Serum interleukin-10 and alpha-fetoprotein: A combined diagnostic approach for hepatocellular carcinoma in Egyptians with HCV.

PURPOSE: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide. Although alpha-fetoprotein (AFP) has been used for 60+ years as an HCC diagnostic serum marker, its accuracy is debated. Notably, the role of interleukin 10 (IL-10) in cancer development and metastasis is elevated in various tumor types, including HCC and chronic HCV infection. Our study aimed to investigate the diagnostic performance of IL-10 and AFP as biomarkers for HCV-induced HCC in an Egyptian population. METHODS: Eighty participants were recruited and categorized into three groups: HCV-related HCC (n=40), HCV-related cirrhosis (n=40), and control (n=20).The collected blood samples were analyzed to evaluate liver function, AFP levels, and IL-10 levels. RESULTS: Our analysis showed that AFP demonstrated low sensitivity (40% false-negative) and low specificity (33% false-positive).IL-10 levels were significantly higher (P < 0.001) in patients with HCC than in the cirrhosis and control groups. The serum AFP and IL-10 combination revealed significantly increased sensitivity (97.5%), diagnostic accuracy (71.1%), AUC (0.798), PPV (73.3%), and NPV ( 69.5%) when compared with either of them alone. CONCLUSION: the reliability of AFP as a major HCC marker was poor. However, IL-10 levels are a novel biomarker for the degree of HCC inflammation, considering IL-10's potential role in HCV-HCC development. We suggest combining AFP with IL-10 to improve the diagnostic and prognostic value of HCC considerably. Future research on these biomarkers should prioritize their clinical validity, prognostic usefulness, and compatibility with other therapeutic approaches as immunotherapy.

A cost analysis of a simplified model for HCV screening and treatment at a tertiary hospital in Zimbabwe.

BACKGROUND: The treatment of chronic hepatitis C virus (HCV) infection using directly acting antivirals was recently adopted in the treatment guidelines of Zimbabwe. The objectives of this study were to design a simplified model of HCV care and estimate the cost of screening and treatment of hepatitis C infection at a tertiary hospital in Zimbabwe. METHODS: We developed a model of care for HCV using WHO 2018 guidelines for the treatment of HCV infection and expert opinion. We then performed a micro-costing to estimate the costs of implementing the model of care from the healthcare sector perspective. Deterministic and probabilistic sensitivity analyses were performed to explore the impact of uncertainty in input parameters on the estimated total cost of care. RESULTS: The total cost of screening and treatment was estimated to be US$2448 (SD=$290) per patient over a 12-week treatment duration using sofosbuvir/velpatasvir. The cost of directly acting antivirals contributed 57.5% to the total cost of care. The second largest cost driver was the cost of diagnosis, US$819, contributing 34.6% to the total cost of care. CONCLUSION: Screening and treatment of HCV-infected individuals using directly acting antivirals at a tertiary hospital in Zimbabwe may require substantial financial resources.

Liver biopsy in the post-hepatitis C virus era in Japan.

In Japan, liver biopsies were previously crucial in evaluating the severity of hepatitis caused by the hepatitis C virus (HCV) and diagnosing HCV-related hepatocellular carcinoma (HCC). However, due to the development of effective antiviral treatments and advanced imaging, the necessity for biopsies has significantly decreased. This change has resulted in fewer chances for diagnosing liver disease, causing many general pathologists to feel less confident in making liver biopsy diagnoses. This article provides a comprehensive overview of the challenges and potential solutions related to liver biopsies in Japan. First, it highlights the importance of considering steatotic liver diseases as independent conditions that can coexist with other liver diseases due to their increasing prevalence. Second, it emphasizes the need to avoid hasty assumptions of HCC in nodular lesions, because clinically diagnosable HCCs are not targets for biopsy. Third, the importance of diagnosing hepatic immune-related adverse events caused by immune checkpoint inhibitors is increasing due to the anticipated widespread use of these drugs. In conclusion, pathologists should be attuned to the changing landscape of liver diseases and approach liver biopsies with care and attention to detail.

Hepatitis C prevalence and cascade of care among patients in the decentralised opioid agonist therapy programme of the canton of St Gallen, Switzerland: a cross-sectional study.

