Treatment Outcomes of HCV Infection in People Living with HIV: A Case Series from a Single Center in Korea.

BACKGROUND: Limited information is available on the clinical course and treatment outcomes of human immunodeficiency virus (HIV) and hepatitis C virus (HCV) coinfection in Korea. MATERIALS AND METHODS: A retrospective case series was conducted of patients with HIV-HCV coinfection who received interferon (IFN)-based or direct-acting antiviral (DAA) treatment for HCV at a tertiary care hospital between 2000 and 2023. Early virological response (EVR) was defined as a 2-log reduction in HCV RNA levels or undetectable HCV RNA levels at treatment week 12. A sustained virologic response (SVR) was defined as undetectable HCV RNA at 12 weeks after treatment completion. RESULTS: Of the 33 patients with HIV-HCV coinfection, 19 received anti-HCV treatment, of whom 12 received IFN-based treatment and 10 received DAA treatment. The median age at the time of anti-HCV treatment was 49 years (interquartile range, 42-57 years) and 15 patients (79%) were male. Of the 12 patients who received IFN-based anti-HCV treatment, 10 showed EVR and 8 achieved SVR. However, 2 patients who achieved SVR experienced recurrence of HCV infection during follow-up; therefore, the overall success rate of IFN-based treatment was 50% (6/12). All 10 patients (including 3 in whom IFN-based treatment failed) who received DAA treatment (5 with previous anti-HCV treatment and 5 treatment-naïve), achieved SVR and did not experience recurrence of HCV infection during follow-up; therefore, the overall success rate of DAA treatment was 100%. CONCLUSION: In Korean patients with HIV-HCV coinfection, treatment outcomes were better with DAA treatment than with IFN-based treatment.

A Programme of Hepatitis C Surveillance With Active Linkage to Care (HEAL) for Inpatients in Two Tertiary Hospitals in Jiangsu, China.

Hepatitis C virus (HCV) infection is a major public health burden in China, affecting more than 10 million individuals. We aimed to evaluate the effectiveness of a hospital-based intervention programme for HCV Surveillance with linkage to care (HEAL) in a prospective cohort. The HEAL programme was carried out targeting inpatients from non-infectious departments of two tertiary hospitals in Jiangsu, China. It consisted of an educational campaign to raise awareness of physicians from non-IDs to promote HCV surveillance, a patient-navigator-centred clinical algorithm responsible for the efficient follow-up of patients with positive HCV antibody, including comprehensive testing, diagnosis and treatment. We characterised the rate of linkage to HCV diagnosis, care and treatment during the pre-intervention period (from 1 July 2016 and June 30, 2018) and after the intervention (from March 2019 to May 2021). During the pre-intervention period, 89,303 (45.3%) out of 196,780 non-ID inpatients were screened for anti-HCV, and 631 patients were tested positive. One hundred and fifty-six (24.7%) patients was followed up for HCV RNA confirmatory testing, and 58 (37.1%) of patients further were diagnosed with chronic HCV infection (CHC). Only 18 (31.3%) of the diagnosed patients with CHC were linked to hepatitis C clinics for treatment, 10 (55.6%) patients received antiviral regimen. Among them, two (11.1%) received DAA treatment, while eight (44.4%) adopted peginterferon/ribavirin regimen. During the intervention period, 232,275 patients were hospitalised in non-infectious department and 151,203 (65.1%) were screened for anti-HCV. Of these, 960 patients tested positive for HCV antibodies, resulting in a prevalence of anti-HCV positivity of 0.63%. Six hundred and seventy (69.8%) patients were enrolled, and 100% were followed up for HCV RNA confirmatory testing. Two hundred and ninety-one (43.4%) individuals with active HCV were identified. Two hundred and thirty-eight (81.8%) of HCV-infected individuals were linked to HCV care, and 157 (65.9%) were linked to treatment. Compared to the pre-intervention period, there was a 2.61-fold increase in the percentage of patients linked to care and a 5.94-fold increase in the proportion of patients who started DAAs therapy. This HEAL programme achieved enhanced HCV Surveillance with linkage to care, which has been demonstrated as an effective strategy in the hospital setting to improve the hepatitis C care continuum by identifying inpatients unaware of their HCV status and facilitating their access to HCV treatment.

