Hepatitis C Research Articles

Shear-wave elastography to predict hepatocellular carcinoma after hepatitis C virus eradication: A systematic review and meta-analysis.

Direct-acting antiviral agents (DAAs) are highly effective treatment for chronic hepatitis C (CHC) with a significant rate of sustained virologic response (SVR). The achievement of SVR is crucial to prevent additional liver damage and slow down fibrosis progression. The assessment of fibrosis degree can be performed with transient elastography, magnetic resonance elastography or shear-wave elastography (SWE). Liver elastography could function as a predictor for hepatocellular carcinoma (HCC) in CHC patients treated with DAAs. To explore the predictive value of SWE for HCC development after complete clearance of hepatitis C virus (HCV). A comprehensive literature search of clinical studies was performed to identify the ability of SWE to predict HCC occurrence after HCV clearance. In accordance with the study protocol, a qualitative and quantitative analysis of the evidence was planned. At baseline and after 12 wk of follow-up, a trend was shown towards greater liver stiffness (LS) in those who go on to develop HCC compared to those who do not [baseline LS standardized mean difference (SMD): 1.15, 95% confidence interval (95%CI): 020-2.50; LS SMD after 12 wk: 0.83, 95%CI: 0.33-1.98]. The absence of a statistically significant difference between the mean LS in those who developed HCC or not may be related to the inability to correct for confounding factors and the absence of raw source data. There was a statistically significant LS SMD at 24 wk of follow-up between patients who developed HCC vs not (0.64; 95%CI: 0.04-1.24). SWE could be a promising tool for prediction of HCC occurrence in patients treated with DAAs. Further studies with larger cohorts and standardized timing of elastographic evaluation are needed to confirm these data.

Feasibility of hepatitis C elimination by screening and treatment alone in high-income countries.

Despite the availability of highly effective direct-acting antiviral therapy, chronic hepatitis C (CHC) continues to cause a major public health burden. In many high-income countries, treatment rates have been declining, which was exacerbated by the impact of the COVID-19 pandemic, threatening the ability to meet the World Health Organization (WHO)'s targets for eliminating HCV as a public health threat by 2030. We sought to model the impact of CHC in Canada, a resource-rich country with ongoing immigration from HCV-endemic regions; which relies exclusively on risk-based screening for case identification. We developed an agent-based model to characterize the HCV epidemic in a high-income country with ongoing immigration. Combinations of prevention such as harm reduction, screening, and treatment strategies were considered. Model parameters were estimated from the literature and calibrated against historical HCV data. Sensitivity analyses were performed to assess uncertainty. Under the current status quo of risk-based screening, we predict the incidence of CHC-induced decompensated cirrhosis, HCC, and liver-related deaths would decrease by 79.4%, 76.1%, and 62.1%, respectively, between 2015 and 2030, but CHC incidence would only decrease by 11.1%. The results were sensitive to HCV transmission rate and an annual number of people initiating treatment. Current risk-based screening, and subsequent treatment, will be inadequate to achieve WHO goals. With extensive scale-up in screening, and treatment, the mortality target may be achievable, but the target for preventing new CHC cases is unlikely reachable, highlighting the importance of developing enhanced harm-reduction strategies for HCV elimination.

The Efficacy of On-Site Integration Screening and Microelimination Programs for Chronic Hepatitis C in a Detection Center: A Comparison of the Treatment Outcomes and Characteristics of Incarcerated Patients and Outpatients.

We aimed to analyze the different patient characteristics and treatment outcomes (such as sustained viral response, SVR) between incarcerated patients with chronic hepatitis C (CHC) and those with CHC from the outpatient department through an on-site integrated screening and microelimination program in a detection center. In this retrospective study, which ran from May 2021 to April 2022, we included 32 consenting male prisoners aged at least 20 years who were willing to participate in the study. Members of the control group (who received DAAs in an outpatient setting) were selected from the treated CHC patient databank of individuals who received DAA regimens at Chi Mei Hospital between January 2021 and December 2022. The patients in the two groups did not differ significantly in terms of age, FIB-4 score, HCV RNA, HBV coinfection, hemogram findings, coagulation profiles, and renal function tests. However, the patients in the incarcerated group had a significantly different genotype distribution compared to the control group, significantly lower liver enzyme levels, and higher albumin and bilirubin levels compared to those in the control group. The rate of SVR to DAA treatment obtained among incarcerated patients did not differ significantly from that obtained among patients in the control group. Loss to follow-up (for several reasons) is a major reason for treatment discontinuation among these patients.

