Hepatitis C virus genotype 5 (HCV-GT-5) is found mainly in South Africa. In our area in central France, the prevalence of HCV-GT-5 is 14%.

Here we evaluated sustained virological response at week 12 post-treatment (SVR12) in 147 HCV-GT-5 patients from 14 French university hospitals (2014-2021) treated with direct-acting antivirals (DAA) in real-life. Patients had mainly received sofosbuvir/ledipasvir ± ribavirin, sofosbuvir/velpatasvir, and glecaprevir/pibrentasvir. Overall SVR12 was 98% (144/147). Two patients experienced relapse: one was successfully retreated with the same DAAs (sofosbuvir/ledipasvir) plus ribavirin, and the other refused further DAA treatment. One patient with virological failure (sofosbuvir/velpatasvir) had received a second treatment (sofosbuvir/velpatasvir/voxilaprevir) and progressed to cure.

HCV-GT-5 patients treated with a DAA regimen had a 99% SVR12 in intention-to-treat (including initial therapy and retreatment) and 100% SVR12 per protocol. Sofosbuvir/ledipasvir, sofosbuvir/velpatasvir, and glecaprevir/pibrentasvir show very good efficacy in real-world HCV-GT-5 patients.

Hepatitis C virus (HCV) genotype 5 was originally identified in South Africa, where it represents 35-60% of all HCV infections. There are limited data on resistance-associated variants (RAVs) in South Africa. Thus, we investigated variability within the NS3/NS4A, NS5A, and NS5B genes of treatment-naïve individuals with HCV genotype 5 infection at the Dr. George Mukhari Academic Hospital (DGMAH) in Pretoria, South Africa.

Nested PCR was performed to amplify the NS3/4A, NS5A, and NS5B genes. RAVs were evaluated using the Geno2pheno tool.

In the NS3/4A gene, F56S and T122A were detected in one sample each. The D168E mutation was detected in 7 samples. Within the NS5A gene, the T62M mutation was detected in 2 individuals. In the NS5B gene, 8 of 12 individuals (67%) had the A421V mutation, while all 12 individuals (100%) had the S486A mutation.

RAVs were detected frequently among treatment-naïve individuals with HCV genotype 5 infection in South Africa. Thus, resistance testing may be prudent when initiating treatment of patients with genotype 5 infection. Additional population-based studies are needed to understand the prevalence of these RAVs during HCV genotype 5 infection.

Hepatitis C virus (HCV) is divided into 7 genotypes and 67 subtypes. HCV genotype studies reflect the viral transmission patterns as well as human migration routes. In a clinical setting, HCV genotype is a baseline predictor for the sustained virological response (SVR) in chronic hepatitis C patients treated with peginterferon or some direct acting antivirals (DAAs). The Versant HCV genotype 2.0 assay has been globally used for HCV genotyping over a decade. Areas covered: The assay is based on reverse hybridization principle. It is evolved from its former versions, and the accuracy and successful genotyping/subtyping rate are substantially improved. It shows an accuracy of 99-100% for genotypes 1-6. It can also reliably identify subtypes 1a and 1b. However, the assay does not allow a high resolution for many other subtypes. Reasons for indeterminate or inaccurate genotyping/subtyping results are discussed. Expert commentary: Genotyping helps to find the most efficacious and cost-effective treatment regimen. The rapid development of anti-HCV treatment regimens, however, is greatly simplifying laboratory tests. In the near future, the need for HCV genotyping and frequent serial on-treatment HCV RNA tests will decrease along with the wide use of the more potent and pan-genotypic DAA regimens.

Around 70 to 100 million people are chronically infected with HCV worldwide. HCV antiviral drug development has revolutionised the treatment of HCV, with several direct-acting antiviral agents offering patients the chance of cure after only 8-12 weeks of treatment. Drug development was initially focussed on HCV genotype 1 (GT1) infection, since this was the most prevalent worldwide, although clinical trials included all genotypes prevalent in the US and Europe. Because the earliest in vitro assays utilised the GT1b and 2 replicons, the initial classes of direct-acting antivirals (protease inhibitors, non-nucleotide polymerase inhibitors) were GT1-specific, albeit they had an effect on other less prevalent genotypes. Epidemiological data has shown the regional importance of other HCV genotypes. More than 50% of all HCV infections around the globe are not with GT1. The prevalence of HCV genotype 4 (GT4), 5 (GT5), and 6 (GT6) is increasing in North America and Europe due to migration from the Middle East, Africa and South-East Asia. With the successful development of the multi and pan-genotypic non-structural protein 5A inhibitors, second generation protease inhibitors and nucleotide non-structural protein 5B inhibitors comes a unique opportunity to achieve global HCV elimination. The goal of this review is to summarise the available information pertaining to GT4, GT5 and GT6, with a specific focus on direct-acting antiviral agents.

