Impact of the COVID-19 pandemic on hepatitis C virus screening in provincial prisons in Montreal, Quebec, Canada.

Background: Little is known about the impact of the COVID-19 pandemic on hepatitis C (HCV) screening efforts in carceral settings. We explored the impact of the pandemic on HCV screening in two of Quebec's largest provincial prisons. Methods: Retrospective data of HCV-related laboratory tests between July 2018 and February 2022 at l'Établissement de détention de Montréal (EDM) and l'Établissement de détention de Rivière-des-Prairies (EDRDP) were obtained. To examine the association between the pandemic and the number of HCV-antibody (HCV-Ab) tests, a three-level time period variable was created: pre-outbreak, outbreak, and post-outbreak. Negative binomial regression (with monthly admissions as an offset) was used to assess the change in HCV-Ab tests across time periods and by prisons. Adjusted odds ratios (aOR) with 95% confidence intervals (95% CI) were calculated. Results: A total of 1,790 HCV-Ab tests were performed; 56 (3%) were positive. Among these, 44 (79%) HCV RNA tests were performed; 23 (52%) were positive. There was a significant decrease in HCV-Ab screening at EDM during the outbreak (aOR 0.29; 95% CI 0.17-0.48) and post-outbreak (aOR 0.49; 95% CI 0.35-0.69) periods, compared to the pre-outbreak period. There was no significant change in HCV-Ab screening at EDRDP during the outbreak (aOR 0.98; 95% CI 0.49-2.11) but a significant increase in HCV-Ab screening post-outbreak (aOR 1.66; 95% CI 1.04-2.72). Conclusion: The COVID-19 pandemic negatively affected HCV screening at EDM but had minimal impact at EDRDP. To eliminate HCV from carceral settings, minimizing screening interruptions during future outbreaks and combined HCV/SARS-CoV-2 screening should be prioritized.

Assessment of hepatitis c core antigen in epithelial salivary gland neoplasms (ex-vivo study).

BACKGROUND: Salivary gland neoplasms (SGNs) pose a challenge to both pathologists and clinicians. Despite research, the etiology of these neoplasms remains unclear. This study aimed to identify any potential association between the presence of hepatitis C virus (HCV) at the protein or gene level and epithelial salivary gland neoplasms. METHODS: Formalin-fixed paraffin-embedded (FFPE) blocks of epithelial salivary gland neoplasms were retrieved from the archives of the Oral and Maxillofacial Pathology Department, Faculty of Dentistry, Cairo University within the 5-year period from 2016 to 2020. Immunohistochemistry was used to assess HCV core antigen, while reverse transcription polymerase chain reaction was employed for the evaluation of HCV RNA. RESULTS: A total of 44 specimens were collected, 28 of which were benign neoplasms and 16 were malignant neoplasms. There was a statistically significant difference in HCV positivity between the two groups (P-value = 0.036). Benign tumors showed a statistically significant lower percentage of positive cases than malignant tumors. The localization of staining was also evaluated, revealing various patterns of HCV core antigen expression, including diffuse cytoplasmic, patchy cytoplasmic, nuclear, and a combination of nuclear and cytoplasmic expression. There was no statistically significant difference between the expression patterns in benign and malignant tumors (P-value = 0.616). Given that Pleomorphic Adenoma and Mucoepidermoid Carcinoma were the predominant tumor types in this study, four cases were selected for RNA detection. HCV RNA was detected in all cases using RT-PCR. CONCLUSIONS: HCV core antigen is frequently detected in SGNs and is suggested to be a potential risk factor for the development of these neoplasms. Further studies are required to discover other biomarkers, their roles, and the pathways associated with HCV in SGNs.

Evaluation of serum ferritin level and hepatitis b and hepatitis c viral infection in chronic hemodialysis patients.

