Epidemiology Of Hepatitis C Virus Research Articles

Molecular Epidemiology of Hepatitis B, Hepatitis C, and HIV-1 Co-Infections in Ethiopia: Implications for Disease Burden and Intervention Strategies

BackgroundHepatitis B virus (HBV) exhibits high prevalence rates within Ethiopia. The genetic diversity of HBV, marked by mixed genotype infections, may hold significant implications for the trajectory of disease and responses to treatment. Ethiopia grapples with a substantial public health challenge posed by co-infections involving HBV, hepatitis C virus (HCV), and human immunodeficiency virus 1 (HIV-1), particularly among vulnerable populations. MethodsA comprehensive investigation into HBV, HCV, and HIV-1 co-infection was conducted. A total of 7,789 blood samples were meticulously analyzed, among which 815 exhibited HBV positivity. Among the HBV-positive samples, 630 were subjected to genotyping procedures, resulting in the identification of a prevalent trend of mixed infections characterized by HBV genotypes A/E/F (67.30%). Serological assessments were performed on 492 specimens to ascertain the presence of HCV and HIV-1 co-infections, revealing respective co-infection rates of 13.02% for HBV/HIV, 3.31% for HBV/HCV, and 2.07% for triple infection. ResultsThe investigation revealed the intricate prevalence of co-infections in Ethiopia, notably underlining the continued transmission of viruses. The prominent occurrence of mixed HBV genotypes A/E/F suggests dynamic viral interactions and ongoing transmission pathways. These findings accentuate the necessity for targeted interventions and enhanced patient care, as co-infections carry significant clinical complexities. ConclusionsThis study furnishes crucial insights into the molecular epidemiology of HBV, HCV, and HIV-1 co-infections in Ethiopia. The acquired knowledge can contribute to the advancement of strategies for clinical management and the formulation of public health interventions aimed at ameliorating the burden of viral infections within the nation.

Prevalence of HCV infection in Europe in the DAA era: Review.

In 2016, the Global Health Sector Strategy, ratified by the 69th World Health Assembly, set the ambitious goal of eliminating hepatitis C virus (HCV) and hepatitis B virus infections by 2030, emphasizing the importance of national screening programmes. Achieving this goal depends on each country's ability to identify and treat 80% of chronic hepatitis C cases, a critical threshold set by the World Health Organization. Traditionally, estimates of HCV prevalence have been based on interferon era studies that focused on high-risk subgroups rather than the general population. In addition, the incomplete data available from national registries also limited the understanding of HCV prevalence. The 2016 report from the European Centre for Disease Prevention and Control highlighted that HCV rates varied across European counties, ranging from .1% to 5.9%. However, data were only available for 13 countries, making the overall picture less clear. Additionally, the epidemiological data may have underestimated the true burden of HCV due to lack of awareness among those with chronic infection. The main objective of this review is to provide a comprehensive summary of HCV epidemiology in Europe in the current era of direct-acting antivirals (DAAs). The data included in the analysis range from the end of 2013 to December 2023 and have been categorised according to the United Nations Geoscheme. The resulting synthesis underscores the noteworthy impact of DAA treatment on the epidemiological situation.

Impact of simplified HCV diagnostic strategies on the HCV epidemic among men who have sex with men in the era of HIV oral pre-exposure prophylaxis in Taiwan: a modelling study.

Simplified hepatitis C virus (HCV) diagnostic strategies have the potential to improve HCV diagnoses and treatment. We aimed to investigate the impact of simplified HCV diagnostic strategies on HCV incidence and its effect on HCV diagnosis and treatment among men who have sex with men (MSM) regardless of HIV status and use of HIV pre-exposure prophylaxis (PrEP) in Taiwan. A compartmental deterministic model was developed to describe the natural history of HCV disease progression, the HCV care cascade and the HIV status and PrEP using among MSM. The model was calibrated to available data for HCV and HIV epidemiology and population demographics in Taiwan. We simulated the epidemic from 2004 and projected the impact of simplified testing strategies on the HCV epidemic among MSM over 2022-2030. Under the current testing approach in Taiwan, total HCV incidence would increase to 12.6 per 1000 person-years among MSM by 2030. Single-visit point-of-care RNA testing had the largest impact on reducing the number of new HCV infections over 2022-2030, with a 31.1% reduction (interquartile range: 24.9%-32.8%). By 2030, single-visit point-of-care HCV testing improved HCV diagnosis to 90.9%, HCV treatment to 87.7% and HCV cure to 81.5% among MSM living with HCV. Compared to status quo, prioritized simplified HCV testing for PrEP users and MSM living with diagnosed HIV had considerable impact on the broader HCV epidemic among MSM. A sensitivity analysis suggests that reinfection risk would have a large impact on the effectiveness of each point-of-care testing scenario. Simplified HCV diagnostic strategies could control the ongoing HCV epidemic and improve HCV testing and treatment among Taiwanese MSM. Single-visit point-of-care RNA testing would result in large reductions in HCV incidence and prevalence among MSM. Efficient risk-reduction strategies will need to be implemented alongside point-of-care testing to achieve HCV elimination among MSM in Taiwan.

