Pegylated interferon alpha (peginterferon alpha) plus ribavirin is the current mainstay of treatment for patients with chronic HCV infection. When peginterferon alpha plus ribavirin is administered ...for the standard duration, a sustained virological response is achieved in around 50% of patients infected with HCV genotype 1 and around 80% of patients infected with HCV genotype 2 or 3. Data now suggest that treatment duration can be shortened or lengthened depending on baseline viral load and/or early on-treatment viral kinetics, offering the prospect of individualizing therapy further to improve response or to prevent treatment from being unnecessarily extended. Further efforts to optimize therapy are likely to involve the use of new anti-HCV agents, several of which are currently in the early stages of development. These agents include HCV protease inhibitors (particularly those against NS3-4A protease), HCV polymerase inhibitors (including both nucleoside and non-nucleoside analogs) and cyclophilin inhibitors. These compounds will be used, at least initially, in combination with peginterferon alpha plus ribavirin, extending the pivotal role of interferon-based therapy in the management of chronic hepatitis C.
At the beginning of April 2022, 10 cases of severe acute hepatitis of unknown origin in children <10 years of age were reported across central Scotland. Since then, case numbers have increased ...rapidly, with 191 probable cases identified across Europe, the United States of America, Israel and Japan. Until now, 17 children required liver transplantation and 1 died. Accordingly, the Centers for Disease Control and Prevention and the European Centre for Diseases Prevention and Control have both issued a warning on a hepatitis of unknown origin in children. This review focuses on the available information concerning this recent outbreak and introduces some of the potential explanations for its development.
Treatment of HCV Infection by Targeting MicroRNA Janssen, Harry L.A; Reesink, Hendrik W; Lawitz, Eric J ...
New England journal of medicine/The New England journal of medicine,
05/2013, Volume:
368, Issue:
18
Journal Article
Peer reviewed
Open access
In this phase 2 trial, an antisense oligonucleotide was tested in the treatment of chronic hepatitis C virus infection. The oligonucleotide was designed to bind to and sequester a microRNA required ...for HCV replication.
Approximately 170 million persons worldwide are chronically infected with the hepatitis C virus (HCV).
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Chronic HCV infection is a major cause of liver cirrhosis, liver failure, and hepatocellular carcinoma and is the leading indication for liver transplantation in many Western countries.
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Sustained eradication of HCV infection has been associated with a reduced risk of liver-related morbidity and all-cause mortality.
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Despite the recent registration of protease inhibitors for the treatment of chronic HCV genotype 1 infection, current therapeutic regimens remain dependent on the administration of pegylated interferon and ribavirin for 24 to 48 weeks.
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Thus, anti-HCV therapy continues to . . .
In patients with HCV infection and no previous treatment, the addition of telaprevir to peginterferon–ribavirin resulted in higher response rates than those achieved with peginterferon–ribavirin ...alone. High rates of response were achieved with only 24 weeks of treatment.
Patients with chronic hepatitis C virus (HCV) infection are at risk for progressive hepatic fibrosis, cirrhosis, portal hypertension, hepatic failure, and hepatocellular carcinoma.
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For the past decade, treatment with pegylated interferon (peginterferon alfa) and ribavirin has been associated with rates of sustained virologic response of 40 to 50% among patients with HCV genotype 1 who had received no previous treatment.
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At least 48 weeks of treatment is required for most of these patients, and toxic effects may limit the extent of treatment in some patients.
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Telaprevir, a linear peptidomimetic HCV NS3/4A serine protease inhibitor, was associated with . . .
Treatment of chronic hepatitis C virus infection has been revolutionised by the development of direct-acting antivirals (DAAs). All-oral, once-daily, 8- to 12-week treatment regimens are now standard ...of care, with viral eradication possible in >95% of patients across different populations. Despite these advances, several unresolved issues remain, including treatment of patients with hepatitis C virus genotype 3, chronic kidney disease, and those in whom DAA therapy has previously failed. Glecaprevir/pibrentasvir and sofosbuvir/velpatasvir/voxilaprevir are the most recently approved DAA regimens. Given the overwhelming success of modern DAA-based therapies, glecaprevir/pibrentasvir and sofosbuvir/velpatasvir/voxilaprevir are also likely to represent the last DAAs to be approved. Both are pangenotypic, once-daily, all-oral DAA combinations that have the potential to close the gaps in the current DAA treatment portfolio. Herein, we review the challenges associated with current DAAs and how these two regimens may be implemented in existing treatment algorithms.
Until recently, the standard of care (SOC) for patients with chronic hepatitis C virus (HCV) infection has consisted of a combination of pegylated interferon-N1 plus ribavirin, administered for 24- ...to 48-weeks depending on the HCV genotype. The sustained virologic response rate for this SOC has been only about 50% in patients infected with genotype 1 HCV, the most prevalent genotype in Europe and North America. HCV therapy has been revolutionised recently by the approval of two direct-acting antiviral agents (DAA) against the NS3/4A serine protease for use in genotype 1 HCV, the ketoamide inhibitors boceprevir and telaprevir. The novel SOC marks the beginning of an extraordinary new era in HCV therapy. We review this new SOC with an emphasis on practical issues related to protease inhibitors, e.g. prescribing guidelines, futility rules and management of adverse events. We also give a perspective on what to expect in the coming years. Newer DAA with simplified dosing regimens and/or minimal toxicity which, when used in combination, will lead to viral eradication in most if not all CHC patients who undergo treatment. The novel agents in clinical development are paving the way for future interferon-sparing regimens.
