Innovations in Hepatitis C Screening and Treatment.
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ABSTRACT:
SUBMITTER: Patel AA
PROVIDER: S-EPMC7917266 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Viral hepatitis is a significant health problem worldwide, associated with morbidity and mortality. Hepatitis B, C, D, and occasionally E viruses (HBV, HCV, HDV, and HEV) can evolve in chronic infections, whereas hepatitis A virus (HAV) frequently produces acute self-limiting hepatitis. In the last years, different studies have been performed to introduce new antiviral therapies. The most important goal in the treatment of viral hepatitis is to avoid chronic liver disease and complications. This review analyzes currently available therapies, in particular for viruses associated with chronic liver disease. The focus is especially on HBV and HCV therapies, investigating new drugs already introduced in clinical practice and clinical trials. We also describe new entry inhibitors, developed for the treatment of chronic HDV and HBV and currently available treatments for HEV. The last drugs introduced have shown important efficacy in HCV, with achievable target HCV elimination by 2030. Concurrently, renewed interest in curative HBV therapies has been registered; current nucleotide/nucleoside analogs positively impact liver-related complications, ensuring high safety and tolerability. Novel approaches to HBV cure are based on new antivirals, targeting different steps of the HBV life cycle and immune modulators. The improved knowledge of the HDV life cycle has facilitated the development of some direct-acting agents, as bulevirtide, the first drug conditionally approved in Europe for HDV associated compensated liver disease. Further studies are required to identify a new therapeutic approach in hepatitis E, especially in immunosuppressed patients.
| S-EPMC8905017 | biostudies-literature
Project description: Not available
| S-EPMC6756955 | biostudies-literature
Project description:The prevalence of hepatitis C virus (HCV) in U.S. prisoners is high; however, HCV testing and treatment are rare. Infected inmates released back into society contribute to the spread of HCV in the general population. Routine hepatitis screening of inmates followed by new therapies may reduce ongoing HCV transmission.To evaluate the health and economic effect of HCV screening and treatment in prisons on the HCV epidemic in society.Agent-based microsimulation model of HCV transmission and progression of HCV disease.Published literature.Population in U.S. prisons and general community.30 years.Societal.Risk-based and universal opt-out hepatitis C screening in prisons, followed by treatment in a portion of patients.Prevention of HCV transmission and associated disease in prisons and society, costs, quality-adjusted life-years (QALYs), incremental cost-effectiveness ratio (ICER), and total prison budget.Implementing risk-based and opt-out screening could diagnose 41,900 to 122,700 new HCV cases in prisons in the next 30 years. Compared with no screening, these scenarios could prevent 5500 to 12,700 new HCV infections caused by released inmates, wherein about 90% of averted infections would have occurred outside of prisons. Screening could also prevent 4200 to 11,700 liver-related deaths. The ICERs of screening scenarios were $19,600 to $29,200 per QALY, and the respective first-year prison budget was $900 to $1150 million. Prisons would require an additional 12.4% of their current health care budget to implement such interventions.Results were sensitive to the time horizon, and ICERs otherwise remained less than $50,000 per QALY.Data on transmission network, reinfection rate, and opt-out HCV screening rate are lacking.Universal opt-out HCV screening in prisons is highly cost-effective and would reduce HCV transmission and HCV-associated diseases primarily in the outside community. Investing in U.S. prisons to manage hepatitis C is a strategic approach to address the current epidemic.National Institutes of Health.
| S-EPMC4854298 | biostudies-literature
Project description:The cooperation of physicians, engineers and other sciences results in a steady launching of effective tools for vascular treatment, which further support the dominating position of endovascular therapy in the field of PAD. Parallel to the treatment options, non-radiation based image guidance is another area, where innovation helps to reduce radiation burden for patient and staff members without losing procedural quality and despite a growing number of radiation based procedures. Meanwhile, the available portfolio of endovascular tools allows to treat every vessel segment with results comparable to or even better then open surgery. This survey presents new techniques, tools and recently published results from related trials, which will probably have further influence on PAD treatment in the coming years.
