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.

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.

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.

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.

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.

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.

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.

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.

Highly sensitive and specific electrochemical biosensor for direct detection of hepatitis C virus RNA in clinical samples using DNA strand displacement.

Hepatitis C virus (HCV) is a common blood-borne infection that can lead to long-term illnesses such as hepatocellular cancer and liver cirrhosis. Early diagnosis is crucial for effective management, as no vaccine is available for preventing HCV infection. However, the high cost and complexity of current molecular diagnostic tools hinder efforts to achieve early diagnosis and prevent transmission, particularly in resource-limited settings. We developed a novel electrochemical biosensor for point-of-care testing (POCT) of HCV RNA. The sensor utilizes a strand displacement method, where the target RNA displaces a gold nanoparticle-labeled reporter probe (AuRP) from a pre-hybridized duplex with a magnetic nanoparticle (MNP)-labeled capture probe. The amount of displaced AuRP, detected using differential pulse anodic stripping voltammetry (DPASV), is directly proportional to the target RNA concentration. The biosensor exhibited excellent analytical performance, with a detection limit of 4 fM for synthetic targets and 43 ng/µL for RT-PCR products. Importantly, it successfully detected HCV RNA directly in clinical plasma samples without the need for RNA extraction or amplification. The sensor was used to analyze 30 RNA samples from HCV-positive patients, 20 cDNA samples from viral RNA, 30 HCV-positive plasma samples, and 22 HCV-negative plasma samples. The sensor results show good concordance with the RT-PCR results, demonstrating the sensor's potential for detecting HCV in clinical samples.

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 in PLCs 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 account for a high proportion of PLCs in China.

Diagnostic performance of CT/MRI LI-RADS v2018 in non-cirrhotic hepatitis C virus infection.

PURPOSE: To evaluate the diagnostic performance of LI-RADS among patients with non-cirrhotic hepatitis C virus (HCV) infection. METHODS: This retrospective, IRB-approved, single-center study included 66 observations from 43 adult patients (11 women, 32 men; median age 65 years). All patients received liver protocol CT or MRI from 2010 to 2023, had HCV, and did not have cirrhosis based on histopathology. Three board-certified abdominal radiologists blinded to histopathology and imaging follow-up assessed each observation for major features and final LI-RADS category, and inter-reader agreements with weighted kappa were calculated. The positive predictive value, sensitivity, specificity, and accuracy of in diagnosing HCC and overall malignancy was calculated. RESULTS: Of the 66 observations, 53 (80%) were malignant and 13 (20%) were benign. Positive predictive value for HCC was 0-0% for LR-1, 0-0% for LR-2, 0-33% for LR-3, 57-100% for LR-4, 98-100% for LR-5, 25-50% for LR-M, and 83-100% for LR-TIV. Positive predictive value for overall malignancy was 0-0% for LR-1, 0-0% for LR-2, 0-33% for LR-3, 57-100% for LR-4, 98-100% for LR-5, 100-100% for LR-M, and 100-100% for LR-TIV. For LR-5 in identifying HCC, sensitivity ranged from 74 to 90%, specificity from 94 to 100%, and accuracy from 80 to 91%. For the composite of LR-5, LR-M, or LR-TIV in identifying overall malignancy, sensitivity was 87-98%, specificity was 92-100%, and accuracy was 89-97%. The inter-reader agreement for major features varied from moderate to substantial, with substantial agreement for the final category. CONCLUSION: CT/MRI LI-RADS v2018 criteria can be applied to non-cirrhotic HCV patients with near-perfect specificity.

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.

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.

Single-Center Retrospective Review of Standard Versus Minimal Monitoring for Hepatitis C Direct Acting Antiviral Therapy.

