Chronic Hepatitis C Virus Patients Research Articles

Assessment of Gene Expression of Some Human Cluster of Differentiation in Chronic HCV Patients

Background: Hepatitis C virus (HCV) is one of the most potential pathogens all over the world. It is one of the main causes of chronic liver diseases. The host immune response against HCV sets off a chain reaction that results in liver damage after HCV infection in addition to necrosis and cellular inflammation, fibrosis, and hepatocellular carcinoma. Objective: This study aimed at evaluation of gene expression of human cluster of differentiation (CD25, CD39 and CD127) in patients with chronic HCV infection. Materials and Methods: The study involved 70 HCV patients who were diagnosed in Hepatology and Gastroenterology Center at Azadi Teaching Hospital and 50 control subjects during October 2023 until April 2024. HCV patients were confirmed with real time PCR. In addition RNA extraction was conducted on patients and control whole blood to assess the gene expression of CD25, CD39 and CD127 in both groups. Result: Regarding gene expression of CD25, CD39 and CD127, our data revealed significant overexpression of those marker in HCV patients in comparison to control group with P value (0.0001, <0.0001 and <0.0001) respectively. Conclusion: The gene expression of CD25, CD39 and CD127 were significantly up-regulated in HCV patients compared to healthy control indicating the role played by these markers.

Interleukin one beta (IL-1B) gene polymorphisms in Iraqi patients with susceptibility to develop hepatitis C infections

Hepatitis C virus (HCV) infection is the main cause of chronic hepatitis, affecting an estimated 150 million people worldwide. Initial exposure to HCV is most often followed by chronic hepatitis, with only a minority of individuals spontaneously clearing the virus. This study aimed to find an associated relationship between HCV susceptibility and Polymorphic gene of IL‐1B targeting a total of 45 individuals: 30 patients with chronic hepatitis C and 15 healthy control from different cities of Iraqi recruited the Hospital for diseases of the digestive system and liver in Baghdad between November 2022 to February 2023. Genomic DNA was extracted and specific promotor sequence was amplified by polymerase chain reaction (PCR) followed by sequencing then measuring serum concentrations of IL-1β by Enzyme-Linked Immunosorbent Assay (ELISA). The results revealed significant difference in serum levels of IL-1B (P≤0.01), from 1.10-+0.09 in Chronic HCV patients in comparison with its level in healthy controls 7.58± 0.28. Molecular results suggested that single nucleotide polymorphisms in the promoter of IL-1B is probably associated with susceptibility to HCV chronic infection according to this sample of Iraqi patients. In conclusion, the results suggested that variation in serum level and polymorphism in IL-1B is probably associated with susceptibility to hepatitis C virus chronic infection.

Individualized HCC surveillance using risk stratification scores in advanced fibrosis and cirrhotic HCV patients who achieved SVR: Prospective study.

Several HCC risk stratification scores were developed; however, none has been prospectively validated. The primary aim is to validate the clinical utility of six HCC risk scores in large prospective study of F3-4 patients achieving SVR following DAAs according to EASL guidelines. The secondary aim is to explore whether individualized risk stratification improves detection of HCC at early stages amenable to curative treatment. This prospective study included two cohorts: Egyptian Liver Research Institute and Hospital (ELRIAH) cohort of 463 chronic HCV patients with advanced liver disease (F3 and F4) achieved SVR with a follow-up every 6 months according to EASL guidelines using 6 simple HCC risk scores and Tanta cohort of 492 comparable patients where individualized surveillance intervals were tailored based on HCC risk assessments using GES score as follows: low-risk patients were followed yearly, intermediate-risk every 6 months and high-risk every 2-3 months. All scores, except Watanabe post, successfully stratified patients into low-, intermediate- and high-risk groups, with log-rank p-value of 0.001 and Harrell's C ranging from 0.669 to 0.728. Clinical utility of these scores revealed that the highest percentage of patients classified as low risk was 42.5% using the GES, while the lowest was 8.9% using the aMAP. ELRIAH cohort, 25 patients developed HCC with 52% diagnosed at BCLC 0 and A. Tanta cohort, 35 patients developed HCC, with 80% diagnosed at BCLC 0 and A. Individualized risk stratification using HCC risk scores was associated with improved early-stage detection and receipt of curative treatment.

Effect of direct-acting antivirals on the titers of human pegivirus 1 during treatment of chronic hepatitis C patients.

