Era Of Direct-acting Antiviral Therapy Research Articles

Ribavirin revisited in the era of direct-acting antiviral therapy for hepatitis C virus infection.

Over the past two decades, ribavirin has been an integral component of treatment for hepatitis C virus (HCV) infection, where it has been shown to improve the efficacy of (pegylated) interferon. However, because of treatment‐limiting side effects and its additive toxicity with interferon, the search for interferon‐ and ribavirin‐free regimens has been underway. The recent approvals of all‐oral direct acting antivirals (DAAs) have revolutionized the HCV therapeutic landscape, and initially it was expected that the role of ribavirin with DAA regimens would be eliminated. On the contrary, what we have witnessed is that ribavirin retains an important role in the optimal treatment of some subgroups of patients, particularly those that historically have been considered the most difficult to cure. Fortunately, it has also been recognized that the safety profile of ribavirin is improved when co‐administered with all‐oral DAA combinations in the absence of interferon. Despite the antiviral mechanism of action of ribavirin being poorly understood, we now have a range of novel insights into the potential role of ribavirin in all‐oral DAA HCV treatment and greater insight into the antiviral mechanism by which it continues to provide clinical benefit for defined patient groups.

Primary Care Physician Perspectives on Hepatitis C Management in the Era of Direct-Acting Antiviral Therapy.

Primary care physicians (PCPs) play a critical role in the care cascade for patients with chronic hepatitis C (CHC). To assess PCP knowledge and perspectives on CHC screening, diagnosis, referral, and treatment. An anonymous survey was distributed to PCPs who participated in routine outpatient care at our hospital. Eighty (36%) eligible PCPs completed the survey. More than half were females (60%) aged 36-50 (55%) from family (44%) or internal (49%) medicine. Overall, PCPs correctly identified high-risk populations for screening, though 19% failed to identify baby boomers and 45% failed to identify hemodialysis patients as populations to screen. Approximately half reported they were able to screen at risk patients <50% of the time secondary to time constraints and difficulty assessing if patients had already been screened. 71% of PCPs reported they refer all newly diagnosed patients to specialty care. 70% of PCPs did not feel up to date with current treatment. The majority grossly underestimated efficacy, tolerability and ease of administration, and overestimated treatment duration. Only 9% felt comfortable treating CHC, even those without cirrhosis. Practice patterns were influenced by specialty and Veterans Affairs Hospital affiliation. Although the majority of PCPs are up to date with CHC screening recommendations, few are able to routinely screen in practice. Most PCPs are not up to date with treatment and do not feel comfortable treating CHC. Interventions to overcome screening barriers and expand treatment into primary care settings are needed to maximize access to and use of curative therapies.

Causes of treatment failure for hepatitis C in the era of direct-acting antiviral therapy.

Hepatitis C therapy in the era of the newer direct-acting antiviral agents has radically changed our treatment schemes by achieving very high rates of sustained virological response. However, treatment with direct antiviral agents fails in a subgroup of patients. This group of so-called difficult-to-treat individuals is the subject of this paper, which reviews the causes of virological failure, their clinical implications, and some final recommendations.

National Survey of Hepatitis C Treatment Practice Patterns in the Era of Direct-Acting Antiviral Therapy

Introduction: Hepatitis C virus (HCV) therapy is amidst a revolution with the introduction of directacting antiviral (DAA) therapy. The aims of our study were to: 1.) characterize provider attitudes and practice patterns for HCV after introduction of DAA therapy in the United States, and 2.) identify patient characteristics driving provider treatment decisions. Methods: We conducted a national web-based survey among providers treating HCV patients 5 months after the AASLD/IDSA published the HCV practice guidelines. The survey included questions on pretherapy evaluation, on-treatment management, and clinical vignettes. Stepwise multivariate logistic regression was performed to determine associations between provider characteristics and HCV treatment practice patterns. Results: Of 1,179 deliverable emails, 125 (10.6%) clinicians responded. The majority of providers were male (64%) and part of an academic practice (74%). Thirty-nine percent of providers had been in practice <10 years, 33% for 11-20 years, and 28% for more than 20 years. All but 8% of providers had treated HCV patients in the past year, with nearly one-third treating more than 1 patient per week. Of those who treated HCV patients, 91% reported continued use of PEG-interferon (IFN) in selected patients. Providers reported being more likely to treat patients with psychiatric comorbidities (85%), decompensated cirrhosis (84%), and cytopenia (89%), given availability of DAA agents. The most important factors for selecting HCV treatment regimens were efficacy (96%), side effect profile (69%), duration of treatment (41%), and number of pills (40%). Cost (22%) and ease of prescribing (5%) were not considered important factors. The majority of providers (62%) prefer to defer therapy in genotype 1 HCV patients with mild fibrosis, but only a minority defer if genotype 3 (39%) or genotype 4 (49%). In genotype 1 patients with advanced fibrosis, most providers (49%) use sofosbuvir (SOF) + simeprevir (SIM) combination therapy, while 37% use SOF + PEG-IFN and RBV. The proportion using SOF + SIM was higher among patients who had failed prior PEG-IFN therapy (65%) or were post-transplant (62%). Most common therapy in genotype 3 HCV with advanced fibrosis was SOF and RBV (57%), while the most common in genotype 4 was SOF + PEG-IFN and RBV (46%). Conclusion: Providers preferentially use IFN-free regimens for HCV and are more willing to treat difficult-to-treat subgroups such as those with psychiatric comorbidities and decompensated cirrhosis. Efficacy, safety, and duration of treatment were the most important factors driving choice of HCV regimen. The survey results are consistent with AASLD/IDSA HCV guidelines published in January 2014. Disclosure - Dr. Alqahtani - Advisroy committees: Gilead, Janssen. Grant/Reserach support: Gilead, Merck; Dr. Sulkowski - Advisory Committees: Pfizer; Consulting: Merck, AbbVie, BIPI, Vertex, Janssen, Gilead, BMS; Grant/Research Support: Merck, AbbVie, BIPI, Vertex, Janssen, Gilead; Dr. Gurakar - Advisory Committees: Gilead, Research Support: BMS.DR. Durand- Grant/Research Support: Gilead, BMS.

Revisiting the Predictors of a Sustained Virologic Response in the Era of Direct-Acting Antiviral Therapy for Hepatitis C Virus

Several host (age, sex, race, fibrosis stage, interleukin 28B polymorphism) and viral factors (hepatitis C virus [HCV] genotype, viral load) allow estimating the response to interferon-based therapies (which includes first-generation protease inhibitors) before treatment. However, treatment should not be denied to any patient based on unfavorable factors alone. Metabolic conditions associated with poor response (diabetes, insulin resistance, obesity) and alcohol abuse can be influenced before starting treatment. "On-treatment" predictors of response allow treatment to be tailored to the individual need of the patient. Patients with undetectable HCV RNA after 4 weeks (rapid virologic response [RVR]) have the highest chance for cure (>85%) both by dual and triple therapy. For triple therapy, the decision to shorten treatment requires that the virus remains undetectable for an additional 8 (telaprevir) to 20 (boceprevir) weeks (extended RVR). Based on viral kinetics, an even earlier prediction after 2 weeks of treatment with direct acting antivirals appears feasible.

Hepatitis C genotype 1 infection in HIV-Infected patients in the era of direct-acting antiviral therapy.

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