Transmission of infectious agents might be associated with iatrogenic actions of charitable help in health care. An example is the vaccination against yellow fever in USA that transmitted hepatitis B virus. Another example is injections of praziquantel for treatment and cure of schistosomiasis in Central and Northern Africa, with a focus in Egypt that has spread hepatitis C virus. There is no indication that human T-lymphotropic virus type 1 was spread by injection treatment for African trypanosomiasis, syphilis and treponematosis, but these treatments might have contributed to the early spread of human immunodeficiency virus type 1 (HIV-1) in Central Africa. Slave trade contributed as well to the spread of viruses from Africa to the Americas; it was stopped in 1850. Until that date HIV-1 was not transported to the Americas. By analysis of nucleic acid sequence data it can be concluded that the continental spread of HCV and HIV-1 might have started around 1920 with an exponential phase from 1940 to 1970. Further iatrogenic actions that promoted the spread of HCV and HIV-1 might be vaccinations to prevent deadly diseases. The successful vaccination was followed by diminution of the infectious agent in the population such as small pox, yellow fever and measles. Measurements to reduce the spread of plague and cholera were further benefits increasing survival of diseased subjects in a population. Thus, the reduction of exposure to deadly infectious agents might have given a chance to HIV-1 infected subjects to survive and for HIV-1 to be distributed around the world starting from Central Africa in the 1950s.

Hepatitis C virus (HCV) genotypes' monitoring allows real-time insight into the dynamic changes that occur in the global epidemiological picture of HCV infection. Intravenous drug use is currently the primary driver for HCV transmission in developed and developing countries. The distribution of HCV genotypes/subtypes differs significantly between people who inject drugs (PWID) and the general population. HCV genotypes that previously exhibited a limited geographical distribution (3a, 4) are becoming more prevalent in this high-risk group. Immigration from HCV-endemic countries and the evolving networks of HCV transmission in PWID influence HCV genotypes distribution in Europe. Social vulnerabilities (e.g., unemployment, homelessness, and limited access to social and healthcare insurances systems) are important triggers for illicit drug use, which increases the associated risks of HCV infection and the frequent emergence of less prevalent genotypes. Genotype/subtype determination bears important clinical consequences in the progression of liver disease, susceptibility to antiviral therapies and the emergence of resistance-associated variants. An estimated half of the chronically HCV-infected PWID are unaware of their infection, and only one in ten of those diagnosed enter treatment. Nevertheless, PWID exhibit high response rates to new antiviral regimens, and the level of HCV reinfection is unexpectedly low. The focus of the healthcare system must be on the early detection and treatment of infection, to avoid late presentations that are associated with high levels of viremia and liver fibrosis, which may diminish the therapeutic success rate.

Pegylated-interferon-α based therapy for the treatment of chronic hepatitis C (CHC) is considered suboptimal as not all patients respond to the treatment and it is associated with several side effects that could lead to dose reduction and/or termination of therapy. The currently used markers to monitor the response to treatment are based on viral kinetics and their performance in the prediction of treatment outcome is moderate and does not combine accuracy and their values have several limitations. Hence, the development of new sensitive and specific predictor markers could provide a useful tool for the clinicians and healthcare providers, especially in the new era of interferon-free therapy, for the classification of patients according to their response to the standard therapy and only subscribing the novel directly acting antiviral drugs to those who are anticipated not to respond to the conventional therapy and/or have absolute contraindications for its use. The importance of activins and follistatin in the regulation of immune system, liver biology, and pathology has recently emerged. This review appraises the up-to-date knowledge regarding the role of activins and follistatin in liver biology and immune system and their role in the pathophysiology of CHC.

Hepatitis C virus (HCV) genotypes 4, 5 and 6 are mainly present in Africa, the Middle East and Asia and they have been less extensively studied with respect to epidemiology, natural disease history and therapeutic endpoints. Response rates to a 48-wk combined peginterferon/ribavirin treatment range to 40%-69% for HCV 4, 55%-60% for HCV 5 and 60%-90% for HCV 6. Response-guided schedules are recommended to optimize the outcomes of peginterferon/ribavirin treatment in HCV 4 and, in form of preliminary data, for HCV 6, but no data are yet available to support such an individualization of therapy for HCV 5. Recently, the direct-acting antivirals (DAAs) with pan-genotypic activities simeprevir, sofosbuvir and daclatasvir have been recommended in triple regimens with peginterferon/ribavirin for the treatment of HCV genotypes 4 to 6 infections. In the future, DAA-based interferon-free therapies are awaited to drastically improve treatment outcomes in HCV. However, efforts to improve treatment outcomes with peginterferon/ribavirin should continue, as the HCV 4-6 infected population is mainly based in resource-limited settings with restricted access to the costly DAAs.