Epidemiology of acute hepatitis C and hepatitis C virus-related cirrhosis in reproductive-age women, 1990-2019: An analysis of the Global Burden of Disease study.

The current study uniquely focuses on the global incidence and temporal trends of acute hepatitis C (AHC) and hepatitis C virus (HCV)-related cirrhosis among women of reproductive age (15-49 years) from 1990-2019. The risk of vertical transmission and adverse perinatal outcomes associated with HCV infection underscores the importance of prioritising these women in HCV prevention efforts. Leveraging the Global Burden of Disease 2019 data, we calculated age-standardised incidence rates (ASIR) and assessed temporal trends via the average annual percent change from joinpoint regression. The age-period-cohort model was employed to understand further the effects of age, period, and birth cohort. Over the 30 years, global incidences of AHC and HCV-related cirrhosis in reproductive-age women increased by 46.45 and 72.74%, respectively. The ASIR of AHC was highest in low sociodemographic index regions but showed a declining trend. Conversely, the ASIR of HCV-related cirrhosis displayed unfavourable trends in low, low-middle, and high sociodemographic index regions. Special attention is necessary for sub-Saharan Africa, high-income North America, Eastern Europe, and Central Asia due to their high incidence rates or increasing trends of AHC and HCV-related cirrhosis. Notably, the age-period-cohort model suggests a recent resurgence in AHC and HCV-related cirrhosis risk. The current study is the first to thoroughly evaluate the trends of AHC and HCV-related cirrhosis among reproductive-age women, shedding light on previously unexplored aspects of HCV epidemiology. Our findings identify critical areas where health care systems must adapt to the changing dynamics of HCV infection. The detailed stratification by region and nation further enables the development of localised prevention and treatment strategies.

Hepatitis C Epidemiology: Insights from a Comprehensive Cohort Study in ASST Melegnano and Martesana, Lombardia Region, Northern Italy.

Hepatitis C virus (HCV) infection is a significant public health problem affecting 58 million people worldwide, including 3.9 million in Europe. Many of these infections go undiagnosed because chronic infection is often asymptomatic. This observational cohort study presents a detailed examination of hepatitis C virus epidemiology in Lombardia (Italy) and was conducted within the ASST "Melegnano e della Martesana". The study involved comprehensive HCV screening of 3290 patients accessing the collection points and/or hospitalized in the facilities of the ASST from 20 May 2022 to 13 April 2023. Screening was conducted using serological assays. The prevalence of anti-HCV-positive patients (HCV-Ab) and then HCV-positive patients (RNA) was calculated. Chi-square tests examined the associations between continuous and categorical variables. Logistic regression was used to evaluate the influence of demographic and geographic variables as predictors of HCV positivity. The study revealed an overall HCV-Ab prevalence of 0.912% (CI (0.59-1.24%)) in the examined cohort, of whom 15.15% (two females and three males) were positive for HCV RNA. The prevalence of HCV RNA positivity was 0.152% (CI (0.05-0.35%)). Sex disparity was evident, with male patients exhibiting a higher prevalence compared to females, confirmed by logistic regression (0.0147 vs. 0.0061-OR = 2.44; CI (0.0059-0.0124)). Age stratification indicated an ascending trend in prevalence with age, peaking at 1.35% in individuals aged over 50. These findings underscore the critical need for targeted HCV screening, contributing valuable insights to the global epidemiology of HCV in the era of DAAs.

SASLT guidelines: Update in treatment of hepatitis C virus infection, 2024.