The most popular treatment for end-stage renal illness is hemodialysis (HD). The study aimed to assess serum ferritin levels and their connection to Epoetin alfa resistance, along with exploring the link between hepatitis C virus, iron overload, and the prevalence of hepatitis C and B infections in chronic HD patients. This was a descriptive-analytical study conducted on 50 Patients with chronic kidney disease (CKD) who were on regular HD in the dialysis unit of Ibin Sina Teaching Hospital in Mosul City, Iraq. Out of 50 patients, 26 (52%) tested positive for Hepatitis C Virus (HCV) Antibody, 10 (20%) for Hepatitis B surface Antigen (HBsAg), and 14 (28%) tested negative for both. Higher serum iron and ferritin levels were found in HCV antibody-positive patients (p < 0.05). Despite Epoetin alfa treatment, patients with elevated ferritin levels exhibited lower Hemoglobin (HB) and Packed Cell Volume (p < 0.05). Non-diabetics exhibited significantly higher serum ferritin, Hemoglobin, Blood urea, and serum creatinine than diabetics (p < 0.05). A noteworthy association was seen between the quantity of blood transfusions and elevated levels of serum ferritin and total serum iron (p < 0.05). Most HD patients were anemic, with Hepatitis B and C prevalent. The main CKD causes were diabetes and hypertension. HCV-positive patients often showed mild to moderate iron overload, and high serum ferritin was linked to poor Epoetin alfa response. Dialysis can elevate blood urea, ferritin, and creatinine, worsening anemia. High ferritin levels may hinder response to Epoetin alfa and iron replacement. Excessive blood transfusions can lead to iron overload and inhibit erythropoiesis. Maintaining HB at 110-120 g/l improves quality of life and reduces anemia-related risks.

Seroprevalence of hepatitis B and C viruses and some possible associated factors among cancer patients at the Oncology Treatment Center, Gondar, Northwest Ethiopia: A cross-sectional study.

BACKGROUND: Cancer patients are prone to infections such as hepatitis B virus (HBV) and hepatitis C virus (HCV), which pose a major public health challenge, especially in developing countries. However, little is known about the magnitude of these infections among cancer patients in Ethiopia. Thus, this study determined the prevalence of HBV and HCV in cancer patients at the Oncology Treatment Center, Gondar, Northwest Ethiopia. MATERIALS AND METHODS: An institutional-based cross-sectional study was conducted on 115 cancer patients from 15 April to 22 July 2023 at the Oncology Treatment Center, Gondar, Northwest Ethiopia. Sociodemographic, clinical, and other relevant data were collected using a pretested structured questionnaire. Five milliliters of venous blood were collected using a vacutainer tube, serum was harvested and tested for HBV and HCV using a one-step HBsAg and anti-HCV test strip with further confirmation through an ELISA test kit. Data were analyzed using SPSS version 20 and Fisher exact test was used to determine the association between HBV/HCV infection and associated factors. RESULTS: Out of 115 cancer patients, the majority (62.6%) were females. The median age was 50 (IQR; 40-56) years. The overall prevalence of HBV and HCV infections was 4.3% (95% CI; 0.6-8%) and 6.1% (95% CI; 1.7-10.5%), respectively. Sex was significantly associated with the prevalence of HCV (p = 0.011) with higher anti-HCV positivity in males (14%) than in females (1.4%). CONCLUSIONS: In this study, the prevalence of HCV was higher and the HBV prevalence was intermediate in cancer patients. To reduce the burden of HBV and HCV infections, it is crucial to provide access to HBV and HCV screening services, strengthen vaccination, and improve prompt treatment in cancer patients.

Field-applicable simultaneous multiplex LAMP assay for screening HBV and HCV co-infection in a single tube.