BACKGROUND: To eliminate chronic hepatitis C virus (HCV) infection by 2030, 90% of those infected must be diagnosed and 80% treated. In Switzerland, >40% of the estimated 32,000 infected people are still undiagnosed. In the canton of St Gallen, HCV prevalence and cascade of care have only been studied in the centralised opioid agonist therapy (OAT) setting (institutions), although about 80% of OAT patients are treated decentrally (general practitioner [GP] or pharmacy). AIM: To describe HCV prevalence and cascade of care among patients in the decentralised OAT programme of the canton of St Gallen, Switzerland, and compare it to contemporaneous data from the centralised setting. METHODS: For each patient receiving his/her OAT from a GP or pharmacy on 1 April 2021, the cantonal medical office sent a questionnaire to the prescribing GP. Patient characteristics, HCV antibody (Ab)/RNA screening uptake, HCV Ab/RNA prevalence and HCV treatment uptake were obtained and compared to those of patients of the Medizinisch-soziale Hilfsstelle 1 in St Gallen (centralised setting). RESULTS: Of the 563 OAT patients under the care of 127 GPs, 107 patients from 41 GPs could be analysed (median age: 48 years [IQR: 40-56]; ongoing intravenous drug use: 25%; OAT provider: 66% GP, 34% pharmacy). HCV Ab screening uptake was 68% (73/107) with an HCV Ab prevalence of 68% (50/73) among those tested. Of the HCV Ab-positive patients, 84% (42/50) were HCV RNA-tested, among whom 57% (24/42) were viraemic. HCV treatment uptake was 83% (20/24), with 95% (19/20) achieving a sustained virological response. Non-uptake of HCV screening and treatment tended to be higher among patients receiving OAT at the pharmacy vs at the GP's office: 37% vs 26% (p = 0.245) for screening and 30% vs 7% (p = 0.139) for treatment. The proportion never HCV Ab-tested and the proportion of HCV Ab-positives never HCV RNA-tested was significantly higher in the decentralised compared to the centralised setting: 32% vs 3% (p <0.001) never Ab-tested and 16% vs 0% (p = 0.002) never RNA-tested. In contrast, HCV treatment uptake (83% vs 78%), sustained virological response rate (95% vs 100%) and residual HCV RNA prevalence among the HCV Ab-positive (12% vs 14%) were comparable for both settings. CONCLUSION: In the decentralised OAT setting of the canton of St Gallen, HCV Ab prevalence is high. Since HCV Ab and RNA screening uptake are markedly lower than in the centralised setting, potentially >40% of patients with chronic HCV are not diagnosed yet. HCV screening in the decentralised setting needs improvement, e.g. by increasing awareness and simplifying testing. High HCV treatment uptake and cure rates are possible in centralised and decentralised settings.

Real-world performance of the NeuMoDx™ HCV Quant Test for quantification of hepatitis C virus (HCV)-RNA.

Quantification of hepatitis C virus (HCV)-RNA in serum or plasma samples is an essential parameter in HCV diagnostics. Here, the NeuMoDx™Molecular System (Qiagen) was tested for the most common HCV genotypes and compared to the cobas c6800 system (Roche). HCV-RNA from 131 plasma/serum samples from chronically infected patients was determined in parallel on the NeuMoDx and c6800 systems. Linearity was analysed using the four most common HCV genotypes (1-4) in our cohort. The coefficient of variation (CV) within (intra-assay) and between (inter-assay) runs was calculated based on HCV-RNA concentration. Quantitative HCV-RNA results were highly correlated on both test systems (R2 = 0.7947; y = 0.94 x + 0.37). On average, the NeuMoDx and c6800 HCV RNA levels showed a mean difference of only 0.05 log10 IU/mL but with a broad distribution (±1.2 2 x SD). The NeuMoDx demonstrated very good linearity across all HCV genotypes tested at concentrations between 1.7 and 6.2 log10 IU/mL (R2 range: 0.9257-0.9991) with the highest mean coefficient of determination for genotype 1 (R2 = 0.9909). The mean intra- and inter-assay CV for both serum and plasma samples was <5 %. The NeuMoDx HCV-RNA Assay demonstrates high subtype-independent comparability, linearity, and reproducibility for the quantification of HCV-RNA in serum and plasma samples from chronically infected patients.

Evaluating hepatitis C cascade of care surveillance system in Tuscany, Italy, through a population retrospective data-linkage study, 2015-2021.

