Hepatitis C Virus Genotype Research Articles

HCV genotype distribution in Istanbul: Adetailed 7 year epidemiological overview andimpact of Covid-19 pandemic.

Hepatitis C virus (HCV) is a leading cause of chronic liver disease, cirrhosis, and hepatocellular carcinomaworldwide. HCV has 8 genotypes (GT) and 86 subtypes and distribution of GTs varies based on geographical regions, transmission routes and even in cultural groups. The determination of viral genotype is crucial in choosing antiviral treatment, determining the duration of therapy, and monitoring treatment respose. Since 2014, with the usage of direct-acting antiviral agents (DAAs) in the treatment of HCV infections, a cure rate over 95% could be possible. Epidemiological data are important to combat a chronic HCV infections. Due to its geographical location, Turkey is like a bridge connecting Asia and Europe. Istanbul is the biggest and most crowded city of Turkey and has received immigration from many different countries, especially from Syria, in recent years and immigration still goes on. In addition, the COVID-19 pandemic has had devastating effects in our country. In this study, we determined the HCV genotypes in Health Sciences University Ümraniye Training and Research Hospital, in Istanbul between 2016 and 2022. Of the 322 patients analyzed during this 7-year period, HCV GT1b was the most prevalent GT in 65.2%, followed by GT3 in 15.5%, GT1a in 10.6%. Our data serve as a great mirror for HCV epidemiology in Turkey and contribute to global data.

Hepatitis C Infection Is Not a Cardiovascular Risk Factor in Young Adults.

Background: Cardiovascular diseases are one of the leading causes of hospitalization and death in Poland and around the world and are still an ongoing problem for modern medicine. Despite advances in diagnosis and treatment, both conservative and invasive, the prevention of cardiovascular disease directed at reducing risk factors remains a problem. The main classical risk factors for the development of cardiovascular disease in Poland include hypertension, lipid disorders, obesity, diabetes and smoking. A new non-classical risk factor is HCV infection. Most of the studies on the impact of HCV infection on cardiovascular disease involve elderly populations with long-term infections and advanced liver fibrosis. Methods: Hence, we set out to analyze the prevalence of risk factors and cardiovascular disease in a population of young adults under 45 years of age infected with HCV, according to gender, HCV genotype and the duration of infection. The study group consisted of 217 patients of both sexes aged 21 to 45 years (mean age 36 years). Results: No cardiovascular disease was found among the young adults infected with HCV in the study group. The most common risk factor was cigarette smoking, which affected 20.7% of the subjects, followed by hypertension (12%) and diabetes mellitus (5.5%); the prevalence was lower than in the general population. Most of the patients were characterized as overweight, with a mean BMI of 26.39 kg/m2. The mean values of other metabolic parameters-total cholesterol, LDL, HDL, uric acid and glucose-were within the population norm. The mean value of CRP was 1.43, which may indicate a moderate cardiovascular risk. Conclusions: Based on the conducted research, it was found that HCV infection in young individuals was not a risk factor for cardiovascular diseases, and the prevalence of risk factors was similar to that in the general population. The effect of HCV on the increase in C-reactive protein requires further study. The early detection of HCV infection and treatment can be considered as a prevention of cardiovascular disease.

Inhibitory peptides derived from Hepatitis C virus NS5A for reducing clinical symptoms of dengue virus infection

Lethal Dengue Hemorrhagic Fever (DHF) and Dengue Shock Syndrome (DSS) caused by Dengue virus (DENV) infection necessitate the development of effective treatments. Peptides derived from the N-terminal amphipathic α-helix of hepatitis C virus (HCV) NS5A exhibit antiviral activity by disrupting liposomes with high curvatures, such as virus envelopes. This study engineered five peptides from HCV genotype 3a NS5A N-terminal α-helix and screened them for neutralizing efficacy against three DENV serotypes. Two peptides, 3a 3/20 and DS-05, showed superior therapeutic efficacy against DENV and were further evaluated in treating DHF/DSS induced by mouse-adapted DENV infection. Administration of 3a 3/20 and DS-05 post-infection significantly improved mortality and weight loss associated with DHF/DSS in AG6 mice. These peptides reduced viral load in internal organs and viremia to levels comparable with the positive control drug, JNJ-A07, a DENV NS3-NS4B inhibitor. Additionally, they attenuated the cytokine storm in the blood and expression of inflammatory cytokines in internal organ tissues, ameliorating liver and kidney dysfunction after DENV infection. Histopathological analysis revealed significant suppression of damages in internal organs. These findings suggest that the 3a 3/20 and DS-05 peptides improve clinical symptoms of DHF/DSS induced by DENV infection, indicating their potential for clinical application.