Human pegivirus 1 coinfections are common in hepatitis C virus (HCV) patients, persisting for years. However, little is known about how pegivirus coinfections are affected by treatment with pangenotypic direct-acting antivirals (DAAs) against HCV. We identified human pegivirus by metagenomic analysis of chronic HCV patients undergoing protease, NS5A, and polymerase inhibitor treatment, in some patients with the addition of pegylated interferon, and followed viral kinetics of both viruses to investigate treatment effects. Only during HCV DAA treatment regimens that included the more broad-spectrum drug sofosbuvir could we detect a consistent decline in pegivirus titers that, however, rebounded to pretreatment levels after treatment cessation. The addition of pegylated interferon gave the highest effect with pegivirus titers decreasing to below the assay detection limit, but without clearance. These results reveal the limited effect of frontline HCV drugs on the closest related human virus, but sofosbuvir appeared to have the potential to be repurposed for other viral diseases.

B cells expressing mutated IGHV1-69-encoded antigen receptors related to virus neutralization show lymphoma-like transcriptomes in patients with chronic HCV infection.

Chronic HCV infection leads to a complex interplay with adaptive immune cells that may result in B cell dyscrasias like cryoglobulinemia or lymphoma. While direct-acting antiviral therapy has decreased the incidence of severe liver damage, its effect on extrahepatic HCV manifestations such as B cell dyscrasias is still unclear. We sequenced B cell receptor (BCR) repertoires in patients with chronic HCV mono-infection and patients with HCV with a sustained virological response (SVR) after direct-acting antiviral therapy. This data set was mined for highly neutralizing HCV antibodies and compared to a diffuse large B cell lymphoma data set. The TKO model was used to test the signaling strength of selected B-BCRs in vitro. Single-cell RNA sequencing of chronic HCV and HCV SVR samples was performed to analyze the transcriptome of B cells with HCV-neutralizing antigen receptors. We identified a B cell fingerprint with high richness and somatic hypermutation in patients with chronic HCV and SVR. Convergence to specific immunoglobulin genes produced high-connectivity complementarity-determining region 3 networks. In addition, we observed that IGHV1-69 CDR1 and FR3 mutations characterizing highly neutralizing HCV antibodies corresponded to recurrent point mutations found in clonotypic BCRs of high-grade lymphomas. These BCRs did not show autonomous signaling but a lower activation threshold in an in vitro cell model for the assessment of BCR signaling strength. Single-cell RNA sequencing revealed that B cells carrying these point mutations showed a persisting oncogenic transcriptome signature with dysregulation in signaling nodes such as CARD11, MALT1, RelB, MAPK, and NFAT. We provide evidence that lymphoma-like cells derive from the anti-HCV immune response. In many patients, these cells persist for years after SVR and can be interpreted as a mechanistic basis for HCV-related B cell dyscrasias and increased lymphoma risk even beyond viral elimination.

Angiopoietin-2 as a Predictor of Fibrosis Regression in Hepatitis C Virus-Patients after Direct Acting Antiviral Drugs

Abstract Background HCV infection is a major health concern. Disease progression to fibrosis, cirrhosis, and HCC is aided by the persistence of inflammatory reactions and cellular damage. Moreover, angiogenesis was found to have a substantial pathogenic role in disease progression. Serum Angiopoietin-2 appears to be correlated with liver stiffness in chronic HCV and its elevation is linked to disease progression from chronic hepatitis to cirrhosis. Aim of the Work The aim of this study was to evaluate the role of serum Angiopoietin-2 in the prediction of regression of fibrosis in chronic HCV patients receiving direct-acting antiviral agents. Patients and Methods Forty Egyptian chronic HCV patients for whom direct-acting antiviral agent (DAA) therapy was planned were included. All patients underwent assessment twice, at baseline and at SVR12, for standard laboratory tests, measurement of fibrosis using FibroScan, FIB-4 and APRI scores, and Angiopoietin-2 level. Results Among 40 patients; 26 (65%) are males and 14 (35%) are females. Their age is ranged between 35 and 60 years old with a mean age of 52.35 ± 6.08 and a median of 53.0 (50.0 – 57.0). The HCV-RNA titer is ranged from 3.60 to 7.20 log IU/mL with a mean titer of 5.99 ± 0.87 before treatment. The median is 6.20 (5.30 – 6.65). There was a significant improvement concerning the fibrosis stage after DAA treatment. Liver fibrosis indices were significantly associated with regression of liver fibrosis stage based on FibroScan data after DAA therapy. Liver size, spleen size and portal vein diameter were improved significantly after successful HCV eradication by DAAs. There was improvement in the Child-Pugh score after successful HCV eradication by DAAs but the difference was no statistically significant (p = 0.500). Baseline Ang-2 was statistically significant after successful HCV eradication by DAAs (p < 0.001). Overall, there was a positive significant correlation between Ang-2 and all the fibrosis stages (p = 0.001) and there was a statistically significant higher mean of Ang-2 in higher stages of liver fibrosis before treatment. Indeed Ang-2 increase significantly when the fibrosis stage increased and vice-versa before treatment. Ang-2 in higher stages of liver fibrosis after treatment. Indeed Ang-2 increase significantly when the fibrosis stage increased and vice-versa after treatment. The correlation between Ang-2 and fibrosis group (F0, F1, F2 & F3) were significant and the correlation between Ang-2 and the liver fibrosis stage (F4) were also significant before treatment. The correlations between Ang-2 levels and fibrosis group (F0, F1, F2 & F3) were significant as well as the advanced liver fibrosis (F4) after DAA therapy. Conclusion Angiopoietin-2 can be a useful predictor of fbrosis regression in chronic HCV patients receiving direct acting antiviral agents. Elevated baseline Angiopoietin-2 and advanced ibrosis stages may predict non-regression of liver fibrosis.

