Chronic Hepatitis C Virus Research Articles

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.

Meta-Analysis of the Effectiveness of Sofosbuvir-Based Regimens in Treating Hepatitis C Genotype 3

Hepatitis C virus (HCV) is an RNA virus with seven primary genotypes. It is highly prevalent in Pakistan, especially genotype 3. HCV infection can progress to a chronic state with further complications. Direct-acting antiviral agents (DAAV) were introduced in 2014 as a treatment option, some of which include Sofosbuvir (SOF), Daclatasvir (DCV), Velpatasvir (VEL) and Ribavirin (RV). This meta-analysis was performed to outline the treatment response and efficacy of DAAV in HCV infected patients. We systematically searched PubMed, Web of Science, MEDLINE, and Google Scholar for studies from January 2019 to December 2023. The studies selected met the criteria of patients having chronic HCV infection (genotype 3) and either compensated cirrhosis or decompensated chronic liver disease. Treatment regimens with DAAV specifically were included. The primary outcomes [sustained viral response (SVR), rapid virological response (RVR), end-of-treatment response (ETR)] were highlighted to assess treatment response. The studies proved that the use of direct-acting antiviral agents in different combinations was very effective against HCV infection with minimal side-effects.

Global epidemiology, natural history, maternal-to-child transmission, and treatment with DAA of pregnant women with HCV: a systematic review and meta-analysis

Pregnant women with hepatitis C virus (HCV) infection represent a special population in which treatment access remains limited despite its increasing prevalence. A reliable estimate of the burden and clinical outcomes of pregnant women with HCV infection is crucial for HCV elimination. We aimed to determine the prevalence, maternal-to-child transmission (MTCT), maternal and fetal complication rates, and direct acting antivirals (DAA) treatment outcomes of chronic HCV infection in pregnant women. We searched PubMed, EMBASE, Scopus, Web of Science from inception until March 1, 2024, for studies reporting on the prevalence, MTCT, complications of HCV infection, and treatment outcomes of DAA in pregnant women. Study quality was assessed using the Newcastle-Ottawa Scale. We performed subgroup analysis based on 9 variables to explore the source of heterogeneity in HCV prevalence. The PROSPERO registration number is CRD42024500023. From a total of 311,905,738 pregnant women from 333 studies, the pooled global seroprevalence of HCV in pregnant women was 2.6% (95% CI: 2.0-3.2, I 2=100%) which increased in patients with intravenous drug use and HIV. Majority of the HCV cases in pregnant women (75%) are diagnosed through universal screening. The pooled MTCT rate was 9.0% (95% CI: 6.6-11.7, I 2=79%), which was higher with HIV co-infection (OR: 3.1, 95% CI: 2.1-4.6, I 2=10%), but was not influenced by the mode of delivery or breastfeeding. Pregnant women with HCV infection had more maternal complications, including intrahepatic cholestasis, preterm delivery, and antepartum hemorrhage. Neonates of mothers with HCV had higher odds of being small for gestational age. The pooled rate of sustained virologic response (SVR12) among the 74 women treated with DAA during pregnancy was 98.4%, with no serious adverse events reported. HCV prevalence in pregnant women varies by geographic region and patient population, while MTCT occurs in almost one in ten viremic mothers. The incidence of both maternal and neonatal complications is significantly higher in patients with HCV infection. Limited data suggest that DAA are safe in pregnant women with HCV infection. None.

Characterization and Outcomes of Hepatocellular Carcinoma in Chronic HCV or HBV Monoinfection

Characterization and Outcomes of Hepatocellular Carcinoma in Chronic HCV or HBV Monoinfection

Pilot postal birth cohort HCV Screening in UK primary care.

Birth cohort screening has been implemented in some countries to identify the potentially 'missed population' of undiagnosed chronic Hepatitis C Virus (HCV) in people who may not be found through targeted approaches. To determine uptake of HCV antibody testing using an oral swab screening method, overall yield, whether those testing positive had risk markers in their primary care record, and cost per case detected. Pilot screening study set in general practices in the Southwest, South London and Yorkshire and Humber. Participants consenting were sent an oral swab kit in the post and saliva samples were tested for antibody to HCV. 16,436/98,396 (16.7%) patients consented and were sent an oral swab kit. 12,216 (12.4%) returned a kit, with 31 participants (yield 0.03%) testing positive for HCV antibody. 45% of those positive had a risk marker for HCV on their primary care record. Two (yield 0.002%) were confirmed RNA positive and referred for treatment, both had HCV risk markers. Cost per case detected was £16,000 per HCV antibody and £247,997 per chronic HCV. Wide-scale screening could be delivered and identified people infected with HCV, however most of these individuals could have been detected through lower-cost targeted screening. Yield and cost per case found were substantially worse than model estimates and targeted screening studies. Birth cohort screening should not be rolled out in primary care in England.