| S-EPMC8361829 | biostudies-literature
Project description:BackgroundWe evaluated the cost-effectiveness of a hepatitis C (HCV) screening and active linkage to care intervention in US methadone maintenance treatment (MMT) patients using data from a randomized trial conducted in New York City and San Francisco.MethodsWe used a decision analytic model to compare 1) no intervention; 2) HCV screening and education (control); and 3) HCV screening, education, and care coordination (active linkage intervention). We also explored an alternative strategy wherein HCV/HIV co-infected participants linked elsewhere. Trial data include population characteristics (67% male, mean age 48, 58% HCV infected) and linkage rates. Data from published sources include treatment efficacy and HCV re-infection risk. We projected quality-adjusted life years (QALYs) and lifetime medical costs using an established model of HCV (HEP-CE). Incremental cost-effectiveness ratios (ICERs) are in 2015 US$/QALY discounted 3% annually.ResultsThe control strategy resulted in a projected 35% linking to care within 6 months and 31% achieving sustained virologic response (SVR). The intervention resulted in 60% linking and 54% achieving SVR with an ICER of $24,600/QALY compared to no intervention from the healthcare sector perspective and was a more efficient use of resources than the control strategy. The intervention had an ICER of $76,500/QALY compared to the alternative strategy. From a societal perspective, the intervention had a net monetary benefit of $511,000-$975,600.ConclusionsHCV care coordination interventions that include screening, education and active linkage to care in MMT settings are likely cost-effective at a conventional $100,000/QALY threshold for both HCV mono-infected and HIV co-infected patients.
| S-EPMC5889754 | biostudies-literature
Project description:ObjectivesHepatitis C virus (HCV) non-nucleoside inhibitors (NNIs) target the viral RNA-dependent RNA polymerase encoded by the NS5B gene. Several NNIs share a similar allosteric binding site, and their antiviral efficacy is attenuated by a cysteine-to-tyrosine mutation at amino acid 316 (C316Y). In the current study, we assessed NS5B resistance mutations in treatment-naive individuals from a prospective natural history study of viral infections in women.MethodsPartial NS5B sequences from HCV-positive women were amplified by RT-PCR. Additionally, subcloning was performed to evaluate intrapatient variability in selected samples.ResultsHCV NS5B genotypes were 45 genotype 1a (57.0%), 11 genotype 1b (13.9%), 5 genotype 2a (6.3%), 3 genotype 2b (3.8%), 9 genotype 3a (11.4%) and 6 genotype 4a (7.6%). One HCV genotype 1a-infected patient was found to have the C316Y mutation (1.3%). Clonal analysis further revealed that all NS5B sequences from this individual--representing three serum samples collected 4 years apart--contained the C316Y mutation. In contrast, the S282T resistance mutation was not found in any samples.ConclusionsThe C316Y polymerase resistance mutation was found in 1.3% of samples from HCV-infected women. The presence of this mutation over time suggests significant replicative fitness of this variant and has implications for development of new specifically targeted antiviral therapies against HCV (STAT-C) targeting this region.
| S-EPMC2766823 | biostudies-literature
Project description:Basal cell carcinoma and squamous cell carcinoma are the most frequent types of cancer in the United States and represent 75 percent and 20 percent, respectively, of all nonmelanoma skin cancers. Since ultraviolet radiation is implicated in their development, photoprotection is fundamental in their prevention. Additional preventive measures include identifying high-risk individuals for early detection along with using agents, such as retinoids, that are effective in decreasing the risk of premalignant cells further developing into carcinomas. Newer agents achieving this goal include perillyl alcohol, T4 endonuclease 5, DL-alpha-tocopherol, and alpha-difluoromethylornithine. Procedural modalities are currently the standard of treatment, but recent evidence has consistently shown that newer (nonsurgical) therapies, such as interferon, imiquimod, retinoids, and 5-fluorouracil, can be used effectively either as monotherapies or as adjuvants to those surgical modalities for the treatment of superficial nonmelanoma skin cancers and premalignant lesions. These newer therapies have achieved significant reductions in morbidity and mortality. Procedural modalities that have been evolving into important tools for the treatment of actinic keratosis and nonmelanoma skin cancers include photodynamic therapy and lasers. Nonsurgical therapies currently proving to be effective in clinical trials include ingenol mebutate and cyclooxygenase-2 inhibitors. Agents that are showing promising results in early phases of clinical trials include betulinic acid; hedgehog signaling pathway inhibitors, such as cyclopamine and GDC-0449; alpha-melanocyte-stimulating hormone analogs, such as afamelanotide; epidermal growth factor receptor inhibitors, such as gefitinib and erlotinib; anti-epidermal growth factor receptor monoclonal antibodies, such as cetuximab and panitumumab; and the 5-fluorouracil prodrug capecitabine.