Clinical Utility of CTNNB1 (c.121A>G) Mutation in Circulating Tumor DNA in Egyptian Patients with Hepatocellular Carcinoma: A Case-Control Study

Abstract Background Hepatocellular carcinoma (HCC) is the most common malignancy of the liver and with 782,000 new cases annually and 600,000 deaths/year globally. In Egypt, HCC causes a significant public health problem with a rising incidence as it is strongly linked to viral hepatitis mainly HCV. CTNNB1 mutations is one of the most common genetic alterations in HCC. Our aim is to investigate the clinical utility of CTNNB1 (rs121913412) single nucleotide variation (SNV) in ctDNA in patients with early and late-stage HCC in comparison to chronic HCV patients and healthy controls. Methods All participants were subjected to history taking, clinical evaluation, laboratory investigations including liver profile, kidney function tests, alfa-fetoprotein. Additionally, complete blood counts and coagulation profile were done. Child and Model for End-Stage Liver Disease (MELD) scores were calculated, BCLC staging was done for each patient and radiological protocol for HCC (spiral triphasic CT or MRI). Genotyping of rs121913412 CTNNB1 (c.121A>G) on extracted DNA from blood samples was done using Real Time PCR System. Results Thirty patients with HCC on top of HCV were recruited including 14 early HCC and 16 with advanced HCC in addition to non-HCC group including 10 HCV-positive patients and 10 healthy controls. All participants have undergone laboratory investigations and radiological protocol for HCC cases. Genotyping of rs121913412 CTNNB1 (c.121A>G) in peripheral blood samples using RT-PCR for all cases was done. The genotype AA was detected in 27out of 30 (30%) of the cases while 3 HCC cases out of 30 (10 %) were positive for the CTNNB1 p.T41A mutation; AG phenotype (heterozygous), no cases showed GG phenotype. In HCV- positive patients’ group and healthy controls none were positive for the CTNNB1 mutation all showed wild AA genotype. No significant differences in the genotype (AA, AG, GG) distribution between HCC and non-HCC groups (χ2=3.619, p = 0.0571). The frequency of AA vs AG + GG genotype was considerably higher in cases when compared to controls however no statistical significance was detected (χ2=3.619, p = 0.0571). Distribution of A vs G allele in cases compared to controls showed statistically significant difference (χ2=4.571, p = 0.0325). Conclusion In this study we were not able to prove the clinical utility of CTNNB1 rs121913412 in Egyptian HCC patients. Further large multi-centric studies are needed to explore the clinical utility of ctDNA in assessment of tumor-specific hotspot somatic mutations in genes including CTNNB1, TERT and TP53 genes that can be identified in the peripheral blood of HCC patients. Comparison studies utilizing both ctDNA and DNA extracted from HCC tissue samples are recommended.

Association of Serum Fetuin-A and Fatty Liver Index as an Indicator of Hepatic Steatosis in Chronic HCV Patients

Association of Serum Fetuin-A and Fatty Liver Index as an Indicator of Hepatic Steatosis in Chronic HCV Patients

Hepatitis C Virus Care Cascade by Race/Ethnicity in a Statewide Correctional Population, 2019-2023.