Diversity, Geographical Distribution and Predictive Factors of Hepatitis C Virus Genotypes and Subtypes in Rwanda

Existing data on the prevalence of hepatitis C virus (HCV) genotypes and subtypes in Rwanda need to be strengthened. The aim of this study was to identify HCV genotypes and subtypes among HCV-infected patients, as well as their geographical distribution in Rwanda, and to identify the social and economic factors that could influence HCV epidemiology which would make it possible to target national preventive and management actions for infected patients. This study included 560 patients with confirmed chronic HCV infection. Patients were recruited from various health facilities in the four provinces of Rwanda as well as in the City of Kigali and had never received treatment with direct-acting antiviral (DAAs). HCV viral loads were measured using Cobas® AmpliPrep/Cobas® TaqMan® HCV Quantitative Test, version 2.0. HCV genotyping was performed using an in-house sequencing protocol targeting the NS5B central region. Genotypic HCV prevalence was correlated with patient geographic location, sociodemographic, behavioral, lifestyle, and clinical factors. HCV genotype 4 was detected in 99.3% of the patients, while genotype 3 was identified in 0.7%. A total of eight (8) HCV subtypes were detected, with 4k being the predominant subtype nationwide (49.5%), followed by subtypes 4r (21.2%), 4q (16.2%), 4v (7.9%), 4b (2.0%), 4l (1.8%), 4c and 3h represent 0.7% each. Our findings reveal subtype distribution variations among provinces. Subtype 4k was prevalent across regions, particularly in Kigali (64.0%) and the Eastern Province (61.6%). Subtype 4q was more common in the northern province (40.7%), 4r in the southern (43.9%) and western provinces (37.1%), and 4v in the eastern province (17.8%). Farmers exhibit a distinct infection profile compared to other occupations, showing a lower prevalence of subtype 4k but a higher prevalence of subtype 4r. Our study revealed that HCV infection is unevenly distributed in Rwanda, dominated by HCV genotype 4, with considerable heterogeneity in the repartition of the different subtypes. We found potential associations between rural/urban lifestyles and HCV subtype profiles. Determined HCV distribution and diversity can serve as basis not only for HCV infection awareness and prevention campaigns, but also success and guidance for personalized treatment.

Efficacy and safety of direct-acting antiviral regimen for patients with hepatitis C virus genotype 2: a systematic review and meta-analysis.

Direct-acting antivirals (DAAs) show high cure rates in treating chronic hepatitis C virus (HCV). However, the effect of DAAs on patients infected with genotype 2 (GT2) is difficult to determine despite the availability of several DAA regimens. A systematic search of six databases (PubMed, Embase, Cochrane Library, Web of Science, CNKI, and Clinicaltrial.gov) was conducted through April 20, 2022. We considered the sustained virological response 12 weeks after treatment (SVR12) as the efficacy outcome, and adverse events (AEs) as the safety outcome. By calculating the mean SVR12 and the proportion of AEs among patients, we considered the intervention effect for each DAA regimen. The random effect model was then used in all meta-analyses. This systematic review and meta-analysis aimed to summarize the evidence on efficacy and safety of DAAs in patients infected with HCV GT2. The Bayesian Markov Chain Monte Carlo (MCMC) network metanalysis was used to indirectly compare regimen in GT2 patients. Among 31 articles included (2,968 participants), consisting of 1,387 treatment-naive patients and 354 patients with cirrhosis. The overall pooled SVR12 rate was 94.62% (95% CI: 92.43-96.52%) among the participants who received all doses of treatment. Meta-analysis results of AEs revealed that fatigue was the most common AE (14.0%, 95% CI: 6.4-21.6%), followed by headache (13.1%, 95% CI: 9.2-17.1%), whereas death and serious adverse events were uncommon. We compared DAA-based treatments indirectly using meta-analysis and found the combination of Sofosbuvir plus Velpatasvir and Glecaprevir plus Pibrentasvir, each administered over a 12-week period, were identified as the most effective and relatively safe in managing chronic hepatitis C virus genotype 2 (HCV GT2) infection. Both treatments achieved a SVR12 of 100% (95% CI 99-100%).

