New Treatments For Chronic Hepatitis Research Articles

PIN50 - Access to New Treatments For Chronic Hepatitis C in Four Latin American Countries

PIN50 - Access to New Treatments For Chronic Hepatitis C in Four Latin American Countries

New treatments for chronic hepatitis C infection

The goal of HCV treatment is to prevent cirrhosis, hepatocellularcarcinoma, liver-related deaths. The development of direct-actingantiviral (DAA) agents which target various steps in HCV lifecycleled to a revolution by providing nearly complete eradication ofHCV. The new treatment regimens with high cure rates havechanged the standards of care in the regions where patients haveaccess to new treatments. This review addresses the recent updatesin management of chronic hepatitis C infection.Keywords: Hepatitis C, New treatments, Direct antiviral agents

Cost-Effectiveness of Genotype 1 Chronic Hepatitis C Virus Treatments in Patients Coinfected with Human Immunodeficiency Virus in the United States.

New treatments for chronic hepatitis C virus (HCV) are highly effective in patients coinfected with human immunodeficiency virus (HIV). This study estimated the cost-effectiveness of treatments for genotype 1 (GT1) HCV in HIV-coinfected patients. A Markov model based on HCV natural history was used. The base-case analysis included both treatment-naïve and -experienced patients. Alternatives were ombitasvir/paritaprevir/ritonavir, dasabuvir with or without ribavirin (3D±R) for 12 or 24weeks, sofosbuvir plus peginterferon and R (SOF+PR) for 12weeks, SOF+R for 24weeks, and no treatment (NT). A subgroup analysis restricted to treatment-naïve, non-cirrhotic patients compared 3D±R for 12weeks to SOF plus ledipasvir (LDV) for 12weeks and NT. Transition probabilities, utilities, and costs were obtained from the published literature. Outcomes were measured over a lifetime horizon and included rates of compensated cirrhosis, decompensated cirrhosis, hepatocellular carcinoma and liver-related death, total costs, life-years, quality-adjusted life-years (QALYs), and the incremental cost-effectiveness ratio (ICER). In the base-case, SOF+R was dominated by both SOF+PR and 3D±R. Compared to SOF+PR, 3D±R had an ICER of $45,581. The lifetime rates of liver morbidity and mortality were lower among those treated with 3D±R compared to SOF+PR, SOF+R, or NT. In the subgroup analysis, 3D±R was cost-effective compared to NT at a threshold of $50,000 per QALY (ICER $27,496). SOF/LDV had an ICER of $104,489 per QALY gained compared to 3D±R. In the GT1 HCV population coinfected with HIV, 3D±R was cost-effective compared to NT, SOF+R, and SOF+PR. In the treatment-naïve sub-population, 3D±R was cost-effective compared to NT and SOF/LDV.

Su1410 New Treatments for Chronic Hepatitis C: Outcomes and Compliance in an Urban Minority Population

Su1410 New Treatments for Chronic Hepatitis C: Outcomes and Compliance in an Urban Minority Population

Chronic Liver Diseases

The term chronic hepatitis encompasses many distinct clinical and pathologic diseases affecting the liver, the most important of which are autoimmune hepatitis (AIH), chronic hepatitis B with or without hepatitis D, and chronic hepatitis C caused by hepatitis C virus (HCV). The standard treatment of AIH is immunosuppressive therapy either with prednisolone alone or in combination with azathioprine. Although mycophenolate mofetil or cyclosporine can be used for retherapy in the case of treatment failure, controlled clinical trials are missing for these immunosuppressive drugs; thus, they are not part of the American Association for the Study of Liver Diseases (AASLD) practice guidelines for AIH. Chronic hepatitis B is a major global health care problem as 5% of the world’s population, or approximately 350 million persons, is chronically infected. Anti–hepatitis B virus (HBV) drugs can be divided into three classes: alfa interferons, nucleoside analogue (lamivudine, entecavir, telbivudine), and nucleotide analogue (adefovir dipivoxil, tenofovir dipivoxil). Interferon alfa has a number of potential side effects, and careful consideration must be given to its use. Tenofovir, which falls under the nucleotide analogue class, was approved by the Food and Drug Administration in 2008 and has been shown in clinical trials to have more potent activity in serum-suppressing HBV DNA levels than the comparable adefovir. More prevalent than chronic hepatitis B is chronic hepatitis C due to the high chronicity rate of HCV infection (approximately 160 million people are chronically infected with HCV worldwide). Until 2011, the only treatment for chronic HCV was a combination therapy of pegylated interferon alfa and ribavirin (RBV); however, new treatments for chronic hepatitis C include the directly acting antivirals (DAAs) sofosbuvir and simeprevir, although host-targeting agents are also being developed. The side effects of pegylated interferon/RBV therapy and DAAs should be considered, of which only sofosbuvir has shown no specific side effects so far in clinical studies. This module contains 5 highly rendered figures, 6 tables, 61 references, and 5 MCQs.