Hepatitis C virus (HCV) care cascade data by race/ethnicity for US correctional populations are sparse. To evaluate the HCV care cascade by race/ethnicity for a state correctional population. This retrospective cohort study used Connecticut Department of Correction data for incarcerated individuals tested, diagnosed, and treated for chronic HCV infection with direct-acting antivirals (DAAs) from 2019 to 2023. HCV care cascade outcomes, including testing, treatment, and cure rates, were compared by race/ethnicity. Poisson regression was used to estimate prevalence ratios (PRs), with adjustment for demographic and legal status factors. A total of 24,867 patients tested for HCV (88.9% men, mean (SD) age 35.6 (11.8), 32.7% White, 37.9% Black, 28.4% Hispanic, 0.6% Asian, 0.4% American Indian/Alaska Native (AIAN), 34.7% sentenced ≥ 1year). Both HCV exposure and chronic HCV were highest for White (27.1% and 15.2%) and lowest for Black individuals (4.6% and 2.6%) (P < 0.01, for both outcomes). While incarcerated, 63.2% of chronic HCV patients started DAAs, and treatment rates did not significantly differ by race/ethnicity (P > 0.05). For those treated and having post-treatment lab data available, cure rates were 98.8% or better for all racial/ethnic groups (P > 0.05). In the adjusted regression analyses, HCV treatment initiation was lower for those sentenced < 1year (PR, 0.76; 95% CI, 0.67-0.87) and unsentenced (PR, 0.85; 95% CI, 0.80-0.91) than those sentenced ≥ 1year. The adjusted prevalence of advanced fibrosis stage/activity grade was not significantly associated with race/ethnicity. In this cohort study, less than two-thirds of chronic HCV patients initiated DAA treatment during their incarceration, and for those with available data, nearly all were cured. While there were disparities in HCV exposure and chronic HCV infection, significant racial/ethnic differences were not observed for treatment initiation or cure rates. Further efforts are needed to increase HCV treatment, especially for patients with shorter incarceration periods.

Host immune players and their response to Hepatitis C therapies.

This study aimed to investigate alterations in the expression of four key cytokines (IL-7, IL-11, IL-15, and IL-27) and assess differential FAM26F expression in response to Hepatitis C virus (HCV) infection. Additionally, it sought to analyze changes in these cytokines after treatment in 244 chronic HCV patients and 28 controls undergoing various treatments, including standard interferon, pegylated interferon, and Direct Acting Antivirals (DAAs). The objective was to compare immune system regulation between treatment groups. The expression levels of FAM26F and the cytokines (IL-7, IL-11, IL-15, and IL-27) were evaluated using Real-time qPCR in PBMCs of treatment groups. Results revealed significant downregulation of IL-7 and IL-27 in infected individuals compared to healthy controls, persisting even after treatment. This suggests the crucial roles of these immune modulators in facilitating the necessary T-cell response for viral clearance. IL-11 expression also remained suppressed post-treatment, supporting viral clearance by restoring the Th1 response. The decrease in IL-11 levels during treatment indicates the restoration of the Th1 response, vital for viral clearance. IL-15, the key cytokine regulating cytotoxic cells (NKT and NK cells), displayed consistent expression across all sample groups, indicating maintained IL-15-induced cytotoxicity in both control and infected individuals. Additionally, FAM26F expression was reduced in the HCV-infected group compared to controls, but higher in HCV-recovered cases, potentially due to reduced infection and enhanced immunity. In conclusion, this research unveils the relationship between FAM26F and HCV infection, highlighting the virus's tendency to suppress cytokine and FAM26F expression. An effective treatment strategy for establishing an ideal host immune response may involve restoring FAM26F and cytokine expression to their normal levels.

A Machine Learning-Based Mortality Prediction Model for Patients with Chronic Hepatitis C Infection: An Exploratory Study.

