Direct-acting Antivirals Use Research Articles

The Impact of the G6PD Gene Mutations in Patients with Chronic Hepatitis C Infection Treated with Direct-Acting Antivirals: A Multicenter Observational Study.

Following the advent of direct-acting antivirals (DAAs), the treatment of hepatitis C virus (HCV) infection is now rarely challenging. However, data are still limited concerning DAA use in patients affected by glucose-6-phosphate dehydrogenase deficiency (G6PDd). Based on these considerations, the goal of this study was to evaluate the effectiveness and safety of DAAs in this subpopulation. A retrospective multicenter observational study (2015-2023) was conducted on all 2754 consecutive HCV-positive patients treated with first- and second-generation all-oral DAAs, and with a G6PDd diagnosis confirmed by quantitative testing (n = 38). At the treating clinician's discretion, an enhanced clinical and laboratory follow-up was performed, generally on a monthly basis both during treatment and up to six months after the end of it. Concerning hematochemical parameters, no significant differences were found between any considered time point. In all cases, no treatment-related adverse events were reported, and virologic response rates were as expected without G6PDd. In conclusion, in a large experience which, to the best of our knowledge, is unprecedented in the literature, the treatment of HCV hepatitis with nearly all available DAAs in patients with G6PDd as a comorbidity-a common occurrence in countries such as Italy-proved to be highly effective and safe.

Regional differences in access to direct-acting antiviral treatments for hepatitis C across Ontario: A cross-sectional study.

Direct-acting antivirals (DAAs) are curative treatments for hepatitis C virus (HCV) infection, a condition affecting over 100,000 Ontarians. Although DAAs are covered under the public drug programs in Ontario, receiving prescriptions depends on access to healthcare. The aim of this study is to understand the relationship between DAA treatment rates and distance to prescriber in Ontario, Canada. We conducted a cross-sectional study and identified patients who filled a DAA prescription through the Ontario Drug Benefit (ODB) in 2019. We calculated crude (per 100,000 ODB recipients) and adjusted (by a regional HCV infection rate) DAA treatment rates by public health unit (PHU). We reported median distances to provider for all visit types, in-person visits, virtual visits, and proportions of visits that were virtual. In 2019, the crude DAA treatment rate for Ontario is 83.0 patients per 100,000 ODB recipients. The HCV-adjusted DAA treatment rate ranges from 28.2 (Northwestern Ontario) to 188.5 (Eastern Ontario) per 100,000. In our primary analysis, patients in rural PHUs, including Northwestern and Porcupine, were among the highest median distances to prescriber for all visit types (1,195 km and 556 km, respectively). These PHUs also had the highest proportions of virtual visits (greater than 60%). Urban PHUs, such as Toronto and Ottawa, had smaller median distances for all visit types, with smaller proportions of virtual visits (10.8% and 12.4%, respectively). We observed heterogeneity in treatment rates, distance to DAA prescribers and use of virtual care in the management of HCV. Increasing use of telemedicine in regions with limited utilization of DAAs may improve access.

Changing Trends of Cirrhotic and Noncirrhotic Hepatocellular Carcinoma in the Era of Directly-Acting Antiviral Agents.