Hepatitis C virus (HCV) infection has been a major global health concern, with a significant impact on public health. In recent years, there have been remarkable advancements in our understanding of HCV and the development of novel therapeutic agents. The Saudi Society for the Study of Liver Disease and Transplantation formed a working group to develop HCV practice guidelines in Saudi Arabia. The methodology used to create these guidelines involved a comprehensive review of available evidence, local data, and major international practice guidelines regarding HCV management. This updated guideline encompasses critical aspects of HCV care, including screening and diagnosis, assessing the severity of liver disease, and treatment strategies. The aim of this updated guideline is to assist healthcare providers in the management of HCV in Saudi Arabia. It summarizes the latest local studies on HCV epidemiology, significant changes in virus prevalence, and the importance of universal screening, particularly among high-risk populations. Moreover, it discusses the promising potential for HCV elimination as a public health threat by 2030, driven by effective treatment and comprehensive prevention strategies. This guideline also highlights evolving recommendations for advancing disease management, including the treatment of HCV patients with decompensated cirrhosis, treatment of those who have previously failed treatment with the newer medications, management in the context of liver transplantation and hepatocellular carcinoma, and treatment for special populations.

High Seroprevalence of Hepatitis C Virus Among Cisgender Women Who Exchange Sex in the Seattle, Washington Area.

Injection drug use (IDU) is a risk factor for hepatitis C virus (HCV) acquisition and occurs disproportionately among women who exchange sex (WES). However, little is known about HCV epidemiology in this population. We estimated HCV seroprevalence, identified correlates of HCV seropositivity, and characterized social networks by HCV serostatus and IDU history among WES in the Seattle, Washington, area. This was a secondary analysis of data from the 2016 National HIV Behavioral Surveillance survey in the Seattle, Washington area, a cross-sectional survey that used respondent-driven sampling (RDS) to enroll WES for money or drugs (N = 291). All participants were offered rapid HCV-antibody testing. We estimated HCV seropositivity and used log regression methods to estimate crude and adjusted prevalence ratios (PRs) for correlates of HCV seropositivity among WES. Using RDS recruitment chain data, we computed homophily indices to estimate the extent to which participants were likely to recruit another participant with the same HCV serostatus and IDU history. In the study sample of WES in the Seattle, Washington area, 79% reported lifetime IDU and 60% were HCV seropositive. HCV seropositivity was strongly associated with ever injecting drugs (PRadj: 7.7 [3.3, 18.0]). The RDS homophily scores for HCV seropositivity (0.07) and ever injecting drugs (0.02) suggested that participants did not tend to recruit others with the same characteristics beyond what would be expected by chance. Among this sample of WES in Seattle, Washington area, HCV seroprevalence was high and strongly associated with a history of IDU. The high burden of HCV among WES suggests this marginalized group would benefit from additional harm reduction services and targeted HCV treatment campaigns to reduce forward transmission. We saw little evidence of preferential recruitment among WES who were HCV seropositive or reported a history of IDU, suggesting the potential futility of peer-based referrals for HCV treatment.

Molecular evolution, virology and spatial distribution of HCV genotypes in Pakistan: A meta-analysis

BackgroundHepatitis C, caused by the Hepatitis C Virus (HCV), is the second most common form of viral hepatitis. The geographical distribution of HCV genotypes can be quite complex, making it challenging to ascertain the most prevalent genotype in a specific area. MethodsTo address this, a review was conducted to determine the prevalence of HCV genotypes across various provinces and as a whole in Pakistan. The scientific literature regarding the prevalence, distribution, genotyping, and epidemiology of HCV was gathered from published articles spanning the years 1996–2020. ResultsGenotype 1 accounted for 5.1% of the patients, with its predominant subtype being 1a at 4.38%. The frequencies of its other subtypes, 1b and 1c, were observed to be 1.0% and 0.31% respectively. Genotype 2 had a frequency of 2.66%, with the most widely distributed subtype being 2a at 2.11% of the patients. Its other subtypes, 2b and 2c, had frequencies of 0.17% and 0.36% respectively. The most prevalent genotype among all isolates was 3 (65.35%), with the most frequent subtype being 3a (55.15%), followed by 3b (7.18%). The prevalence of genotypes 4, 5, and 6 were scarce in Pakistan, with frequencies of 0.97%, 0.08%, and 0.32% respectively. The prevalence of untypeable and mixed genotypes was 21.34% and 3.53% respectively. Estimating genotypes proves to be a productive method in assisting with the duration and selection of antiviral treatment. Different HCV genotypes can exhibit variations in their response to specific antiviral treatments. Different genotypes may have distinct natural histories, including variations in disease progression and severity. Some genotypes may lead to more rapid liver damage, while others progress more slowly. ConclusionsThis information can guide screening and testing strategies, helping to identify individuals at higher risk of developing severe complications. Studying the distribution of HCV genotypes in a population can provide valuable insights into the transmission dynamics of the virus.

