Effectiveness of direct-acting antiviral therapy for hepatitis C in difficult-to-treat patients in a safety-net health system: a retrospective cohort study

Yek, Christina; Flor, Carolina de la; Marshall, John K.; Zoellner, Cindy; Thompson, Grace; Quirk, Lisa; Mayorga, Cristobalina; Turner, Barbara J.; Singal, Amit G.; Jain, Mamta K.

doi:10.1186/s12916-017-0969-3

Cited by 50 publications

(60 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our report of 95.3% of psychiatric patients achieving SVR12 is consistent with most published reports [26][27][28][29][30][31]. Yek et al [31], in a retrospective review of socioeconomically disadvantaged, patients with alcohol and substance use, and mental health disorders, reported an SVR12 of in 90% of patients [31]. According to the same study, SVR12 was significantly lower in patients with decompensated cirrhosis but did not differ by or alcohol/substance use.…”

Section: Discussionsupporting

confidence: 91%

“…We did not find any significant difference in the SVR of patients with and without psychiatric or substance use disorders suggesting that having a psychiatric diagnosis or substance use disorders did not exert any influence on achieving an SVR. Our report of 95.3% of psychiatric patients achieving SVR12 is consistent with most published reports [26][27][28][29][30][31]. Yek et al [31], in a retrospective review of socioeconomically disadvantaged, patients with alcohol and substance use, and mental health disorders, reported an SVR12 of in 90% of patients [31].…”

Section: Discussionsupporting

confidence: 91%

See 1 more Smart Citation

Outcomes of Direct-Acting Antiviral Treatment of Psychiatric Patients with Comorbid Hepatitis C Virus Infection

Gayam

Jegede

Tiongson

et al. 2019

Dig Dis

View full text Add to dashboard Cite

Background: The highest burden of hepatitis C virus (HCV) infection is seen in patients with psychiatric disorders who have been excluded from traditional treatments with Interferon due to treatment-emergent neuropsychiatric adverse effects. The goal of this study is to determine the tolerability, treatment retention, and efficacy of direct-acting antivirals with psychiatric disorders and comorbid substance use disorders in real-life settings. Methods: This is a retrospective cohort observational study of HCV patients treated with direct-acting antivirals between January 2016 and December 2018. Patients were stratified and sub-stratified based on their psychiatric diagnosis and substance use. The primary assessment was the sustained virologic response at 12 weeks post-treatment (SVR12). Results: Among the 291 patients analyzed, patients with psychiatric diagnosis and non-psychiatric patients made up 51.2% (n = 149) and 48.8% (n = 142) respectively. Majority of the patients included in the study were African-Americans (68.7%, n = 200). Overall, 95.3% (142/149) and 94.4% (134/142) of psychiatric and nonpsychiatric patients, respectively, achieved SVR12 and treatment response was similar between the groups (p = 0.72). Among psychiatric patients, only the prior treatment status was identified as a predictor of treatment response (OR 0.153, 95% CI 0.03-0.79; p = 0.05). No statistical difference was observed among the patients with SVR12 based on their primary psychiatric diagnoses or by comorbid substance abuse. Conclusion: The results of our study show that directacting antiviral treatments are well tolerated in psychiatric patients, and an overwhelming majority of patients achieved SVR12. Our study highlights the need to integrate HCV screening with treatment linkage in psychiatry and primary care practice.

show abstract

Section: Discussionsupporting

confidence: 91%

Section: Discussionsupporting

confidence: 91%

Outcomes of Direct-Acting Antiviral Treatment of Psychiatric Patients with Comorbid Hepatitis C Virus Infection

Gayam

Jegede

Tiongson

et al. 2019

Dig Dis

View full text Add to dashboard Cite

show abstract

“…Of the 5552 patients treated with SOF/VEL, only 1% 2,5,7 In addition to the low number of patients that did not achieve SVR12/24 due to virological reasons, only 6.7% of patients did not achieve SVR12/24 due to a non-virological reason, which is consistent with previously reported data in the current DAA era. 34,35 The majority of these patients were LTFU (67%, 222/332). It is likely that many of these patients were cured, but there is no way of confirming this.…”

Section: Ta B L E 3 (Continued)mentioning

confidence: 99%

Global real‐world evidence of sofosbuvir/velpatasvir as simple, effective HCV treatment: Analysis of 5552 patients from 12 cohorts

Mangia

Milligan

Khalili

et al. 2020

Liver International

View full text Add to dashboard Cite

Background and aims: Achieving sustained virological response (SVR; cure) in hepatitis C patients using a simple regimen is key to making elimination by 2030 possible. In the largest real-world analysis to date, the effectiveness of pangenotypic, panfibrotic, single-tablet, sofosbuvir/velpatasvir (SOF/VEL) once-daily for 12 weeks was assessed in 12 clinical real-world cohorts from various geographical areas, settings and treatment practices. Factors affecting risk of not achieving SVR were assessed. Methods: Adults treated with SOF/VEL 400/100 mg, without ribavirin, were included. All HCV patients reaching Week 12 or 24 post-treatment were assessed for SVR12/24. Factors associated with not achieving SVR12/24 for virological reasons were evaluated using logistic regression analysis. Results: Overall, 5552 patients were included: 13.3% treatment-experienced; 20.7% compensated cirrhotic; 30.2% genotype 1; 29.5% genotype 2; 32.9% genotype 3; 4.7% genotype 4; 3.7% HIV coinfection; 13.4% current/former intravenous drug use. Of the 5196 patients evaluated for effectiveness, 98.9% achieved SVR12/24. High SVR12/24 rates occurred in all genotypes including genotype 3 (98.3%; 1649/1677) and in those with compensated cirrhosis (97.9; 1055/1078). Only 55 patients did not achieve SVR12/24 due to a virological reason; the only factor statistically significantly associated with an increased risk of not achieving SVR12/24 was compensated cirrhosis (P = .002). Overall, 6% (332/5552) of patients did not achieve SVR12/24 for nonvirological reasons (67% lost to follow-up; 26.5% early treatment discontinuation). This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

show abstract

“…If untreated, approximately 70–80% of HCV infected individuals will develop complications with progressive liver fibrosis, cirrhosis, and hepatocellular carcinoma [ 3 , 4 ]. The use of pan-genotypic direct-acting antiviral (DAAs) regimens is curative in >95% of HCV infected individuals [ 5 ]. However, access to diagnosis and treatment in some countries is very limited and resistance to some DAA treatment regimens is continuously being reported [ 6 – 8 ].…”

Section: Introductionmentioning

confidence: 99%

Reticulon-3 modulates the incorporation of replication competent hepatitis C virus molecules for release inside infectious exosomes

Li¹,

Abosmaha²,

Coffin³

et al. 2020

PLoS ONE

View full text Add to dashboard Cite

Background Cell released microvesicles specifically, exosomes, play an important role in mediating immunologic escape, treatment resistance, and disease persistence of Hepatitis C virus (HCV) infection. Reports on the molecular compositions of exosomes released by cells under diverse conditions, especially during viral infections, suggest that their cargo contents are not randomly loaded. However, the precise molecular mechanisms directing the selective cargo sorting and loading inside infectious viral exosomes remains elusive. Aim To decipher the role of Reticulon 3 (RTN3) in the selective molecular cargo sorting and loading inside infectious viral exosomes during HCV infection. Methods We used Huh7 cells–JFH1 HCV infection and HCV Full-Length (FL) replicon systems. Additionally, we analyzed human liver and serum exosome samples from healthy and treatment naïve HCV infected individuals. Our experiments made use of molecular biology and immunology techniques. Results HCV infection (JFH1-Huh7 or HCV-FL replicon cells) was associated with increased RTN3L&S isoforms expression in cells and cell released exosomes. Accordingly, increased expression of RTN3L&S was observed in liver and serum exosome samples of HCV infected individuals compared to healthy controls. RNA-ChIP analysis revealed that RTN3L&S interacted with dsHCV RNA. Lentiviral CRISPR/Cas9 mediated knockdown (KD) of RTN3 and plasmid overexpression (OE) of wild type, C- and N-terminal deletion mutants of RTN3L&S in HCV- infected Huh7 cells differentially impacted the cellular release of infectious viral exosomes. RTN3L&S KD significantly decreased, while RTN3S OE significantly increased the number of Huh7 cell-released infectious exosomes. The C-terminal domain of RTN3 interacted with and modulated the loading of dsHCV RNA inside infectious exosomes. Antiviral treatment of HCV infected Huh7 cells reduced virus-induced RTN3L&S expression and attenuated the release of infectious exosomes. Conclusion RTN3 constitutes a novel regulator and a potential therapeutic target that mediates the specific loading of infectious viral exosomes.

show abstract

Effectiveness of direct-acting antiviral therapy for hepatitis C in difficult-to-treat patients in a safety-net health system: a retrospective cohort study

Cited by 50 publications

References 29 publications

Outcomes of Direct-Acting Antiviral Treatment of Psychiatric Patients with Comorbid Hepatitis C Virus Infection

Outcomes of Direct-Acting Antiviral Treatment of Psychiatric Patients with Comorbid Hepatitis C Virus Infection

Global real‐world evidence of sofosbuvir/velpatasvir as simple, effective HCV treatment: Analysis of 5552 patients from 12 cohorts

Reticulon-3 modulates the incorporation of replication competent hepatitis C virus molecules for release inside infectious exosomes

Contact Info

Product

Resources

About