Background: Chronic hepatitis C (HCV) infection presents global health challenges with significant morbidity and mortality implications. Successfully treating patients with cirrhosis may lead to mortality rates comparable to the general population. This study aims to utilize machine learning techniques to create predictive mortality models for individuals with chronic HCV infections. Methods: Data from chronic HCV patients at Sultan Qaboos University Hospital (2009-2017) underwent analysis. Data pre-processing handled missing values and scaled features using Python via Anaconda. Model training involved SelectKBest feature selection and algorithms such as logistic regression, random forest, gradient boosting, and SVM. The evaluation included diverse metrics, with 5-fold cross-validation, ensuring consistent performance assessment. Results: A cohort of 702 patients meeting the eligibility criteria, predominantly male, with a median age of 47, was analyzed across a follow-up period of 97.4 months. Survival probabilities at 12, 36, and 120 months were 90.0%, 84.0%, and 73.0%, respectively. Ten key features selected for mortality prediction included hemoglobin levels, alanine aminotransferase, comorbidities, HCV genotype, coinfections, follow-up duration, and treatment response. Machine learning models, including the logistic regression, random forest, gradient boosting, and support vector machine models, showed high discriminatory power, with logistic regression consistently achieving an AUC value of 0.929. Factors associated with increased mortality risk included cardiovascular diseases, coinfections, and failure to achieve a SVR, while lower ALT levels and specific HCV genotypes were linked to better survival outcomes. Conclusions: This study presents the use of machine learning models to predict mortality in chronic HCV patients, providing crucial insights for risk assessment and tailored treatments. Further validation and refinement of these models are essential to enhance their clinical utility, optimize patient care, and improve outcomes for individuals with chronic HCV infections.

Sustained virological response in chronic hepatitis C patients by direct-acting antiviral treatment significantly reduces liver stiffness over 24 weeks posttreatment.

To investigate whether direct-acting antiviral (DAA) treatment affected liver fibrosis testing, including transient elastography (TE), aspartate aminotransferase-to-platelet ratio index (APRI), and Fibrosis-4 (FIB-4) index, after establishing a sustained virological response for 24 weeks. This prospective cohort study was conducted between October 1, 2019, and September 30, 2020, at Rajavithi Hospital, Bangkok, Thailand. All the patients had significant liver fibrosis (TE ≥ 7.0 kPa) at baseline and completed 12 weeks of DAA therapy. After achieving SVR, liver stiffness measurements were repeated for at least 24 weeks. The primary outcome was a > 30% improvement in TE score at the end of the study compared to baseline. A multivariate logistic regression model was used to identify the parameters associated with the primary outcome. Temporal changes in APRI and FIB-4 indices from baseline to 24 weeks posttreatment were also examined. A total of 110 chronic HCV patients were included in our cohort, of which 57 (52.3%) achieved the primary outcome. The median TE decreased from 15.05 (8.76-23.68) kPa at pretreatment to 9.60 (6.50-14.40) kPa at 24 weeks posttreatment (P < .001). Those who had a baseline TE ≥ 9.5 kPa had higher odds of meeting the primary outcome, and this remained significant after adjusting for age, sex, baseline body mass index, underlying diabetes mellitus, HCV genotype 3, baseline laboratory levels, and treatment regimens (OR 3.04; 95% CI 1.22-7.60, P = .017). Similar to TE, the median APRI and FIB-4 index displayed a considerable reduction from baseline to 24 weeks after successful therapy. Modern DAA treatment has been associated with considerable improvement in liver stiffness measured by TE in chronic HCV patients who achieve SVR, with roughly 52% of patients experiencing a reduction of > 30% in TE over 24 weeks posttreatment compared to baseline. This probably indicates early fibrosis regression, although the effect of resolution of inflammation after treatment completion cannot be ruled out.

Improvement in Thrombocytopenia after Direct Acting Anti-Viral (DAA)Therapy in Patients with Hepatitis C Virus-Related Chronic Liver Disease in Pakistani Population-A Single Centered Study

Background: Hepatitis C Virus (HCV) infection remains a significant global health challenge, often leading to chronic liver diseases such as cirrhosis and associated complications like thrombocytopenia. Directly acting antivirals (DAAs) have revolutionized HCV treatment due to their high efficacy and favorable safety profiles but the impact on thrombocytopenia, particularly in the Pakistani population, has been less studied. Objective: This study aimed to evaluate the effects of DAA therapy on platelet count and other laboratory parameters in chronic HCV patients with thrombocytopenia in Pakistan and to establish correlations between treatment outcomes and baseline laboratory values. Methods: A retrospective observational study was conducted at the Sindh Institute of Urology and Transplantation from January 2018 to December 2022. Patients with chronic HCV genotype 3a infection, compensated cirrhosis, and a baseline platelet count of less than 150 × 10^9/L were included. Exclusion criteria encompassed decompensated liver disease, liver cancer, and other specific conditions. The treatment regimens were Sofosbuvir plus Daclatasvir or Velpatasvir plus Ribavirin over three months. Parameters such as complete blood counts, serum creatinine, liver enzymes, and Child-Turcotte-Pugh (CTP) and Model for End-Stage Liver Disease (MELD) scores were recorded at baseline and post-treatment. Statistical analysis was performed using SPSS version 25, employing paired t-tests and Pearson correlation coefficients. Results: A total of 195 patients were studied, with a mean baseline platelet count of 100.7 × 10^9/L, which significantly increased to 122.2 × 10^9/L post-treatment (p &lt; 0.001). Improvements were also noted in mean serum creatinine (0.96 mg/dL to 0.87 mg/dL; p = 0.009), total bilirubin (1.6 mg/dL to 1.2 mg/dL; p &lt; 0.001), liver enzymes (ALT from 63.9 IU to 45.9 IU; p &lt; 0.001 and AST from 86.8 IU to 59.5 IU; p &lt; 0.001), and MELD scores (11.5 to 9.3; p &lt; 0.001). Hemoglobin levels and total leukocyte counts also showed significant improvements. Conclusion: DAA therapy significantly improves platelet counts and other laboratory parameters in chronic HCV patients with thrombocytopenia, suggesting a positive impact on liver function and patient management. This study highlights the importance of DAAs in the therapeutic regimen for HCV in the Pakistani population, contributing to better clinical outcomes and healthcare practices.