INTRODUCTION:The impact of direct-acting antivirals (DAAs) for hepatitis C virus (HCV) on burden of cirrhotic and noncirrhotic hepatocellular carcinoma (HCC) has not been examined. We assessed recent trends in liver disease etiologies of HCC and proportion of noncirrhotic HCC since DAAs introduction.METHODS:Clinical characteristics including presence or absence of underlying cirrhosis were collected from 2,623 patients diagnosed with HCC between 2009 and 2019 at 2 large US centers. Logistic regression was performed to investigate the annual trends of HCC due to different liver diseases and proportions of noncirrhotic cases.RESULTS:In the DAA era (2014–2019), annual decline in HCV-HCC (odds ratio [OR] = 0.93, 95% confidence interval [CI] 0.88–0.99, P = 0.019), without change in trends of other liver diseases–related HCC, was observed. Annual increase in noncirrhotic HCC (OR 1.13, 95% CI 1.03–1.23, P = 0.009) and decline in cirrhotic HCC (OR 0.89, 95% CI 0.81–0.97, P = 0.009) along with similar trends for HCV-HCC—increase in noncirrhotic cases (OR 1.35, 95% CI 1.08–1.69, P = 0.009) and decrease in cirrhotic cases (OR 0.92, 95% CI 0.86–0.98, P = 0.012)—were observed during the DAA era. Compared with the pre-DAA era, HCC resection rate increased (10.7% vs 14.0%, P = 0.013) whereas liver transplantation rate decreased (15.1% vs 12.0%, P = 0.023) in the DAA era.DISCUSSION:Since introduction of DAAs, proportions of cirrhotic HCC have decreased, whereas proportions of noncirrhotic HCC have increased. These new trends were associated with change in utilization of liver resection and transplantation for HCC. The impact of changing patterns of DAA use on these trends will require further study.

Effect of relaxing hepatitis C treatment restrictions on direct-acting antiviral use in a Medicaid program: an interrupted time series analysis.

BACKGROUND: Although direct-acting antivirals (DAA) have revolutionized the treatment of chronic hepatitis C virus (HCV), many state Medicaid programs have limited coverage because of their expense. In 2015, the Centers for Medicare & Medicaid Services (CMS) notified states about the legality of Medicaid coverage limitations, particularly within managed care programs. OBJECTIVES: To (1) examine how relaxation and alignment of hepatitis C policies within the Oregon Medicaid program affected DAA utilization and (2) describe changes in DAA coverage policies and patient characteristics of treated individuals over time. METHODS: We manually collected DAA Medicaid drug policies in the state of Oregon before and after the CMS notification was released. After categorizing DAA policies into 2 groups based on baseline prior authorization criteria (restrictive and permissive), we evaluated how changes in these DAA policies affected utilization over 3 time periods (pre-CMS period, post-CMS period, and fibrosis policy alignment). Immediate and gradual changes in trend were assessed using an interrupted time series regression model. Finally, we examined patient characteristics and liver disease complications over time as policy restrictions were removed and aligned with one another. RESULTS: From 2014 to 2018, Oregon's coordinated care organizations and fee-for-service drug policies relaxed liver fibrosis and substance abstinence coverage criteria leading to immediate increases in DAA use in 2016 (0.62 prescriptions per 10,000 enrollees per month; 95% CI = 0.17 to 1.08) and 2018 (1.07 prescriptions per 10,000 enrollees per month; 95% CI = 0.63 to 1.51) among more restrictive coordinated care organizations at baseline. This was followed by a decrease in trend after the 2016 and 2018 impact (-0.05; 95% CI = -0.11 to -0.001 and -0.07; 95% CI = -0.13 to -0.02, respectively). Over the 3 periods, there was a decrease in treated individuals with liver-related complications (P < 0.0001) and an increase in those with a substance use diagnosis (P = 0.0013). CONCLUSIONS: Reducing coverage limitations resulted in treatment of patients with fewer liver-related complications and more substance use disorders. Expanding access to treatment did not result in sustained increases in utilization, and additional interventions may be necessary to meet HCV elimination goals. DISCLOSURES: This study was funded in part by AbbVie Pharmaceuticals, which did not have any role in the study design, collection, analysis and interpretation of data, writing the report, or the decision to submit the report for publication. Hartung received support for his work on this study via a grant from AbbVie Pharmaceuticals. The other authors did not receive any financial support for their contributions to this study. The authors have no other financial disclosures to report. This study was presented at the Academy Health Annual Research Meeting in Washington, DC, on June 3, 2019.

Use of Direct-Acting Antiviral Agents and Survival Among Medicare Beneficiaries with Dementia and Chronic Hepatitis C.