Safety and Efficacy of Directly Acting Antivirals (Sofosbuvir & Daclatasvir) in Treatment of Chronic HCV

Abstract Background The introduction of direct-acting antiviral agents, has revolutionized the treatment for chronic HCV with higher cure rates, shorter duration of treatment and more tolerability have been achieved. Aim of the Work The aim of our study is to estimate the efficacy and safety of DAAs in treatment of chronic HCV in patients co-infected with HIV. Patients and Methods This study of previously untreated HCV infection in patients with HCV and HIV co-infection conducted at Abbasia Fever Hospital, from July 2019 to February 2020. Patients included are chronic HCV infection and were receiving antiretroviral therapy for the HIV with a CD4 T-lymphocyte count of 200 cells/mL or greater. Serial measurements of safety parameters, virologic and host immune correlates, and adherence were performed during treatment by combination of daclatasvir 90mg and sofosbuvir 400mg+/- ribavirin 800mg daily for 12 weeks. Results In this study, the rate of a sustained virologic response (SVR) at post-treatment week 12 (SVR 12) were high (29/30, 96.67%). The most common adverse events were fatigue (73.33%), headache (46.67%), and there was a high safety profile on using DAAs. No patient discontinued treatment because of adverse events. No serious adverse events or mortality were reported. In this study, AST & ALT were significantly decreased at end of treatment and 12 weeks after treatment, CD4 count was significantly increased. Otherwise there are no significant changes in both hematological and biochemical laboratory results. Conclusion Combination of daclatasvir and sofosbuvir have showed 96.67% sustained virologic response at 12 weeks after treatment (SVR 12) among HIV/HCV co-infected patients, with a very good safety profile. Moreover, the treated patients showed a significant increase in CD4 count. Accordingly, HIV/HCV co-infected patients should be treated with sofosbuvir and daclatesvir containing regimens.

Assessment of Galectin 3 as a New Biomarker of Liver Fibrosis in Chronic HCV Egyptian Patients and its Correlation to Transient Elastography, FIB-4 Index, and APRI Score

Abstract Background Invasive liver biopsy is the current method for the assessment of liver fibrosis. In search of noninvasive alternatives, galectin-3-binding protein (G3BP) was introduced as a candidate-marker of hepatitis C-related fibrosis based on serum proteomics. Aim of the Work to evaluate serum Galectin-3 as a marker of liver fibrosis and correlate it to the stage of fibrosis assessed by FibroScan, FIB-4 index and APRI score Patients and Methods This was prospective study, was carried out on 30 patients with liver fibrosis/cirrhosis due to chronic HCV inthe Hepatic Virology Unit and the gastroenterology department of Ain Shams university hospitals and 30 health controls with normal, non fibrotic and non cirrhotic, liver, from January 2022 to June 2022 Results There were high significant difference between both groups as regard Serum level of Galectin-3 and APRI score. Conclusion Serum level of galectin-3 was highly expressed in chronic HCV Egyptain patients and positively correlated to FIB-4 index, APRI score and fibroscan.so the serum level of galectin-3 beside other modalities, lab investigations and clinical examination may guide us about the progression to fibrosis and cirrhosis in those patients. In these patients, if galectin-3 levels were found to be high, serum alpha-feto protein level and ultrasonographic examination could be repeated at more frequent intervals. This may also guide us in terms of the treatment plan. Measurement of galectin-3 in sera of large number of patients and follow up may pave the way to pick up early fibrosis and showed its prognostic effect.