BACKGROUND: Highly effective direct acting antiviral (DAA) therapies have transformed the landscape of Hepatitis C Virus (HCV) treatment. However, there continues to be limited data regarding the efficacy and safety of required in-person clinic visits (standard monitoring) versus completely telehealth clinic visits (minimal monitoring) during HCV therapy, which could delay practice adoption. OBJECTIVES: This study aimed to assess the rates of undetectable HCV RNA in sustained viral load 12 weeks after therapy (SVR12) in standard versus minimal monitoring approaches during DAA. METHODS: A 12-month, single-center retrospective cohort study was conducted in treatment-naïve HCV-infected adults who received DAA therapy between 5/1/2020-4/30/2021. The standard monitoring group had > 1 in-person clinic visit with HCV RNA lab monitoring during DAA treatment. The minimal monitoring group had entirely telehealth visits without HCV RNA lab monitoring during treatment. Both groups received telephonic touchpoints throughout DAA treatment from a Clinical Pharmacist Practitioner and Nurse Care Coordinator. The primary outcome was SVR12. RESULTS: From May 2020 to April 2021, 133 HCV patients met inclusion criteria and were treated with DAA (Standard n=56; Minimal: n=77), with no differences in baseline demographics. Overall, total encounters during DAA treatment remained significantly higher in the standard versus minimal monitoring group (Standard: 2.1 ± 0.8, vs MInimal: 1.7 ± 0.9; p <0.01). Although minimal monitoring had higher loss to follow-up rates (Standard: 7.1% vs Minimal: 18.2%; p=0.06), the modified intention-to-treat analysis showed no differences in SVR between standard versus minimal monitoring approaches (Standard: 98.1%, n=51 vs Minimal: 95.3%, n=60; p=0.41). CONCLUSIONS: This single-center retrospective cohort study demonstrated that minimal monitoring during HCV treatment was as effective in achieving SVR cure rates as standard monitoring. Eliminating required in-person clinic visits during DAA therapy alongside a collaborative approach may play a major role in overcoming barriers to HCV care in select patients.

Dynamic strategies and optimal control analysis for hepatitis C management: non-invasive liver fibrosis diagnosis.

This study proposes a novel model employing nonlinear ordinary differential equations to dissect HCV dynamics. Six distinct population groups are delineated: Susceptible, Treatment, Responder, Non-Responder, Cured, and Fibrosis. A detailed numerical analysis of this model was conducted, tracking the predicted trends over a span of 20 years. The primary objective of this analysis is to assess and confirm the model's predictive accuracy and its potential to supplant invasive diagnostic methods in monitoring the progression of liver fibrosis. By incorporating various control parameters, namely u1(t),u2(t), and u3(t), the model offers a nuanced perspective on disease progression and treatment outcomes. Parameter u1(t) modulates treatment-induced fibrosis progression, providing a crucial lever for mitigating treatment-related side effects. u2(t) reflects treatment effectiveness, capturing the proportion of responders within the treatment cohort. Meanwhile, u3(t) governs fibrosis progression in non-responders, shedding light on the disease's natural trajectory without effective treatment.

Thrombospondin 2 as a Predictive Biomarker for HCC in Hepatitis C Patients: A Longitudinal Study Following DAA Therapy.

This multicentre study investigated the dynamics of thrombospondin 2 (TSP2) levels during direct-acting antiviral (DAA) therapy in hepatitis C virus (HCV) infected patients and evaluated TSP2's potential as a predictive marker for hepatocellular carcinoma (HCC). All 134 participants achieved sustained virological response at 12 weeks (SVR12) with DAA therapy, and serum TSP2 levels significantly decreased from before and after treatment (p < 0.001). During the median follow-up period of 6.0 years, HCC after DAA therapy was observed in 16 patients (11.9%). Patients with serum TSP2 High (≥ 32 ng/mL) at SVR12 had a significantly higher cumulative occurrence of HCC than did those without (26.5% vs. 7.0%, p = 0.0033). A multivariate Cox proportional hazards model identified male gender (HR 4.84, p = 0.005), HCC history (HR 4.61, p = 0.017) and TSP2 High (HR 3.93, p = 0.009) as significant independent predictors of HCC occurrence after DAA therapy. The model had a high concordance index of 0.878. Additionally, combining TSP2 High and FIB-4 High (≥ 3.538) at SVR12 yielded high specificity and negative predictive value (0.941 and 0.917, respectively) for predicting HCC. Kaplan-Meier analysis showed a higher HCC incidence in the TSP2 High + FIB-4 High group (log-rank p < 0.0001). In conclusion, TSP2 may be a promising biomarker for personalised HCC surveillance in DAA-treated hepatitis C patients.

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.

Implementing a new HCV model of care for people who use drugs.

