atherosclerosis and pro-atherogenic metabolic, inflammatory and immunological conditions and therefore should reduce the risk of CV events [20,[28][29][30]. The reduction of inflammation is a possible mechanism.…”

The Effect of Viral Clearance Achieved by Direct-Acting Antiviral Agents on Hepatitis C Virus Positive Patients with Type 2 Diabetes Mellitus: A Word of Caution after the Initial Enthusiasm

“…A possible explanation could derive from the observation that viral clearance with DAAs determines a significant improvement of extrahepatic diseases such as cardiovasculopathies and nephropathies, regardless of the presence of DM. A recent American study [54] showed a significant improvement in extrahepatic manifestations accompanying C virus infection in patients with CHC cured after therapy with DAAs. The percentage of diabetics in this population was less than 10%.…”

Hepatitis C virus (HCV) infection and cardiovascular disease: Hepatologists and cardiologists need to talk!

“…HCV infection was associated with a nearly 30% increase of CVD and markedly reduced disability-adjusted life-years [1]. Treatment with novel DAAs was shown to reduce CVD events, which underscores the paramount role of timely HCV diagnosis and antiviral treatment [10].…”