Hepatitis C Vaccine Development in the Era of Direct-Acting Antivirals.
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ABSTRACT:
SUBMITTER: McConnell M
PROVIDER: S-EPMC6385923 | biostudies-literature | 2018 Nov
REPOSITORIES: biostudies-literature
Publications
Hepatitis C Vaccine Development in the Era of Direct-Acting Antivirals.
McConnell Matthew M Lim Joseph K JK
Clinical liver disease 20181101 5
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Project description:IntroductionThe hepatitis C virus (HCV) epidemic remains a public health problem worldwide. A systematic review and meta-analysis were conducted to provide evidence of outcomes attained across the HCV care cascade in the era of direct-acting antivirals.MethodsStudies from North America, Europe, and Australia (January 2014 through March 2021) reporting on HCV care cascade outcomes (screening to cure) were included. When calculating the proportions of individuals completing each step, the numerator for Steps 1-8 was the number of individuals completing each step; the denominator was the number of individuals completing the previous step for Steps 1-3 and Step 3 for Steps 4-8. In 2022, random effects meta-analyses were conducted to estimate pooled proportions with 95% CIs.ResultsSixty-five studies comprising 7,402,185 individuals were identified. Among individuals with positive HCV ribonucleic acid test results, 62% (95% CI=55%, 70%) attended their first care appointment, 41% (95% CI=37%, 45%) initiated treatment, 38% (95% CI=29%, 48%) completed treatment, and 29% (95% CI=25%, 33%) achieved cure. HCV screening rates were 43% (95% CI=22%, 66%) in prisons or jails and 20% (95% CI=11%, 31%) in emergency departments. Linkage to care rates were 62% (95% CI=46%, 75%) for homeless individuals and 26% (95% CI=22%, 31%) for individuals diagnosed in emergency departments. Cure rates were 51% (95% CI=30%, 73%) in individuals with substance use disorder and 17% (95% CI=17%, 17%) in homeless individuals. Cure rates were lowest in the U.S.DiscussionDespite the availability of effective all-oral direct-acting antiviral therapies, persistent gaps remain across the HCV care cascade, especially among traditionally marginalized populations. Public health interventions targeting identified priority areas (e.g., emergency departments) may improve screening and healthcare retention of vulnerable populations with HCV infection (e.g., substance use disorder populations).
| S-EPMC10749988 | biostudies-literature
Project description: Not available
| S-EPMC6484376 | biostudies-literature
Project description: Not available
| S-EPMC6484383 | biostudies-literature
Project description:The prognostic impact of direct-acting antivirals (DAAs) on patients with hepatitis C-related hepatocellular carcinoma (C-HCC) is still unclear. This study aimed to evaluate the prognosis of C-HCC in the DAA era. We enrolled 1237 consecutive patients with treatment-naive C-HCC who underwent radical radiofrequency ablation between 1999 and 2019. We also enrolled 350 patients with nonviral HCC as controls. We divided these patients into three groups according to the year of initial treatment: 1999-2005 (cohort 1), 2006-2013 (cohort 2), and 2014-2019 (cohort 3). The use of antiviral agents and their effect in patients with C-HCC was investigated. Overall survival was evaluated for each cohort using the Kaplan-Meier method and a multivariable Cox proportional hazards regression model. Sustained virologic response (SVR) was achieved in 52 (10%), 157 (26%), and 102 (74%) patients with C-HCC in cohorts 1-3, respectively. The 3- and 5-year survival rates of patients with C-HCC were 82% and 59% in cohort 1; 80% and 64% in cohort 2; and 86% and 78% in cohort 3, respectively (p = 0.003). Multivariable analysis adjusted for age, liver function, and tumor extension showed that the prognosis of C-HCC improved in cohort 3 compared to cohort 1 (adjusted hazard ratio [aHR], 0.49; 95% confidence interval [CI], 0.32-0.73; p < 0.001), whereas the prognosis of nonviral HCC did not improve significantly (aHR, 0.96; 95% CI, 0.59-1.57; p = 0.88). The prognosis of C-HCC drastically improved with the advent of DAAs.
| S-EPMC9426397 | biostudies-literature
Project description:BackgroundThe introduction of oral direct-acting antivirals (DAAs) has dramatically changed the landscape of HCV treatment. However, a small percentage of patients fail to achieve sustained virologic response (SVR). Understanding the number of people who fail on DAAs and require re-treatment is important for budget impact and disease burden projections.AimTo quantify the number of HCV patients who fail to achieve SVR on oral DAAs (NS5A vs. non-NS5A) and require re-treatment.MethodsWe used a mathematical model to simulate clinical management of HCV in the USA, which included the implementation of HCV screening, treatment, and disease progression. We simulated different waves of DAA treatment and used real-world data to extract SVR rates and market shares of available therapies.ResultsOur model projected that the number of people living without viraemia (i.e. cured) would increase from 0.70 million in 2014 to 1.78 million by 2020. Between 2014 and 2020, 1.50 million people would receive treatment with DAAs, of whom 124 000 (8.3%) are projected to fail to achieve SVR. Among those treatment failures, 66 600 (53.7%) patients would fail treatment with NS5A inhibitors and 69 600 (56.1%) would have cirrhosis. During the same period, 34 200 people would progress to decompensated cirrhosis and 27 300 would develop hepatocellular carcinoma after failing to achieve SVR.ConclusionsEven in the era of highly effective DAAs, a significant number of patients will fail to achieve SVR and will require re-treatment options. Timely and effective re-treatment is essential to prevent the long-term sequelae of HCV.