This comprehensive retrospective data-linkage study aimed at evaluating the impact of Direct-Acting Antivirals (DAAs) on Hepatitis C Virus (HCV) testing, treatment trends, and access to care in Tuscany over six years following their introduction. Utilizing administrative healthcare records, our work reveals a substantial increase in HCV tests in 2017, attributed to the decision to provide universal access to treatment. However, despite efforts to eradicate chronic HCV through a government-led plan, the target of treating 6,221 patients annually was not met, and services contracted after 2018, exacerbated by the COVID-19 pandemic. Key findings indicate a higher prevalence of HCV screening among females in the 33-53 age group, influenced by pregnancy-related recommendations, while diagnostic tests and treatment uptake were more common among males. Problematic substance users constituted a significant proportion of those tested and treated, emphasizing their priority in HCV screening. Our paper underscores the need for decentralized HCV models and alternative testing strategies, such as point-of-care assays, especially in populations accessing harm reduction services, communities, and prisons. The study acknowledges limitations in relying solely on administrative records, advocating for improved data access and timely linkages to accurately monitor HCV care cascades and inform regional plans. Despite challenges, the paper demonstrates the value of administrative record linkages in understanding the access to care pathway for hard-to-reach populations. The findings emphasize the importance of the national HCV elimination strategy and the need for enhanced data collection to assess progress accurately, providing insights for future regional and national interventions.

Impact of new direct-acting antiviral therapy on the prevalence and undiagnosed proportion of chronic hepatitis C infection.

BACKGROUND: Patients with chronic hepatitis C (CHC) can be cured with the new highly effective interferon-free combination treatments (DAA) that were approved in 2014. However, CHC is a largely silent disease, and many individuals are unaware of their infections until the late stages of the disease. The impact of wider access to effective treatments and improved awareness of the disease on the number of infections and the number of patients who remain undiagnosed is not known in Canada. Such evidence can guide the development of strategies and interventions to reduce the burden of CHC and meet World Health Organization's (WHO) 2030 elimination targets. The purpose of this study is to use a back-calculation framework informed by provincial population-level health administrative data to estimate the prevalence of CHC and the proportion of cases that remain undiagnosed in the three most populated provinces in Canada: British Columbia (BC), Ontario and Quebec. METHODS: We have conducted a population-based retrospective analysis of health administrative data for the three provinces to generate the annual incidence of newly diagnosed CHC cases, decompensated cirrhosis (DC), hepatocellular carcinoma (HCC) and HCV treatment initiations. For each province, the data were stratified in three birth cohorts: individuals born prior to 1945, individuals born between 1945 and 1965 and individuals born after 1965. We used a back-calculation modelling approach to estimate prevalence and the undiagnosed proportion of CHC. The historical prevalence of CHC was inferred through a calibration process based on a Bayesian Markov chain Monte Carlo (MCMC) algorithm. The algorithm constructs the historical prevalence of CHC for each cohort by comparing the model-generated outcomes of the annual incidence of the CHC-related health events against the data set of observed diagnosed cases generated in the retrospective analysis. RESULTS: The results show a decreasing trend in both CHC prevalence and undiagnosed proportion in BC, Ontario and Quebec. In 2018, CHC prevalence was estimated to be 1.23% (95% CI: .96%-1.62%), .91% (95% CI: .82%-1.04%) and .57% (95% CI: .51%-.64%) in BC, Ontario and Quebec respectively. The CHC undiagnosed proportion was assessed to be 35.44% (95% CI: 27.07%-45.83%), 34.28% (95% CI: 26.74%-41.62%) and 46.32% (95% CI: 37.85%-52.80%) in BC, Ontario and Quebec, respectively, in 2018. Also, since the introduction of new DAA treatment in 2014, CHC prevalence decreased from 1.39% to 1.23%, .97% to .91% and .65% to .57% in BC, Ontario and Quebec respectively. Similarly, the CHC undiagnosed proportion decreased from 38.78% to 35.44%, 38.70% to 34.28% and 47.54% to 46.32% in BC, Ontario and Quebec, respectively, from 2014 to 2018. CONCLUSIONS: We estimated that the CHC prevalence and undiagnosed proportion have declined for all three provinces since the new DAA treatment has been approved in 2014. Yet, our findings show that a significant proportion of HCV cases remain undiagnosed across all provinces highlighting the need to increase investment in screening. Our findings provide essential evidence to guide decisions about current and future HCV strategies and help achieve the WHO goal of eliminating hepatitis C in Canada by 2030.