Comparison of a hepatitis C core antigen assay to nucleic acid amplification testing for detection of hepatitis C viremia in a US population.

The prevalence of hepatitis C virus (HCV) infection in the United States has increased over the past decade despite the development of effective direct-acting antiviral treatments. To meet the World Health Organization's (WHO) goal of eliminating HCV infection by 2030, transmission events must be reduced. Currently, infection screening relies on detection of HCV antibodies, with nucleic acid amplification testing (NAAT) used to confirm HCV viremia and monitor changes in viral load. However, the seroconversion window for detection of HCV antibodies is long, averaging 6 weeks, with delayed seroconversion common in co-infected and immunosuppressed populations. Testing for HCV core antigen, which is present approximately 5 weeks before HCV antibodies, holds promise for earlier detection of HCV infection. It may also hold promise as a cheaper, more accessible, and more rapid alternative to NAAT for infection confirmation. Here, we evaluated the agreement between a research-use HCV Core Antigen Assay and NAAT among US patients receiving clinically indicated NAAT. Among 412 specimens, the overall concordance was 97.1%, with a positive percent agreement of 95.5%. Discrepancies primarily occurred among patients with chronic HCV and low viral loads; 11/12 discrepancies showed viral loads <4,000 IU/mL. Among patients being screened for HCV infection (i.e., excluding those undergoing NAAT for serial monitoring of a previously diagnosed infection), the positive percent agreement was 97.0%. Among patients undergoing serial testing, changes in HCV Core Antigen Assay signal-to-cut-off values were generally correlated with changes in the viral load. Results suggest that the research-use HCV Core Antigen Assay studied here may reliably detect and/or confirm HCV infection. IMPORTANCE: A research-use HCV Core Antigen Assay showed high concordance with nucleic acid amplification testing for the detection of current hepatitis C infection. The assay may enable more rapid and lower-cost detection and/or confirmation of hepatitis C infection.

Real-world trends in acute viral hepatitis in Japan: A nationwide questionnaire-based survey.

AIM: The actual incidence of acute viral hepatitis in Japan remains unclear. We aimed to investigate trends in the incidence of acute hepatitis B and C infections in Japan. METHODS: A nationwide, multicenter, retrospective questionnaire-based survey was conducted. Participating hospitals received questionnaires through nationwide geographically distributed regional core centers certified as specialists in hepatitis treatment. The questionnaire included hospital size and the number of patients diagnosed with acute hepatitis B or C during each fiscal year (FY) from 2015 to 2022. The sex distribution in each FY was also documented. Comparisons were made before and during the COVID-19 era (2015-2019 vs. 2020-2022), and between populous and non-populous prefectures. RESULTS: Responses to the questionnaires were obtained from 127 institutions in 29 prefectures covering eight regions in Japan. A median of 127.0 patients with acute hepatitis B (interquartile range [IQR] 106.5-131.8 patients) were reported during each FY, and the incidence significantly decreased during the fiscal years 2020-2022 compared with the fiscal years 2015-2020 (median 96.0 [IQR 91.0-103.0] patients vs. 131.0 [IQR 128.0-134.0] patients; p = 0.03). A median of 10.0 (IQR, 7.8-13.5) patients were reported with acute hepatitis C during each FY. The proportions of men in acute hepatitis B and C were significantly higher in populous prefectures. CONCLUSIONS: Populous prefectures had a higher proportion of men among viral hepatitis patients than non-populous prefectures. Estimating the high-risk populations in each area could provide insights to advance the elimination of viral hepatitis.