Chronic Liver Diseases

The term chronic hepatitis encompasses many distinct clinical and pathologic diseases affecting the liver, the most important of which are autoimmune hepatitis (AIH), chronic hepatitis B with or without hepatitis D, and chronic hepatitis C caused by hepatitis C virus (HCV). The standard treatment of AIH is immunosuppressive therapy either with prednisolone alone or in combination with azathioprine. Although mycophenolate mofetil or cyclosporine can be used for retherapy in the case of treatment failure, controlled clinical trials are missing for these immunosuppressive drugs; thus, they are not part of the American Association for the Study of Liver Diseases (AASLD) practice guidelines for AIH. Chronic hepatitis B is a major global health care problem as 5% of the world’s population, or approximately 350 million persons, is chronically infected. Anti–hepatitis B virus (HBV) drugs can be divided into three classes: alfa interferons, nucleoside analogue (lamivudine, entecavir, telbivudine), and nucleotide analogue (adefovir dipivoxil, tenofovir dipivoxil). Interferon alfa has a number of potential side effects, and careful consideration must be given to its use. Tenofovir, which falls under the nucleotide analogue class, was approved by the Food and Drug Administration in 2008 and has been shown in clinical trials to have more potent activity in serum-suppressing HBV DNA levels than the comparable adefovir. More prevalent than chronic hepatitis B is chronic hepatitis C due to the high chronicity rate of HCV infection (approximately 160 million people are chronically infected with HCV worldwide). Until 2011, the only treatment for chronic HCV was a combination therapy of pegylated interferon alfa and ribavirin (RBV); however, new treatments for chronic hepatitis C include the directly acting antivirals (DAAs) sofosbuvir and simeprevir, although host-targeting agents are also being developed. The side effects of pegylated interferon/RBV therapy and DAAs should be considered, of which only sofosbuvir has shown no specific side effects so far in clinical studies. This module contains 5 highly rendered figures, 6 tables, 61 references, and 5 MCQs.

Sofosbuvir for the treatment of chronic hepatitis C: between current evidence and future perspectives.

In recent years, clinical research in the field of new treatments for chronic hepatitis C (HCV) has been devoted to developing regimens based on direct-acting antivirals (DAAs), with the goal of increasing treatment efficacy and improving tolerability and safety. This can be achieved by Peginterferon (PegIFN)-free anti-HCV regimens, as PegIFN is responsible for many side effects and limits treatment access due to contraindications in some patient categories. Sofosbuvir (SOF) is the first compound to enter the market with IFN-free combination regimens; it belongs to the nucleotide inhibitors of viral polymerase NS5B and acts as a chain terminator during the HCV replication process, exhibiting pan-genotypic antiviral activity with a high barrier to resistance. Clinical trials in HCV genotype 2/3 patients have demonstrated optimal efficacy in HCV-2, where the combination SOF/ribavirin (Rbv) for 12 weeks resulted in >90% sustained virological response (SVR) rates, while HCV-3 patients with advanced liver fibrosis and previous failure to PegIFN plus Rbv therapy still require individualized and optimized treatment strategies. Historically difficult-to-treat genotypes HCV-1, −4–6 can benefit from reduced duration of PegIFN plus SOF and Rbv, while IFN-free regimens in these patients will be based on SOF in combination with other DAA classes. Due to an optimal tolerability and safety profile with no significant drug-to-drug interactions, SOF is currently undergoing clinical trials in the setting of pre- and post-liver transplantation and HIV-coinfected patients, with the objective to address the until now unmet need for safe and efficient treatment in these populations. This article provides an overview of SOF features and the main clinical trials, discussing key results and potential future developments.

New treatments for chronic hepatitis C: an overview for paediatricians.