Performance of HCV core antigen and PCR testing in a predominantly genotype 3 population.

Hepatitis C core antigen (HCVcAg) is becoming increasingly recognized as an alternative to molecular testing for the confirmation of chronic hepatitis C. However, there are limited data on the performance of this assay in a genotype 3 (GT3) predominant country like Pakistan. We conducted a study to evaluate the diagnostic performance of HCVcAg against the HCV polymerase chain reaction (PCR) molecular test. HCV antibody-positive patients requiring confirmatory testing were recruited from August to October 2018 at the Pakistan Kidney and Liver Institute and Research Center (PKLI&RC), Lahore, Pakistan. Patients with previously known diagnoses or treatment histories were excluded. The Abbott HCV Ag assay was used for HCVcAg testing. Results ≥3.00 fmol/L were considered positive for HCVcAg. The Abbott RealTime HCV assay was used for PCR testing with a lower detection limit of ≥12 IU/mL. We computed the sensitivity, specificity and correlation of HCVcAg against HCV PCR. A total of 394 patients were recruited. The median age of the patients was 42 years. Most participants were females (51.5%, n = 203), 30.7% (n = 121) had HTN, 10.4% DM (n = 41) and 5% had APRI ≥2. The overall sensitivity was 98.0% and the specificity was 98.6%. The lowest detection limit of cAg was an HCV RNA value of 4657 IU/mL. The levels of cAg were highly correlated with those of HCV RNA by Spearman's rank correlation test (r = 0.935, p < .001). HCVcAg represents a suitable alternative with high sensitivity and specificity compared with HCV PCR in the GT3-predominant population and can be incorporated into algorithms to improve linkage to care.

Real-world hepatitis C prevalence and treatment uptake at opioid agonist therapy clinics in Ontario, Canada.

Widespread screening for hepatitis C virus (HCV) is necessary for Canada to meet its HCV elimination goals by 2030. People who currently or previously injected drugs are at high risk for HCV. Opioid agonist therapy (OAT, such as methadone and buprenorphine) has been shown to help stabilize the lives of people who are opioid-dependent. The distribution of OAT in North America typically requires daily, weekly, or monthly clinic visits and presents an opportunity for engagement, screening and treatment for those at high-risk of HCV. In this study, HCV screening was conducted by staff at OAT clinics in Ontario from 2016 to 2020 and those with chronic infections were treated on-site with direct-acting antivirals. Point-of-care or dried blood spot (DBS) testing was used for antibodies, DBS or serum for HCV RNA and serum for HCV RNA at SVR12 (sustained virological response). Clinics screened 1954 people (mean age 40 years ±12, 63% male). Forty-five percent were antibody positive, of whom 64% were HCV RNA+. Eighty percent of those RNA+ set an appointment in which 99% attended. Ninety-six percent started treatment with 87% completing treatment. Sixty-eight percent of people who completed treatment submitted a sample for SVR12 testing of which 97% achieved a virological cure. Results suggest that HCV screening and treatment at OAT clinics is feasible, effective and warrants expansion. Data suggest strong treatment adherence due to high rates of SVR12 comparable with other OAT-based HCV treatment programs. The lack of SVR12 sampling could be addressed by either on-site phlebotomy or incentivizing SVR12 sampling.

Chronic viral hepatitis C micro-elimination program using telemedicine in Guigang city.