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

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

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

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

20 years on from the Dublin Declaration: European Committee for the Prevention of Torture and Inhuman or Degrading Treatment reporting on the provision of prison needle and syringe programmes in the Council of Europe region.

Background: Prisons in Europe remain high-risk environments and conducive for infectious disease transmission, often related to injection drug use. Many infected people living in prison unaware of their infection status (HIV, hepatitis C). Despite all Council of Europe (CoE) member states providing community needle and syringe programmes (NSP), prison NSP are limited to seven countries. The study aim was to scrutinise the Committee for the Prevention of Torture and Inhuman or Degrading Treatment (CPT) reporting of periodic and ad hoc country mission visits to prisons, with an explicit focus on the extent to which member states are/were fulfilling obligations to protect prisoners from HIV/hepatitis C; and implementing prison NSP under the non-discriminatory equivalence of care principle. Study design: Socio-legal review. Methods: A systematic search of the CPT database was conducted in 2024 with no date restriction. All CPT reports were screened in chronological order with the terms; "needle", "syringe", "harm reduction" and "NSP". Relevant narrative content on prison NSP operations, including repeat CPT reminders and any official/publicly expressed reasons for not implementing is presented. Results: CPT reporting reveals limited prison NSP provision in selected prisons visited on mission, with little change in status over time, despite documented evidence of prior observations around absent/insufficient harm reduction measures and explicit (often longstanding) recommendations to address deficits. Reasons for not implementing prison NSP include; existing availability of opioid substitute treatment, lack of evidence for injecting drug use, for security and maintenance of order, and contradiction with prison protocols sanctioning drug use. Conclusions: Prison health is public health. Regular research and evaluations of prison NSP in Europe are warranted. Future CPT visits should also continue to assess availability and standards of provision; recommend where appropriate including when opioid substitute treatment is already provided, and in line with broad availability of community NSP in Europe.

Viral fingerprints of the ion channel evolution: compromise of complexity and function.

Evolution from precellular supramolecular assemblies to cellular world originated from the ability to make a barrier between the interior of the cell and the outer environment. This step resulted from the possibility to form a membrane, which preserves the cell like a wall of the castle. However, every castle needs gates for trading, i.e. in the case of cell, for controlled exchange of substances. These 'gates' should have the mechanism of opening and closing, guards, entry rules, and so on. Different structures are known to be able to make membrane permeable to various substances, from ions to macromolecules. They are amphipathic peptides, their assemblies, sophisticated membrane channels with numerous transmembrane domains, etc. Upon evolving, cellular world preserved and selected many variants, which, finally, have provided both prokaryotes and eukaryotes with highly selective and regulated ion channels. However, various simpler variants of ion channels are found in viruses. Despite the origin of viruses is still under debates, they have evolved parallelly with the cellular forms of life. Being initial form of the enveloped organisms, reduction of protocells or their escaped parts, viruses might be fingerprints of the evolutionary steps of cellular structures like ion channels. Therefore, viroporins may provide us a necessary information about selection between high functionality and less complex structure in supporting all the requirements for controlled membrane permeability. In this review we tried to elucidate these compromises and show the possible way of the evolution of ion channels, from peptides to complex multi-subunit structures, basing on viral examples.

United States Provider Experiences With Telemedicine for Hepatitis C Treatment: A Nationwide Survey.