Impact des antiviraux à action directe sur l'athérosclérose subclinique chez les patients atteints d’une hépatite C chronique

The impact of direct antiviral drugs (DAAs) on extrahepatic manifestations in chronic hepatitis C (CHC) has been poorly studied. To assess the prevalence of subclinical atherosclerosis in patients with CHC and the impact of DAAs on atherosclerotic lesions. Methods A 5-year prospective evaluative study, including patients followed for CHC at hepato-gastroenterology department. The subclinical atherosclerosis was assessed by ultrasound measurement of carotid intima-media thickness (IMTc) and the highest IMTc measurements from the left and right side defined the IMTc maximum (IMTc max). IMTc>75th percentile (IMTc75) define subclinical atherosclerosis with high cardiovascular risk. Patients were evaluated before (T0) and one year after DAAs therapy achievement (T1). At time T0, forty patients (median age: 55 y.; sex ratio M / F = 0.48), were included. Average value of IMTc max was 0.68 ± 0.16 mm. Subclinical atherosclerosis was noted in 82.5 %. At time T1, 28 patients were evaluated, all of whom completed sustained virological response (SVR). Compared to time T0, there was a significant increase in cholesterol (p = 0.001) and triglyceride (p = 0.009) levels. IMTc max was significantly higher at time T1 compared to T0 (0.75 Vs 0.67 mm, p = 0.04). Prevalence of IMTc75 was 82.1% at time T0 and 75% at time T1 (p=0.5). SVR, in CHC patients treated with DAA, was associated with worsening of carotid atherosclerotic lesions.

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

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. 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. 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. 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.

The Fixed Dose Combination of Sofosbuvir and Velpatasvir is Safe and Effective in Patients of Chronic Hepatitis C With End-stage Renal Disease

The burden of hepatitis C virus (HCV) in India is alarming, with a major share of this virus being witnessed in patients with end-stage renal disease (ESRD). A pan-genotypic combination of sofosbuvir and velpatasvir is found to be safe, effective, and economical in resource-constraint countries such as ours. However, there are scanty data on the efficacy and safety of sofosbuvir and velpatasvir combination in patients with ESRD. Hence, we performed this study to evaluate the safety and efficacy of the combination of sofosbuvir and velpatasvir in patients of chronic hepatitis C (CHC) with ESRD. This is an observational study comprising of 40 CHC patients with ESRD on maintenance hemodialysis. All patients were treated with a fixed-dose combination of sofosbuvir and velpatasvir for 12 weeks in case of non-cirrhotic or compensated cirrhosis and 24 weeks in case of decompensated cirrhosis. The efficacy was assessed by sustained virological response defined by negative HCV RNA at 12 weeks (sustained virological response [SVR] 12) post treatment, and safety was assessed by recording any side-effects of all patients. Out of the 40 patients enrolled in our study, majority were non-cirrhotic (77%), and all were treatment-naive. The mean age was 49.87±12.13 years, and 80% patients were male. The mean baseline HCV RNA was 2.61±7.83×106 IU/ml. All the 40 patients (100%) achieved undetectable HCV RNA at the end of treatment; however, 39 patients (97.5%) achieved SVR 12. There was no significant deterioration of estimated glomerular filtration rate (eGFR) after completion of antiviral therapy as compared to the baseline eGFR (13.27±10.32 vs13.54±11.38, P= 0.54). None of the patients reported any serious adverse effects during treatment. The fixed-dose combination of sofosbuvir and velpatasvir is effective and has showed excellent safety profile in patients of CHC with ESRD.