Hepatitis B and C virus knowledge and infections in Enugu State, Nigeria

Despite tremendous biotechnological and therapeutic advances, hepatitis B virus (HBV) and hepatitis C virus (HCV) still constitute a significant global health challenge. With Nigeria known to be a high HBV and HCV burden country, increasing knowledge about viral hepatitis in rural and urban settings, combined with testing and vaccination for unexposed individuals, could be an effective strategy to eliminate these viruses in Nigeria. Therefore, we undertook this prospective study to determine the level of knowledge and epidemiology of HBV and HCV in selected communities and towns in Enugu North geopolitical zone. In this study, 52.3 % of the participants admitted to having previously heard about hepatitis B and/or C. Also 71.2 % of the research participants had no prior vaccination against HBV. Based on our findings, the prevalence rate of HBV is 2.8 % and that of HCV is 0 %. With only the HBsAg marker detected using the five-panel test kits, five of our fourteen samples are designated as being in the acute phase. Another three had HBsAg and HBeAg present and were therefore classified as being either in the late acute or chronic phase. We also recorded a single case of waned immunity to HBV. Further studies to determine viral DNA levels and other new seromarkers is recommended along with vaccination of unvaccinated individuals.

Incidence and molecular epidemiology of hepatitis C virus reinfection in prisons in Catalonia, Spain (Re-HCV study)

Hepatitis C virus (HCV) reinfection may hamper HCV elimination in prisons. We aimed to (i) determine the reinfection rate in people treated for HCV in Catalan prisons, (ii) measure reinfection in people entering prisons, and (iii) characterize the molecular epidemiology of HCV in prisons and people who inject drugs (PWID) in the community. Re-HCV was a prospective study in eight prisons (2019–2020) including two groups: (1) people cured with treatment in prison and followed-up every 6 months, and (2) people testing HCV-RNA positive at incarceration. Bio-behavioral data were collected. HCV isolates were sequenced and phylogenetically analyzed with those of PWID in the community. Reinfection follow-up after treatment was achieved in 97 individuals (103.05 person-years). Two reinfections were detected, resulting in an incidence ≤ 10/100 person-years. Among people entering prison, 2% (359/17,732) were viremic, of which 334 (93.0%) were included, and 44 (13.5%) presented with reinfection (84.7% being PWID). Frequently, HCV isolates in prisons and PWID in the community were phylogenetically related. Although HCV reinfection is low after treatment, it is common in people entering Catalan prisons. To maintain a low HCV prevalence in prisons, harm-reduction services and test-and-treat programs for PWID should be strengthened both inside and outside prisons.

HIV and HCV screening by non-infectious diseases physicians: can we improve testing and hidden infection rates?

Missed opportunities for Human Immunodeficiency Virus (HIV) and Hepatitis C Virus (HCV) testing remain high. We aimed to ascertain the knowledge of screening guidelines and attitudes of non-infectious disease (ID) hospital physicians and assess the impact of a 1-h session on screening rates and diagnoses. This interventional study consisted of a 1-h training session on HIV and HCV epidemiology and testing guidelines for non-ID physicians. Pre-and post-session questionnaires compared the knowledge of the guidelines and attitudes toward screening before and after the session. Rates of screening and diagnoses were compared in three 6 months periods: before, immediately after, and 24 months ±4 after the session. A total of 345 physicians from 31 departments participated in these sessions. Before the session, 19.9% (28% medical, 8% surgical) and 17.9% (30% medical, 2.7% surgical) were aware of HIV and HCV testing guidelines, respectively. The willingness to routinely test increased from 5.6 to 22%, whereas not ordering tests decreased from 34.1 to 2.4%. HIV screening rates significantly increased by 20% after the session (7.7 vs. 9.3 tests per 103 patients; p < 0.001), and the effect persisted until the long-term period. The HIV diagnosis rate increased globally (3.6 vs. 5.2 HIV diagnoses per 105 patients; p = 0.157), mainly because of medical services (4.7 vs. 7.7 per 105 patients; p = 0.082). The HCV screening rate increased significantly immediately and in the long term only in medical services (15.7 and 13.6%, respectively). The new active HCV infection rates increased immediately and declined steeply thereafter. A short session for non-ID physicians can improve HIV/HCV screening, increase diagnosis, and contribute to disease elimination.