Minimal clinically important differences in health-related quality of life after treatment with direct-acting antivirals for chronic hepatitis C: ANRS CO22 HEPATHER cohort (PROQOL-HCV).

Patient Reported Outcomes Quality of Life survey for HCV (PROQOL-HCV) is a specific tool developed to assess health-related quality of life (HRQoL) in patients with chronic hepatitis C receiving direct-acting antivirals (DAA). Thresholds for clinically meaningful changes in PROQOL-HCV scores should be documented to improve the tool's use in clinical practice. This study aimed to estimate the minimal clinically important differences (MCIDs) in PROQOL-HCV scores before and after HCV cure by DAA among participants in the prospective cohort ANRS-CO22 HEPATHER. Data from 460 chronic HCV patients were collected at DAA initiation (baseline) and 24weeks after treatment end. MCIDs were estimated for the six HRQoL dimensions (Physical Health (PH), Emotional Health (EH), Future Uncertainty (FU), Intimate Relationships (IR), Social Health (SH), and Cognitive Functioning (CF)) using two approaches: anchor-based and score distribution-based. Each MCID was estimated for improvement/deterioration both globally and separately for patients with a baseline PRQoL-HCV score ≤ 50 (group1) and patients with a baseline PRQoL-HCV score > 50 (group2). The pooled MCIDs for improvement/deterioration globally, in group1, and in group2, respectively, were as follows: 8.8/-7.6, 9.7/-9.5, and 6.0/-6.9 for PH; 7.1/-4.6, 7.7/-9.6, and 6.6/-6.7 for EH; 6.7/-6.7, 8.2/-8.2, and 6.0/-6.0 for FU; 7.0/-7.0, 5.4/-5.4, and 6.2/-6.2 for IR; 7.7/-7.7, 8.6/-8.6, and 6.5/-6.5 for SH; 7.3/-5.6, 9.1/-8.0, and 6.5/-6.3 for CF. The overall MCID for the PROQOL-HCV scores ranged from 6.7 to 8.8 for improvement and from -7.7 to -4.6 for deterioration. The effect of DAA on PROQOL-HCV scores seemed particularly beneficial for patients with lower baseline scores. This subgroup could be motivated to take DAA if they are informed of the benefits for their HRQoL.

Chronic Viral Infection Compromises the Quality of Circulating Mucosal-Associated Invariant T Cells and Follicular T Helper Cells via Expression of Inhibitory Receptors.

Chronic viral infection results in impaired immune responses rendering viral persistence. Here, we compared the quality of T-cell responses among chronic hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV)-infected individuals by examining the levels of expression of selected immune activation and exhaustion molecules on circulating MAIT cells and Tfh cells. Cytokines were measured using a commercial Bio-plex Pro Human Cytokine Grp I Panel 17-plex kit (BioRad, Hercules, CA, USA). Inflammation was assessed by measuring an array of plasma cytokines, and phenotypic alterations in CD4+ T cells including circulating Tfh cells, CD8+ T cells, and TCR iVα7.2+ MAIT cells in chronic HBV, HCV, and HIV-infected patients and healthy controls. The cells were characterized based on markers pertaining to immune activation (CD69, ICOS, and CD27) proliferation (Ki67), cytokine production (TNF-α, IFN-γ) and exhaustion (PD-1). The cytokine levels and T cell phenotypes together with cell markers were correlated with surrogate markers of disease progression. The activation marker CD69 was significantly increased in CD4+hi T cells, while CD8+ MAIT cells producing IFN-γ were significantly increased in chronic HBV, HCV and HIV infections. Six cell phenotypes, viz., TNF-α+CD4+lo T cells, CD69+CD8+ T cells, CD69+CD4+ MAIT cells, PD-1+CD4+hi T cells, PD-1+CD8+ T cells, and Ki67+CD4+ MAIT cells, were independently associated with decelerating the plasma viral load (PVL). TNF-α levels showed a positive correlation with increase in cytokine levels and decrease in PVL. Chronic viral infection negatively impacts the quality of peripheral MAIT cells and Tfh cells via differential expression of both activating and inhibitory receptors.