Effects of HCV Clearance with Direct-Acting Antivirals (DAAs) on Liver Stiffness, Liver Fibrosis Stage and Metabolic/Cellular Parameters.

Chronic hepatitis C (CHC) is a clinical and pathological syndrome with various causes and is characterized by varying degrees of hepatocellular necrosis and inflammation. It is a significant cause of liver transplantation and liver-related death worldwide. The hepatic manifestations of CHC are typically characterized by slowly progressing liver fibrosis, which is a non-specific and often disproportionate response to tissue damage. A large majority of HCV patients have extrahepatic manifestations with varying degrees of severity. HCV infection is a risk factor for cardiovascular disease and diabetes mellitus, which increases insulin resistance, oxidative stress, and iron overload and causes chronic systemic inflammation. HCV infection is treated using direct-acting antivirals (DAAs) with cure rates of over 95 percent, minimal side effects, and shorter therapeutic courses. Despite the effective elimination of the virus, it seemed pertinent to understand to what extent HCV clearance eliminates or attenuates all the systemic alterations already induced by the virus during infection and chronicity. Our study aimed to determine whether eliminating HCV with DAAs alters the severity of liver disease (liver stiffness and liver fibrosis stage by TE) and the metabolic/cellular profile of patients with CHC. A group of 329 CHC patients from a Gastroenterology and Hepatology outpatient department were prospectively studied. Of these, 134 were also studied with DAAs. The liver fibrosis stage was evaluated by transient elastography (TE) using a FibroScan® device, and two groups were established for the analysis of liver stiffness (LS): mild and moderate stiffness (fibrosis F1 and F2; F1/2) and severe stiffness (fibrosis and cirrhosis F3 and F4; F3/4). Metabolic/cellular parameters were evaluated before and after antiviral treatment using standard methods: alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), γ-glutamyl-transpeptidase (γ-GT), haptoglobin (Hp), total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides (TG), free iron (Fe), transferrin saturation (TS), total iron binding capacity (TIBC), ferritin (Ft), glycemia, insulin, Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) and platelets count. The results were statistically analyzed using SPSS 24.0 for Windows. Comparing the fibrosis stage before and after DAAs treatment, we verify a reduction in LS in 85.7% of patients and an improvement in liver fibrosis stage in 22.2% of them after DAAs treatment. Before DAAs treatment, patients showed a 2.410 risk for higher fibrosis stages (F3/4). Comparing metabolic/cellular parameters before and after DAAs treatment, patients showed lower ALP, AST, ALT, γGT, TG, Fe, TIBC, and Ft values and higher TC, LDL, and Hp values after treatment. As such, HCV elimination reduces iron overload and insulin resistance. On the other hand, it caused dyslipidemia, raising total cholesterol and LDL to levels outside the reference values. The improvement in the liver fibrosis stage by TE was mainly associated with higher baseline platelet count and HDL values and lower insulin resistance. With this study, we were able to contribute to the knowledge of the effects of HCV elimination with DAAs on liver disease and metabolic profile to improve the quality of treatment and follow-up of these patients after HCV elimination.

Hepatitis C Attributable Healthcare Costs and Mortality among Immigrants: A Population-Based Matched Cohort Study.