Hepatitis C virus (HCV) represents a formidable menace to human health, necessitating urgent attention. The objective of this study was to assess the efficacy and safety of HCV health management in the city of Guigang which consists of five districts, employing a comprehensive multi-modal approach. The study systematically carried out HCV screening in Guigang city which consists of five districts, such as Gangbei District, Gangnan District, Guiping District, Qintang District, and Pingnan District from 1 January 2016 to 30 December 2022. The target population consisted of individuals residing in these aforementioned districts, falling within the age range of 30-75 years. A multidisciplinary HCV management team was established to deliver anti-HCV screening, diagnosis, and direct-acting antiviral (DAA) therapy. The primary outcome of interest was the achievement of sustained virologic response (SVR). A total of 2489 individuals were included as the target population, with 1694 individuals residing in Gangbei District, 202 in Gangnan District, 111 in Qintang District, 167 in Pingnan District, and 315 in Guiping District. Out of these individuals, 2478 were subjected to anti-HCV screening. The screening rates varied across the districts, ranging from a peak of 99.55% in Guigang City to a nadir of 98.41% in Guiping District. Remarkably, within Guigang City, a noteworthy enhancement was observed in the HCV-RNA diagnosis rate from 23.4% prior to program implementation to a remarkable 100% following 7 years of intervention and management. Furthermore, the diagnosis and treatment coordination rate experienced a substantial improvement, rising from 26.8% before program inception to 80%. Importantly, a total of 1180 individuals affected by hepatitis C were successfully cured, equating to a 100% cure rate. Logistic regression analysis revealed a significant association between serological status and factors such as Aging, bilirubin, and glutamic oxalacetic transaminase. The findings from our investigation unveil a pioneering HCV management model, exemplified by the Guigang model, which has contributed crucially to HCV microclearance efforts and serves as an invaluable reference for future initiatives.

Universal screening and treatment towards the elimination of chronic hepatitis C in China: an economic evaluation.

OBJECTIVES: China has the largest number of hepatitis C virus (HCV) infection in the world, but current levels of diagnosis and treatment are low. The objective of this study was to assess the cost-effectiveness of various universal HCV screening and treatment strategies in China and inform decisions on health policy. STUDY DESIGN: A cost-effectiveness analytical study. METHODS: We developed a Markov model to investigate cost-effectiveness of different HCV screening and treatment strategies in China. We simulated several screening scenarios for Chinese people aged 18-70 years. We estimated incremental cost-effectiveness ratios (ICERs) of different intervention scenarios compared with status quo. RESULTS: Expanded HCV screening and treatment strategy with prioritisation for high-risk groups (Scenario S5) was the most cost-effective strategy (ICER: USD $11,667.71/quality-adjusted life-year [QALY] gained), which resulted in great reduction in HCV-related diseases and deaths, with a 67.11% reduction in cases of chronic HCV. Universal HCV screening and treatment implementation remains a cost-effective strategy when delayed until 2025 (ICER: USD $17,093.69/QALY), yet the delayed strategy is less effective in reducing HCV-related deaths. CONCLUSIONS: Expanded HCV screening and treatment strategy with prioritisation for high-risk groups is the most cost-effective strategy and has lead to a significant reduction in both HCV morbidity and mortality in China, which would essentially eliminate HCV as a public threat.

Hospital-based screening outperforms primary care screening as a means of achieving hepatitis C virus micro-elimination.

AIM: To assess the respective performances of a HCV screening program in a hospital setting and a HCV screening model applied concomitantly in a primary care centre. METHODS: Adult patients consecutively admitted to hospital for ambulatory surgery were screened for anti-HCV antibodies (hospital screening cohort, HPSC), as were patients receiving blood tests for medical reasons in a primary care centre (primary care screening cohort, PCSC). Serum anti-HCV and HCV RNA levels were tested by ELISA and real-time PCR, respectively. RESULTS: Seroprevalence of HCV infection was 2.2 % in the HPSC and 1.4 % in the PCSC (p = 0.044). All viraemic patients (0.2 % in HPSC and 0.1 % in PCSC) were treated with direct-acting antivirals and 85.7 % experienced a sustained virological response. CONCLUSIONS: Hospital-based HCV screening outperformed primary care-centered screening, significantly increasing HCV case findings.

High prevalence of fatty liver and its association with metabolic syndrome among rural adults with chronic hepatitis C: Implications for primary healthcare.