Background & Aims: An estimated 50 million individuals have chronic hepatitis C virus (HCV) infection worldwide and people who use drugs (PWUD) are disproportionately affected. Persistent stigma and discrimination make it challenging for PWUD to access healthcare, potentially hindering HCV elimination progress in this population. To mitigate healthcare access barriers in PWUD, an HCV care model that simplified screening and linkage to care pathways was developed and rolled out in the Balearic Islands, Spain. Methods: The prospective multicentre community model of care was implemented in 21 centres serving PWUD. This model involved: (1) participant recruitment and HCV antibody screening onsite via a point-of-care anti-HCV test, phlebotomy, or laboratory records; (2) HCV RNA, HBsAg and anti-HIV testing via a dried blood spot or phlebotomy; (3) linkage to specialist care and treatment prescription via telemedicine, when required; and (4) onsite monitoring of: (a) sustained virologic response (SVR) 4 and ≥12 weeks after treatment completion and; (b) potential new HCV infection or reinfection ∼1 year after phase 1 or SVR ≥12 monitoring. Care model acceptability was assessed. Results: Between April 2021 and April 2023, 1,423 participants were recruited, of whom 464 (33%) were anti-HCV+ and 170 (12%) had detectable HCV RNA. Of the latter, 147 (86%) initiated therapy, of whom 124 (84%) completed it. SVR ≥12 monitoring was performed in 95 (77%) of these, of whom 88 (93%) had undetectable HCV RNA. Upon re-screening, four HCV reinfections were detected. Over 90% accepted study participation and screening and treatment decentralisation. Conclusions: This adapted care model, which decentralised screening, diagnosis, and treatment, effectively increased healthcare access among PWUD, improving progress towards HCV elimination in this population in Spain. Impact and implications: People who use drugs (PWUD) are among the most affected by chronic hepatitis C virus (HCV) infection globally. A simplified model of care was implemented in 21 centres serving this population across the Balearic Islands, Spain, to offer HCV care to 1,423 PWUD in 2021-2023. This decentralised screening, diagnosis, and treatment model resulted in an HCV cure rate of 93% of those who both completed therapy and were monitored post treatment completion. The Hepatitis C Free Balears model can guide the HCV elimination efforts of regional health authorities and other stakeholders in the rest of Spain and other parts of the world.

Ensemble for evaluating diagnostic efficacy of non-invasive indices in predicting liver fibrosis in untreated hepatitis C virus population.

BACKGROUND: Hepatitis C virus (HCV) infection progresses through various phases, starting with inflammation and ending with hepatocellular carcinoma. There are several invasive and non-invasive methods to diagnose chronic HCV infection. The invasive methods have their benefits but are linked to morbidity and complications. Thus, it is important to analyze the potential of non-invasive methods as an alternative. Shear wave elastography (SWE) is a non-invasive imaging tool widely validated in clinical and research studies as a surrogate marker of liver fibrosis. Liver fibrosis determination by invasive liver biopsy and non-invasive SWE agree closely in clinical studies and therefore both are gold standards. AIM: To analyzed the diagnostic efficacy of non-invasive indices [serum fibronectin, aspartate aminotransferase to platelet ratio index (APRI), alanine aminotransferase ratio (AAR), and fibrosis-4 (FIB-4)] in relation to SWE. We have used an Artificial Intelligence method to predict the severity of liver fibrosis and uncover the complex relationship between non-invasive indices and fibrosis severity. METHODS: We have conducted a hospital-based study considering 100 untreated patients detected as HCV positive using a quantitative Real-Time Polymerase Chain Reaction assay. We performed statistical and probabilistic analyses to determine the relationship between non-invasive indices and the severity of fibrosis. We also used standard diagnostic methods to measure the diagnostic accuracy for all the subjects. RESULTS: The results of our study showed that fibronectin is a highly accurate diagnostic tool for predicting fibrosis stages (mild, moderate, and severe). This was based on its sensitivity (100%, 92.2%, 96.2%), specificity (96%, 100%, 98.6%), Youden's index (0.960, 0.922, 0.948), area under receiver operating characteristic curve (0.999, 0.993, 0.922), and Likelihood test (LR+ > 10 and LR- < 0.1). Additionally, our Bayesian Network analysis revealed that fibronectin (> 200), AAR (> 1), APRI (> 3), and FIB-4 (> 4) were all strongly associated with patients who had severe fibrosis, with a 100% probability. CONCLUSION: We have found a strong correlation between fibronectin and liver fibrosis progression in HCV patients. Additionally, we observed that the severity of liver fibrosis increases with an increase in the non-invasive indices that we investigated.