Changing Epidemiological Patterns of Infection and Mortality Due to Hepatitis C Virus in Poland.

Limited information is available on trends in hepatitis C virus (HCV) infection, particularly in Central Europe. To address this knowledge gap, we analyzed HCV epidemiology in Poland, considering socio-demographic characteristics, changing patterns over time, and the impact of the COVID-19 pandemic. We examined HCV cases (diagnosis and deaths) reported by national registries and used joinpoint analysis to estimate time trajectories. Between 2009 and 2021, there were changes in the trends of HCV, shifting from positive to negative in Poland. Among men, there was a significant increase initially in diagnosis rate of HCV in rural areas (annual percent change, APC2009-2016 +11.50%) and urban areas (APC2009-2016 +11.44%) by 2016. In subsequent years until 2019, the trend changed direction, but the reduction was weak (Ptrend > 0.05) in rural areas (-8.66%) and urban areas (-13.63%). During the COVID-19 pandemic, the diagnosis rate of HCV dramatically decreased in rural areas (APC2019-2021 -41.47%) and urban areas (APC2019-2021 -40.88%). Among women, changes in the diagnosis rate of HCV were less pronounced. In rural areas, there was a significant increase (APC2009-2015 +20.53%) followed by no significant change, whereas changes occurred later in urban areas (APC2017-2021 -33.58%). Trend changes in total mortality due to HCV were mainly among men, with a significant decrease in rural (-17.17%) and urban (-21.55%) areas from 2014/2015. The COVID-19 pandemic reduced HCV diagnosis rates in Poland, especially for diagnosed cases. However, further monitoring of HCV trends is necessary, along with national screening programs and improved linkage to care.

Growth history of hepatitis C virus among HIV/HCV co-infected patients in Guizhou Province.

Background: The evolutionary and epidemiological history and the regional differences of various hepatitis C virus (HCV) genotypes are complex. Our aim was to better understand the molecular epidemiology and evolutionary dynamics of HCV among HIV/HCV co-infected individuals in Guizhou Province. This information could contribute to improve HCV prevention and control strategies in Guizhou and surrounding provinces. Methods: The HCV RNA was extracted from the serum of HIV/HCV co-infected patients, and reverse transcription/nested PCR was performed to amplify nucleotide sequences of the C-E1 region. Then, the successfully amplified sequences were selected for phylogenetic analysis. The available C-E1 region reference sequences from the surrounding provinces of Guizhou (Guangxi, Yunnan, Hunan, and Sichuan) were retrieved in GenBank, and the evolutionary analysis by Bayesian Markov chain Monte Carlo (MCMC) algorithm was performed using BEAST software to reconstruct a phylogeographic tree in order to explore their migration patterns. Finally, the epidemiological history of HCV in the Guizhou region was retraced by reconstructing Bayesian skyline plots (BSPs) after excluding sequences from surrounding provinces. Results: Among 186 HIV/HCV co-infected patients, the C-E1 region sequence was successfully amplified in 177 cases. Phylogenetic analysis classified these sequences into six subtypes: 1a, 1b, 3a, 3b, 6a, and 6n. Among them, subtype 6a was the most dominant strain (n = 70), followed by 3b (n = 55), 1b (n = 31), 3a (n = 11), 1a (n = 8), and 6n (n = 2). By reconstructing the phylogeographic tree, we estimated that the 6a strain in Guizhou mainly originated from Yunnan and Guangxi, while the 3b strain emerged due to transmission from the IDU network in Yunnan. Subtypes 1b, 3a, 3b, and 6a, as the major subtypes of HCV in HIV/HCV co-infected individuals in Guizhou, emerged and later grew more rapidly than the national average. Notably, BSPs of the currently prevalent HCV predominant strain subtype 6a in Guizhou have shown a rapid population growth since 2004. Although the growth rate slowed down around 2010, this growth has continued to date. Conclusion: Overall, despite the improvement and implementation of a series of HCV prevention and control policies and measures, a delayed growth pattern may indicate a unique history of the spread of 6a in Guizhou. Its trend as the dominant strain in Guizhou in recent years may continue to increase slowly over subsequent years.