BACKGROUND: Chronic hepatitis C (CHC) virus infection is a global health concern that is associated with significant liver-related morbidity and mortality. Owing to the inflammatory pathway, CHC can causefatty liver, liver cirrhosis, and liver cancer and is associated with cardiometabolic diseases, such as hypertension and diabetes. Fatty liver is associated with metabolic disorders, cardiovascular diseases, diabetes, and liver cancer. Hence, the early detection of fatty liver through noninvasive screening in adults with CHC is important in primary healthcare settings. This study aimed to explore the prevalence of fatty liver and its association with metabolic syndrome amongrural adults with CHC. METHODS: This was a series of cohort studies related to the elimination of the CHC burden around the western coastal Yunlin County, Taiwan, between August 2018 and July 2021. A cross-sectional study was conducted after hepatitis C virus RNA confirmation in a hepatitis C- endemic area. A gastrointestinal physician or radiologist assessed fatty liver by ultrasonography. Fatty liver was classified into four grades: normal, mild, moderate, and severe. Three liver enzyme biomarkers were identified. According to the Taiwan national standard, metabolic syndrome was defined based on the presence of three or more of the five abnormal biomarkers, including increased waist circumference, elevated blood pressure, elevated fasting blood glucose level, elevated triglyceride level, and low high-density lipoprotein cholesterol level. RESULTS: A total of 256 rural adults with CHC were enrolled. The mean age of the participants was 67.5 (standard deviation = 11.8) years, with a low educational level. High prevalence of fatty liver (79%), central obesity (54.3%), elevated blood pressure (55.5%),elevated fasting blood glucose (FBG) level (44.9%), and metabolic syndrome (37.9%) were observed.The results showed that adults with CHC with moderate to severe fatty liver were significantly associated with an increased risk of increased waist circumference (P < 0.001), increased blood pressure (P < 0.001), low high-density lipoprotein cholesterol level (P < 0.05), and elevated liver enzyme biomarker levels (all P < 0.05) after adjusting for age, sex, and educational level. Furthermore, adults with CHC with moderate to severe fatty liver were significantly associated with a greater risk of metabolic syndrome (odds ratio = 2.85, 95% confidence interval = 1.66 to 4.92). CONCLUSIONS: The findings demonstrate a high prevalence of fatty liver in rural adults with CHC, which is significantly associated with obesity, metabolic syndrome, and elevated liver biomarker levels. Clinicians and primary healthcare providers must encourage patients with CHC to receive antiviral therapy combined with weight loss management and lifestyle modification, allowing general improvements in their liver and cardiometabolic health.

SASLT guidelines: Update in treatment of hepatitis C virus infection, 2024.

ABSTRACT: Hepatitis C virus (HCV) infection has been a major global health concern, with a significant impact on public health. In recent years, there have been remarkable advancements in our understanding of HCV and the development of novel therapeutic agents. The Saudi Society for the Study of Liver Disease and Transplantation formed a working group to develop HCV practice guidelines in Saudi Arabia. The methodology used to create these guidelines involved a comprehensive review of available evidence, local data, and major international practice guidelines regarding HCV management. This updated guideline encompasses critical aspects of HCV care, including screening and diagnosis, assessing the severity of liver disease, and treatment strategies. The aim of this updated guideline is to assist healthcare providers in the management of HCV in Saudi Arabia. It summarizes the latest local studies on HCV epidemiology, significant changes in virus prevalence, and the importance of universal screening, particularly among high-risk populations. Moreover, it discusses the promising potential for HCV elimination as a public health threat by 2030, driven by effective treatment and comprehensive prevention strategies. This guideline also highlights evolving recommendations for advancing disease management, including the treatment of HCV patients with decompensated cirrhosis, treatment of those who have previously failed treatment with the newer medications, management in the context of liver transplantation and hepatocellular carcinoma, and treatment for special populations.

Artificial intelligence predicts direct-acting antivirals failure among hepatitis C virus patients: A nationwide hepatitis C virus registry program.

BACKGROUND/AIMS: Despite the high efficacy of direct-acting antivirals (DAAs), approximately 1-3% of hepatitis C virus (HCV) patients fail to achieve a sustained virological response. We conducted a nationwide study to investigate risk factors associated with DAA treatment failure. Machine-learning algorithms have been applied to discriminate subjects who may fail to respond to DAA therapy. METHODS: We analyzed the Taiwan HCV Registry Program database to explore predictors of DAA failure in HCV patients. Fifty-five host and virological features were assessed using multivariate logistic regression, decision tree, random forest, eXtreme Gradient Boosting (XGBoost), and artificial neural network. The primary outcome was undetectable HCV RNA at 12 weeks after the end of treatment. RESULTS: The training (n=23,955) and validation (n=10,346) datasets had similar baseline demographics, with an overall DAA failure rate of 1.6% (n=538). Multivariate logistic regression analysis revealed that liver cirrhosis, hepatocellular carcinoma, poor DAA adherence, and higher hemoglobin A1c were significantly associated with virological failure. XGBoost outperformed the other algorithms and logistic regression models, with an area under the receiver operating characteristic curve of 1.000 in the training dataset and 0.803 in the validation dataset. The top five predictors of treatment failure were HCV RNA, body mass index, α-fetoprotein, platelets, and FIB-4 index. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of the XGBoost model (cutoff value=0.5) were 99.5%, 69.7%, 99.9%, 97.4%, and 99.5%, respectively, for the entire dataset. CONCLUSION: Machine learning algorithms effectively provide risk stratification for DAA failure and additional information on the factors associated with DAA failure.