The global burden of hepatitis C (HCV) infection is mostly found in Africa, the Middle East and Asia, where HCV genotypes 4, 5 and 6 are common. The literature on these genotypes is sparse and this synopsis will review characteristics of patients infected with these genotypes.

To review characteristics of patients infected with HCV genotypes 4, 5 and 6.

PubMed search for 'hepatitis C' AND 'genotype 4', 'hepatitis C' AND 'genotype 5', and 'hepatitis C' AND 'genotype 6' was conducted and relevant articles were reviewed.

Intravenous drug use is generally responsible for HCV genotype 4 infection in developed countries, but unsafe medical practices cause most cases of HCV genotypes 4, 5 and 6 in endemic countries. The sustained virological response (SVR) rate for patients with HCV genotype 4 who receive pegylated interferon and ribavirin for 48 weeks ranges from 40% to 70% in various small studies. The SVR rate is in the 60-70% range for HCV genotype 5 and 70-80% range for HCV genotype 6 following 48 weeks with pegylated interferon and ribavirin. Preliminary data suggest that a shorter course of 24 weeks of pegylated interferon and ribavirin may be acceptable for HCV genotype 6, with an SVR rate of approximately 70%.

The current standard-of-care therapy for HCV genotypes 4, 5 and 6 is pegylated interferon and ribavirin for 48 weeks. A shorter course with 24 weeks of therapy may be considered for patients with genotype 6. Newer and much more effective therapies may be forthcoming in the next few years.

An observational seroepidemiological study was carried out in a well-defined primary-care district on the island of Crete in order to determine the recent endemicity of viral hepatitis in Cretan-population.

The setting consisted of a semi-urban group and a remote & rural group. Serum samples were collected from 876 subjects (437 males, 439 females) aged 15 years or above. Subjects were randomly selected from the permanent population of the area that consisted of 5705 individuals. The aim was to measure the prevalence of selected viral-hepatitis markers.

Hepatitis B surface-antigen (HBsAg) was found positive in twenty-nine individuals, (3.3%). Antibodies to hepatitis B virus core-antigen (HBcAb) were detected in 287 subjects (32.8%) and antibodies to hepatitis C virus (anti-HCV) were detected in nineteen subjects (2.2%). Seropositivities for the semi-urban group were: 3.4%, 19.1%, 2.1% and 3.2%, 48.8%, 2.2% in remote & rural group respectively. Virtually, all subjects >45 years old were seropositive for antibodies to hepatitis A, whereas approximately 80% of those in the 15-44 age-group were found to be seropositive.

A threefold increase in the HBV exposure and carrier proportion was found in Cretan native-population and in rural-areas compared to older studies carried out in other rural-populations of the island. It is still unknown whether the recent economic crisis or the demographic changes in Cretan-population contributed to these findings. HCV endemicity remains relatively constant, however an alteration of hepatitis C genotypes was observed. Exposure to HAV was found to be higher in remote and rural areas compared to semi-urban areas.

HCV genotype 5 (HCV-5) is the least known HCV genotype. It is found mainly in South Africa and in restricted areas of Belgium, Spain, France, Syria and Greece. Sporadic cases are reported worldwide. The main modes of transmission are blood transfusion and iatrogenic causes. Little is known about its origin, but various studies have elucidated its spread worldwide. In endemic areas, patients infected with HCV-5 are on average older and have a higher viral load and more advanced fibrosis than those infected with non-HCV-5 genotypes.The current standard of care for HCV-5 chronic infection is 48 weeks of dual therapy with pegylated interferon plus ribavirin. 'Favourable' Il28B polymorphisms are not associated with higher sustained viral response rates. Assessment of shorter duration of therapy is made difficult by the lack of identifiable baseline predictors of response. Whilst there are in vitro data showing good activity of some direct-acting antivirals and of host-targeted agents against HCV-5, no clinical trials of these molecules have yet started.

Analysis of the Hepatitis C Virus (HCV) genotype spread in a particular area has a crucial impact on public health. In this study, we update information on the distribution of HCV genotypes, by evaluating a hospital-based cohort of 2,153 chronic hepatitis C patients, collected prospectively among subjects attending University Hospital of Catanzaro, within an area of Southern Italy. We assessed the rates (%) of HCV genotypes during two consecutive periods, from 2001 to 2005 and from 2006 to 2011, according to age and gender. Considering overall observation time, subtype 1b was predominant followed by subtypes 2a/2c, genotype 3 and 4. Statistical evaluation of the age of HCV patients stratified by genotypes, revealed a slight but significant increase in the median age of 1b, 2a/2c and 3 HCV genotype-infected subjects, during the 2006-2011 period, whilst genotype 4 patients exhibited a decrease in the median age during the same period studied. Moreover genotype 4 increased between 2002 and 2003 as well as between 2010 and 2011. Due to the peculiar diagnostic/clinical/therapeutic features of HCV-4, our findings warrant a deeper investigation to better control infections caused by such genotype.