Performance of Elecsys® HCV Duo Immunoassay for Diagnosis and Assessment of Treatment Response in HCV Patients with or without HIV Infection

Background/Objectives: The Elecsys® HCV Duo immunoassay (Roche Diagnostics International Ltd., Rotkreuz, Switzerland) detects both antibodies to hepatitis C virus (anti-HCV) and HCV core antigen (HCV-Ag) and has shown excellent diagnostic performance in blood donor samples. We aim to validate its use for diagnosing chronic HCV infection and assessing sustained virological response (SVR) post-direct-acting antivirals (DAAs) in patients with or without HIV infection. Methods: Blood samples from 100 healthy controls, as well as 64 HCV mono-infection and 136 HCV-HIV coinfections, were collected before and 12–24 weeks after DAAs. The assay performance for determining active infection at baseline and SVR was compared with HCV RNA. Results: Overall, 156 (78.0%) of HCV-infected patients had HCV genotype 1, and the SVR rate was 96.5%. The sensitivity, specificity, and area under the ROC curve (AUROC) for HCV diagnosis at baseline were 99.50% (95% confidence interval [CI], 96.82–99.97%), 100% (95%CI, 95.39–100%), and 0.998 (95%CI, 0.992–1.003), respectively. The corresponding results for HCV-Ag in determining SVR were 57.14% (95%CI, 20.24–88.19%), 97.41% (95%CI, 93.73–99.04%), and 0.773 (95%CI, 0.543–1.003), respectively. The assay also exhibited comparable sensitivity and specificity between HCV mono- and coinfection. Conclusions: Our study showed that the Elecsys® HCV Duo immunoassay effectively diagnosed HCV infection, regardless of HIV status, making it suitable for managing high-risk populations in resource-limited settings.

Hepatitis C virus genotypes among population with reported risk factors in Assam, north-east India: Emergence of genotype-8.

Background & objectives Hepatitis C virus (HCV) exhibits extensive genetic diversity in infected hosts. There are few published reports of HCV genotype (GT) distribution from the north-east Indian States lying close to the 'Golden Triangle' known for illicit drug trafficking. Real-time knowledge of HCVGT distribution is important for studies on epidemiologic aspects and virus evolution and for the development of new target-specific, direct-acting antiviral drugs. This study aims to examine the distribution of HCVGTs and their subtypes in different risk groups from Assam, north-east India. Methods It is a hospital-based cross-sectional study. Plasma samples reactive for anti-HCV antibody in enzyme-linked immunosorbent assay (ELISA) were subjected to viral load test and genotyping by real-time Reverse Transcription-Polymerase Chain Reaction (RT-PCR) or characterization of non-structural protein NS5B region by nested PCR. Nucleotide sequences were subjected to phylogenetic analysis. Results The most common HCVGT detected was GT-3 (95.89%), followed by GT-1 (3.42%), GT-6xa (0.34%) and GT-8 (0.34%). The mean age of subjects was 30.24 yr, and males outnumbered females. The most commonly associated risk factor was injecting drug use (IDU) (74.31%), followed by tattooing and/or piercing (33.22%), transfusion of blood/blood products (10.27%), and haemodialysis (9.25%). Co-infection with human immunodeficiency virus (HIV) was found in 17.8 per cent, and with Hepatitis B virus (HBV) in 3.42 per cent of the cases. Interpretation & conclusions The detection of HCVGT-8 makes this the first report from Assam and the second from India as per the authors' knowledge. This may indicate strain's endemic nature in India. The increasing trend of HCV infection among young IDUs and HCV-HIV co-infection indicates the need for enhancing surveillance and intensified prevention efforts among young adults.

Intermediate hepatitis C virus (HCV) endemicity and its genotype distribution in Myanmar: A systematic review and meta-analysis.

Comprehensive details on Hepatitis C virus (HCV) infection in Myanmar are lacking. This study determined the prevalence of HCV antibodies and ribonucleic acid (RNA) and the distribution of HCV genotypes across different populations in Myanmar from 1990 to 2023. A systematic search in PubMed, Web of Science, Scopus, and local journals identified studies reporting on HCV antibodies, RNA, and genotypes, excluding clinical research related to liver disease prognosis. Screening and data extraction was done by two authors and study populations were categorized into low-risk, high-risk, liver disease patients, and refugees outside the country. The pooled prevalence was performed by Dersimonian and Laird method using the R program. The publication bias was shown by funnel plot, the Egger test was used to assess the symmetry of the plot, and the heterogeneity was examined by the Cochran Q test and I2 index. Out of 135 reports screened for eligibility, 35 reports comprising 51 studies were included in which 33 studies provided data on HCV seroprevalence in 685,403 individuals, 8 studies reported HCV RNA prevalence in 25,018 individuals, and 10 studies examined HCV genotypes in 1,845 individuals. The pooled seroprevalence of HCV among low-risk, high-risk, liver disease patients and refugees were 2.18%, 37.07%, 33.84%, and 2.52% respectively. HCV RNA-positive rates in these groups were 1.40%, 5.25%, 24.96%, and 0.84% respectively. Seroprevalence studies showed publication bias (Egger test, p = 0.0001), while RNA studies did not (Egger test, p = 0.8392). HCV genotype 3 was predominant in all sub-groups in Myanmar. Our study shows Myanmar has intermediate HCV endemicity with lowest HCV prevalence of 2.18% in low-risk groups and highest prevalence of 37.07% in high- risk groups. However, the findings highlight the need for further epidemiological studies to understand actual disease burden and implement effective countermeasures to achieve the WHO's goal of HCV elimination by 2030.