BACKGROUND: Globally, around 7 to 20 million people are believed to be suffering from coinfection with both hepatitis B virus (HBV) and hepatitis C virus (HCV). The loop-mediated isothermal amplification (LAMP) approach, introduced by Notomi and colleagues, has undergone substantial advancements as an effective molecular tool that enables the simultaneous analysis of multiple samples in a single tube. METHODS: The present study examined the simultaneous detection of HBV and HCV in a single tube using melt curve analysis multiplex LAMP (mLAMP), which is based on the identification of unique melting peak temperatures. Selected regions for primer design including the S gene of HBV and the UTR gene of HCV. Primer optimization is initially performed through individual HBV and HCV LAMP analysis. Following the optimization process, the mLAMP assay was evaluated by optimizing the multiplex reaction mixture, determining the reaction time, and analyzing the limit of detection (LOD). The results are also analyzed using lateral flow dipsticks (LFD), which enable the visual detection of HBV and HCV by adding 20 pmol FITC-labeled LF primers into the reaction mixture prior the mLAMP. RESULTS: The LOD for the mLAMP assay was determined as 10 copies/µl, and no cross-reactivity with other microorganisms was detected. The detection results obtained from patient plasma were also visually demonstrated using LFD, and displayed significant concordance with those obtained from Real-Time Polymerase Chain Assay. The mLAMP assay revealed a diagnostic sensitivity of 95% for detecting the HBV, and LOD is 90% for HCV. The overall diagnostic sensitivity of the mLAMP assay for both viruses was 85%. The assay confirmed a specificity of 100%. CONCLUSION: The mLAMP assay displays significant promise for analyzing coinfected samples by simultaneously detecting the dual targets HBV and HCV within a set temperature of 62 °C, all within a time frame of 1 h. Additionally, when paired with disposable LFD, the mLAMP assay enables rapid visual detection of assay results in a matter of minutes. The result contributes to the mLAMP assay being highly suitable for coinfection screening, particularly in field conditions.

Distinct Characteristic Binding Modes of Benzofuran Core Inhibitors to Diverse Genotypes of Hepatitis C Virus NS5B Polymerase: A Molecular Simulation Study.

The benzofuran core inhibitors HCV-796, BMS-929075, MK-8876, compound 2, and compound 9B exhibit good pan-genotypic activity against various genotypes of NS5B polymerase. To elucidate their mechanism of action, multiple molecular simulation methods were used to investigate the complex systems of these inhibitors binding to GT1a, 1b, 2a, and 2b NS5B polymerases. The calculation results indicated that these five inhibitors can not only interact with the residues in the palm II subdomain of NS5B polymerase, but also with the residues in the palm I subdomain or the palm I/III overlap region. Interestingly, the binding of inhibitors with longer substituents at the C5 position (BMS-929075, MK-8876, compound 2, and compound 9B) to the GT1a and 2b NS5B polymerases exhibits different binding patterns compared to the binding to the GT1b and 2a NS5B polymerases. The interactions between the para-fluorophenyl groups at the C2 positions of the inhibitors and the residues at the binding pockets, together with the interactions between the substituents at the C5 positions and the residues at the reverse ß-fold (residues 441-456), play a key role in recognition and the induction of the binding. The relevant studies could provide valuable information for further research and development of novel anti-HCV benzofuran core pan-genotypic inhibitors.

Serum Phosphatidylcholine Species 32:0 as a Biomarker for Liver Cirrhosis Pre- and Post-Hepatitis C Virus Clearance.

Phosphatidylcholine (PC) is an essential lipid for liver health and lipoprotein metabolism, but its circulating levels have rarely been studied in patients with cirrhosis. Chronic hepatitis C virus (HCV) infection causes lipid abnormalities and is a major cause of cirrhosis. Effective HCV elimination with direct-acting antivirals (DAAs) is associated with the normalization of serum low-density lipoprotein cholesterol levels. Since PC is abundant in all lipoprotein particles, this study analyzed the association between serum PC species levels and liver cirrhosis before and after HCV eradication. Therefore, 27 PC species were measured by Fourier Transform Mass Spectrometry in the serum of 178 patients with chronic HCV infection at baseline and in 176 of these patients at the end of therapy. The PC species did not correlate with viral load, and the levels of 13 PC species were reduced in patients infected with genotype 3a compared to those affected with genotype 1. Four PC species were slightly elevated 12 weeks after DAA initiation, and genotype-related changes were largely normalized. Patients with HCV and cirrhosis had higher serum levels of PC 30:0 and 32:0 before and at the end of therapy. PC species containing polyunsaturated fatty acids were mostly decreased in cirrhosis. The levels of polyunsaturated, but not saturated, PC species were inversely correlated with the model of the end-stage liver disease score. A receiver operating characteristic curve analysis showed area under the curve values of 0.814 and 0.826 for PC 32:0 and 0.917 and 0.914 for % PC 32:0 (relative to the total PC levels) for the classification of cirrhosis at baseline and at the end of therapy, respectively. In conclusion, the specific upregulation of PC 32:0 in cirrhosis before and after therapy may be of diagnostic value in HCV-related cirrhosis.