Pegylated interferon (IFN) α-2a or 2b in combination with ribavirin for children aged 3 years and older is the standard treatment for paediatric chronic hepatitis C. This treatment regimen was developed firstly in adults. In recent years, a number of direct-acting antiviral agents (DAAs) are under development for treatment of chronic hepatitis C virus (HCV) infection. These agents block viral replication inhibiting directly one of the several steps of HCV lifecycle. DAAs are classified into several categories based on their molecular target: HCV NS3/4A protease inhibitors, HCV NS5B polymerase inhibitors and HCV NS5A inhibitors. Other promising compounds are cyclophilin A inhibitors, mi-RNA122 and IFN-λ. Several new drugs associations will be developed in the near future starting from the actual standard of care. IFN-based and IFN-free regimens are being studied in adults. In this constantly evolving scenario new drug regimens targeted and suitable for children would be possible in the next future. Especially for children, it is crucial to identify the right combination of drugs with the highest potency, barrier to resistance and the best safety profile.

Patients’ Willingness to Accept the Risks and Benefits of New Treatments for Chronic Hepatitis C Virus Infection

BackgroundSome patients with chronic hepatitis C virus (HCV) infection forego treatment due to concerns about treatment efficacy, treatment duration, and side effects.ObjectiveThe purpose of this study was to quantify patient preferences among possible outcomes associated with new, direct-acting antiviral agents (DAAs) for the treatment of HCV infection and determine which treatment features are most important to patients in making treatment decisions.MethodsAdult participants with a self-reported physician diagnosis of HCV infection in five countries completed a web-enabled, choice-format conjoint analysis survey. The survey presented participants with 20 treatment-choice questions. Each treatment-choice question included a pair of hypothetical treatment profiles with varying levels of six attributes: treatment duration; chance of getting rid of the virus completely (i.e. likelihood of a sustained virologic response [SVR]); weeks on an additional, third medicine (i.e. a DAA); risk of a severe rash; risk of severe anemia; and number of times a day the third medicine is taken. Treatment-choice questions were based on a predetermined experimental design with known statistical properties. Random-parameters logit was used to estimate preference weights for all attribute levels and the mean relative importance of each attribute.Results284 participants completed the survey. Likelihood of an SVR was the most important outcome to participants, followed by severe anemia risk, severe rash risk, therapy type (a combination of total weeks of treatment and weeks on the third medicine), and dosing of the third medicine. Controlling for other factors, preferences were similar across all therapy types examined.ConclusionPatients with HCV infection indicate a willingness to accept an increased risk of side effects for sufficient improvement in the likelihood of treatment response.Electronic Supplementary MaterialSupplementary material is available for this article at 10.1007/BF03262498 and is accessible for authorized users.

Patientsʼ Willingness to Accept the Risks and Benefits of New Treatments for Chronic Hepatitis C Virus Infection

Patientsʼ Willingness to Accept the Risks and Benefits of New Treatments for Chronic Hepatitis C Virus Infection

The Conundrum of Relapse in STAT-C Therapy: Does HCV Play the Red Queen or Rip Van Winkle?

New treatments for chronic hepatitis C combining direct-acting antivirals (DAAs) with pegylated interferon and ribavirin (PEG-IFN/RBV) have dramatically increased the number of patients whose viral load declines to undetectable levels early in treatment. Most go on to achieve a sustained virologic response, but some patients who maintain undetectable levels of virus throughout treatment later relapse during follow-up. These data suggest that hepatitis C virus (HCV) genomes may persist in form(s) that are refractory to eradication by DAAs and PEG-IFN/RBV. Here we examine the molecular biology of HCV replication and review the clinical virology of relapse for clues as to how the virus might survive months of antiviral therapy to later reappear when treatment is withdrawn.

New treatments for chronic hepatitis C.

Treatments for chronic hepatitis C has evolved significantly in the past 15 years. The standard of care (SOC) is peginterferon alfa-2a/-2b with ribavirin for 48 weeks or 24 weeks in patients infected with HCV genotype 1 or 2/3, respectively. The treatment duration can be individualized based on the baseline viral load and the speed of the virologic response during treatment. However, current therapies are associated with side effects, complications, and poor patient tolerability. Therefore, there is an urgent need to identify better strategies for treating this disease. An improved sustained virologic response (SVR) can be achieved with new HCV-specific inhibitors against NS3/4A and NS5B polymerases. Recent trials have found SVR rates in patients with HCV genotype 1 infection of 61~68% and 67~75% for combining the SOC with the protease inhibitors telaprevir and boceprevir, respectively. Several new HCV-specific inhibitors such as protease inhibitors and nucleoside and non-nucleoside polymerase inhibitors as well as non-HCV-specific compounds with anti-HCV activity are currently in clinical evaluation. In this review we discuss these new treatments for chronic hepatitis C.

Can serum HBV-DNA be used as a primary end point to assess efficacy of new treatments for chronic hepatitis B?

Can serum HBV-DNA be used as a primary end point to assess efficacy of new treatments for chronic hepatitis B?