New developments in the antiviral treatment of hepatitis C (original) (raw)
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Hepatitis C Virus Infection Treatment: Recent Advances and New Paradigms in the Treatment Strategies
Advances in Treatment of Hepatitis C and B, 2017
The advancement in hepatitis C virus (HCV) therapeutics has been profoundly enhanced by an improved understanding of viral life cycle in host cells, development of novel direct-acting antivirals (DAAs), and exploring other emerging treatment paradigms on the horizon. The approvals of first-, second-, and next-wave direct-acting antivirals highlight the swift pace of progress in the successful development of an expanding variety of therapeutic regimens for use in patients with chronic hepatitis C virus infection. Triple or quadruple therapies based on a combination of different direct-acting antivirals with or without pegylated interferon (IFN) and ribavirin (RBV) have raised the hopes to improve the current treatment strategies for other difficult-to-treat individuals. The development of more efficacious, well-tolerated, and cost-effective interferons with a low frequency of adverse events and short treatment durations is also in the pipeline. An experimental protective vaccine against hepatitis C virus demonstrated promise in preliminary human safety trials, and a larger phase II clinical trials are under consideration to further determine the efficacy of the vaccine. This pragmatic book chapter discusses the current state of knowledge in hepatitis C virus therapeutics and provides a conceptual framework of emerging and investigational treatment strategies directed against this silent epidemic.
Hepatic Medicine: Evidence and Research, 2010
Hepatitis C virus (HCV) is a liver-tropic blood-borne pathogen that affects more than 170 million people worldwide. Although acute infections are usually asymptomatic, up to 90% of HCV infections persist with the possibility of long-term consequences such as liver fibrosis, cirrhosis, steatosis, insulin resistance, or hepatocellular carcinoma. As such, HCV-associated liver disease is a major public health concern. Although the currently available standard of care therapy of pegylated interferon α plus ribavirin successfully treats infection in a subset of patients, the development of more effective, less toxic HCV antivirals is a health care imperative. This review not only discusses the limitations of the current HCV standard of care but also evaluates upcoming HCV treatment options and how current research elucidating the viral life cycle is facilitating the development of HCV-specific therapeutics that promise to greatly improve treatment response rates both before and after liver transplantation.
A Synopsis of Hepatitis C Virus Treatments and Future Perspectives
Current Issues Molecular Biology, 2023
Hepatitis C virus (HCV) infection is a worldwide public health problem. Chronic infection with HCV can lead to liver cirrhosis or cancer. Although some immune-competent individuals can clear the virus, others develop chronic HCV disease due to viral mutations or an impaired immune response.IFNs type I and III and the signal transduction induced by them are essential for a proper antiviral effect. Research on the viral cycle and immune escape mechanisms has formed the basis of therapeutic strategies to achieve a sustained virological response (SVR). The first therapies were based on IFN ; then, IFN plus ribavirin (IFN–RBV); and then, pegylated-IFN -RBV (PEGIFN -RIV) to improve cytokine pharmacokinetics. However, the maximum SVR was 60%, and several significant side effects were observed, decreasing patients’ treatment adherence. The development of direct-acting antivirals (DAAs) significantly enhanced the SVR (>90%), and the compounds were able to inhibit HCV replication without significant side effects, even in paediatric populations. The management of coinfected HBV–HCV and HCV–HIV patients has also improved based on DAA and PEG-IFN -RBV (HBV–HCV). CD4 cells are crucial for an effective antiviral response. The IFN3, IL28B, TNF- , IL-10, TLR-3, and TLR-9 gene polymorphisms are involved in viral clearance, therapeutic responses, and hepatic pathologies. Future research should focus on searching for strategies to circumvent resistance-associated substitution (RAS) to DAAs, develop new therapeutic schemes for different medical conditions, including organ transplant, and develop vaccines for long-lasting cellular and humoral responses with cross-protection against different HCV genotypes. The goal is to minimise the probability of HCV infection, HCV chronicity and hepatic carcinoma.
Future directions in therapy for chronic hepatitis C
Antiviral therapy
The development of new antiviral therapies in the treatment of hepatitis C virus (HCV) is reviewed, including a discussion of the potential advances that this treatment will bring. Data from new molecules in Phase I and II clinical trials, specifically polymerase and protease inhibitors, will be discussed. The potential for resistance has been reported when these have been used as monotherapy. However, their use in combination with pegylated interferon, particularly in the presence of ribavirin, has resulted in significant improvements in antiviral activity. Preliminary studies have confirmed that the new molecules are well tolerated and further clinical studies are underway to evaluate their efficacy. Nevertheless, because of its critical role at all stages of therapy, pegylated interferon is likely to remain the cornerstone of HCV therapy.