Biochemical implication of acetylcholine, histamine, IL-18, and interferon-alpha as diagnostic biomarkers in hepatitis C virus, coronavirus disease 2019, and dual hepatitis C virus-coronavirus disease 2019 patients.

Globally, hepatitis C virus (HCV) and coronavirus disease 2019 (COVID-19) are the most common causes of death due to the lack of early predictive and diagnostic tools. Therefore, research for a new biomarker is crucial. Inflammatory biomarkers are critical central players in the pathogenesis of viral infections. IL-18, produced by macrophages in early viral infections, triggers inflammatory biomarkers and interferon production, crucial for viral host defense. Finding out IL-18 function can help understand COVID-19 pathophysiology and predict disease prognosis. Histamine and its receptors regulate allergic lung responses, with H1 receptor inhibition potentially reducing inflammation in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. angiotensin-converting enzyme 2 (ACE-2) receptors on cholangiocytes suggest liver involvement in SARS-CoV-2 infection. The current study presents the potential impact of circulating acetylcholine, histamine, IL-18, and interferon-Alpha as diagnostic tools in HCV, COVID-19, and dual HCV-COVID-19 pathogenesis. The current study was a prospective cross-section conducted on 188 participants classified into the following four groups: Group 1 COVID-19 (n = 47), Group 2 HCV (n = 47), and Group 3 HCV-COVID-19 patients (n = 47), besides the healthy control Group 4 (n = 47). The levels of acetylcholine, histamine, IL-18, and interferon-alpha were assayed using the ELISA method. Liver and kidney functions within all groups showed a marked alteration compared to the healthy control group. Our statistical analysis found that individuals with dual infection with HCV-COVID-19 had high ferritin levels compared to other biomarkers while those with COVID-19 infection had high levels of D-Dimer. The histamine, acetylcholine, and IL-18 biomarkers in both COVID-19 and dual HCV-COVID-19 groups have shown discriminatory power, making them potential diagnostic tests for infection. These three biomarkers showed satisfactory performance in identifying HCV infection. The IFN-Alpha test performed well in the HCV-COVID-19 group and was fair in the COVID-19 group, but it had little discriminative value in the HCV group. Moreover, our findings highlighted the pivotal role of acetylcholine, histamine, IL-18, and interferon-Alpha in HCV, COVID-19, and dual HCV-COVID-19 infection. Circulating levels of acetylcholine, histamine, IL-18, and interferon-Alpha can be potential early indicators for HCV, COVID-19, and dual HCV-COVID-19 infection. We acknowledge that further large multicenter experimental studies are needed to further investigate the role biomarkers play in influencing the likelihood of infection to confirm and extend our observations and to better understand and ultimately prevent or treat these diseases.

Cryoglobulinemic vasculitis triggered by Staphylococcus aureus endocarditis with chronic hepatitis C virus co-infection: a case report and literature review.