Hepatitis C virus (HCV) elimination requires treatment access expansion, especially for underserved populations. Telehealth has the potential to improve HCV treatment access, although data are limited on its incorporation into standard clinical practice. We conducted a cross-sectional, email survey of 598 US HCV treatment providers who had valid email addresses and (1) were located in urban areas and had written ≥ 20 prescriptions for HCV treatment to US Medicare beneficiaries in 2019-2020 or (2) were located in non-urban areas and wrote any HCV prescriptions in 2019-2020. Through email, we notified providers of a self-administered electronic 28-item survey of clinical strategies and attitudes about telemedicine for HCV. We received 86 responses (14% response rate), of which 75 used telemedicine for HCV in 2022. Of those 75, 24% were gastroenterologists/hepatologists, 23% general medicine, 17% infectious diseases and 32% non-physicians. Most (82%) referred patients to commercial laboratories, and 85% had medications delivered directly to patients. Overwhelmingly, respondents (92%) felt that telehealth increases healthcare access, and 76% reported that it promotes or is neutral for treatment completion. Factors believed to be 'extremely' or 'very' important for telehealth use included patient access to technology (86%); patients' internet access (74%); laboratory access (76%); reimbursement for video visits (74%) and audio-only visits (66%). Non-physician licensing and liability statutes were rated 'extremely' or 'very' important by 43% and 44%, respectively. Providers felt that telehealth increases HCV treatment access. Major limitations were technological requirements, reimbursement, and access to ancillary services. These findings support the importance of digital equity and literacy to achieve HCV elimination goals.

Relative contribution of Hepatitis B and C Viruses in primary liver cancer in China: a systematic review and meta-analysis.

OBJECTIVES: China, which has the largest number of patients with primary liver cancer (PLCs), lacks data on the overall prevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) in PLCs. We aimed to comprehensively assess the seroprevalence of HBV and HCV among PLCs in China. METHODS: We included and pooled observational studies reporting seroprevalence of HBsAg and anti-HCV antibodies among PLCs in China by searching PubMed, Web of Science, Cochrane, Scopus, Embase, CNKI, Wanfang, and CBM. Multivariate meta-regression and subgroup analyses were used to explore sources of heterogeneity, and publication bias was assessed by funnel plots and Egger's test. PROSPERO registration number is CRD42023450382. RESULTS: A total of 217 eligible studies were included in the meta-analysis. The estimated seroprevalence of HBV and HCV was 75.09% (95% CI 73.12-77.02) and 11.82% (95% CI 9.79-14.00), respectively. After stratifying and analysing subgroups by region and study period, we found geographic differences in HBV and HCV prevalence among PLCs, with an overall increasing trend in the proportion of HBV and a decreasing trend in the proportion of HCV as well as co-infections in the last 40 years. CONCLUSIONS: HBV and HCV infections still accounts for a high proportion of PLCs in China.

Risk of de novo HCC in patients with MASLD following direct-acting antiviral-induced cure of HCV infection.

BACKGROUND & AIMS: Data are limited on the risk of de novo hepatocellular carcinoma (HCC) in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) after achieving sustained virologic response (SVR12) using direct-acting antivirals (DAAs) for hepatitis C virus (HCV). METHODS: 1598 eligible patients received biannual alpha-fetoprotein (AFP) and liver imaging surveillance to detect de novo HCC beyond achieving SVR12. MASLD was defined as presence of controlled attenuation parameter (CAP) ≥ 248 dB/m and ≥ one cardiometabolic risk factor (CMRF). Cumulative HCC incidence was compared between patients with/without MASLD. We built univariable and multivariable Cox proportional hazards models to evaluate factors associated with HCC. Sensitivity analysis was performed using the Fine-Gray subdistribution hazards model. Additionally, we evaluated the mediation effect of MASLD on CMRFs and of CMRFs on MASLD for HCC using mediation analysis with bootstrapping. RESULTS: The incidence rate of HCC was 1.44 per 100 person-years of follow-up (PYFU) [95% confidence interval (CI): 1.19-1.74]. Patients with MASLD had a higher cumulative HCC incidence than those without MASLD (log-rank test, p < 0.001). Multivariable Cox regression analysis revealed that in addition to age, sex, LSM, platelet count, and AFP, MASLD (adjusted hazard ratio (aHR): 2.07 [95% CI:1.36-3.16], p < 0.001) was independently associated with HCC. This finding was confirmed by the Fine-Gray model, which showed a subdistribution HR (sHR) of 2.07 (95% CI: 1.34-3.19, p < 0.001) for MASLD. MASLD significantly mediated CMRFs for HCC development. CONCLUSION: After achieving SVR12, patients with MASLD exhibited an increased HCC risk compared to those without MASLD. Vigilant HCC surveillance and control of CMRFs to mitigate the effect MASLD on HCC remain crucial for this population. IMPACT AND IMPLICATIONS: The risk of de novo HCC among patients with MASLD, a novel nomenclature of steatotic liver disease (SLD), after the attaining of SVR12 using DAAs remains to be confirmed. In this study recruiting 1598 patients in Taiwan, individuals with MASLD exhibited approximately a two-fold increased risk of de novo HCC, compared to those without MASLD after achieving SVR12. MASLD significantly mediated CMRFs for HCC development. Our findings underscore the critical importance of pharmacological interventions and proactive lifestyle modifications to control CMRFs in patients with MASLD, as well as the need for vigilant HCC surveillance to ensure favorable outcomes following HCV eradication.