High efficacy and safety of direct-acting antivirals for the treatment of chronic hepatitis C: A cohort study conducted in Vietnam.

Direct-acting antivirals (DAAs) have revolutionized hepatitis C virus (HCV) treatment through their high cure rates and improved safety profiles. We aimed to evaluate the efficacy and safety, and identify the optimal combination, of DAAs for the treatment of chronic HCV. A retrospective study was conducted of 613 patients with chronic HCV who were treated with DAAs. Demographic, HCV genotype, treatment regimen, virological response, and adverse drug event (ADE) data were collected at the initial visit and 4, 8, 12, and 24 weeks later. The rapid virologic response (RVR) and sustained virologic response (SVR) rates were 90.4% and 97.8% for HCV genotype 1, 89.2% and 98.7% for genotype 6, 92.8% and 99% for genotype 2, and 90.9% and 100% for mixed genotype 2/6 or unspecified genotypes, respectively. There were no significant differences in the RVR and SVR rates for the various DAA regimens. The mean ALT, AST, and GGT activities decreased, and the PLT count increased during the treatments. ADEs occurred in 8% of the patients. The commonest ADEs were itching (3.1%), fatigue (1.8%), and dizziness (1.1%). None of the patients discontinued treatment because of an ADE. Posttreatment disease progression occurred in 7.7% of the patients, including liver fibrosis (3.6%), cirrhosis (1.1%), hepatocellular carcinoma (1.1%), and high alpha-fetoprotein (AFP) (1%). The factors associated with the achievement of RVR were low viral load, the use of sofosbuvir/ledipasvir or sofosbuvir/daclatasvir regimens, and a treatment duration of 12 weeks. No specific factors were found to be associated with the achievement of SVR. Posttreatment disease progression was associated with a high AFP and the use of sofosbuvir/ledipasvir. Thus, DAAs are highly effective and well-tolerated means of treating chronic HCV, and significantly improve patient outcomes. Their high efficacy and favorable safety profiles highlight the importance of early diagnosis and the use of personalized treatment strategies.

A decade-long retrospective study of hepatitis C virus genetic diversity in Cameroon, 2013-2023: presence of a high proportion of unsubtypable and putative recombinant HCV strains.

While treatment options for hepatitis C virus (HCV) infection have expanded considerably over the past decade thanks to the development of pan-genotypic therapies, genotype testing remains a prerequisite for treatment in sub-Saharan African countries, including Cameroon, where multiple HCV genotypes and subtypes exist. The main objective of this study was to describe the trend in the distribution of HCV genotypes and subtypes from 2013 to 2023 in the Cameroonian population. Viral loads were determined using the Abbott real-time assay, and genotyping/subtyping was based on nested and semi-nested reverse transcription polymerase chain reaction (RT-PCR) amplification of the regions encoding the core and non-structural protein 5B (NS5B) regions, respectively, followed by sequencing and phylogenetic analysis. A total of 512 patients with NS5B and core sequencing results were included in our study. Genotyping revealed a predominance of both genotype 4 (38.48%) and genotype 1 (37.11%), followed by genotype 2, detected in 22.46% of patients. Interestingly, 10 samples (1.95%) had discordant genotypes in both regions, suggesting the presence of putative recombinant forms of HCV. Twelve different subtypes were detected during the study period, with a predominance of subtypes 4f (18.95%) and 1e (16.02%). Furthermore, phylogenetic analysis failed to assign a subtype to a relatively high proportion of sequences (38.67%) for the two genomic regions, and their classification was limited to genotype assignment. The frequency distribution of HCV genotypes did not show any statistical difference according to year or sex. These results confirm the genetic diversity of HCV in Cameroon and the potential for the generation of recombinant strains.