Chronic Hepatitis C Cascade of Care in Prisoners-Is There Still Some Work to Do? Analysis of Two Large Penitentiaries in Northern Italy.

Penitentiaries have a higher burden of communicable diseases compared to the general population. Prisoners should be tested for hepatitis C virus (HCV) and have direct access to treatment. We analysed the HCV cascade of care in two penitentiaries in Brescia, Northern Italy. At admission, prisoners are offered a voluntary screening for HCV, while patients with known infections are tested with an HCVRNA measurement. We performed an observational retrospective study including all the subjects admitted to the penitentiaries from 1 January 2015 to 31 October 2021. We conducted a descriptive analysis. During the study period, 5378 admissions were registered, and 2932 (54.5%) screenings were performed. Hepatitis C virus antibody positivity was found in 269 tests (9.2%). Hepatitis C virus RNA was detectable in 169 people. During the study period, 77 treatments with direct-acting antivirals (DAAs) were administered. Follow-up was available in 45 patients, and sustained virological response (SVR) was documented in 44 of them. Retention in care occurred in less than half of the prisoners after release. Our data demonstrate poor screening adherence that could benefit from educational programs. Treatment rates could be improved with test-and-treat programs. More efforts are needed to eliminate HCV as a public threat by 2030. Dedicated local networks, including infectious diseases (ID) departments, substance abuse services and prisons, could mitigate these issues.

Late presentation for hepatitis C treatment: prevalence and risk factors in the Swiss Hepatitis C Cohort.

OBJECTIVE: Patients with 'late presentation' (LP) of chronic hepatitis C infection (HCV) have already developed advanced liver disease before receiving direct-acting antiviral (DAA) treatment. Even after successful treatment, the risk of morbidity and premature death remains elevated, leading to an unnecessary disease burden. This study aimed to assess the prevalence of LP within the prospective observational Swiss Hepatitis C Cohort (SCCS) and evaluate risk factors as determinants of LP. METHODS: Treatment-naïve participants of SCCS who received DAA treatment between 2014 and 2019 were included. Demographic, clinical and behavioural data were compared between the LP and non-LP strata. LP prevalence was calculated over time and by year. LASSO regression was used to identify potential risk factors for LP, and odds ratios were calculated by refitting logistic regression models. RESULTS: In this explorative, retrospective case-control study using data of n  = 5829 SCCS members, a total of 21.3% received their first HCV treatment. The cumulative LP prevalence decreased from mid-2015 and stabilised at 46.5% ( n  = 579) by the end of 2019. Male gender, higher age and a history of alcohol overuse were associated with a higher risk of LP. CONCLUSION: Despite the study's limitations, LP prevalence was higher than anticipated, considering Switzerland's availability period and universal access to DAAs. Therefore, any HCV LP should be viewed as a healthcare system failure, primarily in high-income economies. As LP is directly linked to the disease burden, it must be included as a mandatory parameter in surveillance response systems of HCV elimination programs.

Patient-centered and integrated outreach care for chronic hepatitis C patients with serious mental illness in Taiwan.

Patients with serious mental illness have a higher risk of hepatitis C virus (HCV) infection but suboptimal HCV care. The current study aimed to facilitate HCV treatment uptake by implementing an integrated outreach care model. Multidisciplinary outreach screening followed by HCV reflex testing and onsite treatment for schizophrenia patients was accomplished through the coordination of nongovernmental organizations, remote specialists, and local care providers. The objective was microelimination effectiveness, defined as the multiplication of the rates of anti-HCV antibodies screening, accurate HCV RNA diagnosis, treatment allocation, treatment completion, and sustained virological response (SVR12; no detectable HCV RNA throughout 12 weeks in the post-treatment follow-up period). A total of 1478 of the 2300 (64.3%) psychiatric patients received HCV mass screening. Seventy-three (4.9%) individuals were seropositive for anti-HCV antibodies. Of the 73 anti-HCV seropositive patients, all (100%) received HCV reflex testing, and 29 (37.7%) patients had HCV viremia. Eight patients (34.8%) had advanced liver disease, including 3 with liver cirrhosis and 2 with newly diagnosed hepatocellular carcinoma. Twenty-three of the 24 (95.8%) patients who stayed in the healthcare system received and completed 8 weeks of glecaprevir/pibrentasvir treatment and post-treatment follow-up without significant DDIs or adverse events. The SVR12 rate was 100%. The microelimination effectiveness in the current study was 61.6%. Individuals with serious mental illness are underserved and suffer from diagnostic delays. This patient-centered and integrated outreach program facilitated HCV care in this marginalized population.