Hepatitis C virus infection and Parkinson's disease: insights from a joint sex-stratified BioOptimatics meta-analysis.

Hepatitis C virus (HCV) infection poses a significant public health challenge and often leads to long-term health complications and even death. Parkinson's disease (PD) is a progressive neurodegenerative disorder with a proposed viral etiology. HCV infection and PD have been previously suggested to be related. This work aimed to identify potential biomarkers and pathways that may play a role in the joint development of PD and HCV infection. Using BioOptimatics-bioinformatics driven by mathematical global optimization-, 22 publicly available microarray and RNAseq datasets for both diseases were analyzed, focusing on sex-specific differences. Our results revealed that 19 genes, including MT1H, MYOM2, and RPL18, exhibited significant changes in expression in both diseases. Pathway and network analyses stratified by sex indicated that these gene expression changes were enriched in processes related to immune response regulation in females and immune cell activation in males. These findings suggest a potential link between HCV infection and PD, highlighting the importance of further investigation into the underlying mechanisms and potential therapeutic targets involved.

Racial and Ethnic Disparities in Hepatitis C Care in Reproductive-Aged Women With Opioid Use Disorder.

BACKGROUND: In the United States, hepatitis C virus (HCV) diagnoses among reproductive-aged women are increasing amidst the ongoing opioid and drug overdose epidemic. While previous studies document racial and ethnic disparities in HCV testing and treatment in largely male populations, to our knowledge no national studies analyze these outcomes in reproductive-aged women with opioid use disorder (OUD). METHODS: We analyzed data from a cohort of reproductive-aged women (aged 15-44 years) with diagnosed OUD captured in the TriNetX Research Network, a network of electronic health records from across the United States. Using a log-binomial model, we assessed differences in achieving HCV cascade of care stages (HCV antibody testing, HCV infection [positive HCV RNA test result], linkage to care, and HCV treatment) by race and ethnicity. RESULTS: From 2014 to 2022, 44.6% of the cohort were tested for HCV antibody. Asian and black/African American individuals had a lower probability of having an HCV antibody test than white individuals (risk ratio, 0.77 [95% confidence interval, .62-.96] and 0.76 [.63-.92], respectively). Among those with HCV infection, only 9.1% were treated with direct-acting antivirals. Hispanic/Latinx individuals had a higher probability of treatment than non-Hispanic/Latinx individuals (risk ratio, 1.63 [95% confidence interval, 1.01-2.61]). CONCLUSIONS: Few reproductive-aged women with OUD are tested or treated for HCV. Disparities by race and ethnicity in HCV testing further exacerbate the risk of perinatal transmission and disease progression among minoritized communities. Interventions are needed to improve overall rates of and equity in HCV screening and treatment for reproductive-aged women.