Data on the economic burden of chronic hepatitis C (CHC) among immigrants are limited. Our objective was to estimate the CHC-attributable mortality and healthcare costs among immigrants in Ontario, Canada. We conducted a population-based matched cohort study among immigrants diagnosed with CHC between May 31, 2003, and December 31, 2018, using linked health administrative data. Immigrants with CHC (exposed) were matched 1 : 1 to immigrants without CHC (unexposed) using a combination of hard (index date, sex, and age) and propensity-score matching. Net costs (2020 Canadian dollars) collected from the healthcare payer perspective were calculated using a phase-of-care approach and used to estimate long-term costs adjusted for survival. We matched 5,575 exposed individuals with unexposed controls, achieving a balanced match. The mean age was 47 years, and 52% was male. On average, 10.5% of exposed and 3.5% of unexposed individuals died 15 years postindex (relative risk = 2.9; 95% confidence interval (CI): 2.6-3.5). The net 30-day costs per person were $88 (95% CI: 55 to 122) for the prediagnosis, $324 (95% CI: 291 to 356) for the initial phase, $1,016 (95% CI: 900 to 1,132) for the late phase, and $975 (95% CI: -25 to 1,974) for the terminal phase. The mean net healthcare cost adjusted for survival at 15 years was $90,448. Compared to unexposed immigrants, immigrants infected with CHC have higher mortality rates and greater healthcare costs. These findings will support the planning of HCV elimination efforts among key risk groups in the province.

INCIDENCE OF HEPATOCELLULAR CARCINOMA IN PATIENTS WITH CHRONIC HEPATITIS C GENOTYPE III AND ADVANCED HEPATIC FIBROSIS AFTER TREATMENT WITH DIRECT-ACTING ANTIVIRALS

A prospective study was conducted at the Gastroenterology Department of Nishtar Hospital from August 2020 to August 2022 to evaluate the incidence of hepatocellular carcinoma (HCC) in chronic hepatitis C (CHC) patients with hepatic fibrosis or cirrhosis, genotype III, who achieved sustained viral response (SVR) after treatment with direct-acting antivirals (DAAs). The study included a total of 500 genotype III patients diagnosed with F3 and F4, who received a 3-month or 6-month course of DAA regimens. HCC was diagnosed by performing triphasic MSCT, and staging was done. During the follow-up, 50 out of 500 patients were diagnosed with HCC. The patients diagnosed with HCC were primarily elderly males and had higher levels of AST, AFP, and bilirubin, as well as reduced platelets and albumin levels compared to non-HCC patients. In cirrhotic patients, the incidence of HCC per year was 2.920 per 100 people. Advanced age, male gender, increased AFP, and decreased albumin were among the predictors of HCC incidence in F4 patients. The study findings suggest that CHC patients with fibrosis and cirrhosis who achieve SVR after treatment with DAAs have a reduced incidence of HCC.

Effect of viral hepatitis on type 2 diabetes: A Mendelian randomization study.

The effects of viral hepatitis (VH) on type 2 diabetes (T2D) remain controversial. To analyze the causal correlation between different types of VH and T2D using Mendelian randomization (MR). Single nucleotide polymorphisms of VH, chronic hepatitis B (CHB), chronic hepatitis C (CHC) and T2D were obtained from the BioBank Japan Project, European Bioinformatics Institute, and FinnGen. Inverse variance weighted, MR-Egger, and weighted median were used to test exposure-outcome associations. The MR-Egger intercept analysis and Cochran's Q test were used to assess horizontal pleiotropy and heterogeneity, respectively. Leave-one-out sensitivity analysis was used to evaluate the robustness of the MR analysis results. The MR analysis showed no significant causal relationship between VH and T2D in Europeans [odds ratio (OR) = 1.028; 95% confidence interval (CI): 0.995-1.062, P = 0.101]. There was a negative causal association between CHB and T2D among East Asians (OR = 0.949; 95%CI: 0.931-0.968, P < 0.001), while there was no significant causal association between CHC and T2D among East Asians (OR = 1.018; 95%CI: 0.959-1.081, P = 0.551). Intercept analysis and Cochran's Q test showed no horizontal pleiotropy or heterogeneity (P > 0.05). Sensitivity analysis showed that the results were robust. Among East Asians, CHB is associated with a reduced T2D risk, but this association is limited by HBV load and cirrhosis. Although VH among Europeans and CHC among East Asians are not associated with the risk of T2D, focusing on blood glucose in patients with CHC is still relevant for the early detection of T2D induced by CHC-mediated pathways of hepatic steatosis, liver fibrosis, and cirrhosis.

Application of an ARFIMA Model to Estimate Hepatitis C Epidemics in Henan, China.

