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Hepatitis C virus (HCV) has emerged as a major global health concern and, if left untreated, can lead to significant liver damage, including cirrhosis, decompensated liver disease, and hepatocellular carcinoma (HCC). Approximately 40% of patients with HCV infection experience extrahepatic manifestations, including renal involvement. HCV-related renal disease is of significant importance among patients with chronic kidney disease (CKD), leading to higher morbidity and mortality. The renal damage due to HCV infection primarily results from cryoglobulinemia and glomerulonephritis, with conditions such as membranoproliferative glomerulonephritis (MPGN) and membranous nephropathy (MN) being most prevalent. Despite advancements in treatment, including the use of directly acting antiviral agents (DAAs), renal complications remain a significant burden in untreated patients. HCV-positive patients on hemodialysis (HD) or those who have undergone kidney transplantation face increased mortality rates compared to their HCV-negative counterparts. Managing HCV infection before kidney transplantation is crucial to mitigate the risk of HCV-related renal complications. Conversely, kidney transplantation from HCV-infected donors is well established, as post-transplant treatment for HCV is safe and effective, potentially reducing mortality and morbidity for patients on transplant waiting lists. This review aims to provide a comprehensive analysis of the renal manifestations of HCV, emphasizing the importance of early diagnosis and treatment to improve patient outcomes.

Introduction: The incidence of sexually transmitted infections (STI) increased in the United States between 2017–2021. There is limited data describing STI co-testing practices and the prevalence of STI co-infections in emergency departments (ED). In this study, we aimed to describe the prevalence of co-testing and co-infection of HIV, hepatitis C virus (HCV), syphilis, gonorrhea, and chlamydia, in a large, academic ED.Methods: This was a single-center, retrospective cross-sectional study of ED patients tested for HIV, HCV, syphilis, gonorrhea or chlamydia between November 27, 2018–May 26, 2019. In 2018, the study institution implemented an ED-based infectious diseases screening program in which any patient being tested for gonorrhea/chlamydia was eligible for opt-out syphilis screening, and any patient 18–64 years who was having blood drawn for any clinical purpose was eligible for opt-out HIV and HCV screening. Weanalyzed data from all ED patients ≥13 years who had undergone STI testing. The outcomes of interest included prevalence of STI testing/co-testing and the prevalence of STI infection/co-infection. We describe data with simple descriptive statistics.Results: During the study period there were 30,767 ED encounters for patients ≥13 years (mean age: 43 ± 14 years, 52% female), and 7,866 (26%) were tested for at least one of HIV, HCV, syphilis, gonorrhea, or chlamydia. We observed the following testing frequencies (and prevalence of infection): HCV, 7,539 (5.0%); HIV, 7,359 (0.9%); gonorrhea, 574 (6.1%); chlamydia, 574 (9.8%); and syphilis, 420 (10.5%). Infectious etiologies with universal testing protocols (HIV and HCV) made up the majority of STI testing. In patients with syphilis, co-infection with chlamydia (21%, 9/44) and HIV (9%, 4/44) was high. In patients with gonorrhea, co-infection with chlamydia (23%, 8/35) and syphilis (9%, 3/35) was high, and in patients with chlamydia, co-infection with syphilis (16%, 9/56) and gonorrhea (14%, 8/56) was high. Patients with HCV had low co-infection proportions (

Hepatitis C virus (HCV) infection is a significant global health concern, prompting the need for effective treatment strategies. This in-depth review critically assesses the landscape of HCV treatment, drawing parallels between traditional interferon/ribavirin therapy historically pivotal in HCV management and herbal approaches rooted in traditional and complementary medicine. Advancements in therapeutic development and enhanced clinical outcomes axis on a comprehensive understanding of the diverse HCV genome, its natural variations, pathogenesis, and the impact of dietary, social, environmental, and economic factors. A thorough analysis was conducted through reputable sources such as Science Direct, PubMed, Scopus, Web of Science, books, and dissertations. This review primarily focuses on the intricate nature of HCV genomes and explores the potential of botanical drugs in both preventing and treating HCV infections.

ABSTRACT An HCV elimination program aims to diagnose more than 90% of Chronic HCV cases. We critically evaluated the performance of a point‐of‐care test (POCT) using an HCV Rapid Antibody Test. PWID from 4 Halfway Houses (HWH) in Singapore were recruited from March 2022 to April 2023. Participants were concurrently screened for HCV via venous blood for anti‐HCV serology and using fingerstick capillary whole blood (FSWB) and oral mucosal transudates (OMT) for POCT, which were interpreted by trained personnel. A blinded study team member independently assessed images of POCTs. Of 207 participants, 37.3% were anti‐HCV positive. Compared to anti‐HCV serology, POCT performance on FSWB and OMT were: Sensitivity 81.8 (73.2–90.4), 74.0 (64.2–83.8), p = 0.014; Specificity 100.0 (100.0–100.0), 98.5 (96.3–100), p = 0.157. Sub‐group analysis of strict 30‐min pre‐test nil‐by‐mouth instruction in 103 subjects reported Sensitivity 77.5 (64.6–90.4), 77.5 (64.6–90.4) and Specificity 100.0 (100.0–100.0) and 98.4 (95.3–100.0). OMT positivity and false‐negative outcomes did not correlate with the sample analytical cutoff index signal distribution of anti‐HCV Serology. Inter‐class correlation between real‐time and imaging readings of POCT for FSWB and OMT at 20 and 40 min were Kappa 0.9666, 0.9674; 0.8803, 0.8940. Proper preparation and patient selection enhance test performance. Differences in oral fluid immunoglobulin secretion, oral pathology, age, and sample collection can affect POCT OMT readings. POCT OMT is promising in serial and self‐testing, complementing its convenience in testing. [ABSTRACT FROM AUTHOR]

ABSTRACT Background & Aims Methods Results Conclusions Glecaprevir/Pibrentasvir (GLE/PIB) has been approved by the European Medicine Agency (EMA) and by the US Food and Drug Administration (US‐FDA) for the treatment of children and adolescents from 3 years of age with chronic hepatitis C virus (CHC) infection. The aim of this study was to confirm the real‐world effectiveness and safety of GLE/PIB in children and adolescents (3 to < 18 years old) with CHC.This prospective, multicentre study involved 11 Italian centres. Children and adolescents (from 3 to < 18 years of age) received a weight‐based dose (up to 300/120 mg) of GLE/PIB once daily for 8 weeks. The effectiveness endpoint was sustained virological response 12 weeks after the end of treatment (SVR12). Safety was assessed by adverse events (AE) and clinical/laboratory data.Sixty‐one patients (median age 12 years, interquartile range 5) were enrolled and treated between June 2020 and October 2023. Genotype distribution was as follows: 24/61 genotype 1 (39.4%), 13/61 genotype 2 (21.3%), 18/61 genotype 3 (29.5%) and 6/61 genotype 4 (9.8%). Sixty (98.4%) patients completed treatment and follow‐up. SVR12 was obtained by 60/61 patients (98.4%). One patient died because of an oncological illness while on treatment. AE occurred in 13.1% of the patients, were mild and no patients prematurely stopped treatment.This study confirmed the real‐life effectiveness and safety of the 8‐week therapy with GLE/PIB for treatment of CHC in children and adolescents. [ABSTRACT FROM AUTHOR]

Sample preparation presents a major challenge in point-of-care (POC) diagnostic assays, including ones requiring whole blood as the starting specimen. This study presents an integrated sample preparation device -- which we call PRECISE -- that performs both plasma separation and nucleic acid extraction, enabling streamlined sample preparation from whole blood requiring only a commercially available blood collection tool and a syringe, and no other external equipment or electricity. Plasma separation is performed using a dual-membrane filter (which filters out blood components while limiting membrane clogging) integrated into the cartridge, and nucleic acid extraction is performed by users moving magnets (to mix the samples, and along a guided track). The plasma filtration demonstrated recovery on par with lab-based centrifugation, and the extraction module showed performance similar to benchtop-based magnetic bead extraction. A sample-to-result demonstration on 50 μL of whole blood spiked with virions of hepatitis C virus (HCV), operating the PRECISE cartridge in 16 minutes followed by benchtop PCR, showed a limit of detection (~6770 IU mL-1) on the order of the minimal requirements of target product profile for POC HCV detection. Future work on the PRECISE cartridge, building on POC accessibility and fast sample preparation demonstrated in this work, may enable detection of bloodborne pathogens from whole-blood specimens collected at the POC. [ABSTRACT FROM AUTHOR]

Background Hepatitis C virus (HCV) and hepatitis B virus (HBV) cause chronic hepatitis with important clinical differences. HCV causes hepatic steatosis and insulin resistance, while HBV confers increased risk of liver cancer. We hypothesized these differences may be due to virus-specific effects on mitochondrial function. Methods Seahorse technology was used to investigate effects of virus infection on mitochondrial function. Cell-based assays were used to measure mitochondrial membrane potential and quantify pyruvate and lactate. Mass spectrometry was performed on mitochondria isolated from HBV-expressing, HCV-infected, and control cells cultured with isotope-labelled amino acids, to identify proteins with different abundance. Altered expression of key mitochondrial proteins was confirmed by real-time polymerase chain reaction (PCR) and western blot. Results Reduced mitochondrial function and ATP production were observed with HCV infection and HBV expression. HCV impaired glycolysis and fatty acid oxidation, promoting lipid accumulation whereas HBV caused lactate accumulation. In HBV-expressing cells enrichment of pyruvate dehydrogenase kinase inhibited pyruvate to acetyl-CoA conversion thereby reducing its availability for mitochondrial oxidative phosphorylation. Conclusions HBV and HCV impair mitochondrial function. HCV infection reduces lipid oxidation causing its accumulation and fatty liver disease. HBV infection affects pyruvate processing causing lactate accumulation, cellular stress, and increased risk of liver disease and cancer. [ABSTRACT FROM AUTHOR]

