Pharmacogenetics of hepatitis C: transition from interferon-based therapies to direct-acting antiviral agents

Sanaa M Kamal1,21Department of Medicine, Division of Hepatology, Gastroenterology and Tropical Medicine, Ain Shams Faculty of Medicine, Cairo, Egypt, 2Department of Medicine, Salman Bin Abdul Aziz College of Medicine, Kingdom of Saudi ArabiaAbstract: Hepatitis C virus (HCV) has emerged as a major v...

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Autor principal:	Kamal SM
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2014
Materias:	Diseases of the digestive system. Gastroenterology RC799-869
Acceso en línea:	https://doaj.org/article/0f57efea98f34f8cbddc989454b0f0d6
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spelling	oai:doaj.org-article:0f57efea98f34f8cbddc989454b0f0d62021-12-02T01:15:28ZPharmacogenetics of hepatitis C: transition from interferon-based therapies to direct-acting antiviral agents1179-1535https://doaj.org/article/0f57efea98f34f8cbddc989454b0f0d62014-06-01T00:00:00Zhttp://www.dovepress.com/pharmacogenetics-of-hepatitis-c-transition-from-interferon-based-thera-a17346https://doaj.org/toc/1179-1535 Sanaa M Kamal1,21Department of Medicine, Division of Hepatology, Gastroenterology and Tropical Medicine, Ain Shams Faculty of Medicine, Cairo, Egypt, 2Department of Medicine, Salman Bin Abdul Aziz College of Medicine, Kingdom of Saudi ArabiaAbstract: Hepatitis C virus (HCV) has emerged as a major viral pandemic over the past two decades, infecting 170 million individuals, which equates to approximately 3% of the world's population. The prevalence of HCV varies according to geographic region, being highest in developing countries such as Egypt. HCV has a high tendency to induce chronic progressive liver damage in the form of hepatic fibrosis, cirrhosis, or liver cancer. To date, there is no vaccine against HCV infection. Combination therapy comprising PEGylated interferon-alpha and ribavirin has been the standard of care for patients with chronic hepatitis C for more than a decade. However, many patients still do not respond to therapy or develop adverse events. Recently, direct antiviral agents such as protease inhibitors, polymerase inhibitors, or NS5A inhibitors have been used to augment PEGylated interferon and ribavirin, resulting in better efficacy, better tolerance, and a shorter treatment duration. However, most clinical trials have focused on assessing the efficacy and safety of direct antiviral agents in patients with genotype 1, and the response of other HCV genotypes has not been elucidated. Moreover, the prohibitive costs of such triple therapies will limit their use in patients in developing countries where most of the HCV infection exists. Understanding the host and viral factors associated with viral clearance is necessary for individualizing therapy to maximize sustained virologic response rates, prevent progression to liver disease, and increase the overall benefits of therapy with respect to its costs. Genome wide studies have shown significant associations between a set of polymorphisms in the region of the interleukin-28B (IL28B) gene and natural clearance of HCV infection or after PEGylated interferon-alpha and ribavirin treatment with and without direct antiviral agents. This paper synthesizes the recent advances in the pharmacogenetics of HCV infection in the era of triple therapies.Keywords: hepatitis C virus, interleukin-28B polymorphisms, PEGylated interferon and ribavirin, direct-acting antiviral agents, pharmacogenetics, rational therapeuticsKamal SMDove Medical PressarticleDiseases of the digestive system. GastroenterologyRC799-869ENHepatic Medicine: Evidence and Research, Vol 2014, Iss default, Pp 61-77 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Diseases of the digestive system. Gastroenterology RC799-869
spellingShingle	Diseases of the digestive system. Gastroenterology RC799-869 Kamal SM Pharmacogenetics of hepatitis C: transition from interferon-based therapies to direct-acting antiviral agents
description	Sanaa M Kamal1,21Department of Medicine, Division of Hepatology, Gastroenterology and Tropical Medicine, Ain Shams Faculty of Medicine, Cairo, Egypt, 2Department of Medicine, Salman Bin Abdul Aziz College of Medicine, Kingdom of Saudi ArabiaAbstract: Hepatitis C virus (HCV) has emerged as a major viral pandemic over the past two decades, infecting 170 million individuals, which equates to approximately 3% of the world's population. The prevalence of HCV varies according to geographic region, being highest in developing countries such as Egypt. HCV has a high tendency to induce chronic progressive liver damage in the form of hepatic fibrosis, cirrhosis, or liver cancer. To date, there is no vaccine against HCV infection. Combination therapy comprising PEGylated interferon-alpha and ribavirin has been the standard of care for patients with chronic hepatitis C for more than a decade. However, many patients still do not respond to therapy or develop adverse events. Recently, direct antiviral agents such as protease inhibitors, polymerase inhibitors, or NS5A inhibitors have been used to augment PEGylated interferon and ribavirin, resulting in better efficacy, better tolerance, and a shorter treatment duration. However, most clinical trials have focused on assessing the efficacy and safety of direct antiviral agents in patients with genotype 1, and the response of other HCV genotypes has not been elucidated. Moreover, the prohibitive costs of such triple therapies will limit their use in patients in developing countries where most of the HCV infection exists. Understanding the host and viral factors associated with viral clearance is necessary for individualizing therapy to maximize sustained virologic response rates, prevent progression to liver disease, and increase the overall benefits of therapy with respect to its costs. Genome wide studies have shown significant associations between a set of polymorphisms in the region of the interleukin-28B (IL28B) gene and natural clearance of HCV infection or after PEGylated interferon-alpha and ribavirin treatment with and without direct antiviral agents. This paper synthesizes the recent advances in the pharmacogenetics of HCV infection in the era of triple therapies.Keywords: hepatitis C virus, interleukin-28B polymorphisms, PEGylated interferon and ribavirin, direct-acting antiviral agents, pharmacogenetics, rational therapeutics
format	article
author	Kamal SM
author_facet	Kamal SM
author_sort	Kamal SM
title	Pharmacogenetics of hepatitis C: transition from interferon-based therapies to direct-acting antiviral agents
title_short	Pharmacogenetics of hepatitis C: transition from interferon-based therapies to direct-acting antiviral agents
title_full	Pharmacogenetics of hepatitis C: transition from interferon-based therapies to direct-acting antiviral agents
title_fullStr	Pharmacogenetics of hepatitis C: transition from interferon-based therapies to direct-acting antiviral agents
title_full_unstemmed	Pharmacogenetics of hepatitis C: transition from interferon-based therapies to direct-acting antiviral agents
title_sort	pharmacogenetics of hepatitis c: transition from interferon-based therapies to direct-acting antiviral agents
publisher	Dove Medical Press
publishDate	2014
url	https://doaj.org/article/0f57efea98f34f8cbddc989454b0f0d6
work_keys_str_mv	AT kamalsm pharmacogeneticsofhepatitisctransitionfrominterferonbasedtherapiestodirectactingantiviralagents
_version_	1718403180408078336

Pharmacogenetics of hepatitis C: transition from interferon-based therapies to direct-acting antiviral agents

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