Hepatitis Virus-associated Non-hodgkin Lymphoma: Pathogenesis and Treatment Strategies.

Over the last decade, epidemiological studies have discovered a link between hepatitis C virus (HCV) and hepatitis B virus (HBV) infection and non-Hodgkin lymphoma (NHL). The regression of HCV-associated NHL after HCV eradication is the most compelling proof supporting HCV infection's role in lymphoproliferative diseases. HBV infection was found to significantly enhance the incidence of NHL, according to the epidemiological data. The exact mechanism of HCV leading to NHL has not been fully clarified, and there are mainly the following possible mechanisms: (1) Indirect mechanisms: stimulation of B lymphocytes by extracellular HCV and cytokines; (2) Direct mechanisms: oncogenic effects mediated by intracellular HCV proteins; (3) hit-and-run mechanism: permanent genetic B lymphocytes damage by the transitional entry of HCV. The specific role of HBV in the occurrence of NHL is still unclear, and the research on its mechanism is less extensively explored than HCV, and there are mainly the following possible mechanisms: (1) Indirect mechanisms: stimulation of B lymphocytes by extracellular HBV; (2) Direct mechanisms: oncogenic effects mediated by intracellular HBV DNA. In fact, it is reasonable to consider direct-acting antivirals (DAAs) as first-line therapy for indolent HCV-associated B-NHL patients who do not require immediate chemotherapy. Chemotherapy for NHL is affected by HBV infection and replication. At the same time, chemotherapy can also activate HBV replication. Following recent guidelines, all patients with HBsAg positive/HBV DNA≥2,000 IU/mL should be treated for HBV. The data on epidemiology, interventional studies, and molecular mechanisms of HCV and HBV-associated B-NHL are systematically summarized in this review.

Budget impact analysis of two treatment approaches for hepatitis C in Malaysia through the use of voluntary and compulsory licensing options.

A scaled-up treatment cascade with direct-acting antiviral (DAA) therapy is necessary to achieve global WHO targets for hepatitis C virus (HCV) elimination in Malaysia. Recently, limited access to sofosbuvir/daclatasvir (SOF/DAC) is available through compulsory licensing, with access to sofosbuvir/velpatasvir (SOF/VEL) expected through voluntary licensing due to recent agreements. SOF/VEL has superior clinical outcomes but has higher drug acquisition costs compared to SOF/DAC. A stratified treatment cascade might be the most cost-efficient approach for Malaysia whereby all HCV patients are treated with SOF/DAC except for patients with cirrhosis who are treated with SOF/VEL. This study aimed to conduct a 5-year budget impact analysis of the proposed stratified treatment cascade for HCV treatment in Malaysia. A disease progression model that was developed based on model-predicted HCV epidemiology data was used for the analysis, where all HCV patients in scenario A were treated with SOF/DAC for all disease stages while in scenario B, SOF/DAC was used only for non-cirrhotic patients and SOF/VEL was used for the cirrhotic patients. Healthcare costs associated with DAA therapy and disease stage monitoring were included to estimate the downstream cost implications. The stratified treatment cascade with 109 in Scenario B was found to be cost-saving compared to Scenario A. The cumulative savings for the stratified treatment cascade was USD 1.4 million over 5 years. A stratified treatment cascade with SOF/VEL was expected to be cost-saving and can result in a budget impact reduction in overall healthcare expenditure in Malaysia.

Mechanisms and Consequences of Genetic Variation in Hepatitis C Virus (HCV).