Many patients with Alzheimer's disease and related dementia (ADRD) have chronic hepatitis C due to the high prevalence of both conditions among elderly populations. Direct-acting antivirals (DAAs) are effective in treating hepatitis C virus (HCV). However, the complexity of ADRD care may affect DAA use and outcomes among patients with HCV and ADRD. Little information exists on uptake of DAAs, factors associated with DAA use, and health benefits of DAAs among patients with HCV and ADRD. To examine use and survival benefits of DAAs in Medicare patients with HCV and ADRD. The study included Medicare patients with HCV between 2014 and 2017. We estimated Cox proportional hazards regressions to examine the association between having ADRD and DAA use, and the relation between DAA use and survival among patients with HCV and ADRD. The adjusted hazard of initiating a DAA was 50% lower in patients with ADRD than those without ADRD (adjusted HR = 0.50, 95% CI: 0.46-0.54). The hazard of DAA use among ADRD patients with behavioral disturbances was 68% lower than non-ADRD patients (adjusted HR = 0.32, 95% CI: 0.28-0.37). DAA treatment was associated with a significant reduction in mortality among ADRD patients (adjusted HR = 0.52, 95% CI: 0.44-0.61). The rate of DAA treatment in patients with HCV and ADRD was low, particularly among those with behavioral disturbance. The survival benefits of DAA treatment for patients with ADRD were substantial.

Direct-Acting Antivirals Improve Overall Survival in Interventional Oncology Patients with Hepatitis C and Hepatocellular Carcinoma

PurposeTo investigate the impact of direct-acting antivirals (DAAs) and 12-week sustained virologic response (SVR12) in patients with hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) treated by interventional oncology (IO) therapies. Materials and MethodsRetrospective analysis of patients diagnosed from 2005 to 2016 with HCC and receiving IO therapies. A total of 478 patients met inclusion criteria. Patients were age 29–90 years (mean 63.6 ± 9.4 years) and 78.9% (n =3 77) male. Two hundred and eighty-five (57%) patients had chronic HCV, 93 (33%) received DAAs, and 63 (68%) achieved SVR12. Liver function, tumor characteristics, and IO therapy including ablation, image-guided transcatheter tumor therapies (ITTT) (eg, chemoembolization and radioembolization), and combination locoregional therapy were assessed in analysis. ResultsMedian overall survival (OS) of the cohort was 26.7 months (95% confidence interval [CI] 21.9–29.9). OS for ablation, combination locoregional therapy and ITTT, was 37.3 (CI 30.7–49.9), 29.3 (CI 24.2–38.0), and 19.7 months (CI 16.5–22.8), respectively (P < .0001). OS in patients with HCV was 30.7 months (CI 24.2–35.2) versus 22.2 months in non-HCV patients (CI 17.8–27.8, P = .03). Patients with HCV who received DAA had higher survival, 49.2 months (CI 36.5–not reached) versus those not receiving DAA, 18.5 months (CI 14.1–25.3, P < .0001). OS was 71.8 months (CI 42.3–not reached) for patients who achieved SVR12 after DAA versus 26.7 months in the non-SVR12 group (CI 15.9–31.1, P < .0001). Multivariable analysis revealed independent factors for OS including IO treatment type, DAA use and achieving SVR12 (P < .05). ConclusionsDAA use and SVR12 is associated with higher OS in patients with HCV-related HCC treated by IO therapies.