Serum Angiopoietin-2 Levels Predict the Development of Hepatocellular Carcinoma following Hepatitis C Virus Eradication Using Direct-Acting Antiviral Agents

Plain Language SummaryOur previous studies showed that serum angiopoietin-2 (Ang-2) and C-X-C motif chemokine ligand 10 (CXCL10) levels predicted improvement in liver fibrosis following sustained virological response (SVR) of hepatitis C virus (HCV) obtained with administration of with direct-acting antiviral agents (DAAs). These levels were evaluated retrospectively as predictive indicators of hepatocellular carcinoma (HCC) development following SVR. We enrolled individuals from a historical cohort of 89 chronic HCV patients without history of HCC at baseline with SVR following DAA therapy and had baseline serum levels of Mac-2 binding protein glycosylation isomer ≥2.0 C.O.I. Multivariate analyses of patients revealed that only the Ang-2 level at 24 weeks following the end of treatment (EOT24W) was significantly related to HCC development (hazard ratio 2.27; p = 0.003). This result was reproduced in individuals with advanced liver fibrosis (M2BPGi level ≥3.3 C.O.I. at baseline). Time-dependent receiver operating characteristic curve analyses for the future risk of developing HCC within 5 years of follow-up (5y-HCC) showed the best cut-off Ang-2 level at EOT24W was 2,780 pg/mL, and significantly stratified the cumulative incidence of HCC (≥2,780 vs. < 2,780 pg/mL, 5y-HCC: 45.5 vs. 8.2%, p < 0.001). The serum Ang-2 level at EOT24W is a feasible predictor of HCC development after achieving SVR to DAAs therapy.

Efficacy and safety of glecaprevir and pibrentasvir in Saudi patients with chronic hepatitis C virus infection at a major tertiary hospital.

To evaluate the effectiveness and safety of glecaprevir/pibrentasvir (GLE/PIB) in chronic hepatitis C (HCV) patients, and to assess the prescribers' adherence to Food and Drug Administration recommendations on treatment duration. A retrospective cohort study was carried out on chronic HCV patients of ≥18 years, with or without cirrhosis, naive or experienced, and with normal kidney function or chronic kidney disease (including dialysis patients) at Prince Sultan Military Medical City in Riyadh, Saudi Arabia, between February 2020 and March 2021. The primary effectiveness end-point was the number and percentage of patients who achieved a sustained virologic response (SVR12), virologic failure, and non-response. Safety was determined considering both serious and non-serious adverse events. A total of 92 patients were enrolled in this study. Among patients, 52 (56.5%) were female, 84 (91.3%) were naive, and 45 (48.9 %) had HCV genotype 4. The SVR12 was achieved in 91 (98.9%, 95% CI: [94-99.8]) patients. Only one patient (1.1%, 95% CI: [0.2-5.9]) developed virologic non-response and there were missing data on virologic failure. Overall, non-serious adverse events were observed in 26 (28.5%) patients, and none of them had serious adverse events that led to treatment discontinuation. Approximately 75% of the patients received an inappropriate treatment duration (12 weeks vs. the recommended 8 weeks) and most (n=40, 58%; p<0.022) of the exceedingly long treatments were prescribed by registrars. The GLE/PIB was highly effective and safe in chronic HCV Saudi patients.

Efficacy of Direct-Acting Antiviral in Treatment-Naive Chronic HCV Patients and in Those Previously Treated with Interferon and Ribavirin

Efficacy of Direct-Acting Antiviral in Treatment-Naive Chronic HCV Patients and in Those Previously Treated with Interferon and Ribavirin

Serum omentin-1 is correlated with the severity of liver disease in patients with chronic hepatitis C.