Chronic infection with hepatitis C virus (HCV) is an important contributor to the global incidence of liver diseases, including liver cirrhosis and hepatocellular carcinoma. Although common for single-stranded RNA viruses, HCV displays a remarkable high level of genetic diversity, produced primarily by the error-prone viral polymerase and host immune pressure. The high genetic heterogeneity of HCV has led to the evolution of several distinct genotypes and subtypes, with important consequences for pathogenesis, and clinical outcomes. Genetic variability constitutes an evasion mechanism against immune suppression, allowing the virus to evolve epitope escape mutants that avoid immune recognition. Thus, heterogeneity and variability of the HCV genome represent a great hindrance for the development of vaccines against HCV. In addition, the high genetic plasticity of HCV allows the virus to rapidly develop antiviral resistance mutations, leading to treatment failure and potentially representing a major hindrance for the cure of chronic HCV patients. In this chapter, we will present the central role that genetic diversity has in the viral life cycle and epidemiology of HCV. Incorporation errors and recombination, both the result of HCV polymerase activity, represent the main mechanisms of HCV evolution. The molecular details of both mechanisms have been only partially clarified and will be presented in the following sections. Finally, we will discuss the major consequences of HCV genetic diversity, namely its capacity to rapidly evolve antiviral and immunological escape variants that represent an important limitation for clearance of acute HCV, for treatment of chronic hepatitis C and for broadly protective vaccines.

Epidemiology and Genotype Distribution of Hepatitis C Virus in Russia

The hepatitis C virus (HCV) causes both acute and chronic infection of the liver that can lead to liver cirrhosis, cancer, and liver failure. HCV is characterized by high genetic diversity and substantial variations in the prevalence of specific HCV genotypes throughout the world. Many effective regimens of direct-acting antivirals (DAAs), including pan-genotypic, can successfully treat HCV infection. Additionally, genotype-specific treatments for HCV are being actively employed in national plans for eliminating HCV infection around the world. The evaluation of HCV genotype prevalence in a given country is necessary for the successful implementation of the HCV elimination plans and for allocating financial resources to the DAAs which are the most effective against those specific HCV genotypes prevalent in a given country. Here, we analyzed HCV genotypes, subgenotypes, and recombinants in 10,107 serum samples collected in 2015-2017 from patients with chronic HCV infection living in all federal districts of Russia. This is the first and largest evaluation of HCV genotypes performed on samples from all territories of Russia, from its Central federal district to the Far East. Moreover, we have updated retrospective epidemiological analysis of chronic and acute HCV infection in Russia from 2001 to 2021. We demonstrate that the incidence of acute HCV (AHC) infection in Russia decreased from 16.7 cases per 100,000 people in 2001 to 0.6/100,000 in 2021. The number of cases of chronic HCV (CHC) infection also decreased from 29.5 to 16.4 per 100,000 people during this period. The HCV genotype analysis indicated that HCV genotype 1 dominates in Russia (53.6%), while genotypes 3 and 2 were detected in 35.4% and 7.8% of patients, respectively. These proportions are virtually identical in all regions of Russia except for the Far East, where HCV genotype 2 was detected in only 1% of the samples. HCV genotypes 1 and 2 are more widespread in women, and HCV genotype 3 in men. Genotype 3 was the most prevalent in 31-40-year-olds (44.9%), and genotype 1 was most prevalent in those over 70 years of age (72.2%). HCV genotype 2 was predominant among HCV-infected persons older than 40 years. Discriminating between HCV genotype 2 and recombinant RF1_2k/1b, which are frequently misclassified, is important for successful antiviral treatment. For the first time, we demonstrate, here, countrywide prevalence of HCV RF1_2k/1b in different regions of Russia. HCV RF1_2k/1b makes up 3.2% of HCV genotypes, reaching 30% among samples classified as genotype 2 by some commercial genotyping tests. The highest proportion of HCV RF1_2k/1b was detected in the North-West (60%), Southern (41.6%), and Central (31.6%) federal districts; its frequency in the Far Eastern and North Caucasus districts was ~14.3%. HCV RF1_2k/1b, and it was not detected in the Volga, Ural, or Siberian districts. To conclude, this is the first and most complete evaluation of HCV epidemiology and genotype/subgenotype distribution in Russia.

Characterizing trends and associations for hepatitis C virus antibody prevalence in the Middle East and North Africa: meta-regression analyses

This study characterized population-level trends and associations with hepatitis C virus (HCV) antibody (Ab) prevalence in the Middle East and North Africa (MENA). Data source was the standardized and systematically gathered MENA HCV Epidemiology Synthesis Project Database. Random-effects univariable and multivariable meta-regressions were conducted. 2,621 HCV Ab prevalence measures on 49,824,108 individuals were analyzed. In the analysis including all populations, 71% of the variation in prevalence was explained, mostly by at-risk population type. Compared to the general population, prevalence was 23-fold higher among people who inject drugs, and 14-fold higher among high-risk clinical populations. In the analysis including only the general population, 67% of the variation in prevalence was explained, mostly by country/subregion. Compared to Afghanistan, prevalence was highest in Egypt and Pakistan. Prevalence in the general population was declining at a rate of 4% per year, but outside the general population, the decline was at only 1% per year. HCV Ab prevalence in MENA is declining rapidly, but this decline is largely occurring in the general population following introduction of blood and injection safety measures. The decline in populations at higher risk of exposure is slow and below the level needed to achieve HCV elimination by 2030.