Changing Epidemiology of Chronic Hepatitis C: A University Hospital Experience

Background: Hepatitis C virus (HCV) infection remains a significant public health problem worldwide, with varying epidemiological trends over time necessitating continual surveillance and intervention strategies. Objectives: This retrospective study aimed to examine trends in demographics, transmission routes, and disease characteristics among 635 patients diagnosed with HCV infection between 2003 and 2023. Methods: Data on demographics, HCV RNA levels, liver enzymes, genotype distribution, and transmission routes were retrospectively analyzed. The study period was divided into four segments for detailed analysis. Results: There was a gradual increase in the diagnosed cases over the study period, particularly noticeable after 2012. The mean age at diagnosis remained stable from 2003 - 2007 to 2008 - 2012 but decreased significantly in the following years (P = 0.001). Male predominance was observed throughout the study, with a notable increase in the male/female ratio over time (P < 0.001). Intravenous drug use (IVDU) emerged as the predominant transmission route, reaching 68.3% in 2018 - 2022 (P < 0.001). The prevalence of incarceration history among patients increased significantly, reaching 24.6% in 2018 - 2022 (P < 0.001). Disease characteristics varied between periods; median HCV RNA levels were highest in 2018 - 2022, and median alanine aminotransferase (ALT) levels differed significantly between periods (P = 0.001). The genotype distribution showed a shift over time, with genotype 1 predominating initially and genotypes 3, 4, and 5 becoming more prevalent in later years (P < 0.001). Conclusions: This study highlights the dynamic changes in hepatitis C epidemiology over two decades in southern Turkey, highlighting the increasing burden in younger populations, the increasing prevalence of IVDU as a transmission route, and the changing genotype distribution.

The prevalence of hepatitis C virus genotypes and factors associated with cirrhosis, fatty liver, and viral load: A registry-based cross-sectional cohort study in Western Iran during 1999-2023.

Hepatitis C virus (HCV) is an important infectious disease that imposes a significant burden on healthcare systems. Determining the prevalence of HCV genotypes in a area is essential for the successful implementation of HCV elimination programs and allocation of financial resources to direct-acting antiviral direct-acting antivirals (DAA) treatments against prevalent HCV genotypes. Accordingly, we conducted a registry-based cross-sectional cohort study to investigate the prevalence of HCV genotypes and factors associated with cirrhosis, fatty liver, and viral load in Kermanshah Province, Western Iran. Patients presenting to the Hepatitis Clinic of the Research Center for Infectious Diseases affiliated with Kermanshah University of Medical Sciences between 1999 and 2023 were enrolled in this study. Serum samples were collected to assess HCV genotypes and viral load. Additionally, demographic data and the status of cirrhosis and fatty liver were extracted from the registry system records throughout the study period. Records of 828 patients with an average age of 40.38 ± 11.72 years (range: 11-80 years) were included in the study that 721 individuals were male, and 107 were female. The prevalence of fatty liver and cirrhosis was 30.3% and 12.9%, respectively. Four genotypes (1, 2, 3, and 4) and four subtypes (1a, 1b, 3a, and 3b) were identified, with subtype 3a (55.7%) being the most prevalent, followed by subtype 1a (34.3%). None of the variables including age, gender, viral load level, and genotypes 1 and 3 were associated with fatty liver or cirrhosis. However, age, gender, and genotype were correlated with the viral load (p ≤ 0.05). The most common HCV subtypes in Kermanshah were 3a and 1a. Genotypes 2 and 4 were identified in one case each. Further studies on identifying HCV subtypes in different regions of the country are recommended to manage HCV infection and predict the prognosis.

Distribution of HCV Genotypes in Patients with Chronic Hepatitis C Infection: A Three-Year Single-Center Retrospective Study

Objective: Hepatitis C virus (HCV) is a single-stranded, positive-sense RNA virus belonging to the genus Hepacivirus in the Flaviviridae family. It has eight known genotypes and 93 subtypes. HCV can be transmitted through various routes, including blood transfusion, surgical procedures, sexual contact, and intravenous drug use, leading to both acute and chronic hepatitis. Genotype (GT) determination and viral load assessment are essential for selecting an appropriate antiviral treatment regimen and duration, and for monitoring treatment efficacy. We aimed to ascertain the genotype distribution over a three-year period. Methods: In this study, patients diagnosed with chronic HCV infection and followed at Afyonkarahisar Health Sciences University Health Practice and Research Hospital between July 1, 2020, and June 30, 2023, were retrospectively evaluated for their age, gender, and HCV genotype data. Results: A total of 91 patients’ HCV genotype data were included in the study. The study revealed that 95.6% of the patients were Turkish citizens, while 4.4% were of foreign nationality. Among the 91 patients, 60 (65.9%) were found to have genotype 1b, 12 (13.2%) had genotype 1a, 10 (11%) had genotype 3, 6 (6.6%) had genotype 4, 2 (2.2%) had genotype 2, and one patient (1.1%) had a co-infection of genotypes 3 and 4. Conclusion: Genotype 1b was dominant in our region. Identifying HCV genotypes is important in guiding the prognosis and treatment of chronic HCV infections and monitoring the epidemiologic changes. This information will be of great value in the health policy that targets HCV and in elimination efforts.