| S-EPMC2921754 | biostudies-other
Project description:Background: Chronic hepatitis C (HCV) is a significant public health problem affecting more than three million Americans. The US health care systems are ramping up costly HCV screening and treatment efforts with limited budget. We determine the optimal implementation of HCV birth-cohort screening and treatment strategies under budget constraints and health care payer's perspective. Methods: Markov model and scenario-based simulation optimization. The target population is birth cohort born between 1945 and 1975. The interventions are allocating annual budget to screen a proportion of the target population and treat a proportion of the identified chronic HCV-positive patients over 10 years. Outcomes measure is to maximize lifetime discounted quality-adjusted life-years. Results: Allocate a percentage of the annual budget to screening, then treat patients with the remaining budget and prioritize the sickest patients. When the budget is $1 billion/year, the best strategy is to allocate the entire budget to treatment. When the budget is $5 billion/year, it is optimal to allocate 60% of the budget to screening in the first 2 years and 0% thereafter for age cohort 40 to 49; and allocate 20% of the budget to screening starting in year 3 for age cohorts 50 to 59 and 60 to 69. Health benefits are sensitive to budget in the first 2 years. Results are not sensitive to distribution of fibrosis stages by awareness of HCV. Conclusion: When budget is limited, all efforts should be focused on early treatment. With higher budget, better population health outcomes are achieved by reserving some budget for HCV screening while implementing a priority-based treatment strategy. This work has broad applicability to diverse health care systems and helps determine how much effort should be devoted to screening versus treatment under resource limitations.
| S-EPMC6124932 | biostudies-literature
Project description:BackgroundThe effectiveness of interferon-free direct-acting antivirals (DAA) in treating chronic hepatitis C virus (HCV) is limited by low screening and treatment rates, particularly among people who inject drugs (PWIDs).MethodsTo evaluate the levels of screening and treatment with interferon-free DAAs that are required to control HCV incidence and HCV-associated morbidity and mortality, we developed a transmission model, stratified by age and by injection drug use, and calibrated it to epidemiological data in the United States from 1992 to 2014. We quantified the impact of administration of DAAs at current and at enhanced screening and treatment rates, focusing on outcomes of HCV incidence, prevalence, compensated and decompensated cirrhosis, hepatocellular carcinoma, liver transplants, and mortality from 2015 to 2040.ResultsIncreasing annual treatment of patients 4-fold-from the approximately 100 000 treated historically to 400 000-is predicted to prevent 526 084 (95% confidence interval, 466 615-593 347) cases of cirrhosis and 256 315 (201 589-316 114) HCV-associated deaths. By simultaneously increasing treatment capacity and increasing the number of HCV infections diagnosed, total HCV prevalence could fall to as low as 305 599 (222 955-422 110) infections by 2040. Complete elimination of HCV transmission in the United States through treatment with DAAs would require nearly universal screening of PWIDs, with an annual treatment rate of at least 30%.ConclusionsInterferon-free DAAs are projected to achieve marked reductions in HCV-associated morbidity and mortality. Aggressive expansion in HCV screening and treatment, particularly among PWIDs, would be required to eliminate HCV in the United States.
| S-EPMC4706637 | biostudies-literature
Project description:Breast cancer continues to be a difficult disease to treat due to high rates of metastasis. Metastasis to the brain presents a unique and often overlooked challenge. In this focused review, we discuss the epidemiology of breast cancer and which types frequently metastasize to the brain. Novel treatment approaches are highlighted with supporting scientific evidence. The role of the blood-brain barrier and how it may become altered with metastasis is addressed. We then highlight new innovations for Her2-positive and triple-negative breast cancer. Finally, recent directions for luminal breast cancer are discussed. This review serves to enhance understanding of pathophysiology, spark continued innovation, and provide a user-friendly resource through tables and easy-to-process figures.
| S-EPMC10310293 | biostudies-literature