Existing and future therapeutic options for hepatitis C virus infection
Acta Biochimica Polonica, 2005
Hepatitis C virus (HCV) infection is an important cause of chronic hepatitis, cirrhosis, hepatocellular carcinoma and liver failure worldwide. Chronic hepatitis C virus infection is treated with interferon-a (IFN-alpha), pegylated interferon-alpha (PEG-IFNalpha) alone or in combination with ribavirin; however, a significant fraction of patients either fail to respond or relapse after cessation of therapy. Efforts to identify and develop highly specific and potent HCV inhibitors have intensified recently. Each of the virally encoded replication enzymes has been a focus of studies as well as viral receptors and the host immune system. This review summarizes recent progress in the search for novel anti-HCV agents.
Hepatitis C Treatment: current and future perspectives
Virology Journal, 2010
Hepatitis C virus (HCV) is a member of Flaviviridae family and one of the major causes of liver disease. There are about 175 million HCV infected patients worldwide that constitute 3% of world's population. The main route of HCV transmission is parental however 90% intravenous drug users are at highest risk. Standard interferon and ribavirin remained a gold standard of chronic HCV treatment having 38-43% sustained virological response rates. Currently the standard therapy for HCV is pegylated interferon (PEG-INF) with ribavirin. This therapy achieves 50% sustained virological response (SVR) for genotype 1 and 80% for genotype 2 & 3. As pegylated interferon is expensive, standard interferon is still the main therapy for HCV treatment in under developed countries. On the other hand, studies showed that pegylated IFN and RBV therapy has severe side effects like hematological complications. Herbal medicines (laccase, proanthocyandin, Rhodiola kirilowii) are also being in use as a natural and alternative way for treatment of HCV but there is not a single significant report documented yet. Best SVR indicators are genotype 3 and 2, < 0.2 million IU/mL pretreatment viral load, rapid virological response (RVR) rate and age <40 years. New therapeutic approaches are under study like interferon related systems, modified forms of ribavirin, internal ribosome entry site (HCV IRES) inhibitors, NS3 and NS5a inhibitors, novel immunomodulators and specifically targeted anti-viral therapy for hepatitis C compounds. More remedial therapies include caspase inhibitors, anti-fibrotic agents, antibody treatment and vaccines.
Hepatitis C therapies: A chronology of Past, Present and Future Strategies
The key role of antiviral therapy of patients with chronic HCV is the sustained eradication of HCV. Different therapeutic plans such as herbal formulations against hepatitis symptoms were put forward for hundreds of years. However, lesser efficacy and, adverse effects constrained the large scale use of herbal medicines. The modern approach, thrived after the discovery of HCV made use of ''interferon-based'' regimens in different dose, duration of treatment and combination. After, ribavirin used in combination with interferon alpha became the centerpiece, pegylation of interferon alpha also aided in enhancing the efficacy of therapeutic plans. Keeping in view the genotype of HCV, viral load and virologic response to treatment, pegylated interferon alpha in combination with ribavirin soon became the standard of care for treating hepatitis C. Adverse effects and lower sustained virologic response rates associated with ''interferon-based'' regimen made in...
An Overview of Emerging Therapies for the Treatment of Chronic Hepatitis C
Clinics in Liver Disease, 2011
Hepatitis C virus (HCV) infection afflicts w170 million persons worldwide and is a leading cause of chronic hepatitis, cirrhosis, liver failure, and hepatocellular carcinoma (HCC). Chronic hepatitis C (CHC) is also the leading indication for orthotopic liver transplantation in the United States and abroad. 1 The prevalence of CHC in the United States is w1.6%, which equates to 4.1 million people with anti-HCV antibodies and 3.3 million with viremia. 2 Currently, standard of care (SOC) antiviral therapy for all HCV genotypes is pegylated interferon-a combined with weight-based ribavirin (Peg-IFN-a/R) for 24 weeks for genotypes 2 and 3 or 48 weeks for genotypes 1 and 4. Peg-IFN-a/R therapy results in variable rates of sustained virological response (SVR, defined as undetectable HCV RNA !24 weeks after cessation of antiviral therapy) depending on genotype. 3-5 SVR rates are lowest in genotype 1 infections (40%-50%) and highest in genotype 2 and 3 infections (70%-90%). 6 SOC treatment Authors' disclosures: JAI is a subinvestigator and JMV is the principal investigator for clinical trials sponsored by grants from Abbott, Bristol-