Lack of evidence of an effect of direct-acting antivirals on the recurrence of hepatocellular carcinoma: Data from three ANRS cohorts

Chronic HCV infections represent a major worldwide public health problem and are responsible for a large proportion of liver related deaths, mostly because of HCV-associated hepatocellular carcinoma and cirrhosis. The treatment of HCV has undergone a rapid and spectacular revolution. In the past 5 years, the launch of direct acting antiviral drugs has seen sustained virological response rates reach 90% and above for many patient groups. The new treatments are effective, well tolerated, allow for shorter treatment regimens and offer new opportunities for previously excluded groups. This therapeutic revolution has changed the rules for treatment of HCV, moving the field towards an interferon-free era and raising the prospect of HCV eradication. This manuscript addresses the new challenges regarding treatment optimisation in the real world, improvement of antiviral efficacy in ‘hard-to-treat’ groups, the management of patients whose direct acting antiviral drug treatment was unsuccessful, and access to diagnosis and treatment in different parts of the world.

https://gut.bmj.com/content/gutjnl/64/11/1824.full.pdf

Hepatitis C virus treatment in the real world: optimising treatment and access to therapies

Abstract: The treatment of hepatitis C virus has changed dramatically with the rapid advent of numerous new antiviral agents, including direct-acting antivirals and agents with non-viral targets (cyclophilin inhibitors, interferon-lambda, vaccine therapy). Given the better safety profile and high antiviral potency of direct-acting antivirals, their combination in interferon-free oral regimens is becoming the standard of care for hepatitis C virus infection, tailored to individual patients according to the degree of disease progression (fibrosis), hepatitis C virus genotype and subtype, resistance profile, and prior therapeutic history. Results from clinical studies as well as preliminary real-life data regarding the combination of sofosbuvir (a nucleotide polymerase inhibitor) and daclatasvir, a first-in-class NS5A replication complex inhibitor, demonstrate that it is one of the most promising antiviral therapies, with once-daily oral dosing, a low pill burden, good tolerability, and limited drug–drug interactions, in addition to high antiviral potency, with >90% sustained virologic response rates. This combination has high pangenotypic antiviral potency regardless of the severity and patient characteristics. The combination of sofosbuvir and an NS5A inhibitor with ribavirin for 12 weeks appears to be a very good further treatment option in both cirrhotic and treatment-experienced patients whatever the stage of fibrosis. Keywords: hepatitis C virus, direct-acting antivirals, sofosbuvir, daclatasvir 

Daclatasvir–sofosbuvir combination therapy with or without ribavirin for hepatitis C virus infection: from the clinical trials to real life

The treatment of hepatitis C virus has changed dramatically with the rapid advent of numerous new antiviral agents, including direct-acting antivirals and agents with non-viral targets (cyclophilin inhibitors, interferon-lambda, vaccine therapy). Given the better safety profile and high antiviral potency of direct-acting antivirals, their combination in interferon-free oral regimens is becoming the standard of care for hepatitis C virus infection, tailored to individual patients according to the degree of disease progression (fibrosis), hepatitis C virus genotype and subtype, resistance profile, and prior therapeutic history. Results from clinical studies as well as preliminary real-life data regarding the combination of sofosbuvir (a nucleotide polymerase inhibitor) and daclatasvir, a first-in-class NS5A replication complex inhibitor, demonstrate that it is one of the most promising antiviral therapies, with once-daily oral dosing, a low pill burden, good tolerability, and limited drug-drug interactions, in addition to high antiviral potency, with >90% sustained virologic response rates. This combination has high pangenotypic antiviral potency regardless of the severity and patient characteristics. The combination of sofosbuvir and an NS5A inhibitor with ribavirin for 12 weeks appears to be a very good further treatment option in both cirrhotic and treatment-experienced patients whatever the stage of fibrosis.

/pdf/daclatasvir-sofosbuvir-combination-therapy-with-or-without-38br0wo9zh.pdf

Daclatasvir-sofosbuvir combination therapy with or without ribavirin for hepatitis C virus infection: from the clinical trials to real life.

https://thelancet.com/pdfs/journals/langas/PIIS2468-1253(16)30001-2.pdf

Ombitasvir, paritaprevir, and ritonavir plus ribavirin in adults with hepatitis C virus genotype 4 infection and cirrhosis (AGATE-I): a multicentre, phase 3, randomised open-label trial

LO3 : Safety and efficacy of the combination daclatasvir-sofosbuvir in HCV genotype 1-mono-infected patients from the french observational cohort ANRS CO22 hepather*

LP28 : Efficacy of the oral sofosbuvir-based combinations in HCV genotype 4-mono-infected patients from the french observational cohort anrs CO22 hepather

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LO3 : Safety and efficacy of the combination daclatasvir-sofosbuvir in HCV genotype 1-mono-infected patients from the french observational cohort ANRS CO22 hepather*

LP28 : Efficacy of the oral sofosbuvir-based combinations in HCV genotype 4-mono-infected patients from the french observational cohort anrs CO22 hepather