Hepatitis C genotype 4: The past, present, and future

Abstract

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 healthcare 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.

Single nucleotide polymorphisms of interleukins associated with hepatitis C virus infection in Egypt

“…Notably, genotype 4a is the most common HCV variant in Egypt (78% of cases). HCV genotype 4 represents more than 17 million total global HCV infections and is prevalent in Africa, the Middle East, and some European countries [29,30]. The analysis of HCV genotype 4 in Egypt demonstrated that HCV genotype 4a is extremely variable from other genotypes in terms of sequences and immunological determinants that might alter virus-host interaction and cytokine production [31].…”

Resistance characterization of ledipasvir and velpatasvir in hepatitis C virus genotype 4

“…In study GS‐US‐342‐1138, all GT4 patients treated with SOF/VEL for 12 weeks achieved SVR12 . Other recommended treatments for GT4 HCV infection include combinations of NS3 protease inhibitors, NS5A inhibitors, NS5B polymerase inhibitors and/or ribavirin, with SVR rates above 90% (ombitasvir/paritaprevir/ritonavir + ribavirin, elbasvir/grazoprevir) …”

Genetic diversity of hepatitis C virus in Ethiopia

“…These subtypes are of interest because subtype 4r is not commonly reported while 4d is mostly reported in Saudi Arabia and in the majority of European IDU population [9, 28, 30, 36]. This result is thus different from studies in other African countries where subtypes 4a is the predominant subtype in Egypt [28, 35], 4f in Cameroon [37], 4e in Gabon [10, 29], 4k in the Central African Republic and Democratic Republic of the Congo [20, 38], 4c in the Republic of Congo [39], and 4q/4v in Rwanda [20]. The high diversity and predominance of genotype 4 suggests that this genotype has been endemic for a longer time in Ethiopian population.…”

“…In addition, genotype 4 is considered difficult to treat and has a poor sustained virological response rate of 43–63% to the standard pegylated IFN/ribavirin combination therapy [32]. This is relatively higher than genotype 1 but lower than genotypes, 2, 3, 5, and 6 [34, 35]. …”