Utilising integrated bio-behavioural surveillance (IBBS) to investigate declining hepatitis C antibody prevalence among people who inject drugs in the Australian Needle and Syringe Program Survey.

BACKGROUND: Prevalence of hepatitis C virus (HCV) antibody (Ab) on dried blood spot (DBS) samples in the Australian Needle and Syringe Program Survey (ANSPS) decreased nationally from 57 % in 2015 to 32 % in 2022. We aimed to investigate potential explanations for this decline. METHODS: Changes in DBS HCV Ab prevalence were investigated by redefining positive cases as those with those with either a positive HCV Ab test result or a self-reported history of ever having HCV treatment (modified prevalence), examining HCV Ab prevalence by birth and age cohorts, and assessing trends in key risk behaviours. RESULTS: Overall prevalence of DBS HCV Ab declined rapidly and significantly from 57 % in 2015 to 32 % in 2022 (p < 0.001) however modified HCV Ab prevalence remained stable over time (85 % and 88 % in 2015 and 2022, respectively, p = 0.357). The proportion of participants with negative HCV Ab and self-reported HCV infection increased from 20 % in 1995 to 40 % in 2022 (p < 0.001) and the proportion with negative HCV Ab and lifetime HCV treatment increased from 3 % in 1999 to 67 % in 2022 (p < 0.001). We also observed a decreasing trend in DBS HCV Ab prevalence in all birth and age cohorts with a noticeable acceleration in the decline commensurate with the advent of HCV DAA treatment. A long-term decreasing trend was also observed for key risk behaviours (p < 0.001) however the short-term trend was not significant for recent receptive syringe sharing. CONCLUSION: The temporal decline in HCV Ab prevalence appears related to reduced sensitivity of DBS HCV Ab detection with viral clearance following treatment. Since 2016, HCV treatment uptake has increased markedly including among people who inject drugs. In this context, continuing to monitor HCV Ab prevalence by DBS testing is problematic, with a shift to surveillance of active infection the most relevant to guide policy and practice in this setting.

Prevalence of and Risk Factors for Liver Enzyme Elevation After Hepatitis C Virologic Cure.

A subset of patients with chronic hepatitis C virus (HCV) infection demonstrate liver enzyme elevation (LEE) after achieving sustained virologic response (SVR). Risk factors for LEE are not well characterised. We conducted a single-centre retrospective cohort study of adults with HCV infection in the Duke University Health System who received direct-acting antiviral therapy and achieved SVR. We performed multivariable logistic regression to assess the relationship between potential risk factors and LEE. We used generalised linear mixed-effects models to explore longitudinal relationships between HIV and LEE. Among 1356 patients, 556 (41.0%) had LEE after achieving SVR. Higher pretreatment alanine aminotransferase (ALT) (adjusted odds ratio [aOR] 1.08 per 10 IU/L increase; 95% confidence interval [CI] 1.05-1.11) and pretreatment cirrhosis (aOR 2.26, 95% CI 1.60-3.21) were associated with higher odds of LEE; male sex was associated with lower odds of LEE (aOR 0.28, 95% CI 0.21-0.38). There was insufficient evidence of an association between HIV and LEE (aOR 0.83, 95% CI 0.47-1.44). Pretreatment ALT, cirrhosis and female sex predicted LEE in this cohort of patients with HCV infection who achieved SVR. These findings can help to identify patients at greatest risk of post-SVR liver injury.

Prevalence of Drug Resistance Associated Substitutions in Persons With Chronic Hepatitis C Infection and Virological Failure Following Initial or Re-treatment With Pan-genotypic Direct-Acting Antivirals: A Systematic Review and Meta-analysis.

