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Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Dec 8, 2015; 7(28): 2792-2810
Published online Dec 8, 2015. doi: 10.4254/wjh.v7.i28.2792
Hepatitis C genotype 4: The past, present, and future
Tawhida Y Abdel-Ghaffar, Mostafa M Sira, Suzan El Naghi
Tawhida Y Abdel-Ghaffar, Pediatric Department, Ain Shams University, Cairo 11566, Egypt
Tawhida Y Abdel-Ghaffar, Suzan El Naghi, Yassin Abdel Ghaffar Charity Center for Liver Disease and Research, Cairo 11566, Egypt
Mostafa M Sira, Pediatric Hepatology Department, National Liver Institute, Menofiya University, Shebin El-koom, Menofiya 32511, Egypt
Suzan El Naghi, Pediatric Department, National Hepatology and Tropical Medicine Research Institute, Cairo 11441, Egypt
Author contributions: Abdel-Ghaffar TY, Sira MM and El Naghi S were involved in the study concept and design and shared in preparation; El Naghi S wrote the article; Abdel-Ghaffar TY and Sira MM reviewed the article.
Conflict-of-interest statement: The authors declare no conflict of interest for this article.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Correspondence to: Suzan El Naghi, MD, Pediatric Department, National Hepatology and Tropical Medicine Research Institute, 10 - Kasr El Aini Street, Cairo 11441, Egypt.
Telephone: +20-2-24197255 Fax: +20-2-23504240
Received: April 22, 2015
Peer-review started: April 24, 2015
First decision: July 21, 2015
Revised: September 24, 2015
Accepted: November 24, 2015
Article in press: November 25, 2015
Published online: December 8, 2015

Hepatitis C virus (HCV) genotype (GT) 4 represents 12%-15% (15-18 million) of total global HCV infection. It is prevalent in Northern and Equatorial Africa and the Middle East, and is also present in some countries in Europe. GT-4 (and subtype 4a in particular) dominates the HCV epidemic in Egypt. In underdeveloped countries, risk factors associated with HCV infection may be due to unsafe medical practices or other factors such as familial transmission, mother’s HCV status, or illiteracy. HCV prevention and control programs should include health education, increased community awareness towards the disease, controlling infection distribution in health-care centers, proper sterilization of medical and dental instruments, and ensuring safe supply of blood and blood-products. Response rates to a 48-wk combined pegylated-interferon (PEG-IFN) and ribavirin (RBV) treatment range from 40%-69%, and HCV-GT-4 has been considered better than GT-1 but worse than GT-2 and GT-3 in treatment with PEG-IFN/RBV. However, with the introduction of the HCV-GT-1 effective protease inhibitors boceprevir and telaprevir in 2011, HCV-GT-4 became the “most difficult (GT) to treat”. Recently, the direct-acting antivirals (DAAs) with pan- genotypic activities simeprevir, sofosbuvir, and daclatasvir have been recommended in triple regimens with PEG-IFN/RBV for the treatment of HCV-GT-4. An IFN-free regimen will be available for treatment of all genotypes of HCV in the near future. To date, several DAAs have been developed and are currently being evaluated in various combinations in clinical trials. As new regimens and new agents are being approved by the Food and Drug Administration, we can expect the guidelines for HCV treatment to be changed. The availability of shorter, simpler, and more tolerable treatment regimens can reduce the morbidity and mortality associated with HCV infection. With such a large number of therapeutic agents available, we can end up with a range of choices that we can select from to treat patients.

Keywords: Hepatitis C virus, Genotypes, Transmission, Pegylated-interferon, Ribavirin, Direct acting antivirals, Hepatitis C virus vaccine

Core tip: Hepatitis C virus (HCV) genotype (GT) 4 represents 12%-15% of total global HCV infection. It is higher in limited resource countries. Response rates to a 48-wk peg-interferon/ribavirin combination ranges from 40%-69% for HCV-GT-4. Direct-acting antivirals may significantly improve treatment outcomes in HCV- GT-4, but use of these agents in countries endemic for HCV-GT-4 is currently precluded by the very high costs. A new hepatitis C vaccine from GlaxoSmithKline has shown promise in early clinical tests, prompting strong and broad immune responses. Another Egyptian clinical trial in the field of HCV vaccination: Clinical Trials phases I and II, started on March 2011. Identifier NCT01718834.