Dataset Information

Neutrophil and Monocyte Function in Patients with Chronic Hepatitis C Undergoing Antiviral Therapy with Regimens Containing Protease Inhibitors with and without Interferon.

ABSTRACT: Real-life data showed an increased incidence of bacterial infections in patients with advanced liver disease receiving a protease inhibitor (PI)-containing antiviral regimen against hepatitis C (HCV). However, the causes of this event are unknown. We hypothesized that PIs might impair innate immune responses through the inhibition of proteases participating in the anti-bacterial functions of neutrophils and monocytes. The aims of the study were to assess phagocytic and oxidative burst capacity in neutrophils and monocytes obtained from patients receiving a PI containing-antiviral regimen, and to determine cytokine secretion after neutrophil stimulation with flagellin. Forty patients with chronic HCV (80% with cirrhosis) were enrolled in the study, 28 received triple therapy (Group A) with pegylated-interferon and ribavirin for 4 weeks followed by the addition of a PI (telaprevir, boceprevir or simeprevir), and 12 patients received an interferon-free regimen (Group B) with simeprevir and sofosbuvir. Phagocytosis and oxidative burst capacity were analyzed by flow cytometry at baseline, week 4, and week 8 of therapy. In neutrophils from Group A patients, oxidative burst rate and oxidative enzymatic activity per cell significantly decreased throughout the study period (p = 0.014 and p = 0.010, respectively). Pairwise comparisons showed a decrease between baseline and week 4 and 8 of therapy. No differences were observed after the introduction of the PI. The oxidative enzymatic activity per cell in monocytes significantly decrease during the study period (p = 0.042) due to a decrease from baseline to week 8 of therapy (p = 0.037) in patients from Group A. None of these findings were observed in Group B patients. Cytokine secretion did not significantly change during the study in both groups. In conclusion, our data suggest that the use interferon (rather than the PI) has a deleterious effect on neutrophil and monocyte phagocytic and oxidative burst capacity in this cohort of patients with HCV-related advanced liver fibrosis.

SUBMITTER: Gambato M

PROVIDER: S-EPMC5115763 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Neutrophil and Monocyte Function in Patients with Chronic Hepatitis C Undergoing Antiviral Therapy with Regimens Containing Protease Inhibitors with and without Interferon.

Gambato Martina M Caro-Pérez Noelia N González Patricia P Cañete Nuria N Mariño Zoe Z Lens Sabela S Bonacci Martín M Bartres Concepció C Sánchez-Tapias José-María JM Carrión José A JA Forns Xavier X Juan Manel M Pérez-Del-Pulgar Sofía S Londoño María-Carlota MC

PloS one 20161118 11

Real-life data showed an increased incidence of bacterial infections in patients with advanced liver disease receiving a protease inhibitor (PI)-containing antiviral regimen against hepatitis C (HCV). However, the causes of this event are unknown. We hypothesized that PIs might impair innate immune responses through the inhibition of proteases participating in the anti-bacterial functions of neutrophils and monocytes. The aims of the study were to assess phagocytic and oxidative burst capacity i ...[more]

PMID: 27861593

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Project description:Patients' experience during treatment may affect treatment adherence. Our aim was to assess the impact of patient-reported outcomes (PROs) on adherence to different anti-hepatitis C virus (HCV) regimens.Clinical, demographic, and PRO data (short form-36 [SF-36], chronic liver disease questionnaire-hepatitis C version [CLDQ-HCV], functional assessment of chronic illness therapy-fatigue [FACIT-F], work productivity and activity impairment: specific health problem [WPAI:SHP]) from 13 multinational clinical trials of anti-HCV treatment were available. Treatment adherence was defined as >80% of prescribed doses taken.Included were 4825 HCV patients. Regimens were grouped into: interferon- and ribavirin (RBV)-containing (±sofosbuvir [SOF]), interferon-free RBV-containing (RBV?+?SOF?±?ledipasvir [LDV]), and interferon-free RBV-free (LDV/SOF). The adherence to these regimens were 77.6%, 84.3%, and 96.2%, respectively (P?<?0.0001). Nonadherent patients were more likely to be unemployed and to have a greater PRO impairment at baseline (up to -5.3% lower PRO scores, P?<?0.0001). During treatment with interferon- or RBV-based regimens, nonadherent patients experienced lower PROs and had larger decrements from their baseline PRO scores. In contrast, there were no significant declines in PRO scores (all P?>?0.05) for the small number of patients who were nonadherent to LDV/SOF. In multivariate analysis, being treatment-naive, longer treatment duration, and receiving an interferon- or RBV-containing regimen were associated with a lower likelihood of adherence (all P?<?0.003). Better baseline and on-treatment PRO scores were associated with a higher likelihood of adherence to interferon and RBV.The use of interferon and/or RBV, longer duration of treatment, and lower baseline and on-treatment PRO scores were linked to a decreased likelihood of being adherent to interferon?+?RBV-containing or interferon-free RBV-containing antiviral regimens. Interferon- and RBV-free regimens were associated with excellent adherence.

Project description:Recently approved, interferon-free medication regimens for treating hepatitis C are highly effective, but extremely costly. We aimed to identify cost-effective strategies for managing treatment-naïve U.S. veterans with new hepatitis C medication regimens. We developed a Markov model with 1-year cycle length for a cohort of 60-year-old veterans with untreated genotype 1 hepatitis C seeking treatment in a typical year. We compared using sofosbuvir/ledipasvir or ombitasvir/ritonavir/paritaprevir/dasabuvir to treat: (1) any patient seeking treatment; (2) only patients with advanced fibrosis or cirrhosis; or (3) patients with advanced disease first and healthier patients 1 year later. The previous standard of care, sofosbuvir/simeprevir or sofosbuvir/pegylated interferon/ribavirin, was included for comparison. Patients could develop progressive fibrosis, cirrhosis, or hepatocellular carcinoma, undergo transplantation, or die. Complications were less likely after sustained virological response. We calculated the incremental cost per quality-adjusted life year (QALY) and varied model inputs in one-way and probabilistic sensitivity analyses. We used the Veterans Health Administration perspective with a lifetime time horizon and 3% annual discounting. Treating any patient with ombitasvir-based therapy was the preferred strategy ($35,560; 14.0 QALYs). All other strategies were dominated (greater costs/QALY gained than more effective strategies). Varying treatment efficacy, price, and/or duration changed the preferred strategy. In probabilistic sensitivity analysis, treating any patient with ombitasvir-based therapy was cost-effective in 70% of iterations at a $50,000/QALY threshold and 65% of iterations at a $100,000/QALY threshold.Managing any treatment-naïve genotype 1 hepatitis C patient with ombitasvir-based therapy is the most economically efficient strategy, although price and efficacy can impact cost-effectiveness. It is economically unfavorable to restrict treatment to patients with advanced disease or use a staged treatment strategy. (Hepatology 2016;63:428-436).

Dataset Information

Neutrophil and Monocyte Function in Patients with Chronic Hepatitis C Undergoing Antiviral Therapy with Regimens Containing Protease Inhibitors with and without Interferon.

Publications

Neutrophil and Monocyte Function in Patients with Chronic Hepatitis C Undergoing Antiviral Therapy with Regimens Containing Protease Inhibitors with and without Interferon.

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