BACKGROUND: The advent of short-course, curative treatment with direct-acting antivirals (DAA) has given promise for the global elimination of hepatitis C virus (HCV) infections by 2030. Virological failure occurs in 2%-12% of persons receiving curative DAA treatment and may be presaged by pre-existing polymorphisms or result from selection of drug resistant variants during therapy. METHODS: We conducted a systematic review to assess the prevalence of HCV resistance associated substitutions (RAS) among individuals with chronic hepatitis C infection who had virological failure following initial or re-treatment with pan-genotypic DAA regimens. We included 34 and 22 studies assessing RAS in people with virological failure published between January 2014 and July 2023. Pooled RAS prevalence was estimated using random-effects meta-analysis. RESULTS: The pooled prevalence of RAS in people with virological failure following initial DAA treatment was 78.0% (95% confidence interval [CI]: 62.0-92.0) for sofosbuvir/velpatasvir, 81.0% (95% CI: 67.0-93.0) for sofosbuvir/daclatasvir, and 79.0% (95% CI: 70.0-87.0) for glecaprevir/pibrentasvir, with a high prevalence of resistance to the NS5A inhibitors. Among those with virological failure following re-treatment regimens, RAS were present in 93.0% (95% CI: 83.0-99.0) for sofosbuvir/velpatasvir/voxilepravir and in 100% (95% CI: 92.0-100) for glecaprevir/pibrentasvir, with resistance driven by RAS to NS5A inhibitors. DISCUSSION: At least 1 RAS is present in a high proportion of the few individuals with virological failure following initial or re-treatment with pan-genotypic DAA regimens. There is a need for ongoing surveillance for DAA-associated resistance, to assess risk factors for their development and clinical impact to inform best practice strategies for re-treatment.

Self-testing strategy to eliminate Hepatitis C as per WHO's goal: Analysis of disease burden and cost-effectiveness.

BACKGROUND/AIMS: The World Health Organization (WHO) aims to eliminate hepatitis C Virus (HCV) by 2030, therefore, widespread HCV screening is required. The WHO recommends HCV self-testing (HCVST) as a new approach. We aimed to evaluate disease burden reduction using the HCVST screening strategy and identify the most cost-effective approach. METHODS: We developed a dynamic open-cohort Markov model to assess the long-term effects and cost-effectiveness of HCVST in the Republic of Korea from 2024 to 2030. Strategies for comparison included universal, birth cohort, high-risk group screening, and no screening, focusing on the following: (1) incremental cost-effectiveness ratio (ICER) per disability-adjusted life-year (DALY) saved; (2) severe liver disease cases; and (3) liver-related death reduction. RESULTS: Universal HCVST screening is the most effective strategy for achieving the WHO goal by 2030, substantially lowering the incidence of severe liver disease by 71% and preventing liver-related deaths by 69 %, thereby averting 267,942 DALYs. Moreover, with an ICER of $8,078 per DALY and high cost-effectiveness, the sensitivity results prove that cost-effectiveness is robust. Although high-risk group screening offers the lowest cost compared with other strategies, its effectiveness in preventing severe liver disease is minimal, falling short of the current WHO goal. CONCLUSIONS: Our study confirms that universal HCVST screening is a cost-effective strategy aligned with the WHO goal to eliminate HCV by 2030. Despite its higher costs compared to risk-based screening, the disease burden can be significantly reduced by providing effective HCVST access to individuals who might otherwise not be tested.

Hepatitis C virus detection in hospital emergency departments. / Detección de la hepatitis C en los servicios de urgencias hospitalarios.

TEXT: The prevalence of active hepatitis C virus (HCV) infection is higher in hospital emergency departments (EDs) than in the general population. Numerous patients who seek emergency care are unaware that they have detectable viremia, yet they fall outside established ED protocols for HCV screening. Often they belong to groups with difficult access to health care who use the ED as their point of entry to the system. The aim of this consensus paper was to develop an approach to guide ED detection of HCV infection in all Spanish hospitals. Experts from the Spanish Society of Emergency Medicine (SEMES), the Spanish Association for Study of the Liver (AEEH), and the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC) met to establish criteria to guide health care professionals' decisions. The experts' review of the literature and discussion in consensus-building meetings resulted in evidence-based recommendations that consider the following aspects: 1) the population to target for HCV screening in the ED, 2) how to inform patients of the process, 3) how to carry out HCV screening, 4) how to order an HCV test, and 5) additional issues such as bundling HCV with other viral tests for comprehensive diagnosis, recording results in medical records, and implementing ways to retain and follow all patients with positive results. This consensus report provides guidelines and tools to facilitate emergency physicians' work and ensure effective detection of HCV infections and subsequent incorporation of patients into the health care system.