ABSTRACT Despite available curative treatments, global rates of hepatitis C virus (HCV) infection persist with significant burden in low‐ and middle‐income countries (LMICs). Long‐acting (LA) antiviral products are in development. This study explored the challenges and opportunities in LA‐HCV treatment across three LMICs: Egypt, Ethiopia and India. The survey focused on understanding barriers and facilitators to treatment, with emphasis on LA treatment preferences. Four‐hundred respondents completed a survey including demographics, HCV treatment history and preferences for injections, implants and microarray patches (MAPs) compared to pills. Overall, 78% of respondents were willing to receive injections, 43% were willing to receive implants and 55% were willing to receive MAPs. Marked heterogeneity in acceptability of non‐oral treatments was observed. Among respondents who had not previously received HCV treatment, 94%, 43%, and 75% were willing to receive injections, implants, or MAPs, respectively. In contrast, among those already cured by oral HCV treatment, 61%, 40% and 43% were willing to receive injections, implants or MAPs. Other characteristics associated with willingness to receive an injection included urban residence, younger age, male sex, higher education level and taking pills for any reason (all results p < 0.001). The most common concern for all LA modalities was lack of effectiveness. Prior experience with injection or implant increased willingness to receive any LA modality (p < 0.001). Coupled with a point‐of‐care HCV diagnostic test, availability of and willingness to receive HCV treatment delivered by a LA formulation could simplify and expand treatment access in LMICs and contribute towards global HCV elimination goals. [ABSTRACT FROM AUTHOR]

Background: The transplantation of human organs, and some human tissues, is often the only life-saving therapy available for serious and life-threatening congenital, inherited or acquired diseases. However, it is associated with a risk of transmission of communicable diseases from donor to recipient. It is imperative to understand the characteristics of the donor population (including both potential and actual donors) to inform policies that protect recipient safety. The Tissue and Organ Donor Epidemiology Study (TODES) was a pilot project designed to identify and collect standardized information on deceased persons referred for organ, tissue and/or eye donation, and to estimate (to the extent possible) infectious disease prevalence and incidence of human immunodeficiency virus (HIV), hepatitis B virus (HBV) and hepatitis C virus (HCV) in this population. TODES is summarized here to shed light on addressable limitations on accessing data needed for transplant recipient safety. Limitations, future research needs and potential pathways to solve the remaining data needs are explored. Methods: Retrospective data for all deceased donors during a 5-year period from 2009 to 2013 were obtained from participating organ procurement organizations (OPOs), tissue establishments and eye banks. These decedent data were used to ascertain whether the available real-world data (RWD) could be used to inform donor screening and testing policy. Results: The TODES database contains 291 848 records received from nine OPOs and 42 451 records received from four eye banks. Data were analysed from deceased donors with at least one organ, tissue or ocular tissue recovered with the intent to transplant. Results for potential donors were not analysed. Available RWD at the time of the TODES study were not fit-for-purpose to help characterize the organ, tissue and eye donor populations and/or to inform donor screening policy. Conclusions: Recent advances in electronic data collection systems make it more realistic to now collect fit-for-purpose RWD that address the research needed to improve transplant safety. [ABSTRACT FROM AUTHOR]

ABSTRACT Background Methods and Results Conclusions Hepatitis C virus genotype 5 (HCV‐GT‐5) is found mainly in South Africa. In our area in central France, the prevalence of HCV‐GT‐5 is 14%.Here we evaluated sustained virological response at week 12 post‐treatment (SVR12) in 147 HCV‐GT‐5 patients from 14 French university hospitals (2014–2021) treated with direct‐acting antivirals (DAA) in real‐life. Patients had mainly received sofosbuvir/ledipasvir ± ribavirin, sofosbuvir/velpatasvir, and glecaprevir/pibrentasvir. Overall SVR12 was 98% (144/147). Two patients experienced relapse: one was successfully retreated with the same DAAs (sofosbuvir/ledipasvir) plus ribavirin, and the other refused further DAA treatment. One patient with virological failure (sofosbuvir/velpatasvir) had received a second treatment (sofosbuvir/velpatasvir/voxilaprevir) and progressed to cure.HCV‐GT‐5 patients treated with a DAA regimen had a 99% SVR12 in intention‐to‐treat (including initial therapy and retreatment) and 100% SVR12 per protocol. Sofosbuvir/ledipasvir, sofosbuvir/velpatasvir, and glecaprevir/pibrentasvir show very good efficacy in real‐world HCV‐GT‐5 patients. [ABSTRACT FROM AUTHOR]

The Hepatitis C virus (HCV) is a blood-transmitted virus responsible for persistent inflammation, presenting a substantial worldwide health challenge. HCV, characterized by a positive-stranded ribonucleic acid genome, possesses an intricate genetic makeup encoding both structural and non-structural proteins, crucial for sustaining its life cycle. The Direct Acting Antivirals have revolutionized the treatment landscape of HCV promoting higher Sustained Virological Response rates. Despite significant advancements in treatment, no vaccines are currently available against HCV. The development of effective HCV vaccines becomes challenging as the genetic diversity of HCV virus and its complex nature of the immune response required for protection. In this work, the immunoinformatics methods were utilized to develop a multiple-epitope-based vaccine towards an effective treatment against the viral HCV polyprotein. The vaccine was constructed by T-cell epitopes extracted from the viral polyprotein of HCV genotypes 1a and 1b. The vaccine was highly antigenic, non-toxic, and non-allergenic. Effective binding of the designed vaccine construct was studied by forming complexes with the human immune Toll-Like Receptors; TLR3 and TLR8. The MD simulation of these receptor-vaccine complexes were performed for 50ns and the immunological simulation of modeled vaccine in presence of receptors for 365 days timeline validated the stability of the constructed vaccine. The in-silico vaccine construct developed from this work might be beneficial as prophylactic measures against the HCV variants, if explored further in in vivo and in vitro methods. Consequently, this research outcome is presumed to have implications in the development of safer and more efficient vaccines for lethal diseases. [ABSTRACT FROM AUTHOR]

Background: Eliminating hepatitis C virus (HCV) infections is a goal set by the World Health Organization. This has become possible with the introduction of highly effective and safe direct-acting antivirals (DAA) but limitations remain due to undiagnosed HCV infections and loss of patients from the cascade of care at various stages, including those lost to follow-up (LTFU) before the assessment of the effectiveness of the therapy. The aim of our study was to determine the extent of this loss and to establish the characteristics of patients experiencing it. Methods: Patients with chronic HCV infection from the Polish retrospective multicenter EpiTer-2 database who were treated with DAA therapies between 2015 and 2023 were included in the study. Results: In the study population of 18,968 patients, 106 had died by the end of the 12-week post-treatment follow-up period, and 509 patients did not report for evaluation of therapy effectiveness while alive and were considered LTFU. Among patients with available assessment of sustained virological response (SVR), the effectiveness of therapy was 97.5%. A significantly higher percentage of men (p<0.0001) and a lower median age (p=0.0001) were documented in LTFU compared to the group with available SVR assessment. In LTFU patients, comorbidities such as alcohol (p<0.0001) and drug addiction (p=0.0005), depression (p=0.0449) or other mental disorders (p<0.0001), and co-infection with human immunodeficiency virus (HIV) (p<0.0001) were significantly more common as compared to those with SVR assessment. They were also significantly more often infected with genotype (GT) 3, less likely to be treatment-experienced and more likely to discontinue DAA therapy. Conclusions: In a real-world population of nearly 19,000 HCV-infected patients, we documented a 2.7% loss to follow-up rate. Independent predictors of this phenomenon were male gender, GT3 infection, HIV co-infection, alcohol addiction, mental illnesses, lack of prior antiviral treatment and discontinuation of DAA therapy. [ABSTRACT FROM AUTHOR]