Impact of Direct Acting Antivirals on Survival in Patients with Chronic Hepatitis C and Hepatocellular Carcinoma

With the increasing use of direct-acting antivirals (DAA) for treatment of chronic hepatitis C virus (HCV) infection, we looked at the impact of DAA use and 12-week sustained viral response (SVR12) in patients with hepatocellular carcinoma (HCC) and HCV. This is a retrospective analysis of 969 HCC patients diagnosed from 2005 to 2016 at an urban tertiary-care hospital. Kaplan-Meier curves and multivariable Cox proportional hazards models were used to assess survival. Median overall survival of the cohort was 24.2 months. 470 patients had HCV (56%). 123 patients received DAA therapies for HCV (26.2%), 83 of whom achieved SVR12 (67.4%). HCV-positive and HCV-negative patients had similar survival, 20.7 months vs 17.4 months (p = 0.22). Patients receiving DAA therapy had an overall survival of 71.8 months vs 11.6 months for patients without (p < 0.0001). DAA patients who achieved SVR12 had an overall survival of 75.6 months vs. 26.7 months in the non SVR12 group (p < 0.0001). Multivariable analysis revealed AJCC, Child-Pugh Score, MELD, tumor size, tumor location, cancer treatment type, receiving DAA treatment and achieving SVR12 had independent influence on survival (p < 0.05). This suggests DAA therapy and achieving SVR12 is associated with increased overall survival in HCV patients with HCC.

Scaling up prevention and treatment towards the elimination of hepatitis C: a global mathematical model

SummaryBackgroundThe revolution in hepatitis C virus (HCV) treatment through the development of direct-acting antivirals (DAAs) has generated international interest in the global elimination of the disease as a public health threat. In 2017, this led WHO to establish elimination targets for 2030. We evaluated the impact of public health interventions on the global HCV epidemic and investigated whether WHO's elimination targets could be met.MethodsWe developed a dynamic transmission model of the global HCV epidemic, calibrated to 190 countries, which incorporates data on demography, people who inject drugs (PWID), current coverage of treatment and prevention programmes, natural history of the disease, HCV prevalence, and HCV-attributable mortality. We estimated the worldwide impact of scaling up interventions that reduce risk of transmission, improve access to treatment, and increase screening for HCV infection by considering six scenarios: no change made to existing levels of diagnosis or treatment; sequentially adding the following interventions: blood safety and infection control, PWID harm reduction, offering of DAAs at diagnosis, and outreach screening to increase the number diagnosed; and a scenario in which DAAs are not introduced (ie, treatment is only with pegylated interferon and oral ribavirin) to investigate the effect of DAA use. We explored the effect of varying the coverage or impact of these interventions in sensitivity analyses and also assessed the impact on the global epidemic of removing certain key countries from the package of interventions.FindingsBy 2030, interventions that reduce risk of transmission in the non-PWID population by 80% and increase coverage of harm reduction services to 40% of PWID could avert 14·1 million (95% credible interval 13·0–15·2) new infections. Offering DAAs at time of diagnosis in all countries could prevent 640 000 deaths (620 000–670 000) from cirrhosis and liver cancer. A comprehensive package of prevention, screening, and treatment interventions could avert 15·1 million (13·8–16·1) new infections and 1·5 million (1·4–1·6) cirrhosis and liver cancer deaths, corresponding to an 81% (78–82) reduction in incidence and a 61% (60–62) reduction in mortality compared with 2015 baseline. This reaches the WHO HCV incidence reduction target of 80% but is just short of the mortality reduction target of 65%, which could be reached by 2032. Reducing global burden depends upon success of prevention interventions, implemention of outreach screening, and progress made in key high-burden countries including China, India, and Pakistan.InterpretationFurther improvements in blood safety and infection control, expansion or creation of PWID harm reduction services, and extensive screening for HCV with concomitant treatment for all are necessary to reduce the burden of HCV. These findings should inform the ongoing global action to eliminate the HCV epidemic.FundingWellcome Trust.

Treatment of Hepatitis C during Pregnancy-Weighing the Risks and Benefits in Contrast to HIV.