Hepatitis C (HC) presents a substantial burden, and a goal has been established for ending HC epidemics by 2030. This study aimed to monitor HC epidemics by designing a paradigmatic autoregressive fractionally integrated moving average (ARFIMA) for projections until 2030, and evaluating its efficacy compared with the autoregressive integrated moving average (ARIMA). Monthly HC incidence data in Henan from January 2004 to June 2023 were obtained. Two periods (January 2004 to June 2022 and January 2004 to December 2015) were treated as training sets to build both models, whereas the remaining periods served as test sets to perform performance evaluation. There were 465,196 HC cases, with an escalation in incidence (average annual percentage change = 8.64, 95% CI: 3.71-13.80) and a peak in March and a trough in February. For both the 12 and 90 holdout data forecasts, ARFIMA generated lower errors than ARIMA across various metrics: mean absolute deviation (252.93 versus 262.28 and 235.37 versus 1,689.65), mean absolute percentage error (0.17 versus 0.18 and 0.14 versus 0.87), root mean square error (350.31 versus 362.31 and 311.96 versus 1,905.71), mean error rate (0.14 versus 0.15 and 0.11 versus 0.82), and root mean square percentage error (0.26 versus 0.26 and 0.24 versus 1.01). Autoregressive fractionally integrated moving average predicted 181,650 (95% CI: 46,518-316,783) HC cases, averaging 22,706 (95% CI: 5,815-39,598) cases annually during 2023-2030. Henan faces challenges in eliminating HC epidemics, emphasizing the need for strengthened strategies. Autoregressive fractionally integrated moving average can offer evidence-based insights for public health measures.

Diabetic patients with chronic hepatitis C virus response compared to non diabetics when treated with directly acting antiviral therapy

Background and study aimsHepatitis C virus (HCV) impairs glucose homoestasis, thus influences its clinical picture and prognosis.This study aimed at evaluating Diabetes mellitus (DM) on Egyptian patients with chronic hepatitis C (CHC), and its impact on their virologic response when treated with directly acting antiviral (DAA) medications. Patients and methodsAdult patients with CHC were divided into 2 groups; Diabetic patients, and Non diabetic patients serving as control group. All patients were subjected to thorough clinical evaluation, basic biochemical laboratory tests including fasting blood glucose/glycosylated haemoglobin (HbA1C), and virologic assay. They were treated with various combined DAAs, and were monitored during, at and after end of treatment. ResultsDiabetic patients constituted 9.85 % of CHC, and had generally worse laboratory tests (significantly higher transaminases, platelet count, Fib4 and hepatic steatosis) than non diabetic patients, and a less sustained virologic response (SVR) (significantly in Sofosbuvir (SOF) + pegylated interferon (PegIFN) + ribavirin (RBV), SOF + RBV, SOF + daclatasvir (DAC)). Although DM did not play a significant influence on SVR, yet Fib4 and SOF + RBV + PEG-IFN were significant factors affecting SVR among diabetics, while female gender and viraemia were significant factors affecting SVR among non diabetics. Hepatic fibrosis and SOF/RBV significantly influenced SVR in both groups. ConclusionsDiabetic patients with CHC have worse liver biochemical profile, yet DM per se did not influence the virologic response to DAAs, however, some factors played roles in affecting SVR among them.

A case report of chronic hepatitis-C genotype 4c infection: Non-specific symptoms can become contextually relevant in clinical diagnosis

Chronic hepatitis C (CHC) infection is one of the leading causes of liver disease worldwide and its early diagnosis is often considered a challenge because of its non-symptomatic presentation until late disease progression stages. We report the case of a 52-year-old, South-Indian male with CHC genotype 4c infection. We start with the patient’s initial presentation 12 weeks before the diagnosis with seemingly non-specific symptoms of pedal edema, purpura, peripheral neuropathy, arthralgia, and recent onset of diabetes mellitus (DM). We then present the employed direct-acting antiviral (DAA) management regimen and the patient’s response over the span of 48 weeks. Correlating with observations from recent literature highlighting CHC’s extra-hepatic role in inducing cryoglobulinemic vasculitis (CV) and pancreatic dysfunction, we discuss some educational perspectives on how CV and DM-related symptoms may sometimes become contextually specific in clinically suspecting, assessing risk, and warranting CHC screening and diagnostic confirmation.