Objectives: Viral hepatitis caused by hepatitis B virus (HBV) and hepatitis C virus (HCV) infections remain a major global public health challenge, particularly in low- and middle-income countries. It is crucial to utilize a pointof-care (POC) testing platform that is sensitive, specific, rapid, and user-friendly for screening and diagnosis of the two infections. Here, a novel molecular diagnostic assay, integrating multiplex loop-mediated isothermal amplification with a gold nanoparticle-based lateral flow biosensor (mLAMP-AuNPs-LFB) was developed and applied for one-step, visual, rapid, sensitive, and specific identification of HBV and HCV. Methods: The AuNPs-based LFB was devised and constructed for the simultaneous detection of HBV and HCV. The HBV-LAMP and HCV-LAMP primers were designed against the S and 5′-untranslated region (5′-UTR) genes from the major HBV genotypes (B, C, D, B/C recombinant, and C/D recombinant) and HCV subtypes (1b, 2a, 3a, 3b, and 6a) in China, respectively. Our assay conditions, both multiplex-LAMP amplification temperature and time were optimized. The sensitivity and specificity of our assay were tested, and the feasibility of our assay was verified through clinical samples. Results: The AuNPs-based LFB used here was successfully manufactured according to our devise manual. The two unique independent primer pairs were successfully designed based on the S and 5′-UTR genes, respectively. The optimal mLAMP-AuNPs-LFB detection process, involving rapid nucleic acid isolation (10 min), mLAMP (63 °C for 35 min), and visual AuNPs-LFB interpretation (less than 2 min), could be completed within 50 min. The HBV&HCV-mLAMP-AuNPs-LFB assay can detect the target genes (HBV-S and HCV-5′-UTR) with as low as 20 copies of plasmid template per test, and the specificity was 100% for the experimental pathogens. Conclusions: The preliminary results manifested that our mLAMP-AuNPs-LFB assay is a valuable tool and has tremendous potential as a POC testing approach for HBV and HCV identification, especially in undeveloped regions. [ABSTRACT FROM AUTHOR]

Background: Healthcare workers (HCWs) are at higher risk of contracting hepatitis B virus (HBV) and hepatitis C virus (HCV) infections. Currently, there is no estimate of pooled data on the prevalence of HBV and HCV infections among HCWs in the country. Thus, this review aimed to determine the pooled prevalence of hepatitis B and C infections among HCWs in Ethiopia. Materials and methods: A comprehensive literature search was conducted using electronic databases, including PubMed, Cochrane Library, Science Direct, Hinari, and African Journals Online to identify pertinent articles from the inception to April 2024. The protocol has been registered in the International Prospective Register of Systematic Reviews (PROSPERO; CRD42024527940) and conducted per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Data were extracted independently by two authors and analyzed using STATA version 11 software. A random-effect model and Egger's test were computed to estimate the pooled prevalence and assess publication bias, respectively. Results: A total of 18 studies involving4,948 healthcare workers were included in this review to estimate the pooled prevalence of HBV and HCV infections among HCWs in Ethiopia. The overall prevalence of HBV was 5.93% (95% CI; 3.22–8.63). The sub-group analysis showed that the prevalence of HBV among medical waste handlers and health professionals was8.6% (95% CI; 3.01–14.13) and 4.98% (95% CI; 1.85–8.11), respectively. The combined prevalence of HCV was 1.12% (95% CI; -4.19–6.43). In the sub-group analysis, the prevalence of HCV among medical waste handlers and health professionals was1.44% (95% CI; -5.28–8.18) and 0.59% (95% CI; -8.09–9.27), respectively. Conclusion: In this review, we found a higher (5.93%) and moderate (1.12%) prevalence of HBV and HCV infections, respectively among Ethiopian HCWs. Therefore, to reduce the infectious burden of HBV and HCV among HCWs; there is a need to strict adherence to infection prevention and control measures. In addition, adequate HBV vaccination coverage for HCWs is mandatory to reduce the burden of HBV infection in the country. [ABSTRACT FROM AUTHOR]

ABSTRACT Chronic hepatitis C virus (HCV) infection can be associated with neuropsychiatric symptoms like fatigue and cognitive impairment, independent of the liver status. The present study aims to assess changes in the pattern and extent of neuropsychological symptoms after successful treatment with interferon (IFN)‐based and IFN‐free therapy. HCV‐infected patients who underwent neuropsychological assessment in previous studies were invited to a follow‐up examination. Patients were grouped according to the treatment status: Sustained virological response (SVR) after IFN treatment (IFN SVR, n = 14) or after therapy with direct acting antivirals (DAA SVR, n = 28) or ongoing HCV infection (HCV RNA+, n = 11). A group of 33 healthy controls served as reference. Patients completed self‐report questionnaires addressing health‐related quality of life (HRQoL), mood and sleep quality and a neuropsychological test battery including tests of memory and attention (Luria's list of words, PSE test, cancelling “d” test, Word–Figure–Memory Test and computer‐based test battery for the assessment of attention [TAP]). At baseline, all three patient groups had worse fatigue, depression, anxiety and HRQoL scores compared to healthy controls. Longitudinal analysis revealed that fatigue and mood slightly improved in all patient groups over time, while HRQoL improved in SVR patients but not in HCV RNA+ patients. Memory test results improved significantly in all patient groups, irrespective of their virological status. In contrast, the attention test results showed no clear change from baseline to follow‐up. Our data can be considered as a hint that HCV eradication—independent of therapy regimen—does not substantially ameliorate neuropsychiatric symptoms in HCV‐afflicted patients. [ABSTRACT FROM AUTHOR]

Background: The high rates of the sustained virologic response 12 weeks after treatment (SVR12) in real world settings provoked the adoption of shortened courses of the costly direct-acting antivirals (DAAs) regimens. This study provides, to our knowledge, the first systematic review and meta-analysis for the efficacy of the shortened 8-week course of sofosbuvir (SOF) plus daclatasvir (DCV), the most accessible DAAs in the low-middle income countries (LMICs). Methods: We performed a proportion meta-analysis to determine a reliable rate of SVR12 by pooling all studies that evaluated the results of the 8-week regimen of DCV + SOF. In addition, we applied sensitivity analyses using two imputation paradigms: a conservative approach, and a pragmatic approach to avoid overestimating the efficacy of the 8-week regimen in studies that followed a response-guided treatment (RGT) approach. Results: Six studies with a total of 159 patients were included. The pooled SVR12 rate ranged from 91 to 97% in the included scenarios. The pragmatic scenario showed that the pooled SVR12 was 97% (95% confidence interval (CI) 91%; 100%) with lower variability as assessed by the prediction interval. The conservative approach revealed an SVR12 of 93% (95% CI 84%; 95%). Conclusion: The 8-week course of 60 mg DCV with SOF provided a comparable SVR12 to the standard 12-week regimen in treatment-naïve, non-HIV co-infected patients with a minimum estimated efficacy of 90%. [ABSTRACT FROM AUTHOR]

An effective vaccine against hepatitis C virus (HCV) should elicit both humoral and cellular immune responses. Previously, we characterized a bivalent vaccine candidate against hepatitis B (HBV) and HCV using chimeric HBV-HCV virus-like particles (VLP), in which the highly conserved epitope of HCV E2 glycoprotein (residues 412–425) was inserted into the hydrophilic loop of HBV small surface antigen (sHBsAg). While sHBsAg_412–425 elicited cross-neutralizing antibodies, it did not trigger a T-cell response against HCV. Thus, this study aimed to develop a vaccine candidate engaging both arms of adaptive immune response, potentially offering stronger protection against HCV. We evaluated the immunogenicity of minicircle (MC) DNA vaccines encoding sHBsAg_412–425 and HCV nonstructural (NS) proteins in BALB/c mice. Co-administration of sHBsAg_412–425 and NS induced a potent T-cell response, especially against NS3 and high titers of antibodies specific to HCV E2. Additionally, these antibodies recognized native HCV envelope glycoprotein heterodimers (E1E2) across multiple HCV genotypes and showed binding profiles to E1E2 alanine mutants comparable to the broadly neutralizing AP33 antibody. Overall, the findings demonstrate that MC DNA vaccine incorporating both sHBsAg_412–425 and HCV NS protein sequences induces robust, T-cell and AP33-like antibody responses, highlighting its potential as pan-genotypic prophylactic vaccine against HCV. [ABSTRACT FROM AUTHOR]

Aim Methods Results Conclusion In Japan, despite low nationwide hepatitis C (HCV) incidence, new infections among people who inject drugs (PWID) and men who have sex with men (MSM) hinder HCV elimination. We explored HCV transmission dynamics and screened HCV recombination within these populations.This cross‐sectional study recruited HCV‐infected patients from Osaka National Hospital, Osaka, Japan, from January 2010 to September 2023. Data from questionnaires and medical records were analyzed. Serum samples collected before anti‐HCV treatment underwent HCV RNA extraction, and sequencing of full core (576 bp) and NS5B (267 bp) regions using the Sanger method. Genotype distribution was determined by phylogenetic analysis, and recombinant screening was conducted.A total of 115 patients were categorized into non‐MSM PWID (31), MSM PWID (15), MSM non‐PWID (25), and non‐MSM non‐PWID (44). Positive amplification rates were 99.1% (114/115) for the full‐core region, and 96.5% (111/115) for NS5B. No intergenotypic recombination was detected. The predominant genotype in non‐MSM PWID was 2a (58%), whereas genotype 1b was most common in MSM PWID, MSM non‐PWID, and non‐MSM non‐PWID groups (79%, 64%, and 68%, respectively). Nucleotide sequence similarity of 94.75%–100% was found in HCV strains from MSM PWID and MSM non‐PWID in both full‐core and NS5B regions, whereas strains from non‐MSM PWID and non‐MSM non‐PWID were distinct.The findings suggest that the transmission route in PWID is determined by MSM status, whereas MSM groups showed the same transmission route regardless of PWID. HCV control measures should be focused not only on PWID, but also on MSM to achieve HCV elimination in Japan. [ABSTRACT FROM AUTHOR]