Predicting de-novo portal vein thrombosis after HCV eradication: A long-term competing risk analysis in the ongoing PITER cohort.

BACKGROUND & AIMS: Sustained virological response (SVR) by direct-acting antivirals (DAAs) may reverse the hypercoagulable state of HCV cirrhosis and the portal vein thrombosis (PVT) risk. We evaluated the incidence and predictive factors of de novo, non-tumoral PVT in patients with cirrhosis after HCV eradication. METHODS: Patients with HCV-related cirrhosis, consecutively enrolled in the multi-center ongoing PITER cohort, who achieved the SVR using DAAs, were prospectively evaluated. Kaplan-Meier and competing risk regression analyses were performed. RESULTS: During a median time of 38.3 months (IQR: 25.1-48.7 months) after the end of treatment (EOT), among 1609 SVR patients, 32 (2.0%) developed de novo PVT. A platelet count ≤120,000/µL, albumin levels ≤3.5 mg/dL, bilirubin >1.1 mg/dL, a previous liver decompensation, ALBI, Baveno, FIB-4, and RESIST scores were significantly different (p < 0.001), among patients who developed PVT versus those who did not. Considering death and liver transplantation as competing risk events, esophageal varices (subHR: 10.40; CI 95% 4.33-24.99) and pre-treatment ALBI grade ≥2 (subHR: 4.32; CI 95% 1.36-13.74) were independent predictors of PVT. After HCV eradication, a significant variation in PLT count, albumin, and bilirubin (p < 0.001) versus pre-treatment values was observed in patients who did not develop PVT, whereas no significant differences were observed in those who developed PVT (p > 0.05). After the EOT, esophageal varices and ALBI grade ≥2, remained associated with de novo PVT (subHR: 9.32; CI 95% 3.16-27.53 and subHR: 5.50; CI 95% 1.67-18.13, respectively). CONCLUSIONS: In patients with HCV-related cirrhosis, a more advanced liver disease and significant portal hypertension are independently associated with the de novo PVT risk after SVR.

The metabolic fingerprint of chronic hepatitis C progression: Metabolome shifts and cutting-edge diagnostic options.

Hepatitis C virus infection causes chronic diseases such as cirrhosis and hepatocellular carcinoma. Metabolomics research has been shown to be linked to pathophysiologic pathways in liver illnesses. The aim of this study was to investigate the serum metabolic profile of patients with chronic hepatitis C (CHC) infection and to identify underlying mechanisms as well as potential biomarkers associated with the disease. Nuclear magnetic resonance (NMR) was used to evaluate the sera of 83 patients with CHC virus and 52 healthy control volunteers (NMR). Then, multivariate statistical analysis was used to find distinguishing metabolites between the two groups. Sixteen out of 40 metabolites including include 3-HB, betaine, carnitine, creatinine, fucose, glutamine, glycerol, isopropanol, lysine, mannose, methanol, methionine, ornithine, proline, serine, and valine-were shown to be significantly different between the CHC and normal control (NC) groups (variable importance in projection >1 and p < 0.05). All the metabolic perturbations in this disease are associated with pathways of Glycine, serine, and threonine metabolism, glycerolipid metabolism, arginine and proline metabolism, aminoacyl-tRNA biosynthesis, cysteine and methionine metabolism, alanine, aspartate, and glutamate metabolism. Multivariate statistical analysis constructed using these expressed metabolites showed CHC patients can be discriminated from NCs with high sensitivity (90%) and specificity (99%). The metabolomics approach may expand the diagnostic armamentarium for patients with CHC while contributing to a comprehensive understanding of disease mechanisms.