TEXTO: La prevalencia de la infección activa por el virus de la hepatitis C (VHC) en los servicios de urgencias hospitalarios (SUH) es superior a la de la población general. Muchos pacientes, desconocedores de su estado de infección y atendidos en urgencias, no cumplen con los criterios establecidos para el cribado del VHC o, muchas veces, son poblaciones de difícil acceso para el sistema sanitario, cuyo único vínculo de entrada son los SUH. Este documento tiene por objetivo elaborar una estrategia que sirva de guía para la detección de VHC en los SUH, de forma que homogenice el abordaje de la infección en todos los hospitales españoles. Un grupo de expertos de la Sociedad Española de Urgencias y Emergencias (SEMES), la Asociación Española para el Estudio del Hígado (AEEH) y la Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica (SEIMC), se reunieron para establecer los criterios que orienten las decisiones de los profesionales sanitarios. Estos se basan en la evidencia científica identificada mediante una revisión bibliográfica, y consensuada en reuniones deliberativas posteriores. Los aspectos abordados son: 1) población diana para la detección del VHC que acude al SUH; 2) información al paciente; 3) realización de la prueba del VHC; 4) solicitud de la prueba del VHC; y 5) otras consideraciones (diagnóstico integral de otras infecciones, registro de la prueba en la historia clínica y estrategias de vinculación y seguimiento). Este consenso proporciona pautas y herramientas para facilitar la labor del urgenciólogo y garantiza la detección efectiva del VHC y la subsiguiente vinculación al sistema sanitario.

A systematic PCR record-based re-call of HCV-RNA-positive people enables re-linkage to care and HCV elimination in Austria - The ELIMINATE project.

BACKGROUND AND AIMS: Identification of people living with hepatitis C virus (HCV) via readily available laboratory records could be a key strategy for macro-elimination, aligning with the WHO elimination goal. Therefore, the ELIMINATE(ELIMINation of HCV in AusTria East) project aimed to systematically re-link people with a 'last-positive' HCV-RNA PCR record to care. METHODS: In 10 major liver centres in Eastern Austria, a systematic readout of 'last-positive' HCV-RNA PCR test records obtained between 2008 and 2020 were conducted and linked to available patient contact data. Between 2020 and 2023, individuals were contacted first by phone, then by letter, to inform them about the availability of effective direct-acting antiviral (DAA) treatment and invite them for pre-treatment evaluation. RESULTS: The overall cohort of last-positive HCV+ individuals included 5695 subjects (62.5% males, mean age 57.3 ± 17.3 years); of note, 1931 (34%) of them had died and 759 (13%) individuals had no valid contact information. Of the remaining 3005 individuals, 1171 (40.0%) had already achieved sustained virological response (SVR) at the time of re-call. We successfully reached 617 (20.5%), of whom 417 (67.6%) attended their pre-treatment visit, and 397 (64.3%) commenced DAA-therapy. HCV cure has been confirmed in 326 individuals, corresponding to an SVR rate of 82.1%. CONCLUSION: The ELIMINATE project identified 5695 people living with HCV who were 'lost to care' despite documented HCV viraemia. While invalid contact data were an evident barrier to HCV elimination, premature deaths among the cohort underscored the severity of untreated HCV. The implementation of a systematic HCV-RNA PCR recorded-based re-call workflow represents an effective strategy supporting the WHO goal of HCV elimination.