Background: Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that is responsible for Chikungunya fever, which is characterized by fever, rash, and debilitating polyarthralgia. Since its re-emergence in 2004, CHIKV has continued to spread to new regions and become a severe health threat to global public. Development of safe and single dose vaccines that provide durable protection is desirable to control the spread of virus. The recombinant adeno-associated virus (rAAV) vectors represent promising vaccine platform to provide prolonged protection with a single-dose immunization. In this study, we developed a rAAV capsid serotype 1 vector based CHIKV vaccine and evaluated its protection effect against CHIKV challenge. Methodology: The recombinant AAV1 encoding the full-length structural proteins of CHIKV (named as rAAV1-CHIKV-SP) was generated in vitro by transfecting the plasmids of AAV helper-free system into HEK-293T cells. The safety and immunogenicity of rAAV1-CHIKV-SP were tested in 4-week-old C57BL/6 mice. The antibody responses of the mice receiving prime-boost or single-dose immunization of the vaccine were determined by ELISA and plaque reduction neutralizing test. The immunized mice were challenged with CHIKV to evaluate the protection effect of the vaccine. Conclusions: The rAAV1-CHIKV-SP showed remarkable safety and immunogenicity in C57BL/6 mice. A single dose intramuscular injection of rAAV1-CHIKV-SP elicited high level and long-lasting antibody responses, and conferred complete protection against a heterologous CHIKV strain challenge. These results suggest rAAV1-CHIKV-SP represents a promising vaccine candidate against different CHIKV clades with a simplified immunization strategy. Author summary: Recently, a live attenuated CHIKV was approved as the first vaccine to combat the virus infection. Despite the general safety of this vaccine, several severe chikungunya-like adverse reactions have been reported, and the long-term safety should be assessed after marketing, highlighting the urgent need to develop more safe and effective vaccines against CHIVK. The rAAV vectored vaccines against several viruses such as SARS-CoV-2, HIV, HCV and Nipah virus have been developed. Here, we constructed a rAAV capsid serotype 1 based CHIKV vaccine that encoded the full-length structural proteins of CHIKV (rAAV1-CHIKV-SP), and evaluated the safety, immunogenicity and protection effect of the vaccine. The results demonstrated that a single dose immunization of the vaccine induced high level and long-lasting CHIKV-specific antibodies and neutralizing antibodies, and completely protected against CHIKV challenge in C57BL/6 mice. Our study suggested that the rAAV1-CHIKV-SP represents a promising vaccine candidate to prevent CHIKV infection. [ABSTRACT FROM AUTHOR]

Background and Objectives: In 2016, France allowed men who have sex with men (MSM) to donate blood if they had not had sex with men in the previous 12 months. In April 2020, this restriction was relaxed to 4 months due to the lack of negative impact observed on blood safety. This study assesses the impact of reducing this deferral period on epidemiological surveillance indicators. Materials and Methods: This study compares infection surveillance indicators between two 30‐month periods before (P1) and after (P2) this second deferral change. Results: Overall, 79 donations tested positive for human immunodeficiency virus (HIV) (49 in P1 and 30 in P2), 322 for hepatitis C virus (HCV) (185 and 137), 622 for hepatitis B virus (HBV) (355 and 267) and 1684 for syphilis (799 and 885). Positive donation rates decreased between P1 and P2, except for syphilis: HIV (0.07/10,000 donations vs. 0.04; p > 0.5), HCV (0.25 vs. 0.20; p < 0.05), HBV (0.49 vs. 0.39; p < 0.01) and syphilis (1.10 vs. 1.29; p < 0.001). For all three viruses, residual risks of transmission by transfusion did not increase: HIV (1/7,800,000 donations vs. 1/10,500,000), HCV (1/25,200,000 vs. 1/47,300,000) and HBV (1/6,400,000 vs. 1/6,000,000). Conclusion: Reducing the deferral period for MSM in April 2020 did not negatively impact residual risks, which remained very low, or the rate of positive donations, except for syphilis, which requires careful monitoring. To ensure equal access to blood donation, MSM have been allowed to donate blood under the same conditions as other donors since March 2022 (i.e., no more than one sexual partner in the last 4 months). [ABSTRACT FROM AUTHOR]

Hepatitis C virus (HCV) is a pathogen that causes cirrhosis and hepatocellular carcinoma through chronic hepatitis C. This study focused on the anti-HCV activity of a 70% ethanol extract of Kirengeshoma koreana Nakai (KKE) and its bioactive chemical constituent(s). The KKE and its n-butanol (n-BuOH) fraction induced a significant reduction in HCV RNA levels without inducing cytotoxicity. A high-performance liquid chromatography–mass spectrometry (HPLC-MS) analysis revealed the presence of roseoside in the n-butanol fraction of the KKE, which inhibited HCV RNA replication in a concentration- and time-dependent manner without exerting cytotoxicity. Consistent with in silico molecular docking analysis data, roseoside targets and inhibits HCV NS5A/B replicase. Collectively, our findings demonstrate that roseoside is a chemical constituent in KKE that interferes with HCV replication by targeting NS5A/B replicase. [ABSTRACT FROM AUTHOR]

Background: Acute kidney injury (AKI) is one of the common complications of liver cirrhosis. It occurs in nearly 20% of patients with cirrhosis who are hospitalized. Prior literature demonstrated that the AKI occurrence in patients with cirrhosis is independently associated with higher mortality. However, there are data assessing predictors and outcomes of AKI resolution in hospitalized patients with cirrhosis. Therefore, the aim of the current study was to identify clinical predictors of AKI resolution among inpatients with cirrhosis that are easily obtained and to evaluate the clinical outcomes of those patients. Methods: The current study is a retrospective cohort of patients with cirrhosis who were hospitalized and had AKI between 2012 and 2020 at a tertiary referral center. Patients included in this study were identified using the International Classification of Diseases 9 codes and then they were manually verified by two independent chart reviewers. AKI was classified according to the AKI Network (AKIN) serum creatinine (Cr) criteria, with AKIN resolution defined as AKIN stage 1 or lower at the time of discharge, while unresolved AKIN was defined as AKIN stage 2 or 3 at the time of discharge. For univariate analysis, Fisher's exact and the two-sample T-test were utilized. For multivariable analysis, stepwise logistic regression was performed to evaluate variables associated with AKIN resolution. Survival curves were estimated and compared using the Kaplan–Meier method and Log-Rank Test. A p-value cutoff of 0.05 was used for statistical significance. Results: Between 2012 and 2020, there were 140 patients who were included (59% males). The majority of patients had viral hepatitis (54%) as the cirrhosis etiology with 80% of them having hepatitis C virus. Most patients had fluid-responsive AKI (49%), and stage 1 AKIN (69%). In terms of outcomes, the majority of patients (117 patients; 84%) had AKIN resolution at the time of discharge. In the multivariable analysis, after adjusting for clinical meaningful variables, our study shows that higher albumin value at the time of admission (adjusted Odds Ratio "aOR" = 3.28; p = 0.01) and non-metabolic dysfunction-associated steatotic liver disease (non-MASLD) cirrhosis (aOR = 9.43; p < 0.01) were variables associated with higher odds of AKIN resolution at the time of discharge. Conversely, we show that a higher Cr value at the time of admission was associated with lower odds of AKIN resolution at the time of discharge (aOR = 0.31; p < 0.01). When evaluating mortality, patients with unresolved AKIN at the time of discharge had higher rates of in-hospital mortality (p < 0.01) compared to those with resolved AKIN. Survival curve analyses using the Kaplan–Meier method indicated that patients with resolved AKIN experienced higher 90-day survival rates (p < 0.01). Additionally, those with resolved AKIN demonstrated greater transplant-free survival compared to patients with unresolved AKIN at both the 1-year (p = 0.04) and 3-year (p < 0.01) follow-ups. Conclusions: When evaluating clinical predictors of AKIN resolution in admitted patients with cirrhosis, our study showed that a higher admission albumin value and non-MASLD etiology of cirrhosis were associated with higher odds of AKIN resolution at the time of discharge. Conversely, a higher admission Cr value was associated with lower odds of AKIN resolution at the time of discharge. We also demonstrate that AKIN resolution during index admission was associated with improved short- and long-term transplant-free survival (up to 3 years). Our findings warrant external validation in larger cohorts to further evaluate the impact of inpatient AKI resolution on cirrhosis outcomes. Our findings can help clinicians predict AKIN outcomes and encourage more aggressive management of AKI, especially in high-risk patients, which can improve mortality. [ABSTRACT FROM AUTHOR]

The article provides a comprehensive overview of various synthetic approaches to 1,2,3-triazoles, focusing on up-to-date procedures from 2000 to 2023. The significance of 1,2,3-triazoles in pharmaceuticals and their diverse applications in different fields is highlighted. The text covers classical methods as well as modern approaches, including Cu-catalyzed cycloaddition reactions and metal-free methods, under microwave, ultrasound, and continuous flow conditions. The review emphasizes the importance of click chemistry in simplifying and enhancing the synthesis of 1,2,3-triazoles for future molecular diversity explorations. [Extracted from the article]