Directly Acting Anti-Viral Drugs and Its Metabolic Side Effects in Patients with Chronic HCV

Abstract Background Hepatitis C virus (HCV) is a major cause of chronic liver disease, with an estimated 170 million people infected worldwide. Treatment of hepatitis C virus has traditionally been difficult because of low rates of treatment success and high rates of treatment discontinuation due to side effects. Aim of the Work The aim of this work is to study side effects of directly acting anti HCV drug (DAA) and its progression in metabolism of lipid profile, blood sugar level, and renal function. Patients and Methods This case study had been carried out on 200 subjects presented to Department of Internal Medicine at Kobbri ELkobba hospital inpatient and outpatient clinics between March 2016 and September 2016. Results sustained virological response (12 weeks) after end of the treatment in more than 90% of patients, Liver function parameters including albumin, bilirubin, and prothrombin time and liver enzymes Ast, Alt improved in the majority of patients during and after the end of therapy,but there is significant increase in urea level, serum creatinin and HbA1C. There is significant decrease in LDL and mild increase in TG level. Conclusion Once-daily oral daclatasvir plus sofosbuvir with or without Ribavirin was associated with high rates of sustained virologic response among patients infected with HCV, including chronic cirrhotic patients and relapsers, successful treatment associated with Improvement of liver function parameters in the majority of patients, Increase in urea level, serum creatinin and HbA1C. There is significant decrease in LDL and mild increase in TG level.

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.

Association of Serum M2BPGi Levels with Nutritional Status (Using CONUT score) in Hepatitis C Virus Related Compensated Liver Cirrhosis Patients

Abstract Background Protein-energy malnutrition (PEM), which is one of the most common complications seen in LC patients and associated with high morbidity and mortality. So, predicting the presence of PEM and providing appropriate nutritional support help improve the prognosis of those patients. Mac-2-binding protein glycosylation isomer (M2BPGi) was recently identified as a serum glycobiomarker for liver fibrosis. However, the relationship between M2BPGi and malnutrition in patients with chronic liver disease (CLD) is unclear. Aim of the Work The aim of this study is to evaluate the role of serum M2BPGi levels as a surrogate marker for malnutrition in HCV related cirrhotic patients, correlated with CONUT score as the nutritional status marker. Patients and Methods This is a Cross-sectional - Analytic study that included patients with chronic HCV infection and normal control group selected from patients attending to Hepatology Outpatient Clinics at Ain Shams University Hospital. This study was carried out from 30 patients (child A) attending to Hepatology Outpatient Clinics at Ain Shams University Hospital and 30 healthy individuals as a control. Results The M2BPGi levels increased with CONUT score. The correlation coefficient between M2BPGi and CONUT score was r = 0.315 (p = 0.05), indicating a positive weak correlation between M2BPGi and CONUT score. The cut-off for M2BPGi to predict CONUT low vs. moderate was 1.43 with a sensitivity 93.33% and specificity 100% when AUC =0.9 and CONUT moderate vs. severe was 1.7 with a sensitivity 91.67% and specificity 100% when AUC =0.9. Conclusion We found that there is correlation between M2BPGi and CONUT score and both can be useful as a marker for malnutrition in HCV related cirrhotic patients cut of point

Safety and Efficacy of Directly Acting Antiviral Drugs in Treatment of Chronic HCV Egyptian Patients

Abstract Background The emergence of direct antiviral agents (DAAs), and the campaign done by the National Committee for Control of Viral Hepatitis (NCCVH) have reduced chronic hepatitis C (CHC) prevalence in Egypt. Objectives evaluate the efficacy and safety of used DAAs in affiliated centers. Methods an observational prospective and retrospective study including140 eligible patients from October 2017 till December 2019 and who were either starting treatment or during follow- up for 1 year after the end of therapy (EOT). Patients were divided according to the treatment regimen into Group I (SOF/DAC for 12 weeks), Group II (SOF/DAC/RBV for 12 weeks), Group III (SOF/SIM for 12 weeks), Group IV (SOF/DAC for 24 weeks) and Group V (SOF/DAC/RBV for 24 weeks). Results DAAs were effective in all groups. Adverse effects occurred in 54 patients (38.6%). The most common complications that occurred were ascites (n = 18) followed by jaundice (n = 17) and hepatocellular carcinoma (HCC) (n = 14). Almost all patients (97.1%) in group IV complained of adverse effects compared to other groups with a statistically significant difference (p < 0.001). Hematemesis occurred in one patient among the whole groups and this patient had been in group IV. There was also a significantly higher proportion of ascites (38.2%) in group IV compared to other groups (p < 0.01), however no significant differences between groups regarding HCC and renal impairment (RI) (p-value= 0.316 and 0.758 respectively) were found. 49 naïve patients suffered from side effects, 31 patients were in group IV, followed by group I (n = 7) then group II (n = 6). 5 experienced patients reported side effects. RI was the most reported side effect (12.5%) among interferon (IFN) experienced and SOF/DAC experienced patients and who were treated among group IV and group V. Hepatic encephalopathy was equally reported (12.5%) in IFN experienced and SOF/RBV experienced patients among group IV or group V. Ascites (6.3%) and jaundice (6.3%) also were reported among group IV. No experienced patient has complained of hematemesis or HCC. Conclusion SOF/RBV treatment for 24 weeks had many side effects and should be used with caution.