Infective endocarditis is a rare but life-threatening condition, occasionally linked to diverse immunologic manifestations, including mixed cryoglobulinemia. This can lead to cryoglobulinemic vasculitis, which has the potential for widespread organ damage. Although some cases have highlighted the relationship between infective endocarditis and cryoglobulinemic vasculitis, no comprehensive epidemiological evaluation or optimal treatment strategies have been advanced for such a combination. We present a case of methicillin-sensitive Staphylococcus aureus infective endocarditis associated with cryoglobulinemic vasculitis and conduct a literature review to compare management and outcomes in similar cases. Our patient presented with classical Meltzer's triad and mild renal involvement. Cryoimmunofixation confirmed type III cryoglobulinemia, and serum cytokines showed elevated IL-6 levels. The differential diagnosis included infective endocarditis and chronic active hepatitis C virus infection. Rapid symptom resolution after antibiotic treatment identified infective endocarditis as the likely cause of cryoglobulinemic vasculitis. Our case and review of the literature highlight that early identification of the cause of cryoglobulinemic vasculitis is crucial for selecting appropriate treatment and preventing recurrence or morbidity.

Prevalence and Modes of Transmission of Hepatitis C Virus Infection: A Historical Worldwide Review.

Hepatitis C virus infection affects over 58 million individuals and is responsible for 290,000 annual deaths. The infection spread in the past via blood transfusion and iatrogenic transmission due to the use of non-sterilized glass syringes mostly in developing countries (Cameroon, Central Africa Republic, Egypt) but even in Italy. High-income countries have achieved successful results in preventing certain modes of transmission, particularly in ensuring the safety of blood and blood products, and to a lesser extent, reducing iatrogenic exposure. Conversely, in low-income countries, unscreened blood transfusions and non-sterile injection practices continue to play major roles, highlighting the stark inequalities between these regions. Currently, injection drug use is a major worldwide risk factor, with a growing trend even in low- and middle-income countries (LMICs). Emerging high-risk groups include men who have sex with men (MSM), individuals exposed to tattoo practices, and newborns of HCV-infected pregnant women. The World Health Organization (WHO) has proposed direct-acting antiviral (DAA) therapy as a tool to eliminate infection by interrupting viral transmission from infected to susceptible individuals. However, the feasibility of this ambitious and overly optimistic program generates concern about the need for universal screening, diagnosis, linkage to care, and access to affordable DAA regimens. These goals are very hard to reach, especially in LMICs, due to the cost and availability of drugs, as well as the logistical complexities involved. Globally, only a small proportion of individuals infected with HCV have been tested, and an even smaller fraction of those have initiated DAA therapy. The absence of an effective vaccine is a major barrier to controlling HCV infection. Without a vaccine, the WHO project may remain merely an illusion.

Molecular epidemiology of hepatitis B, hepatitis C, and HIV-1 co-infections in Ethiopia: Implications for disease burden and intervention strategies.

BACKGROUND: Hepatitis 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. METHODS: A 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. RESULTS: The 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. CONCLUSIONS: This 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.

HCV 5-Methylcytosine Enhances Viral RNA Replication through Interaction with m5C Reader YBX1.

Hepatitis C virus (HCV) is a positive-stranded RNA virus that mainly causes chronic hepatitis, cirrhosis and hepatocellular carcinoma. Recently we confirmed m5C modifications within NS5A gene of HCV RNA genome. However, the roles of the m5C modification and its interaction with host proteins in regulating HCV's life cycle, remain unexplored. Here, we demonstrate that HCV infection enhances the expression of the host m5C reader YBX1 through the transcription factor MAX. YBX1 acts as an m5C reader, recognizing the m5C-modified NS5A C7525 site in the HCV RNA genome and significantly enhancing HCV RNA stability. This m5C-modification is also required for YBX1 colocalization with lipid droplets and HCV Core protein. Moreover, YBX1 facilitates HCV RNA replication, as well as viral assembly/budding. The tryptophan residue at position 65 (W65) of YBX1 is critical for these functions. Knockout of YBX1 or the application of YBX1 inhibitor SU056 suppresses HCV RNA replication and viral protein translation. To our knowledge, this is the first report demonstrating that the interaction between host m5C reader YBX1 and HCV RNA m5C methylation facilitates viral replication. Therefore, hepatic-YBX1 knockdown holds promise as a potential host-directed strategy for HCV therapy.

