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Achieving a high cure rate with direct-acting antivirals for chronic Hepatitis C virus infection in Cameroon: a multi-clinic demonstration project.

ABSTRACT: OBJECTIVES:Highly effective direct-acting antivirals (DAAs) for Hepatitis C treatment are largely inaccessible in sub-Saharan Africa. Data on treatment feasibility and outcomes in clinical settings are limited. We assessed the feasibility of achieving a high (?90%) cure rate with DAAs in six gastroenterology clinics in Cameroon. METHODS:Patients with chronic Hepatitis C virus (HCV) infection were treated for 12 or 24 weeks with ledipasvir/sofosbuvir, ledipasvir/sofosbuvir/ribavirin or sofosbuvir/ribavirin, depending on the stage of liver disease and HCV genotype. The cure rate was defined as the proportion of patients with a sustained virological response 12 weeks after treatment completion (SVR12) among all treatment completers. RESULTS:We identified 190 HCV RNA positive patients between September-2017 and August-2018, 161 (84.7%) of whom started treatment. 105 (65.2%) were female, median age was 61.3 years [IQR = 55.9-66.9] and 11 (6.8%) were HIV-positive. Median plasma HCV RNA was 6.0 log10 IU/mL [IQR = 5.6-6.4]. HCV genotypes identified were 1 (34.8%), 2 (13.7%), 4 (50.9%), 1 and 4 (0.6%); 46 (28.6%) strains of 160 single-genotype infections were non-subtypeable. Of 158 treatment completers, 152 (96.2%, 95%CI = 91.9-98.6%) achieved SVR12. Six patients did not achieve SVR12: five carried HCV with NS5A resistance mutations and one with NS5B resistance mutations. Three patients died before and two after treatment completion. The most common adverse events were asthenia (12.0%), headache (11.4%) and dizziness (18.9%). CONCLUSION:High cure rates of Hepatitis C with DAAs are achievable in clinical settings of Cameroon. However, the accessibility and provision of HCV screening, diagnosis, treatment, monitoring and care should be addressed for large-scale implementation.

SUBMITTER: Coyer L

PROVIDER: S-EPMC7540389 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Achieving a high cure rate with direct-acting antivirals for chronic Hepatitis C virus infection in Cameroon: a multi-clinic demonstration project.

Coyer Liza L Njoya Oudou O Njouom Richard R Mossus Tatiana T Kowo Mathurin Pierre MP Essomba Frida F Boers Alexander A Coutinho Roel R Ondoa Pascale P

Tropical medicine & international health : TM & IH 20200705 9

<h4>Objectives</h4>Highly effective direct-acting antivirals (DAAs) for Hepatitis C treatment are largely inaccessible in sub-Saharan Africa. Data on treatment feasibility and outcomes in clinical settings are limited. We assessed the feasibility of achieving a high (≥90%) cure rate with DAAs in six gastroenterology clinics in Cameroon.<h4>Methods</h4>Patients with chronic Hepatitis C virus (HCV) infection were treated for 12 or 24 weeks with ledipasvir/sofosbuvir, ledipasvir/sofosbuvir/ribaviri ...[more]

PMID: 32502290

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Project description:The increasing worldwide prevalence of Hepatocellular carcinoma (HCC), characterized by resistance to conventional chemotherapy, poor prognosis and eventually mortality, place it as a prime target for new modes of prevention and treatment. Hepatitis C Virus (HCV) is the predominant risk factor for HCC in the US and Europe. Multiple epidemiological studies showed that sustained virological responses (SVR) following treatment with the powerful direct acting antivirals (DAAs), which have replaced interferon-based regimes, do not eliminate tumor development. We aimed to identify an HCV-specific pathogenic mechanism that persists post SVR following DAAs treatment. We demonstrate that HCV infection induces genome-wide epigenetic changes by performing chromatin immunoprecipitation followed by next-generation sequencing (ChIP-seq) for histone post-translational modifications that are epigenetic markers for active and repressed chromatin. The changes in histone modifications correlate with reprogramed host gene expression and alter signaling pathways known to be associated with HCV life cycle and HCC. These epigenetic alterations require the presence of HCV RNA or/and expression of the viral proteins in the cells. Importantly, the epigenetic changes induced following infection persist as an "epigenetic signature" after virus eradication by DAAs treatment, as detected using in vitro HCV infection models. These observations led to the identification of an 8 gene signature that is associated with HCC development and demonstrate persistent epigenetic alterations in HCV infected and post SVR liver biopsy samples. The epigenetic signature was reverted in vitro by drugs that inhibit epigenetic modifying enzyme and by the EGFR inhibitor, Erlotinib. This epigenetic "scarring" of the genome, persisting following HCV eradication, suggest a novel mechanism for the persistent pathogenesis of HCV after its eradication by DAAs. Our study offers new avenues for prevention of the persistent oncogenic effects of chronic hepatitis infections using specific drugs to revert the epigenetic changes to the genome.

Dataset Information

Achieving a high cure rate with direct-acting antivirals for chronic Hepatitis C virus infection in Cameroon: a multi-clinic demonstration project.

Publications

Achieving a high cure rate with direct-acting antivirals for chronic Hepatitis C virus infection in Cameroon: a multi-clinic demonstration project.

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