Effectiveness of Ledipasvir-Sofosbuvir 12 Weeks After Hepatitis C Virus Genotype 1 Infection and the Factors Associated With Sustained Virologic Response: A Retrospective Study.

The combination of ledipasvir and sofosbuvir (LDV/SOF) has been licensed to treat genotype 1 hepatitis C virus infection (HCV) with a 12-week regimen. However, there is scant data from Yemenregarding this combination regimen. Here, we investigate sustained virologic responses (SVR) 12 weeks after HCV treatment with LDV/SOF regimens and the factors that contribute to SVR failure. A retrospective cross-sectional study was conducted at Althora General Hospital in Ibb, Yemen, from June 1, 2019, to October 31, 2022, on 53 cases with HCV genotype 1 infection who received combined therapy of LDV/SOF and completed treatment for 12 weeks. The clinical characteristics and treatment follow-up were obtained from patient medical records. Factors associated with SVR failure were investigated in univariate analysis with odds ratio (OR) and 95% confidence interval (CI). The mean age was 50 ± 15.3 years, and most cases were female (n=36, 67.9%). Comorbidities were diabetes, hypertension, and fatty liver, which were represented in 12 (22.6%), nine (17.0%), and eight (15.1%) cases, respectively. A total of 13 (24.5%) patients had compensated liver cirrhosis, while the remaining 40 patients (75.5%) were non-cirrhotic healthy individuals. The baseline viral load (HCV RNA) was more than 800000 IU/mL in 21 patients (39.6%). Early virological response (ERV) was achieved in 51 patients (96.2%). After treatment, 46 of the patients (86.8%) achieved SVR at Week 12, while failure occurred in two patients (3.8%) and relapse occurred in five patients (9.4%). Blood liver enzymes, including alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase, returned to normal, with statistically significant improvements in non-cirrhotic healthy persons than compensated liver cirrhosis individuals (p= 0.006, 0.006, and 0.010; respectively). Factors associated with SVR failure were older age (OR:1.13; 95% CI: 1.03-1.30, p=0.009), presence of liver cirrhosis (OR: 5.48; 95% CI: 1.04-28.98, p=0.031), having diabetes (OR: 6.33; 95% CI: 1.19-37.93, p= 0.019), baseline higher viral load (OR: 2.27; 95% CI: 0.45-12.73, p<0.001), and not achieving EVR (OR:7.63; 95% CI: 3.77- 17.78, p= 0.009). In this study, we found that LDV/SOF regimens are effective against HCV genotype one infection, allowing for the expansion of 12-week treatment for suitable patients in clinical settings. Additionally, older age, liver cirrhosis, diabetes, higher pretreatment viral load, and non-completion of EVR were associated with SVR failure. However, due to the small number of HCV genotype 1 infected individuals in this study, more corporate data is required to get a clear conclusion.

Sustained Long-Term Decline in Anti-HCV Neutralizing Antibodies in HIV/HCV-Coinfected Patients Five Years after HCV Therapy: A Retrospective Study.

Background: This study evaluated titers and amplitudes of anti-E2 antibodies (anti-E2-Abs) and neutralizing antibodies against hepatitis C virus (HCV; anti-HCV-nAbs) in HIV/HCV-coinfected individuals over five years after successful HCV treatment completion. Methods: We retrospectively analyzed 76 HIV/HCV-coinfected patients achieving sustained virologic response post-HCV treatment. Plasma levels of anti-E2-Abs and anti-HCV-nAbs against five HCV genotypes (Gt1a, Gt1b, Gt2a, Gt3a, and Gt4a) were determined using ELISA and microneutralization assays, respectively. Statistical analyses comparing the three follow-up time points (baseline, one year, and five years post-HCV treatment) were performed using generalized linear mixed models, adjusting p-values with the false discovery rate (q-value). Results: Compared to baseline, anti-E2-Abs titers decreased at one year (1.9- to 2.3-fold, q-value < 0.001) and five years (3.4- to 9.1-fold, q-value < 0.001) post-HCV treatment. Anti-HCV-nAbs decreased 2.9- to 8.4-fold (q-value < 0.002) at one year and 17.8- to 90.4-fold (q-value < 0.001) at five years post-HCV treatment. Anti-HCV-nAbs titers against Gt3a were consistently the lowest. Nonresponse rates for anti-E2-Abs remained low throughout the follow-up, while anti-HCV-nAbs nonresponse rates increased 1.8- to 13.5-fold (q-value < 0.05) at five years post-HCV treatment, with Gt3a showing the highest nonresponse rate. Conclusions: Humoral immune responses against HCV decreased consistently one and five years post-HCV treatment, regardless of HCV genotype and previous HCV therapy or type of treatment (IFN- or DAA-based therapy). This decline was more pronounced for anti-HCV-nAbs, particularly against Gt3.