Impact of Direct Acting Antivirals Therapy on Novel Fibrosis Index for Assessment of Hepatic Fibrosis in Comparison with AST to Platelet Ratio and Fibrosis-4 (FIB-4) Indices in Egyptian Patients with Chronic Hepatitis C Infection in Correlation with Fibroscan

Abstract Background Chronic viral infection causes multiple waves of inflammation and tissue repair which involves deposition of extracellular matrix resulting in scarring or progressive fibrosis over time and ultimately leading to liver cirrhosis. The introduction of DAAs has improved eradication rate of HCV and achievement of SVR. In addition to the high rates of sustained virological response (SVR), hepatic fibrosis may regress, and the risks of complications, such as hepatic failure and portal hypertension are reduced after SVRs, Stage of liver fibrosis in chronic HCV infection is a well-established factor that determines the severity of disease and associated complications. Numerous noninvasive fibrosis scores, imaging techniques and new serum fibrosis markers have been applied to evaluate the phases of liver fibrosis, and have mostly replaced liver biopsy Transient elastography (TE) is the most accurate method with high sensitivity and specificity for advanced fibrosis the aminotransferase (AST)/platelet ratio index (APRI) and the fibrosis-4 (FIB-4) scores are the most widely used in viral hepatitis C patients, particularly in those with significant fibrosis and cirrhosis. Objective The aim of this study is to evaluate Impact of Direct Acting Antivirals therapy on Novel fibrosis index for assessment of hepatic fibrosis in comparison with AST to Platelet ratio and fibrosis-4(FIB-4) indices in Egyptian patients with chronic hepatitis C infection in correlation with fibro scan. Patients and Methods This is a prospective Cohort clinical study performed on 100 Egyptian patients are ≥18 years of age who have chronic infection with hepatitis C who will be treated with combination of IFN-free DAAs (Sofosbuvir & Daclatasvir ± Ribavirin) for 3 months. oral informed consent was taken from all patients included in the study. Results In the current study, there was significant regression of degree of fibrosis after treatment with DAAs in all patients achieving SVR by fibroscan, APR and fib4. novel fibrosis index is reliable and good tool in assessment of liver fibrosis in correlation to fibroscan, APRI and FIB4 especially significant fibrosis with the cut off value in prediction of hepatic fibrosis stage 4 was >3.1 and has sensitivity of 81.5% while the specificity was 74.1%. The positive predictive value was 66% while the negative predictive value was 86.8% Conclusion Novel fibrosis index has been found to be good reliable marker for assessment of liver fibrosis with high accuracy of predicting f4 fibrosis stage. There was significant marked reduction of fibrosis degree by fibroscan and non invasive indices (APRI &FIB4) after treatment with directly acting antiviral in both cirrhotic and non cirrhotic patients regardless the treatment regimen used with improved overall liver function tests especially albumin level, liver enzymes, hemoglobin level and platelet count in patients who reached SVR.

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.

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.

Prevalence of chronic hepatitis C infection in the general population: results from a national survey, Estonia, July to December 2022.