Unraveling IL-17 and IL-22 role in occult hepatitis C versus chronic hepatitis C virus infection

BackgroundCytokines play a crucial role in regulating the function of the immune system by controlling the production, differentiation, and activity of immune cells. Occult hepatitis C virus (OHCV) infection can lead to liver damage, including cirrhosis and hepatocellular carcinoma. This study investigates the immunopathogenic impact of the cytokines IL-17 and IL-22 in OHCV infection compared to chronic hepatitis C (CHC) infection.MethodsWe studied three groups of patients: 35 with OHCV, 100 untreated patients with CHC, and 30 healthy control subjects. All subjects underwent physical examination and biochemical testing. We used the sandwich enzyme-linked immunosorbent assay method to measure serum IL-17 and IL-22 levels in all groups.ResultsCompared to the occult and control groups, the CHC group had significantly higher serum IL-17 levels (p < 0.001). The occult group also had higher serum IL-17 levels compared to the control group (p < 0.0001). There were no significant differences in IL-22 levels across the research groups. In the OHCV group, individuals with moderate inflammation (A2-A3) had significantly higher serum IL-17 levels than those with minimal inflammation (A0-A1), while in the CHC group, this difference was not statistically significant (p = 0.601). Neither the occult nor the CHC groups showed a correlation between serum IL-22 and inflammatory activity. There was no significant correlation between the levels of IL-17 or IL-22 and the stage of fibrosis/cirrhosis in either group. ROC curves were calculated for serum IL-17 and IL-22 levels and occult HCV infection, with cut-off values set at ≤ 32.1 pg/ml and < 14.3 pg/ml for IL-17 and IL-22, respectively. The AUROC (95%CI) was significantly higher for IL-17 than IL-22 (0.829 (0.732–0.902) vs. 0.504 (0.393–0.614), p < 0.001), suggesting that IL-17 has a stronger correlation with infection risk than IL-22.ConclusionThis study suggests that IL-17 may be involved in the immunopathogenesis of OHCV infection, especially in patients with moderate inflammation.

Universal screening for HCV infection in China: An effectiveness and cost-effectiveness analysis

Approximately 10 million people live with chronic HCV infection in China, and less than 20% of people with HCV were diagnosed. We aim to determine the cost-effectiveness of one-time HCV screening compared with no screening in the Chinese population from the healthcare system perspective. A decision-tree plus Markov model was adopted to project chronic hepatitis C (CHC) prevalence, probability of complications, quality-adjusted life years (QALYs), and costs in the Chinese general population undiagnosed for CHC for different screening strategies. Once CHC was diagnosed, pan-genotypic direct-acting antiviral agent treatment was administered regardless of fibrosis. The population was simulated in a model spanning a lifetime. Input parameters were obtained from published literature. The incremental cost-effectiveness ratio between screening and no screening was estimated. The one-time Chinese gross domestic product per capita in 2021 ($12,558/QALY) was used as the willingness-to-pay threshold. Universal screening in the population aged 3-80 years led to the lowest probability of complications, which yielded a 62% reduction of excess mortality. Compared with no screening, implementing screening and treatment for HCV in populations aged 3-80 years resulted in the greatest marginal QALYs (15.2 per 1,000 population) with an increase in total costs of $109,136. Calculating the incremental cost-effectiveness ratio yields a value of $9,503/QALY (95% uncertainty interval $3,738-$22,566). The robustness of the model was demonstrated through various sensitivity analyses. If the CHC prevalence was over 0.3%, screening could be cost-effective. HCV screening for Chinese people aged 3-80 years may be a cost-effective intervention to reduce the disease burden related to HCV infection. This strategy should certainly be implemented. This study found that screening Chinese people aged 3-80 years yielded the greatest health benefits and was a cost-effective alternative. The findings indicated that national efforts eliminating HCV should be invested and strengthened in China. The results of this study are important because they provide strong evidence that universal screening can be a cost-effective way to reduce the burden of HCV in China. These findings are important for policymakers, physicians, patients, caregivers, and the public because they promote awareness and inform decision-making for HCV prevention and treatment.