A pilot project harnessing surveillance systems to support clinicians providing clinical care for people diagnosed with hepatitis C in Victoria, Australia, September 2021 to 31 March 2022.

BackgroundActive follow-up of chronic hepatitis C notifications to promote linkage to care is a promising strategy to support elimination.AimThis pilot study in Victoria, Australia, explored if the Department of Health could follow-up on hepatitis C cases through their diagnosing clinicians, to assess and support linkage to care and complete data missing from the notification.MethodsFor notifications received between 1 September 2021 and 31 March 2022 of unspecified hepatitis C cases (i.e. acquired > 24 months ago or of unknown duration), contact with diagnosing clinicians was attempted. Data were collected on risk exposures, clinical and demographic characteristics and follow-up care (i.e. HCV RNA test; referral or ascertainment of previous negative testing or treatment history). Reasons for unsuccessful doctor contact and gaps in care provision were investigated. Advice to clinicians on care and resources for clinical support were given on demand.ResultsOf 513 cases where information was sought, this was able to be obtained for 356 (69.4%). Reasons for unsuccessful contact included incomplete contact details or difficulties getting in touch across three attempts, particularly for hospital diagnoses. Among the 356 cases, 307 (86.2%) had received follow-up care. Patient-management resources were requested by 100 of 286 contacted diagnosing clinicians.ConclusionsMost doctors successfully contacted had provided follow-up care. Missing contact information and the time taken to reach clinicians significantly impeded the feasibility of the intervention. Enhancing system automation, such as integration of laboratory results, could improve completeness of notifications and support further linkage to care where needed.

Decrease in active hepatitis C infection among people who use drugs in Madrid, Spain, 2017 to 2023: a retrospective study.

BackgroundPeople who use drugs (PWUD) are a key target population to reduce the burden of hepatitis C virus (HCV) infection.AimTo assess risk factors and temporal trends of active HCV infection in PWUD in Madrid, Spain.MethodsWe conducted a retrospective study between 2017 and 2023, including 2,264 PWUD visiting a mobile screening unit. Data about epidemiology, substance use and sexual risk behaviour were obtained through a 92-item questionnaire. HCV was detected by antibody test, followed by RNA test. The primary outcome variable was active HCV infection prevalence, calculated considering all individuals who underwent RNA testing and analysed by logistic regression adjusted by the main risk factors.ResultsOf all participants, 685 tested positive for anti-HCV antibodies, and 605 underwent RNA testing; 314 had active HCV infection, and 218 initiated treatment. People who inject drugs (PWID) were identified as the main risk group. The active HCV infection rate showed a significant downward trend between 2017 and 2023 in the entire study population (23.4% to 6.0%), among PWID (41.0% to 15.0%) and PWUD without injecting drug use (7.0% to 1.3%) (p < 0.001 for all). These downward trends were confirmed by adjusted logistic regression for the entire study population (adjusted odds ratio (aOR): 0.78), PWID (aOR: 0.78), and PWUD non-IDU (aOR: 0.78).ConclusionsOur study demonstrates a significant reduction in active HCV infection prevalence among PWUD, particularly in PWID, which suggests that efforts in the prevention and treatment of HCV in Madrid, Spain, have had an impact on the control of HCV infection.

After the Storm: Persistent Molecular Alterations Following HCV Cure.

The development of direct-acting antivirals (DAAs) against hepatitis C virus (HCV) has revolutionized the management of this pathology, as their use allows viral elimination in a large majority of patients. Nonetheless, HCV remains a major public health problem due to the multiple challenges associated with its diagnosis, treatment availability and development of a prophylactic vaccine. Moreover, HCV-cured patients still present an increased risk of developing hepatic complications such as hepatocellular carcinoma. In the present review, we aim to summarize the impact that HCV infection has on a wide variety of peripheral and intrahepatic cell populations, the alterations that remain following DAA treatment and the potential molecular mechanisms implicated in their long-term persistence. Finally, we consider how recent developments in single-cell multiomics could refine our understanding of this disease in each specific intrahepatic cell population and drive the field to explore new directions for the development of chemo-preventive strategies.