Introduction: Emergency medical services (EMS) systems are piloting interventions to respond to overdoses with additional services such as leave‐behind naloxone and medication for opioid use disorder, but little is known about the perspectives of people who use drugs (PWUD) on these interventions being delivered by EMS during an overdose response. Methods: The Consolidated Framework for Implementation Research guided the development of data collection tools, the analytic strategy and the organisation of results. A community engaged method was used which included both academically trained researchers and community trained researchers who are also PWUD. This study used semi‐structured interviews to gather data from 13 PWUD in King County, Washington in June 2022. Data were analysed using thematic analysis. Results: The people interviewed for this study viewed EMS distribution of leave‐behind naloxone and field‐based buprenorphine favourably. They viewed EMS facilitation of hepatitis C virus and HIV testing in the field less favourably and were concerned about stigmas associated with those results. Additional themes emerged regarding: the need for different approaches to post‐overdose care; the need for new services, including post‐overdose trauma counselling and an alternative destination to the emergency department; and the harms of law enforcement presence at overdose responses. Discussion and Conclusions: This study found strong support for leave‐behind naloxone and field‐initiated buprenorphine. Further training for EMS should include trauma‐informed care and strategies to address burnout and increase compassion. Alternatives to the emergency department as a post‐overdose destination are needed. These strategies should be considered by jurisdictions revising overdose response protocols. [ABSTRACT FROM AUTHOR]

Aim: It is not uncommon to encounter outpatients in the hepatology department with harmful alcohol habits. When treating such chronic liver disease (CLD) patients, an adequate intervention method for harm reduction of alcohol use, such as brief intervention (BI) or BI and nalmefene, should be considered. This study aimed to elucidate the clinical effectiveness of BI for CLD patients affected by harmful alcohol use. Methods: From June 2021 to 2023, 123 Japanese CLD outpatients (hepatitis B virus : hepatitis C virus : alcoholic liver disease : others = 32:18:42:31) with an Alcohol Use Disorders Identification Test (AUDIT) score of ≥8 at the initial interview and a repeat interview with AUDIT 9 months later were enrolled. Clinical features related to patient behavior following the initial AUDIT interview were retrospectively evaluated, and compared between patients without and with BI treatment. Results: For the non‐BI and BI groups, baseline AUDIT score (median 10 [interquartile range (IQR) 9–13] vs. 12 [IQR 10–17], p = 0.016) and relative change in AUDIT score (median 0 [IQR −3 to 2] vs. −3 [IQR −7 to 0], p < 0.01) showed significant differences, whereas there was no significant difference between the groups for AUDIT score at the time of the second interview (p = 0.156). Following BI, significant improvements were observed for items 1, 2, 3, 4, 5, 8, and 10 of AUDIT (each p < 0.05). Conclusion: Patients with an alcohol use disorder as well as those with alcohol dependency who received BI showed a significant decline in AUDIT score, although the score of the follow‐up AUDIT indicated continued alcohol use disorder. In addition to BI, medication with nalmefene should be considered, based on individual factors. [ABSTRACT FROM AUTHOR]

Background: Incidence of hepatocellular carcinoma (HCC) had been increasing steadily among older Americans but plateaued in 2015–2017. Chronic infection with hepatitis B virus (HBV) or hepatitis C virus (HCV) are important causes of HCC. The impact of improved treatments for these infections on recent trends in HCC incidence is unclear. Aims: To examine the relationship between use of antiviral therapy for chronic viral hepatis and HCC incidence in older Americans. Methods: We used 2007–2017 data from the Surveillance, Epidemiology, and End Results—Medicare database to estimate age-standardized incidence rates and average annual percent changes (AAPCs) for viral hepatitis-attributable HCC among individuals ≥66 years. We analyzed data from Medicare Part D to determine the frequency of HBV and HCV treatment utilization in this population. Results: Overall HCC incidence increased 10.5%, from 22.2/100,000 in 2007 to 24.5/100,000 in 2017 (AAPC, 1.3%). During that time, HBV-attributable HCC rates decreased from 2.5 to 2.0/100,000 (AAPC, -1.6%), while HCV-attributable HCC rose from 6.6 to 8.0/100,000 (AAPC, 2.0%). HBV treatment among patients with HBV infection increased by 66% (2007, 7.4%; 2015, 12.3%). Treatment for HCV was stable at <2% during 2006–2013 but rose to 6.9% in 2014 and 12.7% in 2015, coinciding with the introduction of direct acting antiviral agents for HCV. Conclusions: A decreased incidence of HBV-attributable HCC corresponded with an increased uptake in treatment for that infection. Despite a marked increase in the effectiveness and frequency of HCV treatment in 2014 and 2015, HCV-attributable HCC had not begun to fall as of 2017. [ABSTRACT FROM AUTHOR]

Background and aim: MicroRNAs (miRs) are now a well-known subject in various tumor genesis and are studied as early diagnostic biomarker. Many arrays of miRs were incorporated in the pathogenesis of HCV-related hepatocellular carcinomas (HCV-HCC). In this respect, we aimed to evaluate the diagnostic role of circulating miR-21, miR-122, and miR-222 in Egyptian patients with HCV-HCC. Patient and methods: Between June 2018 and April 2019, a cross-sectional comparative study was designed to evaluate the circulating miR-21, miR-122, and miR-222 by quantitative Real-Time PCR. For analytical purposes, patients were categorized into three groups: chronic HCV group (CHC-group, n = 22), HCV-related liver cirrhosis (LC-group, n = 22), and HCV-related hepatocellular carcinoma (HCV-HCC-group, n = 54). Results: Serum levels of miR-21 and miR-222 increased with the progressive course from CHC to LC and HCC; p <.001. Serum levels of miR-122 in HCC patients were significantly lower than non-HCC patients (CHC and LC patients, n = 44); p <.001. However, the differences in levels of serum miR-122 between CHC and LC were not statistically significant; P = 0.8. ROC curve analysis showed that the sensitivity and specificity of miR-21 were 61.1% and 95.5%, miR-222 were 71.7% and 93.2%, and miR-122 were 98.2% and 100%. The positive predictive value for miRNA-21, miRNA-122, and miRNA-222 were 13.4%, 93.3%, and 10.5% respectively. The Negative predictive value for miRNA-21, miRNA-122, and miRNA-222 were 94.3%, 97.8%, and 92.7% respectively. Conclusion: MiR-21 and miR-222 could be potential markers for advanced liver damage, while miR-122 had the best diagnostic accuracy and could be a promising marker for detection of HCC. [ABSTRACT FROM AUTHOR]

Background: Although adult transplant centers are successfully transplanting organs from hepatitis C virus (HCV)‐infected donors with detectable viral load by nucleic acid testing (NAT+) into HCV‐negative recipients, this practice has not yet been adopted widely by the pediatric heart transplant community. Methods: We present a case series of four patients who received heart transplants from HCV NAT+ donors at a pediatric transplant center, including two pediatric patients < 18 years of age. Results: All recipients tolerated a 12‐week course of glecaprevir/pibrentasvir and achieved a sustained virologic response with no HCV or liver complications with over 1 year of follow‐up (range 1.4–2.5 years). All four have had good post‐heart transplant outcomes with normal graft function and good functional status without rejection or cardiac allograft vasculopathy at time of last follow‐up. Conclusions: This case series details the successful multidisciplinary implementation of a protocol to accept cardiac allografts from HCV NAT+ donors for transplantation into HCV negative recipients at our pediatric transplant center. With the limited donor pool in pediatrics and the morbidity associated with prolonged durations on the transplant waitlist, pediatric centers should consider utilizing organs from HCV NAT+ donors to broaden the donor pool. Future work should evaluate other organs beyond heart and optimal timing and duration of direct acting antiviral therapy. [ABSTRACT FROM AUTHOR]

Background: Defective hepatitis C virus (HCV) genomes with deletion of the envelope region have been occasionally reported by short-read sequencing analyses. However, the clinical and virological details of such deletion HCV have not been fully elucidated. Methods: We developed a highly accurate single-molecule sequencing system for full-length HCV genes by combining the third-generation nanopore sequencing with rolling circle amplification (RCA) and investigated the characteristics of deletion HCV through the analysis of 21 patients chronically infected with genotype-1b HCV. Result: In 5 of the 21 patients, a defective HCV genome with approximately 2000 bp deletion from the E1 to NS2 region was detected, with the read frequencies of 34–77%, suggesting the trans-complementation of the co-infecting complete HCV. Deletion HCV was found exclusively in decompensated cirrhosis (5/12 patients), and no deletion HCV was observed in nine compensated patients. Comparing the amino acid substitutions between the deletion and complete HCV (DAS, deletion-associated substitutions), the deletion HCV showed higher amino acid mutations in the ISDR (interferon sensitivity-determining region) in NS5A, and also in the TMS (transmembrane segment) 3 to H (helix) 2 region of NS2. Conclusions: Defective HCV genome with deletion of envelope genes is associated with decompensated cirrhosis. The deletion HCV seems susceptible to innate immunity, such as endogenous interferon with NS5A mutations, escaping from acquired immunity with deletion of envelope proteins with potential modulation of replication capabilities with NS2 mutations. The relationship between these mutations and liver damage caused by HCV deletion is worth investigating. [ABSTRACT FROM AUTHOR]