IntroductionObtaining epidemiological data on chronic hepatitis C virus (HCV) infection is essential to monitor progress towards the hepatitis C elimination targets.AimWe aimed to estimate the prevalence of chronic HCV and the seroprevalence of HCV in the adult general population in Estonia.MethodsThis cross-sectional study, conducted between 12 July and 6 December 2022, included anonymised residual sera collected prospectively from patients 18 years and older visiting a general practitioner in all counties of Estonia. Specimens were considered HCV-seropositive if they tested positive for HCV antibodies by enzyme-linked immunoassay, confirmed by line-immunoblot assay. Chronic HCV infection was determined by positive RT-qPCR.ResultsWe tested a total of 4,217 specimens. The estimated HCV seroprevalence and prevalence of chronic HCV infection were 1.8% (95% CI: 1.4-2.2) and 0.8% (95% CI: 0.5-1.1), respectively, with ca 8,100 persons estimated to have chronic HCV infection in the general adult population of Estonia. No statistically significant differences in the prevalence of chronic HCV infection were observed between sexes, counties or age groups, with the highest prevalence rates observed in men (sex ratio: 1.7), Ida-Virumaa County (1.8%; 95% CI: 0.8-3.6) and the age group 40-49 years (1.7%; 95% CI: 0.9-2.9).ConclusionThis study found an overall low prevalence of chronic HCV infection in Estonia. Continued efforts should be made for the targeted screening, diagnosis and treatment of individuals with chronic HCV infection to achieve hepatitis elimination targets.

Hepatitis C virus-induced differential transcriptional traits in host cells after persistent infection elimination by direct-acting antivirals in cell culture.

Chronic hepatitis C virus infection (HCV) causes liver inflammation and fibrosis, leading to the development of severe liver disease, such as cirrhosis or hepatocellular carcinoma (HCC). Approval of direct-acting antiviral drug combinations has revolutionized chronic HCV therapy, with virus eradication in >98% of the treated patients. The efficacy of these treatments is such that it is formally possible for cured patients to carry formerly infected cells that display irreversible transcriptional alterations directly caused by chronic HCV Infection. Combining differential transcriptomes from two different persistent infection models, we observed a major reversion of infection-related transcripts after complete infection elimination. However, a small number of transcripts were abnormally expressed in formerly infected cells. Comparison of the results obtained in proliferating and growth-arrested cell culture models suggest that permanent transcriptional alterations may be established by several mechanisms. Interestingly, some of these alterations were also observed in the liver biopsies of virologically cured patients. Overall, our data suggest a direct and permanent impact of persistent HCV infection on the host cell transcriptome even after virus elimination, possibly contributing to the development of HCC.

Viral Load of HBV and HCV Correlation to Torque Teno Virus (TTV) Co-Infection in Iraqi Patients

Abstract Background: While hepatitis viruses A–E are established, emerging evidence points to additional, novel viral hepatitis agents. The torqueteno virus (TTV) has garnered interest due to its prevalence among patients with hepatitis, suggesting potential hepatotropism. Aim: This study was conducted to detect TTV antigens in individuals infected with chronic hepatitis B (HBV) and/or C (HCV) using molecular diagnostics and to explore any associations between TTV presence and demographic characteristics of the cohort. Materials and Methods: The current study was conducted from the period of September 2022 to April 2023, the investigation involved Iraqi patients aged between 32 and 83 years and diagnosed with HBV and HCV in National Iraqi Central Laboratories, Virology Section. We employed real-time PCR to quantify HBV and HCV viral loads and conventional PCR for TTV DNA detection. Results: TTV DNA was detected in 17 of the 60 patients (28.3%) with chronic HBV and HCV infections. Viral load distribution was found to be similar for both HBV and HCV. An age-related increase in viral load was noted, suggesting a trend where older individuals exhibited higher concentrations. However, no significant variation was observed that could link alterations in HBV and HCV viral loads to TTV status directly. Statistical analysis indicated a positive correlation between age and the likelihood of presenting with the virus, aligning with observed trends in other age-associated chronic conditions, such as Type 2 diabetes mellitus and chronic kidney disease. Conclusion: The presence of TTV in patients with enduring HBV or HCV infection could implicate the virus as a contributing factor to hepatitis pathology. Studies such as this are pivotal for elucidating the age-associated risk profiles for various pathologies and shaping corresponding public health policies and preventative approaches.

Prevalence of chronic hepatitis C infection in the general population: results from a national survey, Romania, 2020 to 2023.