Cholestatic HCV Cryoglobulinemia: A New Clinical and Pathological Entity before and after Direct-Acting Antiviral Therapies-A Case-Control Study.

Twenty-nine patients with HCV infection (HCV+) and mixed cryoglobulinemia (MC+) were retrospectively selected and matched for age and sex with 31 HCV+ MC- patients. Biomarkers of cholestasis (direct bilirubin, alkaline phosphatase, and gamma-glutamyl transferase), HCV-RNA and genotype, and plasma cryoprecipitates were measured before and after virus eradication; liver histology and plasma cells (aggregation and distribution), observed blinded by two pathologists, were analyzed. Sixty participants (mean age: 56.5; range: 35-77, males: 50%) with HCV infection were enrolled. Cholestasis (≥2 pathologically increased cholestasis biomarkers) was significantly higher in the MC group (p = 0.02) and correlated with cryoglobulinemia (OR 6.52; p = 0.02). At liver histological assessment, plasma cells were significantly increased in the MC+ group (p = 0.004) and tended to form aggregates more than the control group (p = 0.05). At multivariate analysis with MC, age, HCV-RNA, HBV diabetes, and cirrhosis, cholestasis was only significantly correlated to MC (OR 8.30; p < 0.05). In 25% patients, MC persisted after virus eradication with new antiviral treatment. Our study identified for the first time an association between MC, cholestasis, and an increased number of intrahepatic plasma cells in chronic hepatitis C (CHC) patients before virus eradication. Future studies are required to understand how MC contributes to liver damage and how its persistence affects the patients' follow-up after antiviral therapies.

Analyzing risk factors and developing a stratification system for hepatocellular carcinoma recurrence after interferon-free direct-acting antiviral therapy in chronic hepatitis C patients.

The introduction of direct-acting antiviral agents (DAAs) has revolutionized the therapeutic landscape of chronic hepatitis C (CHC), however real-world data on the risk factors of hepatocellular carcinoma (HCC) recurrence following DAA treatment in CHC-HCC patients are limited in Taiwan. We aimed to evaluate the therapeutic efficacy of DAAs in Taiwanese patients with prior hepatitis C virus (HCV)-induced HCC and identify the posttreatment risk factors for HCC recurrence. Between January 2017 and August 2021, 208 CHC-HCC patients underwent DAA treatment at Taipei Veterans General Hospital. Among them, 94 patients met the inclusion criteria (Barcelona clinic liver cancer [BCLC] stage 0/A after treatment with complete radiological response) for analysis. Comprehensive demographic, clinical, and laboratory data were collected before and after DAA treatment. The primary outcome was HCC recurrence post-DAA treatment, and independent variables were assessed using multivariate Cox proportional hazards models. The mean age of the enrolled patients was 75.9 ± 8.9 years; 44.7% were male, and 94.7% were Child-Pugh class A. Before DAA treatment, 31.9% experienced HCC recurrence. The median follow-up after DAA treatment was 22.1 months (interquartile range, 8.6-35.9 months). After treatment, 95.7% of the patients achieved a sustained virological response (SVR 12 ), but HCC recurrence occurred in 54.3%. Cumulative HCC recurrence rates after treatment were 31.1% at 1 year, 57.3% at 3 years, and 68.5% at up to 5.69 years. Multivariate analysis revealed that prior HCC recurrence before DAA treatment (hazard ratio [HR] = 3.15, p = 0.001), no SVR 12 after treatment (HR = 6.829, p = 0.016), 12-week posttreatment alpha-fetoprotein (AFP) level >10 ng/mL (HR = 2.34, p = 0.036), and BCLC A3 lesions (two or three nodules without any tumor exceeding 3 cm) (HR = 2.31, p = 0.039) were independent risk factors for HCC recurrence. We further developed a risk stratification system based on these significant independent factors. This investigation underscores the critical influence of factors such as prior HCC recurrence, successful attainment of SVR 12 , posttreatment AFP level, and specific tumor characteristics in determining the risk of HCC recurrence after treatment with DAAs. Our proposed innovative risk stratification system may not only contribute to enhanced personalized care but also holds the potential to optimize treatment outcomes.