Background and Aims: The impact of hepatitis C virus (HCV) eradication via direct‐acting antiviral (DAA) therapy on overall mortality, particularly non‐liver‐related mortality, is understudied. Methods: We recruited 4180 patients with chronic HCV infection who achieved sustained virological response (SVR) (HCV eradication) through DAA therapy (n = 2501, SVR group) or who did not receive antiviral therapy (n = 1679, non‐SVR group); 1236 from each group were chosen using propensity score matching. Causes of death and all‐cause mortality, including non‐liver‐related diseases, were investigated. Results: Of the 4180 patients, 592 died during the follow‐up period. In the SVR group, the mortality rates from liver‐related and non‐liver‐related diseases were 16.5% and 83.5%, respectively. Compared to the non‐SVR group, mortality rates from liver‐related and non‐liver‐related diseases were 50.1% and 49.9%, respectively (p <.001). In non‐cirrhotic patients, multivariable analysis revealed that SVR was an independent factor associated with both liver‐related (hazard ratio [HR],.251; 95% confidence interval [CI],.092–.686) and non‐liver‐related (HR,.641; 95% CI,.415–.990) mortalities. In cirrhotic patients, multivariable analysis revealed that SVR remained an independent factor significantly associated with liver‐related mortality (HR,.151; 95% CI,.081–.279). In propensity score‐matched patients, the eradication of HCV (SVR group) decreased both liver‐related (p <.001) and non‐liver‐related mortality (p =.008) rates compared to persistent HCV infection (non‐SVR group). Conclusions: The elimination of HCV via DAA therapy reduced not only liver‐related mortality but also non‐liver‐related mortality in patients with chronic HCV. [ABSTRACT FROM AUTHOR]

Background and Aims: Hepatitis C virus (HCV) burden is higher among people in prison given high prevalence of injecting drug use. This study evaluated direct‐acting antiviral (DAA) treatment outcome in prisons. Methods: The Surveillance and Treatment of Prisoners with hepatitis C (SToP‐C) study enrolled individuals incarcerated in four Australian prisons (2017–2019). Participants with detectable HCV RNA were offered sofosbuvir‐velpatasvir for 12 weeks. Sustained virological response (SVR) was assessed in intention‐to‐treat (ITT; participants commencing treatment and due for SVR assessment before study close) and per‐protocol (PP; participants with documented treatment completion and SVR assessment) populations. Results: Among 799 participants with HCV, 324 (41%) commenced treatment (94% male; median age, 32 years; median duration of incarceration, 9 months). In ITT population (n = 310), 201 had documented treatment completion (65% [95% CI: 59–70]), and 137 achieved SVR (ITT‐SVR: 44% [95% CI: 39–50]). In PP population (n = 143), 137 achieved SVR (PP‐SVR: 96% [95% CI: 91–98]). Six participants had quantifiable HCV RNA at SVR assessment from treatment failure (n = 2) or reinfection (n = 4). Release or inter‐prison transfer was common reasons for no documented treatment completion (n = 106/109 [97%]) and no SVR assessment (n = 57/58 [98%]). In ITT analysis, longer incarceration was associated with increased SVR (adjusted OR per month 1.03 [95% CI: 1.01–1.04]). Conclusion: Among participants who completed DAA treatment and were assessed for SVR, treatment outcome was consistent with non‐prison clinical studies. However, most individuals did not complete treatment or lacked study‐documented treatment outcome due to release or transfer. Strategies to accommodate dynamic prisoner populations are required to ensure continuity of HCV care, including treatment completion and post‐treatment care. [ABSTRACT FROM AUTHOR]

It is critical to address hepatitis C virus (HCV) in carceral settings to achieve worldwide elimination of the virus. We describe New Mexico's (NM) experience expanding HCV treatment in state prisons, supplemented with Project ECHO (ECHO; virtual mentorship through guided practice) and the NM Peer Education Program (NMPEP). We describe how using these programs may be a model for expanding treatment in prisons globally. ECHO, NM Corrections Department (NMCD) and Wexford Health Services (WHS) collaborate to treat HCV in state prisons and increase HCV knowledge among incarcerated persons using NMPEP. Each person arriving in prison is tested for HCV and those with active infection receive baseline labs, which are reviewed. Patients not meeting criteria for simplified treatment are presented to ECHO for expert guidance. Otherwise, patients are treated by WHS without consultation. NMPEP provides patient‐to‐patient education in prisons, addressing HCV myths and exploring treatment refusals. From December 2020 to June 2023, 3603 people had HCV viremia. In this study, 1685 people started treatment: 1280 were treated using the simplified algorithm and 405 were presented to ECHO. Of the 988 people who completed treatment and had sustained virologic response (SVR) labs drawn, 89.2% achieved SVR (i.e., cure). Most of the 107 people who did not achieve SVR had presumed reinfection. NMPEP trained 148 peer educators who educated 3832 peers about HCV prevention and treatment. HCV treatment in prisons can be expanded by implementing simplified treatment algorithms, use of the ECHO model for patients with advanced disease and peer education. [ABSTRACT FROM AUTHOR]

HCV RNA test determines current active infection and is a requirement prior to initiating HCV treatment. We investigated trends and factors associated with post‐diagnosis HCV RNA testing rates prior to HCV treatment, and risk factors for first positive HCV RNA among people living with HIV (PLHIV) with HCV in the Asia‐Pacific region. PLHIV with positive HCV antibody and in follow‐up after 2010 were included. Patients were considered HCV‐antibody positive if they ever tested positive for HCV antibody (HCVAb). Repeated measures Poisson regression model was used to analyse factors associated with post‐diagnosis HCV RNA testing rates from positive HCVAb test. Factors associated with time to first positive HCV RNA from positive HCVAb test were analysed using Cox regression model. There were 767 HCVAb positive participants included (87% from LMICs) of whom 11% had HCV RNA tests. With 163 HCV RNA tests post positive HCVAb test, the overall testing rate was 5.05 per 100 person‐years. Factors associated with increased testing rates included later calendar years of follow‐up, HIV viral load ≥1000 copies/mL and higher income countries. Later calendar years of follow‐up, ALT >5 times its upper limit of normal, and higher income countries were associated with shorter time to first positive HCV RNA test. Testing patterns indicated that uptake was predominantly in high income countries possibly due to different strategies used to determine testing in LMICs. Expanding access to HCV RNA, such as through lower‐cost point of care assays, will be required to achieve elimination of HCV as a public health issue. [ABSTRACT FROM AUTHOR]

The prevalence of mixed hepatitis C virus (HCV) genotype infection in a representative Canadian HCV cohort is reported and virological response with direct acting antiviral (DAA) treatment was evaluated. 3272 HCV‐positive participants were enrolled, of which 2945 (90.0%) initiated DAA therapy. 0.8% were identified with mixed genotype infection. Overall sustained virological response (SVR) was 99.1% and did not differ based on mixed genotype status. Any historical disadvantage to achieving cure with HCV treatment in mixed genotype infection has been overcome by current DAA regimens. [ABSTRACT FROM AUTHOR]

Pakistan harbours a large burden of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection. We utilised repeat sero‐surveys to assess progress achieved towards hepatitis elimination in Pakistan. Multilevel logistic regression evaluated the change in HBV infection (HBV surface antigen (HBsAg)‐positive) prevalence and HCV exposure (HCV antibody (HCV‐Ab)‐positive) prevalence between two sero‐surveys from 2007 and 2019 for Sindh province and associated risk factors. Adjusted odds ratios (aORs) were estimated and population‐attributable fractions (PAF) for modifiable risk factors for HCV exposure. The 2007 and 2019 surveys included 8855 and 6672 individuals. HBsAg prevalence decreased from 2.6% (95% confidence intervals (95% CI): 2.2–2.9) in 2007 to 1.1% (95% CI: 0.8–1.3) in 2019, while HCV‐Ab prevalence increased from 5.1% (95% CI: 4.6%–5.5%) to 6.2% (95% CI: 5.6%–6.8%). The age and gender‐adjusted HBsAg prevalence decreased by 80% (aOR = 0.2, 95% CI: 0.1–0.4) among children and 60% (aOR = 0.4, 95% CI: 0.3–0.6) among adults over 2007–2019, while HCV‐Ab prevalence decreased by 60% (aOR = 0.4, 95%CI:0.2–0.7) in children and increased by 40% (aOR = 1.4, 95% CI: 1.2–1.7) in adults. HCV‐Ab prevalence was lower in adults with secondary (aOR = 0.6, 95% CI: 0.5–0.8) and higher (aOR = 0.5, 95%CI:0.3–0.8) education compared to illiterates and higher among adults reporting blood transfusion (aOR = 1.7, 95% CI: 1.2–2.4), family history of hepatitis (aOR = 2.5, 95% CI: 1.9–3.3), past year medical injection (aOR = 2.1, 95% CI: 1.6–2.7), being tattooed (aOR = 1.4, 95% CI: 1.0–1.9) and shaved by traditional barber (aOR = 1.2, 95% CI: 1.0–1.5). Modifiable risk factors accounted for 45% of HCV exposure, with medical injection(s) accounting for 38% (95%CI,25.7–48.4%). Overall HCV has increased over 2007–2019 in Sindh province, while HBV prevalence has decreased. Medical injections should be an important focus of prevention activities. [ABSTRACT FROM AUTHOR]

Chronic HCV infection results in abnormal immunological alterations, which are not fully normalized after viral elimination by direct-acting antiviral (DAA) treatment. Herein, we longitudinally examined phenotypic, transcriptomic, and epigenetic alterations in peripheral blood regulatory T (Treg) cells from patients with chronic HCV infection before, during, and after DAA treatment. Patients with chronic genotype 1b HCV infection who achieved sustained virologic response by DAA treatment and age-matched healthy donors were recruited. Phenotypic characteristics of Treg cells were investigated through flow cytometry analysis. Moreover, the transcriptomic and epigenetic landscapes of Treg cells were analyzed using RNA sequencing and ATAC-seq (assay for transposase-accessible chromatin with sequencing) analysis. The Treg cell population – especially the activated Treg cell subpopulation – was expanded in peripheral blood during chronic HCV infection, and this expansion was sustained even after viral clearance. RNA sequencing analysis revealed that viral clearance did not abrogate the inflammatory features of these Treg cells, such as Treg activation and TNF signaling. Moreover, ATAC-seq analysis showed inflammatory imprinting in the epigenetic landscape of Treg cells from patients, which remained after treatment. These findings were further confirmed by intracellular cytokine staining, demonstrating that Treg cells exhibited inflammatory features and TNF production in chronic HCV infection that were maintained after viral clearance. Overall, our results showed that during chronic HCV infection, the expanded Treg cell population acquired inflammatory features at phenotypic, transcriptomic, and epigenetic levels, which were maintained even after successful viral elimination by DAA treatment. Further studies are warranted to examine the clinical significance of sustained inflammatory features in the Treg cell population after recovery from chronic HCV infection. During chronic HCV infection, several immune components are altered both quantitatively and qualitatively. The recent introduction of direct-acting antivirals has led to high cure rates. Nevertheless, we have demonstrated that inflammatory features of Treg cells are maintained at phenotypic, transcriptomic, and epigenetic levels even after successful DAA treatment. Further in-depth studies are required to investigate the long-term clinical outcomes of patients who have recovered from chronic HCV infection. [Display omitted] • Increased Tregs persist in patients with chronic HCV after DAA-induced viral clearance. • DAA-induced HCV clearance does not abrogate inflammatory features of Tregs. • HCV clearance does not reverse inflammatory imprinting in the epigenome of Tregs. • Increased TNF+ Tregs persist in patients with chronic HCV after viral clearance. [ABSTRACT FROM AUTHOR]

Risk stratification for patients with a higher risk of hepatocellular carcinoma (HCC) is crucial. We aimed to investigate the role of the Fibrosis-4 (FIB-4) index in predicting chronic hepatitis C (CHC)-related HCC. A retrospective cohort study consecutively included treatment-naive CHC patients receiving longitudinal follow-up at the National Taiwan University Hospital from 1986 to 2014. The clinical data were collected and traced for HCC development. Multivariable Cox proportional hazard regression analysis was used to investigate the predictors for HCC. A total of 1285 patients in the ERADICATE-C cohort were included. The median age was 54, 56% were females, and 933 had HCV viremia. There were 33%, 38%, and 29% of patients having FIB-4 index <1.45, 1.45–3.25, and ≥3.25, respectively. After a median of 9-year follow-up, 186 patients developed HCC. Multivariable analysis revealed that older age, AFP≥20 ng/mL, cirrhosis, and a higher FIB-4 index were independent predictors for HCC. Compared with patients with FIB-4 index <1.45, those with FIB-4 1.45–3.25 had a 5.51-fold risk (95% confidence interval [CI]: 2.65–11.46), and those with FIB-4 ≥ 3.25 had 7.45-fold risk (95% CI: 3.46–16.05) of HCC. In CHC patients without viremia, FIB-4 index 1.45–3.25 and FIB-4 ≥ 3.25 increased 6.78-fold and 16.77-fold risk of HCC, respectively, compared with those with FIB-4 < 1.45. The baseline FIB-4 index can stratify the risks of HCC in untreated CHC patients, even those without viremia. The FIB-4 index should thus be included in the management of CHC. [ABSTRACT FROM AUTHOR]

The advent of direct-acting antiviral (DAA) therapy has revolutionized hepatitis C virus (HCV) treatment, enabling most HCV-infected patients to achieve a sustained viral response (SVR) easily and safely in a short period. On the other hand, it is gradually being recognized that a significant proportion of patients are still at risk of developing de novo and recurrent hepatocellular carcinoma (HCC), even after HCV elimination, and therefore, elucidation of the risk of de novo and recurrent HCC, investigation of its molecular basis, and construction of accurate prediction models are emerging as new important clinical topics. In this review, we present recent advances regarding these issues. [ABSTRACT FROM AUTHOR]

Introduction and Objectives: The most widely used staging system for hepatocellular carcinoma (HCC) is the Barcelona Liver Clinic Cancer (BCLC) system, which considers tumor burden, performance status, and liver function. Tumor burden is assessed with cross sectional imaging of the abdomen and chest, controversy surrounds the routine use of bone scintigraphy (BS) for detecting extrahepatic metastases. This study evaluated the role of BS in staging HCC in Mexican patients. Patients and Methods: Retrospective cross-sectional study of all adults with HCC at a Mexican referral center from 2000 to 2018. Staging included abdominal computed tomography (CT) or magnetic resonance imaging, chest CT, and BS. The main outcome was the impact of BS on staging and/or therapy plans. Results: Among 238 patients, 2 with fibrolamellar variant and 44 with incomplete data were excluded. Median age was 66 years, 84 % had cirrhosis, and the predominant etiology was hepatitis C virus (43 %). BCLC stages were distributed as follows: A (14 %), B (7 %), C (68 %), and D (11 %). Extrahepatic disease was present in 18 %; only 8 % patients had a positive BS. Among the positive cases, 4 were true positives, but they did not alter staging or therapy plans. Conclusions: Routine BS in HCC staging demonstrated low yield, with a notable rate of false positives. Considering the implications of extrahepatic disease, BS may be justified for liver transplant candidates outside conventional criteria. Our study highlights the limited role of BS in early-stage HCC and advocates for a more selective utilization. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is one of the deadliest cancers. For patients with advanced HCC, liver function decompensation often occurs, which leads to poor tolerance to chemotherapies and other aggressive treatments. Therefore, it remains critical to develop effective therapeutic strategies for HCC. Etiological factors for HCC are complex and multifaceted, including hepatitis virus infection, alcohol, drug abuse, chronic metabolic abnormalities, and others. Thus, HCC has been categorized as a "genomically unstable" cancer due to the typical manifestation of chromosome breakage and aneuploidy, and oxidative DNA damage. In recent years, immunotherapy has provided a new option for cancer treatments, and the degree of genomic instability positively correlates with immunotherapy efficacies. This article reviews the endogenous and exogenous causes that affect the genomic stability of liver cells; it also updates the current biomarkers and their detection methods for genomic instabilities and relevant applications in cancer immunotherapies. Including genomic instability biomarkers in consideration of cancer treatment options shall increase the patients' well-being. [ABSTRACT FROM AUTHOR]

Universal neonatal hepatitis B virus (HBV) vaccination and the advent of direct‐acting antivirals (DAA) against hepatitis C virus (HCV) have reshaped the epidemiology of chronic liver diseases. However, some aspects of the management of chronic liver diseases remain unresolved. Nucleotide analogs can achieve sustained HBV DNA suppression but rarely lead to a functional cure. Despite the high efficacy of DAAs, successful antiviral therapy does not eliminate the risk of hepatocellular carcinoma (HCC), highlighted the need for cost‐effective identification of high‐risk populations for HCC surveillance and tailored HCC treatment strategies for these populations. The accessibility of high‐throughput genomic data has accelerated the development of precision medicine, and the emergence of artificial intelligence (AI) has led to a new era of precision medicine. AI can learn from complex, non‐linear data and identify hidden patterns within real‐world datasets. The combination of AI and multi‐omics approaches can facilitate disease diagnosis, biomarker discovery, and the prediction of treatment efficacy and prognosis. AI algorithms have been implemented in various aspects, including non‐invasive tests, predictive models, image diagnosis, and the interpretation of histopathology findings. AI can support clinicians in decision‐making, alleviate clinical burdens, and curtail healthcare expenses. In this review, we introduce the fundamental concepts of machine learning and review the role of AI in the management of chronic liver diseases. [ABSTRACT FROM AUTHOR]

Background: In the United States (US), hepatitis C virus (HCV) screening is not covered by payers in settings outside of primary care. A non-traditional, emergency department (ED)-based HCV screening program can be cost-effective and identify infection in vulnerable populations with a high HCV risk. This study examined the long-term cost-effectiveness of routine HCV screening and linkage-to-care for high-risk patients in the ED from the payer's perspective. Methods: The University of Illinois Hospital and Health Sciences System (UIH) implemented Project HEAL (HIV & HCV Screening, Education, Awareness, Linkage-to-Care). Under this initiative, patients who presented to the ED received opt-out HCV screening if they were at high risk for HCV infection (birth cohort between 1945 and 1964, persons who inject drugs, and HIV infection) with subsequent linkage-to-care if infected. Using the summary data from Project HEAL, a hybrid decision-analytic Markov model was developed based on the HCV screening procedure in the ED and the natural history of HCV. A 30-year time horizon and 1-year cycle length were used. All patients who received the ED-based HCV screening were referred for treatment with direct-acting antiviral (DAA) regardless of their fibrosis stage. Results: When unscreened/untreated patients received DAA treatment at F1, F2, F3, and compensated cirrhosis stages, the incremental cost-effectiveness ratio (ICER) ranged from $6,084 to $77,063 per quality-adjusted life year (QALY) gained. When unscreened/untreated patients received DAA treatment at the decompensated cirrhosis stage, no HCV screening was dominated. Conclusion: ED-based HCV screening and linkage-to-care was cost-effective at the willingness-to-pay (WTP) threshold of $100,000/QALY in all scenarios. A reduction in infected persons in the community may provide additional benefits not evaluated in this study. [ABSTRACT FROM AUTHOR]

Hepatitis C virus (HCV) transmission remains a significant public health concern. It is well documented globally, however, Nowshera district, Pakistan, is lacking such profile. This study aims to explore the relationship between HCV infection and several risk factors, including socio-demographic, clinical and personal life-style factors. This study using a cross-sectional design, examined 606 randomly selected individuals visiting the Pathology department at Qazi Hussain Medical Complex and District Headquarter (DHQ) Hospital Nowshera between May 1, 2022 and Jun 30, 2023. This research investigation employed a methodical approach involving formal interviews in conjunction with structured questionnaires to gather comprehensive information related to socio-demographic characteristics, clinical history, and personal hygiene practices. We collected 10 ml of blood samples and tested the separated serum to identify markers using the Immuno-Chromatographic Test (ICT) and the Enzyme-Linked Immunosorbent Assay (ELISA). IBM SPSS Statistics version 27 was used for data analysis. To measure the association between dependent variable and independent variables, a chi-square and risk analysis was carried out; multiple logistic regression was employed for modeling the risk factors associated with independent variable. A statistical significance level was established at a P-value of less than 0.05. In present study, which included 606 participants, 12% were found to be infected with HCV. Importantly it revealed that facial shave at barber (adjusted odds ratio, aOR = 40.65, p = 0.000) represents the most prevalent mode of HCV transmission. Additionally, a strong association was observed between HCV infection and history of past surgery (RR = 2.98, p = 0.001), HCV infected family member (aOR = 4.28, p = 0.001), workplace injuries (aOR = 6.68, p = 0.000), history of hospital admission (RR = 2.09), practicing ear and nose piercing (aOR = 5.01, p = 0.001), dental treatment (RR = 2.31) and the frequency of injections (aOR = 8.607, p = 0.000). These findings underscore the pressing need for targeted interventions. This study highlights the paramount importance of understanding the modes of HCV transmission and their associated risk factors. The results emphasize the need for educational initiatives, both within the healthcare sector and among the general public, to combat HCV transmission effectively. By implementing sterilization procedures and increasing awareness, we can make significant strides in reducing the burden of HCV infection. Moreover, proactive measures within families can help contain the spread of the virus, ultimately contributing to improved public health. [ABSTRACT FROM AUTHOR]

In this paper, we study a dynamic model of hepatitis C virus (HCV) infection with density‐dependent proliferation of uninfected and infected hepatocytes and two time delays, which is derived from a three‐dimensional model by the quasi‐steady‐state approximation. The model can exhibit forward bifurcation or backward bifurcation, and an explicit control threshold parameter Rc$R_c$ is obtained for the case of backward bifurcation. It is shown that if the proliferation rate of infected hepatocytes is greater than the proliferation rate of uninfected hepatocytes by a certain amount, it becomes more difficult for the virus to be removed. The model has rich dynamical properties: (i) In some parameter regions, bistability can occur; (ii) both time delays τ1$\tau _{1}$ (virus‐to‐cell delay) and τ2$\tau _{2}$ (cell‐to‐cell delay) can lead to Hopf bifurcations; (iii) same length of time delays τ1$\tau _{1}$ and τ2$\tau _{2}$ can lead to at most one stability switch, but different time delays can lead to multiple stability switches. Several sufficient conditions for the global stability of the disease‐free equilibrium and the endemic equilibrium are obtained for both forward and backward bifurcation scenarios. In particular, several sharp results on global stability are obtained. Theoretical and numerical results portray the complexity of viral evolutionary dynamics in chronic HCV‐infected patients. [ABSTRACT FROM AUTHOR]

Background: Eliminating hepatitis C virus (HCV) infections is a goal set by the World Health Organization. This has become possible with the introduction of highly effective and safe direct-acting antivirals (DAA) but limitations remain due to undiagnosed HCV infections and loss of patients from the cascade of care at various stages, including those lost to follow-up (LTFU) before the assessment of the effectiveness of the therapy. The aim of our study was to determine the extent of this loss and to establish the characteristics of patients experiencing it. Methods: Patients with chronic HCV infection from the Polish retrospective multicenter EpiTer-2 database who were treated with DAA therapies between 2015 and 2023 were included in the study. Results: In the study population of 18,968 patients, 106 had died by the end of the 12-week post-treatment follow-up period, and 509 patients did not report for evaluation of therapy effectiveness while alive and were considered LTFU. Among patients with available assessment of sustained virological response (SVR), the effectiveness of therapy was 97.5%. A significantly higher percentage of men (p<0.0001) and a lower median age (p=0.0001) were documented in LTFU compared to the group with available SVR assessment. In LTFU patients, comorbidities such as alcohol (p<0.0001) and drug addiction (p=0.0005), depression (p=0.0449) or other mental disorders (p<0.0001), and co-infection with human immunodeficiency virus (HIV) (p<0.0001) were significantly more common as compared to those with SVR assessment. They were also significantly more often infected with genotype (GT) 3, less likely to be treatment-experienced and more likely to discontinue DAA therapy. Conclusions: In a real-world population of nearly 19,000 HCV-infected patients, we documented a 2.7% loss to follow-up rate. Independent predictors of this phenomenon were male gender, GT3 infection, HIV co-infection, alcohol addiction, mental illnesses, lack of prior antiviral treatment and discontinuation of DAA therapy. [ABSTRACT FROM AUTHOR]

ABSTRACT Hepatitis B virus (HBV) infection is a significant contributor to the development of hepatocellular carcinoma (HCC), a leading cause of cancer‐related mortality worldwide. Iron, a central co‐factor in various metabolic pathways, plays an essential role in liver function, but its dysregulation can lead to severe health consequences. Accumulation of iron within hepatic cells over time is linked to increased liver injury and is strongly associated with sensitive exposure to a range of conditions, including cirrhosis, fibrosis and ultimately, HCC. This review explores the intricate interplay between iron metabolism and HCC within the context of HBV infection. Hepatic iron overload can arise from liver injury and disruptions in iron homeostasis, causing hepatic necrosis, inflammation, and fibrosis, ultimately culminating in carcinogenesis. Moreover, alterations in serum iron components in HBV‐related scenarios have been observed to impact the persistence of HBV infection. Notably, the progression of HBV‐associated liver damage exhibits distinct characteristics at various stages of liver disease. In addition to elucidating the complex relationship between iron metabolism and HCC in the context of HBV infection, this review also investigates the prognostic implications of systemic iron levels for HCC. Furthermore, it aims to provide a comprehensive understanding of the intricate interplay between iron metabolism and HCC, extending the discussion to the context of hepatitis C virus (HCV) infection. By shedding light on these multifaceted connections, this review aims to contribute to our understanding of the pathogenesis of HBV‐associated HCC and potentially identify novel therapeutic avenues for intervention. [ABSTRACT FROM AUTHOR]

ABSTRACT Meeting the World Health Organisation 2030 target of treating 80% of people with hepatitis C virus (HCV) in Australia requires accessible testing and treatment services for at‐risk populations. Previous clinical trials, including those in Australia, have demonstrated the efficacy of outreach programmes to community pharmacies offering opioid agonist therapy (OAT). This analysis evaluates the potential cost‐effectiveness of introducing an outreach programme in community pharmacies. Using a decision analytic model, we estimated the impact of adding a temporary hepatitis C outreach and treatment programme in community pharmacies to the standard treatment pathway available through general practice. We compared the expected number of tests, diagnoses, cures and costs occurring through the addition of this outreach and treatment programme to those expected through general practice alone over a 12‐month time horizon. We examined costs from the perspective of the health system and conducted one‐way and probabilistic sensitivity analyses to assess uncertainty in model parameters and test key assumptions. In the model adding the outreach programme pathway increased the number of tests from 4178 to 8737, the number of diagnoses from 615 to 1285 and the number of cures from 223 to 777 among people on OAT over a 12‐month period. Each additional cure achieved through the addition of the outreach programme was estimated to incur $48,964 (AUD 2023) to the health system, with > 85% of these costs attributable to medication and dispensing expenses. The average cost per cure was estimated to be $49,152 through routine care and $49,018 in the outreach programme. Although outreach models of care incur large upfront costs, they can capture otherwise unreached populations and result in comparable or favourable cost per cure, due to higher levels of engagement and lower rates of loss to follow‐up. [ABSTRACT FROM AUTHOR]