IntroductionA national study from 2006 to 2008 showed a high antibody prevalence of 3.2% against hepatitis C virus (HCV) in Romania, but more recent epidemiological data on hepatitis C prevalence are lacking.AimWe aimed to estimate the current prevalence of HCV antibodies (anti-HCV) and chronic HCV infection in the general adult population in Romania, as a crucial element in monitoring progress towards eliminating hepatitis C.MethodsWe used anonymised leftover sera from a SARS-CoV-2 survey conducted between July and October 2020 (n = 2,100), supplemented with sera collected prospectively between July 2022 and March 2023 (n = 574). These included sera collected from adults visiting laboratories for routine medical check-ups. Sera were tested for anti-HCV and HCV core antigen and classified according to anti-HCV and chronic infection status.ResultsOf the total 2,674 specimens tested, 44 were anti-HCV-positive with a weighted anti-HCV prevalence of 1.4% (95% CI: 1.0-1.9), and 29 were HCV core antigen-positive with a weighted prevalence of chronic infection of 0.9% (95% CI: 0.5-1.2). The prevalence of chronic infection did not differ significantly between men and women. It was higher in persons 60 years and older (2.0%; 95% CI: 1.1-3.0) and in specimens from the North-East region (2.2%; 95% CI: 0.8-3.7).ConclusionAlthough the overall HCV prevalence in Romania is currently low, targeted screening, prevention measures and treatment scale-up are needed especially for the population 60 years and older and in the north-eastern part of the country to achieve the goal of ending the hepatitis C epidemic.

Liver Fibrosis Stages Affect Organic Cation Transporter 1/2 Activities in Hepatitis C Virus-Infected Patients.

This study aims to evaluate the impact of liver fibrosis stages of chronic infection with hepatitis C virus (HCV) on the in vivo activity of organic cation transporters (hepatic OCT1 and renal OCT2) using metformin (MET) as a probe drug. Participants allocated in Group 1 (n = 15, mild to moderate liver fibrosis) or 2 (n = 13, advanced liver fibrosis and cirrhosis) received a single MET 50 mg oral dose before direct-acting antiviral (DAA) drug treatment (Phase 1) and 30 days after achieving sustained virologic response (Phase 2). OCT1/2 activity (MET AUC0-24) was found to be reduced by 25% when comparing the two groups in Phase 2 (ratio 0.75 (0.61-0.93), p < 0.05) but not in Phase 1 (ratio 0.81 (0.66-0.98), p > 0.05). When Phases 1 and 2 were compared, no changes were detected in both Groups 1 (ratio 1.10 (0.97-1.24), p > 0.05) and 2 (ratio 1.03 (0.94-1.12), p > 0.05). So, this study shows a reduction of approximately 25% in the in vivo activity of OCT1/2 in participants with advanced liver fibrosis and cirrhosis after achieving sustained virologic response and highlights that OCT1/2 in vivo activity depends on the liver fibrosis stage of chronic HCV infection.

Pharmacokinetics of Sofosbuvir/Velpatasvir and efficacy of an alternate-day treatment in hemodialysis patients with chronic hepatitis C infection.

Sofosbuvir/Velpatasvir (SOF/VEL) is a combination drug used for chronic hepatitis C (HCV) infection. However, limited information exists regarding the pharmacokinetics of SOF/VEL and its metabolites in hemodialysis patients. We conducted a prospective investigation of the pharmacokinetic parameters of SOF/VEL after a single dose of SOF/VEL (400/100 mg) on days with and without dialysis in 12 Thai hemodialysis patients with chronic HCV infection, who had been undergoing hemodialysis for a duration of 0.5-20 years. Blood samples were collected before dose (0) and 0.5, 1.0, 2.0, 2.5, 3.0, 3.5, 4.0, 5.0, 6.0, 8.0, and 12.0 h after dose. Dialysate samples were also collected before dose (0) and 1.0, 2.0, 3.0, and 4.0 h after dose. Plasma and dialysate samples were quantified for SOF and its metabolite, GS-331007, and VEL concentrations using a fully validated LCMS technique. In addition, a preliminary efficacy study was conducted using the proposed SOF/VEL dose reduction regimen in all patients. No differences in SOF/VEL PK parameters between on- and off-dialysis studies. On the contrary, GS-331007 exhibited a 30% reduction in the area under the plasma concentration-time curve from time 0 to 24 h (AUC0-24h) on dialysis days compared with non-dialysis days (AUC0-24h ratio 0.68 vs. 1.04, respectively). The dialysis clearance of SOF and GS-331007 was 9.35 (8.72-15.11) and 8.89 (8.52-14.07) mL/min, respectively. Subsequently, an alternate-day regimen of SOF/VEL (400/100 mg) was administered for 12 weeks, resulting in an undetectable plasma HCV viral load without side effects. Further clinical studies are warranted to validate the efficacy and safety of our proposed dose reduction regimen.