Coordinated expansion of memory T follicular helper and B cells mediates spontaneous clearance of HCV reinfection.

Introduction: Follicular helper T cells are essential for helping in the maturation of B cells and the production of neutralizing antibodies (NAbs) during primary viral infections. However, their role during recall responses is unclear. Here, we used hepatitis C virus (HCV) reinfection in humans as a model to study the recall collaborative interaction between circulating CD4 T follicular helper cells (cTfh) and memory B cells (MBCs) leading to the generation of NAbs. Methods: We evaluated this interaction longitudinally in subjects who have spontaneously resolved primary HCV infection during a subsequent reinfection episode that resulted in either another spontaneous resolution (SR/SR, n = 14) or chronic infection (SR/CI, n = 8). Results: Both groups exhibited virus-specific memory T cells that expanded upon reinfection. However, early expansion of activated cTfh (CD4+CXCR5+PD-1+ICOS+FoxP3-) occurred in SR/SR only. The frequency of activated cTfh negatively correlated with time post-infection. Concomitantly, NAbs and HCV-specific MBCs (CD19+CD27+IgM-E2-Tet+) peaked during the early acute phase in SR/SR but not in SR/CI. Finally, the frequency of the activated cTfh1 (CXCR3+CCR6-) subset correlated with the neutralization breadth and potency of NAbs. Conclusion: These results underscore a key role for early activation of cTfh1 cells in helping antigen-specific B cells to produce NAbs that mediate the clearance of HCV reinfection.

On leveraging self-supervised learning for accurate HCV genotyping.

Hepatitis C virus (HCV) is a major global health concern, affecting millions of individuals worldwide. While existing literature predominantly focuses on disease classification using clinical data, there exists a critical research gap concerning HCV genotyping based on genomic sequences. Accurate HCV genotyping is essential for patient management and treatment decisions. While the neural models excel at capturing complex patterns, they still face challenges, such as data scarcity, that exist a lot in computational genomics. To overcome this challenges, this paper introduces an advanced deep learning approach for HCV genotyping based on the graphical representation of nucleotide sequences that outperforms classical approaches. Notably, it is effective for both partial and complete HCV genomes and addresses challenges associated with imbalanced datasets. In this work, ten HCV genotypes: 1a, 1b, 2a, 2b, 2c, 3a, 3b, 4, 5, and 6 were used in the analysis. This study utilizes Chaos Game Representation for 2D mapping of genomic sequences, employing self-supervised learning using convolutional autoencoder for deep feature extraction, resulting in an outstanding performance for HCV genotyping compared to various machine learning and deep learning models. This baseline provides a benchmark against which the performance of the proposed approach and other models can be evaluated. The experimental results showcase a remarkable classification accuracy of over 99%, outperforming traditional deep learning models. This performance demonstrates the capability of the proposed model to accurately identify HCV genotypes in both partial and complete sequences and in dealing with data scarcity for certain genotypes. The results of the proposed model are compared to NCBI genotyping tool.

Trends in hepatitis C virus seroprevalence and associated risk factors among msm in Pakistan: insights from a community-based study.

Pakistan bears a substantial burden of hepatitis C virus (HCV) infection, with the second-highest prevalence globally. This community-based cross-sectional study, conducted from January to December 2022 in Punjab, Pakistan, investigates the seroprevalence of HCV among the men who have sex with men (MSM) population. The study identifies demographic and behavioral risk factors associated with HCV infection within this population group. Among the 501 participants, the study found an HCV seroprevalence of 14.86%. The association between demographic characteristics and seroprevalence is assessed by calculating the percentage of positive cases, revealing notable associations with age, education level, and self-identified sexual orientation. Furthermore, the study identified several behavioral risk factors positively associated with HCV seroprevalence, including sharing personal items such as razors and toothbrushes, histories of surgery, blood transfusion, dental procedures, intravenous drug use, and therapeutic injection histories. These risk factors were identified through structured interviews, and the prevalence of HCV seropositivity among the exposed groups was calculated accordingly. Interestingly, a lower HCV positivity rate was observed among self-reported HIV-positive individuals, contradicting previous research. The findings underscore the need for comprehensive, targeted prevention strategies such as risk factor awareness campaigns and educational programs tailored for the MSM population in Pakistan. Further research is warranted to validate these findings and better understand the complex interplay of factors contributing to HCV seroprevalence in this high-risk population.

Seroprevalence of hepatitis B virus and hepatitis C virus infection among pregnant women attending antenatal care at Guhala Primary Hospital, Northwestern Ethiopia.

BACKGROUND: Hepatitis B virus (HBV) and Hepatitis C Virus (HCV) infections are global issues that disproportionately affect developing countries. Pregnancy-related HBV and HCV infections are associated with a high risk of vertical transmission and complications for the mother as well as the newborn. Therefore, this study aims to determine the seroprevalence of hepatitis B virus and hepatitis C virus infection among pregnant women attending antenatal care at Guhala Primary Hospital, Northwestern Ethiopia. METHODS: A hospital-based retrospective study was conducted from July to September 2022 on HBV and HCV registered books from September 1, 2017, to August 30, 2019, for a year. The presence of HBsAg and anti-HCV in serum was detected using the One Step Cassette Style HBsAg and anti-HCV antibody test kit. Data were analyzed using SPSS version 26 software. RESULTS: In this study, a total of 2252 participants for HBsAg and 538 participants for ant-HCV rapid tests of records in the laboratory logbook were included. The mean age of the study participants was 25.6years (± 5.8SD). The overall prevalence of HBsAg and anti-HCV was 6.0% (134/2252) and 2.4% (13/538), respectively. There were 0.4% (2/538) coinfection results between HBV and HCV among pregnant women. CONCLUSION AND RECOMMENDATION: In this study, intermediate seroprevalence of HBV and HCV infection was detected among pregnant women attending antenatal care. The Hepatitis B virus was predominantly higher among pregnant women aged between 25 and 34 years. To manage and stop the potential vertical transmission of these viral agents during the early stages of pregnancy, routine prenatal testing for HBV and HCV infections should be taken into consideration.

Surface antigen serocleared hepatitis B virus infection increases the risk of mixed cryoglobulinemia vasculitis in male patients with chronic hepatitis C.

Mixed cryoglobulinemia vasculitis (MCV) is caused in ~90% of cases by chronic hepatitis C virus (HCVposMCV) and more rarely by hepatitis B virus (HBV) infection, or apparently noninfectious. HCVposMCV develops in only ~5% of patients with chronic hepatitis C (CHC), but risk factors other than female gender have not been identified so far. We conducted a retrospective case control study investigating whether past active HBV infection, defined by hepatitis B surface antigen (HBsAg) seroclearance and anti-core antibody (HBcAb) positivity, could be a risk factor for developing HCVposMCV. The prevalence of HBsAg seroclearance was 48% within 123 HCVposMCV patients and 29% within 257 CHC patients (p=0.0003). Multiple logistic regression including as variables gender, birth year, age at HBV testing, cirrhosis, and hepatocellular carcinoma, confirmed an association of HBsAg seroclearance with HCVposMCV [adjusted odds ratio (OR) 2.82, 95% confidence interval (95% CI) 1.73-4.59, p<0.0001]. Stratification by gender, however, showed that HBsAg seroclearance was associated with HCVposMCV in male [OR 4.63, 95% CI 2.27-9.48, p<0.0001] and not in female patients [OR 1.85, 95% 95% CI 0.94-3.66, p=0.076]. HBsAg seroclearance, and more likely occult HBV infection, is an independent risk factor for HCVposMCV in male CHC patients.