Update on Hepatitis C Vaccine: Results and Challenges.

Therapy against the Hepatitis C virus (HCV) has significantly improved with the introduction of direct-acting antiviral drugs (DAAs), achieving over 95% sustained virological response (SVR). Despite this, the development of an effective anti-HCV vaccine remains a critical challenge due to the low number of patients treated with DAAs and the occurrence of HCV reinfections in high-risk groups. Current vaccine strategies aim to stimulate either B-cell or T-cell responses. Vaccines based on E1 and E2 proteins can elicit broad cross-neutralizing antibodies against all major HCV genotypes, though with varying efficiencies and without full protection against infection. In humans, the neutralizing antibodies induced by such vaccines mainly target the AR3 region, but their levels are generally insufficient for broad neutralization. Various HCV proteins expressed through different viral vectors have been utilized to elicit T cell immune responses, showing sustained expansion of HCV-specific effector memory T cells and improved proliferation and polyfunctionality of memory T cells over time. However, despite these advancements, the frequency and effectiveness of T-cell responses remain limited.

Hepatitis C Virus Seroprevalence and Genotypic Distribution Among Hemodialysis Patients at a Teaching and Training Hospital in Western Rajasthan, India.

Background Hepatitis C virus (HCV) infection is a chronic hepatotropic blood-borne infection. The transmission of HCV in patients undergoing hemodialysis (HD) is more common in comparison to the general population due to factors such as frequent blood transfusions, prolonged vascular access, and the potential for nosocomial infections. Western Rajasthan in India is home to numerous teaching and training hospitals that cater to a large number of HD patients. Understanding the seroprevalence and genotypic distribution of HCV in this specific patient population is crucial for assessing the extent of infection within this vulnerable group for targeted surveillance and developing effectively tailored treatment protocolsin healthcare settings. Hence, this study was conducted with an aim to determine seroprevalence, seroconversion, and genotypes of HCV in HD patients at a tertiary care hospital. Methods This was a cross-sectional observational study. The duration of the study was from July 2019 to March 2022. In this study, the patients undergoing maintenance HD due to chronic kidney disease (CKD) were recruited. The data collected include patients' demographics, etiology of CKD, underlying other co-morbidities, duration of dialysis, and biochemical and blood count parameters. The patients recruited at the start of the study were screened for anti-HCV antibodies by HCV enzyme-linked immune sorbent assay (ELISA). The anti-HCV antibody-negative patients were followed up for the detection of anti-HCV antibodies. At the end of the follow-up period, all anti-HCV antibody negative samples in the pool of five and all anti-HCV antibody positive samples were subjected to a real-time polymerase chain reaction (RT-PCR) of 5' untranslated region (5'UTR) and core region, followed by line probe assay (LiPA). Results In this study, after applying inclusion and exclusion criteria, a total of 109 patients were recruited, out of which 64 (58.7%) were males and 45 (41.3%) were females. The age range of participants was 11-88 years with a mean and standard deviation of 46.75 and 16.35 years, respectively. A total of 39 patients (20 on screening, 19 on follow-up) were detected anti- HCV antibody positive. By RT-PCR, 24 patients tested HCV RNA positive (10 on screening, 14 on follow-up). Among 24 HCV RNA-positive samples, LiPA showed, HCV genotype 1a (n=21), genotype 3b (n=1), and two samples were detected to be inconclusive. Conclusion The increasing duration of dialysis is significantly associated with acquiring HCV infection. The majority of the cases of CKD in this geographical region are due to hypertensive nephropathy. There can be discordance between antibody and viral RNA positivity in HCV infection. The predominant HCV genotype identifiedin the dialysis ward of tertiary care hospital was genotype 1a.

