Hepatitis C genotype 4: What we know and what we don't yet know

Abstract

H epatitis C virus (HCV), a member of the Flaviviridae family of RNA viruses, is characterized by genetic heterogeneity. At least 6 major HCV genotypes are identified. 1,2 Each genotype differs from the others by 30%-35% of its nucleotide site sequence and also exists as numerous genetically distinct isolates. [1][2][3] Each HCV genotype is unique with respect to its nucleotide sequence, geographic distribution, and response to therapy. 3 Thus, each genotype can be considered a phylogenetically distinct entity requiring its own specific clinical appreciation. Knowledge of the epidemiology of HCV genotypes is essential not only for epidemiological reasons but also from a clinical standpoint. The infecting HCV strain is known to be one of the main independent factors that influence the outcome of antiviral therapy. 2,3 Genotypes 1, 2, and 3 are common throughout the United States and Europe 2,4 and have thus become the focus of much interest and research. The clinical presentation and management of infections arising from these viral genotypes has advanced rapidly. In contrast, genotypes 4, 5, and 6 have not been adequately studied; therefore, the management strategies for patients infected with these genotypes are not as well developed. 4,5 HCV genotype 4 (HCV-4) is common in the Middle East and in Africa, where it is responsible for more than 80% of HCV infections, and has recently spread to several European countries. 4,5 Egypt has the highest prevalence of HCV worldwide (15%) 6 and the highest prevalence of HCV-4, which is responsible for almost 90% of infections and is considered a major cause of chronic hepatitis, liver cirrhosis, hepatocellular carcinoma, and liver transplantation in the country. [5][6][7] Although HCV-4 is the cause of approximately 20% of the 170 million cases of chronic hepatitis C in the world, it has simply not been the subject of widespread research; therefore, the features of this genotype and management strategies for patients infected with this genotype are not as well developed as for

Vitamin D Receptor FokI Gene Polymorphism Predicted Poor Response to Treatment in Chronic HCV Genotype 4

“…[ 1,2] For genotype 4, which is the most prevalent form in Egypt, pegIFNα-2a and ribavirin remain the suboptimal "gold standard" for treatment with sustained virologic response rates (SVR) of about 40%-60%. [2] Despite the emergence of novel direct-acting antivirals, to date no interferon-free regimen has proved as effective as interferon-incorporating regimens and none has yet been approved for the treatment of HCV. [3,5] In the quest to enhance treatment response there has been a relentless search for predictors of response, especially modifiable factors.…”

Molecular study of HCV detection, genotypes and their routes of transmission in North West Frontier Province, Pakistan

“…Type 4 is found in Middle East, Egypt and central Africa. The South African population is mostly infected with genotype 5 [13] . Genotype 6 is found in the population of Hong Kong [14] .…”

Phylogenetic Analysis of Isolated HCV Strains from Tunisian Hemodialysis Patients

“…This genotype is highly prevalent in the Middle East (Teheran, Yemen, Kuwait, Iraq, and Saudi Arabia) and in Africa, particularly in Egypt due to the use of unsterile equipment during mass treatment of the population with parenteral antischistosomal therapy from the 1920s to the 1980s (7,13,15,18). HCV-4 has recently spread in several Western countries, especially in Europe (28,33) and North America, due to the variations in population structure, immigration, and routes of transmission, particularly among IVDU populations, who represent the main reservoir for HCV in Europe.…”