Hepatitis C prevalence in incarcerated settings between 2013–2021: a systematic review and meta-analysis

BackgroundThe introduction of highly effective direct-acting antiviral therapy has changed the hepatitis C virus (HCV) treatment paradigm. However, a recent update on HCV epidemiology in incarcerated settings is necessary to accurately determine the extent of the problem, provide information to policymakers and public healthcare, and meet the World Health Organization's goals by 2030. This systematic review and meta-analysis were performed to determine the prevalence of HCV Ab and RNA in incarcerated settings.MethodsFor this systematic review and meta-analysis, we searched PubMed, Embase, Scopus, and Web of Science for papers published between January 2013 and August 2021. We included studies with information on the prevalence of HCV Ab or RNA in incarcerated settings. A random-effects meta-analysis was done to calculate the pooled prevalence and meta-regression to explore heterogeneity.ResultsNinety-two unique sources reporting data for 36 countries were included. The estimated prevalence of HCV Ab ranged from 0.3% to 74.4%. HCV RNA prevalence (available in 46 sources) ranged from 0% to 56.3%. Genotypes (available in 19 sources) 1(a) and 3 were most frequently reported in incarcerated settings. HCV/HIV coinfection (available in 36 sources) was highest in Italy, Estonia, Pakistan, and Spain. Statistical analysis revealed that almost all observed heterogeneity reflects real differences in prevalence between studies, considering I2 was very high in the meta-analysis.ConclusionsHCV in incarcerated settings is still a significant problem with a higher prevalence than in the general population. It is of utmost importance to start screening for HCV (Ab and RNA) in incarcerated settings to give clear, reliable and recent figures to plan further treatment. This is all in the context of meeting the 2030 WHO targets which are only less than a decade away.Trial registrationPROSPERO: CRD42020162616

Modelling the microelimination of chronic hepatitis C in the canton of Bern, Switzerland: Reaching the Swiss Hepatitis Strategy goals despite the impact of the COVID 19 pandemic.

Aims of the studySince 2014, the Swiss Hepatitis Strategy (SHS) has targeted the elimination of Hepatitis C Virus (HCV) in Switzerland. The epidemiology of HCV is diverse across Swiss cantons, therefore cantonal-level screening and treatment strategies should be developed. This study aimed to identify scenarios to achieve HCV elimination in the canton of Bern by 2030.MethodsA preexisting Markov disease burden model was populated with data for Bern, and used to forecast the current and future prevalence of HCV, annual liver-related deaths (LRDs), and incidence of hepatocellular carcinoma and decompensated cirrhosis until 2030. Scenarios were developed to assess the current standard of care and potential long-term impact of the COVID-19 crisis on the HCV infected population. Additionally, potential scenarios for achieving the WHO 2030 targets and the SHS 2025 and 2030 targets (reduction of new cases of HCV, HCV-related mortality and viremic HCV cases) were identified.ResultsIn 2019, there were an estimated 4,600 (95% UI: 3,330–4,940) viremic infections in the canton of Bern and 57% (n = 2,600) of viremic cases were diagnosed. This modelling forecasted a 10% increase in LRDs (28 in 2020 to 31 in 2030) with the current standard of care and a 50% increase in LRDs in a scenario assuming long-term delays. To achieve the WHO and SHS targets, the canton of Bern needs to increase the annual number of patients diagnosed (from 90 in 2019 to 250 per year in 2022–2024 [WHO], or 500 per year in 2022–2025 [SHS]) and treated (from 130 in 2019 to 340 per year in 2022–2024 [WHO] or 670 per year in 2022–2025 [SHS]).ConclusionsThe SHS goals and the WHO targets for HCV elimination can be achieved in the Swiss canton of Bern by 2030; however, not at the current pace of screening, linkage to care and treatment.