Evaluation of the Fluorion HCV QNP v3.0 real-time PCR assay for quantifying HCV RNA in Moroccan patients: A comparative study with COBAS AmpliPrep/COBAS TaqMan HCV v2.0

PurposeHepatitis C Virus (HCV) RNA quantification is crucial for diagnosing and monitoring chronic HCV treatment. Cost-effective methods are crucial to ensure accessibility. This study evaluated the Fluorion HCV QNP v3.0 Real-Time PCR assay's effectiveness in EDTA-plasma and serum, comparing it with the COBAS AmpliPrep/COBAS TaqMan HCV v2.0 (CAP/CTM HCV v2.0) test. Methods105 matched pairs of EDTA-plasma and serum specimens (91 positive and 14 negative) from HCV infected Moroccan patients were analyzed using the Fluorion HCV QNP v3.0 assay and compared to the CAP/CTM HCV v2.0 test, being the reference method. ResultsThe values obtained by the Fluorion HCV QNP v3.0 in plasma were slightly higher than those in serum (3.94 ± 2.23 log10 IU/mL versus 3.91 ± 2.22 log10 IU/mL) and were both significantly lower than those quantified by the CAP/CTM HCV v2.0 assay (4.34 ± 2.28 log10 IU/mL; p < 0.001). High correlations were observed between the Fluorion HCV QNP v3.0 serum and CAP/CTM HCV v2.0 (R2 = 0.9433), the Fluorion HCV QNP v3.0 plasma and CAP/CTM HCV v2.0 (R2 = 0.949) and the Fluorion HCV QNP v3.0 serum and plasma (R2 = 0.9954). HCV RNA was detected in all tested genotypes by both assays. ConclusionThe Fluorion HCV QNP v3.0 assay demonstrated excellent performance in comparison with the CAP/CTM HCV v2.0 on both plasma and serum samples which can be used interchangeably for HCV quantification. The test was shown to be suitable for disease monitoring including all HCV genotypes.

Pharmacophore-Assisted Covalent Docking Identifies a Potential Covalent Inhibitor for Drug-Resistant Genotype 3 Variants of Hepatitis C Viral NS3/4A Serine Protease.

The emergence of drug-resistance-inducing mutations in Hepatitis C virus (HCV) coupled with genotypic heterogeneity has made targeting NS3/4A serine protease difficult. In this work, we investigated the mutagenic variations in the binding pocket of Genotype 3 (G3) HCV NS3/4A and evaluated ligands for efficacious inhibition. We report mutations at 14 positions within the ligand-binding residues of HCV NS3/4A, including H57R and S139P within the catalytic triad. We then modelled each mutational variant for pharmacophore-based virtual screening (PBVS) followed by covalent docking towards identifying a potential covalent inhibitor, i.e., cpd-217. The binding stability of cpd-217 was then supported by molecular dynamic simulation followed by MM/GBSA binding free energy calculation. The free energy decomposition analysis indicated that the resistant mutants alter the HCV NS3/4A-ligand interaction, resulting in unbalanced energy distribution within the binding site, leading to drug resistance. Cpd-217 was identified as interacting with all NS3/4A G3 variants with significant covalent docking scores. In conclusion, cpd-217 emerges as a potential inhibitor of HCV NS3/4A G3 variants that warrants further in vitro and in vivo studies. This study provides a theoretical foundation for drug design and development targeting HCV G3 NS3/4A.

Efficacy, safety, and quality of life profile of Genotype-3 Chronic Hepatitis-C Pakistani patients receiving ledipasvir plus sofosbuvir treatment.

This study aimed to assess the overall treatment response of Genotype-3 Chronic HCV Pakistani Patients with or without cirrhosis to Ledipasvir plus Sofosbuvir combination. In this observational study, HCV Genotype-3 patients were enrolled from Liver Center, DHQ Hospital, Faisalabad and divided into two groups, i.e., non-cirrhotic and compensated cirrhotic patients. The study spanned for a period of 24 months (November 2019 - November 2021) from the first enrollment to the last follow up. Non-cirrhotic patients received Ledipasvir/Sofosbuvir (LDV/SOF) 90/400mg for 12 weeks and cirrhotic patients received LDV/SOF with Ribavirin (RBV) for 12 weeks and without RBV for 24 weeks. The treatment efficacy in terms of sustained virological response (SVR12) was monitored 12 weeks post-treatment. The safety profile, and health-related quality of life (HRQoL) were monitored from baseline to follow-up visits. Two hundred and ninety out of 309 (93.85%) non-cirrhotic and 31 out of 33 (93.94%) compensated cirrhotic patients achieved SVR-12. The safety profile of the non-cirrhotic and compensated cirrhotic patients was comparable throughout the study duration. Fatigue was the most commonly reported adverse event (AE) in non-cirrhotic and compensated cirrhotic patients, followed by headache, nausea, and fever. The HRQoL improved from baseline to follow-up visits among patients of both groups. It is concluded that LDV and SOF combination regimen is safe and effective for treating Genotype-3 HCV patients without cirrhosis/compensated cirrhosis, and also improves the patient's HRQoL.