Patients with chronic hepatitis C virus (HCV) infection have increased serum omentin-1. Omentin-1 is an anti-inflammatory adipokine, and higher levels may be a direct effect of HCV infection. Successful elimination of HCV by direct acting antivirals almost normalized circulating levels of various molecules with a role in inflammation. To evaluate the effect of HCV infection on serum omentin-1, serum omentin-1 levels of HCV patients were measured before therapy and at 12 wk after therapy end. Associations of serum omentin-1 with parameters of inflammation and liver function were explored at both time points. Serum omentin-1 levels of patients with and without liver cirrhosis, which was defined by ultrasound or the fibrosis-4 (FIB-4) score, were compared. Serum omentin-1 levels were measured by enzyme-linked immunosorbent assay in 84 chronic HCV patients before therapy and at 12 wk after therapy end where sustained virological response 12 (SVR12) was achieved in all patients. Serum omentin-1 of 14 non-infected controls was measured in parallel. In patients with chronic HCV, serum omentin-1 levels were not related to viral load or viral genotype. HCV patients with liver steatosis and HCV patients with diabetes had serum omentin-1 levels comparable to patients not suffering from these conditions. Serum omentin-1 levels at SVR12 were similar in comparison to pretreatment levels. In addition, serum levels did not differ between HCV-infected patients and non-infected controls. Serum omentin-1 levels did not correlate with leukocyte count or C-reactive protein. Positive correlations of serum omentin-1 with bilirubin and the model for end-stage liver disease score (MELD) were detected before therapy and at SVR12 in the whole cohort. Bilirubin and the MELD score also positively correlated with serum omentin-1 levels in the subgroup of patients with ultrasound diagnosed liver cirrhosis before therapy. At SVR12, serum omentin-1 levels of patients with liver cirrhosis negatively correlated with albumin. Before therapy start, patients with high FIB-4 scores had increased serum omentin-1 in comparison to patients with a low score. Serum omentin-1 levels of patients with liver cirrhosis defined by ultrasound were increased at baseline and at SVR12. Present study showed that liver cirrhosis, but not HCV infection per se, is related to elevated serum omentin-1 levels.

A multicentric and nationwide predictive study role of T cell sub-population in the prevalence and prognosis of cryoglobulinemia among genotype 4 chronic hepatitis C patients.

The infection caused by the hepatitis C virus (HCV) is a significant global health concern. The prevailing genotype of HCV in Egypt is 4a, commonly referred to as GT-4a. A significant proportion exceeding 50% of patients infected with HCV experience extrahepatic manifestations (EHMs), encompassing a diverse range of clinical presentations. These manifestations, including essential mixed cryoglobulinemia (MC), can serve as initial and solitary indicators of the disease. The complete understanding of the pathogenesis of EHM remains unclear, with autoimmune phenomena being recognized as the primary causative factor. In this study, we examined the predictive significance of T-cell subpopulations in relation to the occurrence and prognosis of cryoglobulinemia in HCV patients. A total of 450 CHC genotype four treatment naïve patients were enrolled in this analytic cross-sectional study after thorough clinical, laboratory, and radiological examinations. All patients underwent laboratory investigations, including testing for cryoglobulin antibodies and measurements of CD4 and CD8 levels; two groups were described according to their test results: Group 1 consists of patients who have tested positive for cryoglobulin antibodies and Group 2 consists of patients who have tested negative for cryoglobulin antibodies. The exclusion criteria encompassed individuals with HIV infection or chronic HBV infection. Additionally, pelvi-abdominal ultrasonography was performed. Our study included 450 treatment naïve CHC patients (59% male, mean age 50.8 years). The patients were categorized according to their cryoglobulin antibodys test results into two groups: group A, CHC patients with cryoglobulin antibodies (Abs) negative (364 patients), and group B, CHC patients with cryoglobulin Ab positive (86 patients). Group B demonstrated a higher average age, elevated international normalized ratio, more prolonged duration of HCV infection, lower albumin, higher alanine aminotransferase, higher aspartate aminotransferase, higher bilirubin, lower CD8, lower CD4, and lower CD4:CD8 ratio. In contrast, 27 out of 86 (31.40%) patients in group B had symptoms; 85.8% had purpura and arthralgia, 74.3% had paresthesias, 86.7% had weakness, and 12.2% had non-Hodgkin's lymphoma. The levels of CD4 and CD8 were found to be decreased in chronic HCV patients with MC. T-cell subpopulation serves as a reliable indicator for assessing the prevalence and prognosis of MC in individuals with genotype 4 chronic hepatitis C. However, additional research is needed to further understand the development and spread of various emerging infectious diseases. Nevertheless, it is noteworthy that a critical threshold may exist beyond which EHM reaches a point of no return.