Real-World Safety and Effectiveness of an 8-Week Regimen of Glecaprevir/Pibrentasvir in Patients with HepatitisC and Cirrhosis.

In 2019, an 8-week regimen of glecaprevir/ pibrentasvir (GLE/PIB) was FDA-approved for treatment of chronic hepatitisC (HCV) in patients with cirrhosis. We used data from the Chronic HepatitisCohort Study (CHeCS) to evaluate treatment response and adverse events among patients with HCV and cirrhosis under routine clinical care. Using an intention-to-treat (ITT)/modified ITT (mITT) approach, endpoints were (1) sustained virological response (SVR) at 12weeks (SVR12) post-treatment; and (2) adverse events (AEs)/serious AEs during treatment. Patients with cirrhosis from two CHeCS sites were included if they were prescribed GLE/PIB from August 2017 to June 2020. Detailed treatment and clinical data were collected. Patient baseline characteristics were described with mean/standard deviation (std) for continuous variables, and proportions for categorical variables. Analyses were propensity score adjusted. The final model retained variables that were significant with pvalue < 0.05. The ITT sample included 166 patients, with 43, 116, and 7 patients in the 8-week, 12-week, and > 12-week planned treatment groups. Among them, 159had confirmed SVR (95.8%, LCL 93.2%). The mITT analysis included 160 patients after excluding 6 with unknown HCV RNA results; 159 achieved SVR (99.4%, LCL 98.3%). There were no significant differences in rates of SVR between the 8-weekand 12-week regimens in either analysis, nor any association with patient characteristics. SAEs were experienced by 1 patient (2%) in the 8-week group, 7 (5%) in the 12-week group (including one death), and 2 (29%) in the > 12-week group; 4 patients (from the 12-week group) experienced serious AEs or hepatic events that were "likely attributable" to GLE/PIB treatment. An 8-week regimen of GLE/PIB is well tolerated and highly effective among US patients with HCV and cirrhosis receiving routine clinical care.

Evolutionary relationship between antimitochondrial antibody positivity and primary biliary cholangitis in Taiwan: a 16-year hospital cohort study.

How antimitochondrial antibody (AMA)-positive patients evolve to have primary biliary cholangitis (PBC) in viral hepatitis-endemic areas is unknown. We aimed to investigate this evolution in Taiwan. A 16-year medical center-based cohort study of 2,095,628 subjects was conducted in Taiwan, an Asian country endemic to viral hepatitis. AMA-positive subjects were those with positive AMA with alkaline phosphatase (ALP) ⩽1.5 times the upper limit of normal (ULN), and PBC was defined as positive AMA with ALP >1.5 × ULN. AMA-positive subjects had a lower average age- and sex-adjusted prevalence than PBC patients (4.68/105 versus 11.61/105, p = 0.0002), but their incidence was comparable (0.99/105 versus 1.12/105, p = 0.36). The former group had a borderline significantly lower mean age (56.59 years versus 58.10 years, p = 0.06) and a lower female-to-male ratio (2.85:1 versus 5.44:1, p < 0.0001). Both AMA-positive subjects (prevalence change: 20.0%, p < 0.01; incidence change: -9.2%, p < 0.01) and PBC patients (prevalence change: 14.6%, p < 0.01; incidence change: -4.7%, p < 0.01) prevalence rate increased but the incidence rate decreased. