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Efficacy and Safety of Direct-acting Antivirals in Hepatitis C Virus-infected Patients Taking Proton Pump Inhibitors.

ABSTRACT: Background and Aims: Direct-acting antiviral (DAA) therapy is the cornerstone of the treatment of chronic hepatitis C virus (HCV) infection. Eradication of HCV, predicted by the attainment of a sustained virologic response (SVR) 12 weeks following DAA therapy, is the goal of this treatment. Interestingly, recent studies have reported the possible association between HCV-infected patients with DAA therapy concomitant use of proton pump inhibitors (PPIs) and lower odds of achieving SVR. This meta-analysis was conducted to summarize all available data and to estimate this potential association. Methods: Comprehensive literature review was conducted by first searching the Medline and Embase databases through March 2017 to identify all studies that investigated the safety and efficacy of DAAs in patients with HCV infection taking PPIs versus those without PPIs. Adjusted point estimates from each study were combined by the generic inverse variance method of DerSimonian and Laird. Results: Nine cohort studies with 32,684 participants met the eligibility criteria and were included in the meta-analysis. The use of PPIs concomitant with DAAs among HCV-infected patients was associated with lower odds of achieving SVR compared with non-PPI users (pooled odds ratio (OR): 0.74, 95% confidence interval (CI): 0.63-0.88, I2 = 24%). Subgroup analysis addressed the association between PPIs use and SVR12 demonstrated the association of PPI users showing lower odds of achieving SVR12 compared with those with no use of PPIs (pooled OR: 0.68, 95% CI: 0.51-0.9, I2 = 33%). Conclusions: This study demonstrated a significantly increased risk of failure to achieve SVR in HCV-infected patients taking DAA with PPIs compared to non-PPI users. Providers should consider whether PPI therapy is indicated for patients and withdraw of PPI therapy in the absence of indications, especially while on DAA therapy.

SUBMITTER: Wijarnpreecha K

PROVIDER: S-EPMC5719190 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Efficacy and Safety of Direct-acting Antivirals in Hepatitis C Virus-infected Patients Taking Proton Pump Inhibitors.

Wijarnpreecha Karn K Chesdachai Supavit S Thongprayoon Charat C Jaruvongvanich Veeravich V Ungprasert Patompong P Cheungpasitporn Wisit W

Journal of clinical and translational hepatology 20170818 4

<b><i>Background and Aims</i>:</b> Direct-acting antiviral (DAA) therapy is the cornerstone of the treatment of chronic hepatitis C virus (HCV) infection. Eradication of HCV, predicted by the attainment of a sustained virologic response (SVR) 12 weeks following DAA therapy, is the goal of this treatment. Interestingly, recent studies have reported the possible association between HCV-infected patients with DAA therapy concomitant use of proton pump inhibitors (PPIs) and lower odds of achieving S ...[more]

PMID: 29226099

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Project description:BackgroundDirect acting antivirals (DAAs) have revolutionized hepatitis C (HCV) treatment with >90% cure rates even in real-world studies, giving hope that HCV can be eliminated. However, for DAAs to have a population-level impact on the burden of HCV disease, treatment uptake needs to be expanded. We investigated temporal trends in HCV treatment uptake and evaluated factors associated with second-generation DAA initiation and efficacy among key HIV-HCV co-infected populations in Canada.MethodsThe Canadian HIV-HCV Co-Infection Cohort Study prospectively follows 1699 participants from 18 centres. Among HCV RNA+ participants, we determined the incidence of HCV treatment initiation per year overall and by key populations between 2007 and 2015. Key populations were based on World Health Organization (WHO) guidelines including: people who actively inject drugs (PWID) (reporting injection drug use, last 6 months); Indigenous people; women and men who have sex with men (MSM). Multivariate Cox models were used to estimate adjusted hazard ratios (aHR) and 2-year probability of initiating second-generation DAAs for each of the key populations.ResultsOverall, HCV treatment initiation rates increased from 8 (95% CI, 6-11) /100 person-years in 2013 to 28 (95% CI, 23-33) /100 person-years in 2015. Among 911 HCV RNA + participants, there were 202 second-generation DAA initiations (93% with interferon-free regimens). After adjustment (aHR, 95% CI), active PWID (0.60, 0.38-0.94 compared to people not injecting drugs) and more generally, people with lower income (<$18 000 CAD/year) (0.50, 0.35, 0.71) were less likely to initiate treatment. Conversely, MSM were more likely to initiate 1.95 (1.33, 2.86) compared to heterosexual men. In our cohort, the population profile with the lowest 2-year probability of initiating DAAs was Indigenous, women who inject drugs (5%, 95% CI 3-8%). Not having any of these risk factors resulted in a 35% (95% CI 32-38%) probability of initiating DAA treatment. Sustained virologic response (SVR) rates were >82% in all key populations.ConclusionWhile treatment uptake has increased with the availability of second-generation DAAs, marginalized populations, already engaged in care, are still failing to access treatment. Targeted strategies to address barriers are needed to avoid further health inequities and to maximize the public health impact of DAAs.

Project description:The prevalence of Hepatitis C Virus (HCV) infection is significantly higher in patients with end-stage renal disease compared to the general population and poses important clinical challenges in patients who undergo kidney transplantation. Historically, interferon-based treatment options have been limited by low rates of efficacy and significant side effects, including risk of precipitating rejection. Limited data exist on the use of all-oral, interferon-free direct-acting antiviral (DAA) therapies in kidney transplant recipients. In this study, we performed a retrospective chart review with prospective clinical follow-up of post-kidney transplant patients treated with DAA therapies at three major hospitals in Boston, MA. A total of 24 kidney recipients with HCV infection received all-oral DAA therapy post-transplant. Patients were predominantly male (79%) with a median age of 60 years (range 34-70 years), median creatinine of 1.2 mg/dL (0.66-1.76), and 42% had advanced fibrosis or cirrhosis. The majority had HCV genotype 1a infection (58%). All patients received full-dose sofosbuvir; it was paired with simeprevir (9 patients without and 3 patients with ribavirin), ledipasvir (7 patients without and 1 patient with ribavirin) or ribavirin alone (4 patients). The overall sustained virologic response (SVR12) was 91% (21 out of 23 patients). One patient achieved SVR4 but demised prior to SVR12 check point due to treatment unrelated cause. Two treatment failures were successfully retreated with alternative DAA regimens and achieved SVR. Both initials failures occurred in patients with advanced fibrosis or cirrhosis, with genotype 1a infection, and prior HCV treatment failure. Adverse events were reported in 11 patients (46%) and were managed clinically without discontinuation of therapy. Calcineurin inhibitor trough levels did not significantly change during therapy. In this multi-center series of patients, all-oral DAA therapy appears to be safe and effective in post-kidney transplant patients with chronic HCV infection.

Project description:BACKGROUND: There is evidence that barriers exist for the initiation of direct-acting antiviral (DAA) treatment for hepatitis C virus (HCV) for those with substance use disorders (SUDs). However, real world clinical evidence of DAA treatment initiation following receipt of a prescription and continuation among those with SUDs and HCV is lacking. OBJECTIVES: To (1) compare HCV treatment initiation (prescription fill) rates and early discontinuation rates between HCV-infected patients with and without SUDs in the DAA era, and (2) identify patient-level factors associated with HCV treatment initiation and early discontinuation in patients with SUDs. METHODS: A retrospective cohort analysis of the MarketScan databases (January 2012-December 2018) was conducted for newly diagnosed treatment naïve HCV-infected patients (age ≥ 18) with and without SUDs. We used multivariable Cox regression to estimate adjusted hazard ratios (aHRs) with 95% confidence intervals of treatment initiation and early discontinuation in those with SUDs versus those without. RESULTS: We identified a total of 29,228 newly diagnosed HCV-infected patients (6,385 with SUDs and 22,843 without SUDs). Overall, DAA treatment initiation for patients with SUDs was significantly lower than that for those without SUDs (24% vs 34%; P < 0.01). After adjusting for demographics and clinical characteristics, patients with SUDs were less likely to initiate DAA treatments than those without SUDs (aHR, 0.87 [0.82-0.92]). There was no difference in discontinuation of DAA treatment between those with and without SUDs (4% vs 3%: aHR, 1.13 [0.81-1.60]). Among patients with SUDs (n = 6,385), lower rates of initiating DAA treatment was associated with younger age, and comorbidities including alcoholic liver disease (ALD; aHR, 0.44 [0.33-0.57), chronic kidney disease (CKD) (aHR, 0.52 [0.36-0.75]), and hepatitis B virus (HBV; aHR, 0.64 [0.44-0.92]). DAA treatment discontinuation was associated with younger age, ribavirin (RBV) therapy (aHR, 3.78 [2.21-6.47]), and cirrhosis diagnosis (aHR, 2.42 [1.21-4.84]) but not SUD treatment (aHR, 0.68 [0.34-1.34]). CONCLUSIONS: HCV-infected patients with SUDs had significantly lower treatment initiation rates, especially in young females and those with ALD, CKD, and HBV. No difference was found in DAA discontinuation. However, younger patients with RBV treatment and/or cirrhosis were more likely to stop treatment. Interventions directed towards these groups are needed to enhance DAA initiation and treatment maintenance among HCV-infected patients with SUDs. DISCLOSURES: Research reported in this publication was supported in part by the National Institute on Drug Abuse of the National Institutes of Health under award number K01DA045618 (to Park). The other authors have nothing to disclose that may present a potential conflict of interest.

Dataset Information

Efficacy and Safety of Direct-acting Antivirals in Hepatitis C Virus-infected Patients Taking Proton Pump Inhibitors.

Publications

Efficacy and Safety of Direct-acting Antivirals in Hepatitis C Virus-infected Patients Taking Proton Pump Inhibitors.

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