Increasing hepatitis C virus (HCV) cases over the past decade have raised concerns about subsequent increased cases in infants due to mother to child transmission (MTCT). Many are reminded of the early days of HIV and the rationale for using antiretroviral agents during pregnancy. Direct-acting antivirals (DAAs) that are highly potent, all-oral, short-duration regimens that cure HCV have led many to consider what it would entail to use DAAs for pregnant women. Considering HIV and Hepatitis B virus (HBV) as two infections with MTCT to draw lessons from, DAA use to interrupt HCV MTCT comes with risks, costs, and many potential benefits. When considering how to effectively curb the current epidemic of HCV in the US population, using DAAs to treat pregnant women with HCV offers potential benefits to the mother immediately, to the pair in the short-term and to the child, family, and society over a lifetime.

The Incidence of Hepatocellular Carcinoma Is not Increased in Individuals with Chronic Hepatitis C After Treatment with Interferon-free Regimens: an ERCHIVES Study

BackgroundSustained virologic response (SVR) after interferon-based treatment for chronic hepatitis C virus (HCV) infection has been strongly linked with decreased incidence of hepatocellular carcinoma (HCC). Surprisingly, several recent studies have reported higher rates of HCC in individuals treated with direct-acting antivirals (DAAs). However, making definitive conclusions has been challenging due to the heterogeneous populations and methodologies of these reports. As such, we sought to investigate whether DAA use is associated with increased rates of incident HCC.MethodsUsing the Electronically Retrieved Cohort of HCV Infected Veterans (ERCHIVES) database, we identified 17,836 patients without a prior diagnosis of HCC and divided them into 3 groups based on treatment: (a) pegylated interferon and ribavirin (IFN) (n = 3,534); (b) DAA-based therapy (n = 5,734); and (c) an untreated control group (n = 8,468). Predictors of HCC were identified using multivariate Cox proportional hazards analysis. HCC-free survival in cirrhotics was assessed by Kaplan–Meier analysis.ResultsSVR was achieved by 66.6% and 96.2% of the IFN and DAA groups, respectively. In our cohort, the incidence rate of HCC was not different between IFN and DAA groups (7.48/1000 vs. 7.92/1000 patient-years of follow-up; P = 0.72). Moreover, DAA treatment was not associated with an increased risk of HCC (HR 1.16; [95% CI: 0.79, 1.71]) compared to IFN treatment. Other risk factors for HCC included older age, alcohol abuse/dependance history, smoking history, HCV genotype 3 infection, proton-pump inhibitor use, AFP > 20, and cirrhosis. Notably, among cirrhotics who achieve SVR, HCC-free survival was not different between IFN and DAA treated groups, and both groups had significantly improved HCC-free survival compared with untreated patients.ConclusionAmong cirrhotic patients with HCV, DAA treatment is associated with a comparable risk of HCC to IFN treatment. Furthermore, the rate of HCC after SVR by any treatment was significantly lower than for those untreated or who failed to achieve SVR. Previously reported increases in HCC associated with DAA treatment appear to be explained by the presence of pre-existing risk factors for HCC.Disclosures R. T. Chung, Gilead: Investigator, Research grant; Abbvie: Investigator, Research grant; Merck: Investigator, Research grant; Janssen: Investigator, Research grant; A. Butt, Merck: Investigator, Grant recipient

Hepatitis C Virus Postexposure Prophylaxis in the Healthcare Worker: Why Direct-Acting Antivirals Don't Change a Thing.

Currently, 380 000-400 000 occupational exposures to blood-borne pathogens occur annually in the United States. The management for occupational HIV or hepatitis B virus exposures includes postexposure prophylaxis (PEP) when necessary; however, PEP is not recommended for hepatitis C virus (HCV) exposures. Recent approval of HCV direct-acting antivirals (DAAs) has renewed discussions as to whether these therapies could be used to prevent infection after exposure. There are no published studies addressing this question, but the prescribing of DAAs for PEP has been reported. We will discuss the differences in transmission of the 3 most common blood-borne pathogens, the natural history of early HCV infection, and the scientific rationale for PEP. In particular, we will discuss how the low feasibility of conducting an adequately powered clinical trial of DAA use for PEP and the low cost-effectiveness of such an intervention is not supportive of targeting limited resources for such use.