Interferon‐free, direct‐acting antiviral therapy for chronic hepatitis C

Gutiérrez, Julio; Lawitz, Eric; Poordad, Fred

doi:10.1111/jvh.12422

Cited by 79 publications

(65 citation statements)

References 53 publications

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“…These results indicate that HCV infection impairs normal M1 differentiation. New regimens of DAAs emerge with a cure rate of more than 90%, even in patients who failed on interferon therapy31. The NS5A inhibitor is one of DAAs known to disrupt multimeric arrays of dimers of NS5A and block the formation of the replication complex32.…”

Section: Discussionmentioning

confidence: 99%

HCV core protein inhibits polarization and activity of both M1 and M2 macrophages through the TLR2 signaling pathway

Zhang

Wang

Zhai

et al. 2016

Sci Rep

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Hepatitis C virus (HCV) establishes persistent infection in most infected patients, and eventually causes chronic hepatitis, cirrhosis, and hepatocellular carcinoma in some patients. Monocytes and macrophages provide the first line of defense against pathogens, but their roles in HCV infection remains unclear. We have reported that HCV core protein (HCVc) manipulates human blood-derived dendritic cell development. In the present study, we tested whether HCVc affects human blood-derived monocyte differentiating into macrophages. Results showed that HCVc inhibits monocyte differentiation to either M1 or M2 macrophages through TLR2, associated with impaired STATs signaling pathway. Moreover, HCVc inhibits phagocytosis activity of M1 and M2 macrophages, M1 macrophage-induced autologous and allogeneic CD4+ T cell activation, but promotes M2 macrophage-induced autologous and allogeneic CD4+ T cell activation. In conclusion, HCVc inhibits monocyte-derived macrophage polarization via TLR2 signaling, leading to dysfunctions of both M1 and M2 macrophages in chronic HCV infected patients. This may contribute to the mechanism of HCV persistent infection, and suggest that blockade of HCVc might be a novel therapeutic approach to treating HCV infection.

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Section: Discussionmentioning

confidence: 99%

HCV core protein inhibits polarization and activity of both M1 and M2 macrophages through the TLR2 signaling pathway

Zhang

Wang

Zhai

et al. 2016

Sci Rep

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“…However, our data might be used as a reference with which future cost studies on CHC would be compared. [12] Considering that the era of treatment with interferon-free direct-acting antivirals (DAAs) has begun for the management of CHC globally, [13] it might be relevant to draw such cost data in the last period for therapy with pegylated interferon.…”

Section: Discussionmentioning

confidence: 99%

Estimation of direct medical cost related to the management of chronic hepatitis C and its complications in South Korea

Kim

Yoon

Kim³

et al. 2016

Medicine

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Background:This study aimed to estimate the direct medical costs of managing chronic hepatitis C (CHC) and its complications based on health-care resources in South Korea.Methods:The study design was multicenter, retrospective, non-interventional, and observational. Between September 2013 and April 2014, health-care resource data from patients chronically infected with hepatitis C virus, regardless of genotype, were collected from 8 institutions, including data related to outpatient management, emergency care, and hospitalization. The observation period was between January 2011 and December 2012. The disease state was classified as CHC, compensated cirrhosis (CC), decompensated cirrhosis (DC), or hepatocellular carcinoma (HCC).Results:A total of 445 patients were recruited and mean age was 60.1 ± 12.3 years. Among 155 patients with reported outcomes of antiviral therapy, 107 (69%) had sustained virologic response (SVR). The rate of patients who did not receive antiviral therapy was 52.8% (n = 235). The distribution of disease state was CHC in 307 patients (69.0%), CC in 75 (16.9%), HCC in 45 (10.1%), and DC in 18 (4.0%). All direct medical costs, whether reimbursed or nonreimbursed by the National Health Insurance System, were included. After excluding patients whose observational period was <1 month for each disease status, the mean costs per month increased as disease state progressed (CHC: 77 ± 80 USD; CC: 98 ± 94 USD; DC: 512 ± 1115 USD; HCC: 504 ± 717 USD). The mean total costs per person were 3590 ± 8783 USD, and approximately 72% of patients were reimbursed. When 44 patients with an observation period <1 month were excluded, the mean medical costs per month for patients with CHC who achieved SVR (n = 69) were significantly lower than for those (n = 215) who did not (42 ± 16 vs 79 ± 83 USD, P < 0.001). The cost also tended to be lower for patients with CC with SVR (n = 8) than for those without SVR (n = 70; 48 ± 20 vs 95 ± 96 USD, P = 0.177). The cost of antiviral therapy (pegylated interferon and ribavirin) corresponded to 19.0% of total medical costs and 53.7% of prescription/pharmacy.Conclusion:The direct medical costs increased as disease state progressed from CHC to cirrhosis or HCC. The achievement of SVR by antiviral therapy would decrease the costs.

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“…7 The next generation of treatments promises to reduce the treatment duration and allow many more HCV-infected patients to be treated. 8 Like many European countries, Germany faces an ongoing HCV epidemic with a non-declining rate of new infections since 2009. 9 With its generally open access to HCV treatment, Germany provides a good environment for modelling the impact of increases in HCV treatment capacity resulting from the expected introduction of shorter treatment regimens.…”

Section: Summary Boxmentioning

confidence: 99%

Economic study of the value of expanding HCV treatment capacity in Germany

Sbarigia

Wirth

Nuys³

et al. 2017

BMJ Open Gastroenterol

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BackgroundToday's highly efficacious, low-toxicity interferon-free treatment regimens for chronic hepatitis C virus (HCV) can cure most patients with HCV in 12–24 weeks. The aim of this study was to understand how the introduction of shorter duration treatment regimens for HCV will impact the capacity for treatment and value to society.MethodsA Markov model of HCV transmission and progression was constructed, incorporating nationally representative data on HCV prevalence, incidence and progression; mortality, treatment costs, medical expenditures, employment probabilities and disability payments in Germany. The model was stratified by HCV genotype and exposure route (1-time healthcare exposure, injection drug use and sexual activity). Treatment scenarios were based on German treatment guidelines and projected treatment capacity. The impact of different treatment scenarios on disease transmission and prevalence, quality-adjusted life years (QALYs), treatment costs, medical expenditures, employment and disability expenditures was calculated.ResultsDepending on their adoption profile, new treatment regimens and protocols introduced over the next several years will increase HCV treatment capacity in Germany by 8–30%, reducing disease transmission and prevalence, increasing QALYs and adding €94–310 million in discounted social value (QALYs plus medical savings net of treatment costs) over a 30-year horizon. Additional social value in the form of higher employment and lower disability would also result.ConclusionsThe introduction of shorter HCV treatment regimens and the resulting increased treatment capacity in Germany would result in large gains to society by reducing disease transmission and prevalence, resulting in longer, healthier, more productive lives for current and future generations.

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Interferon‐free, direct‐acting antiviral therapy for chronic hepatitis C

Cited by 79 publications

References 53 publications

HCV core protein inhibits polarization and activity of both M1 and M2 macrophages through the TLR2 signaling pathway

HCV core protein inhibits polarization and activity of both M1 and M2 macrophages through the TLR2 signaling pathway

Estimation of direct medical cost related to the management of chronic hepatitis C and its complications in South Korea

Economic study of the value of expanding HCV treatment capacity in Germany

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