| S-EPMC5842132 | biostudies-literature
Project description:Oral direct-acting antivirals (DAAs) represent a major advance in hepatitis C virus (HCV) treatment. Along with recent updates in HCV screening policy and expansions in insurance coverage, treatment demand in the United States is changing rapidly. Our objective was to project the characteristics and number of people needing antiviral treatment and HCV-associated disease burden in the era of oral DAAs. We used a previously developed and validated Hepatitis C Disease Burden Simulation model (HEP-SIM). HEP-SIM simulated the actual clinical management of HCV from 2001 onward, which included antiviral treatment with pegylated interferon (Peg-IFN)-based therapies as well as the recent oral DAAs, risk-based and birth-cohort HCV screening, and the impact of the Affordable Care Act. We also simulated two hypothetical scenarios-no treatment and treatment with Peg-IFN-based therapies only. We estimated that in 2010, 2.5 (95% confidence interval [CI], 1.9-3.1) million noninstitutionalized people were viremic, which dropped to 1.9 (95% CI, 1.4-2.6) million in 2015, and projected to drop below 1 million by 2020. A total of 1.8 million HCV patients will receive HCV treatment from the launch of oral DAAs in 2014 until 2030. Based on current HCV management practices, it will take 4-6 years to treat the majority of patients aware of their disease. However, 560,000 patients would still remain unaware by 2020. Even in the oral DAA era, 320,000 patients will die, 157,000 will develop hepatocellular carcinoma, and 203,000 will develop decompensated cirrhosis in the next 35 years.ConclusionsHCV-associated disease burden will still remain substantial in the era of oral DAAs. Increasing HCV screening and treatment capacity is essential to further decreasing HCV burden in the United States. (Hepatology 2016;64:1442-1450).
| S-EPMC5035714 | biostudies-literature
Project description:In recent years, great progress has been made in the field of new therapeutic options for hepatitis C virus (HCV) infection. The new direct-acting antiviral agents (DAAs) represent a great hope for millions of chronically infected individuals because their use may lead to excellent cure rates with fewer side effects. In Latin America, the high prevalence of HCV genotype 1 infection and the significant association of Native American ancestry with risk predictive single-nucleotide polymorphisms (SNPs) in IFNL4 and ITPA genes highlight the need to implement new treatment regimens in these populations. However, the universal accessibility to DAAs is still not a reality in the region as their high cost is one of the major, although not the only, limiting factors for their broad implementation. Therefore, under these circumstances, could the assessment of host genetic markers be a useful tool to prioritize DAA treatment until global access to these new drugs can be achieved? This review will summarize the scientific evidences and the potential implications of HCV pharmacogenomics in this rapidly evolving era of anti-HCV drug development.
| S-EPMC5378445 | biostudies-literature
Project description:Background:Treatment of hepatitis C virus (HCV) infection with direct-acting antivirals (DAAs) results in sustained virologic response (SVR) in > 90% of patients. However, some patients required retreatment with newer DAA options. Treatment was selected after consultation with a clinical pharmacy specialist. Methods:A retrospective chart review of patients at the West Palm Beach Veterans Affairs Medical Center (WPBVAMC) in Florida retreated from January 2015 to December 2019 was conducted. Data collected included HCV genotype, previous therapy, newly prescribed medications, and treatment outcomes. Results:Since 2015, > 900 patients have been treated at WPBVAMC, including 22 patients who had previously failed interferon combined with DAA regimens and 46 patients who needed retreatment after failure with an all-oral therapy. This review documents the outcomes of retreatment with DAA after initial failure to achieve SVR Of 28 patients treated with a boceprevir-based regimen, 10 ended in failure. All 10 were retreated, and all achieved SVR with ledipasvir/sofosbuvir. Of 53 patients treated with a sofosbuvir-based interferon regimen, 12 failed treatment. All 12 were retreated and all achieved SVR. Thirty patients were retreated after failure with an all-oral DAA. Of 27 tested, 21 achieved SVR. All patients who failed therapy again had cirrhosis. Conclusions:Veterans retreated with DAAs for HCV infection had a high success rate. Repeat failures of DAAs were rare, but cirrhosis seems to be common among these patients.
| S-EPMC7473721 | biostudies-literature
Project description:When interferons (IFNs) bind to their receptors, they upregulate numerous IFN-stimulated genes (ISGs) with antiviral and immune regulatory activities. Hepatitis C virus (HCV) is a single-stranded, positive-sense RNA virus that affects over 71 million people in the global population. Hepatocytes infected with HCV produce types I and III IFNs. These endogenous IFNs upregulate a set of ISGs that negatively impact the outcome of pegylated IFN-? and ribavirin treatments, which were previously used to treat HCV. In addition, the IFNL4 genotype was the primary polymorphism responsible for a suboptimal treatment response to pegylated IFN-? and ribavirin. However, recently developed direct-acting antivirals have demonstrated a high rate of sustained virological response without pegylated IFN-?. Herein, we review recent studies on types I and III IFN responses to in HCV-infected hepatocytes. In particular, we focused on open issues related to IFN responses in the direct-acting antiviral era.
| S-EPMC7177520 | biostudies-literature
Project description:The development and evaluation of antiviral agents through carefully designed clinical trials over the last 25 years have heralded a new dawn in the treatment of patients chronically infected with the hepatitis B and C viruses, but not so for the D virus (HBV, HCV, and HDV). The introduction of direct acting antivirals (DDAs) for the treatment of HBV carriers has permitted the long-term use of these compounds for the continuous suppression of viral replication, whilst in the case of HCV in combination with the standard of care [SOC, pegylated interferon (PegIFN), and ribavirin] sustained virological responses (SVRs) have been achieved with increasing frequency. Progress in the case of HDV has been slow and lacking in significant breakthroughs.This paper aims to summarise the current state of play in treatment approaches for chonic viral hepatitis patients and future perspectives.
| S-EPMC3820491 | biostudies-literature