In this phase 3 study involving patients with HCV genotype 1, 2, 4, 5, or 6 infection, including those with compensated cirrhosis, treatment with 12 weeks of sofosbuvir and velpatasvir resulted in a ...sustained virologic response in 99% of patients.
The hepatitis C virus (HCV), a single-stranded RNA virus of the family Flaviviridae with six major genotypes, infects up to 150 million people worldwide.
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Chronic HCV infection causes progressive liver fibrosis, which can lead to cirrhosis, hepatic decompensation, and hepatocellular carcinoma.
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As many as half a million people die annually from liver disease associated with chronic HCV infection.
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In recent years, the development of drugs that directly interfere with HCV replication has revolutionized HCV treatment. There are now effective combinations of direct-acting antiviral agents for most patients, but in choosing an appropriate regimen, clinicians must take into account . . .
In this phase 2 study, peginterferon-free regimens were effective in patients with hepatitis C virus genotype 1 infection.
Chronic hepatitis C virus (HCV) infection is a leading cause of cirrhosis, ...liver cancer, and end-stage liver disease.
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The current standard of care for chronic HCV genotype 1 infection is pegylated interferon (peginterferon) and ribavirin, with a protease inhibitor (boceprevir or telaprevir).
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Although the addition of a protease inhibitor has been associated with a significant increase in response rates, only approximately one third of patients who had not had a response to prior therapy with peginterferon and ribavirin had a sustained virologic response when re-treated with the addition of a protease inhibitor.
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Furthermore, these therapies are associated with adverse . . .
Coronavirus disease 2019 (COVID-19) has placed a significant strain on national healthcare systems at a critical moment in the context of hepatitis elimination. Mathematical models can be used to ...evaluate the possible impact of programmatic delays on hepatitis disease burden. The objective of this analysis was to evaluate the incremental change in HCV liver-related deaths and liver cancer, following a 3-month, 6-month, or 1-year hiatus in hepatitis elimination programs.
Previously developed models were adapted for 110 countries to include a status quo or ‘no delay’ scenario and a ‘1-year delay’ scenario assuming significant disruption in interventions (screening, diagnosis, and treatment) in the year 2020. Annual country-level model outcomes were extracted, and weighted averages were used to calculate regional (WHO and World Bank Income Group) and global estimates from 2020 to 2030. The incremental annual change in outcomes was calculated by subtracting the ‘no-delay’ estimates from the ‘1-year delay’ estimates.
The ‘1-year delay’ scenario resulted in 44,800 (95% uncertainty interval UI: 43,800–49,300) excess hepatocellular carcinoma cases and 72,300 (95% UI: 70,600–79,400) excess liver-related deaths, relative to the ‘no-delay’ scenario globally, from 2020 to 2030. Most missed treatments would be in lower-middle income countries, whereas most excess hepatocellular carcinoma and liver-related deaths would be among high-income countries.
The impact of COVID-19 extends beyond the direct morbidity and mortality associated with exposure and infection. To mitigate the impact on viral hepatitis programming and reduce excess mortality from delayed treatment, policy makers should prioritize hepatitis programs as soon as it becomes safe to do so.
COVID-19 has resulted in many hepatitis elimination programs slowing or stopping altogether. A 1-year delay in hepatitis diagnosis and treatment could result in an additional 44,800 liver cancers and 72,300 deaths from HCV globally by 2030. Countries have committed to hepatitis elimination by 2030, so attention should shift back to hepatitis programming as soon as it becomes appropriate to do so.
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•With only 10 years left to meet the WHO's hepatitis elimination targets, COVID-19 is impacting progress.•A 1-year delay in HCV programs could cause excess HCV morbidity and mortality.•A 1-year delay could cause 72,000 excess deaths from HCV.•Most excess deaths would be in the lower middle income and high-income groups.
In two phase 3 trials involving patients with hepatitis C virus infection, including those with cirrhosis, 12 weeks of sofosbuvir–velpatasvir resulted in a sustained virologic response in 99% of ...patients with genotype 2 and 95% of those with genotype 3.
Hepatitis C virus (HCV) genotypes 2 and 3 account for an estimated 35% of global HCV infections, affecting up to 58 million persons.
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Unlike HCV genotype 1, genotypes 2 and 3 are common in low-income regions in Asia, sub-Saharan Africa, Latin America, and Eastern Europe.
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Before the advent of direct-acting antiviral agents, HCV genotypes 2 and 3 were grouped together in treatment guidelines as “easy-to-treat” genotypes. However, recent studies have shown that HCV genotype 3 is associated with more rapid disease progression and lower rates of response to treatment than is HCV genotype 2, especially in patients with cirrhosis . . .
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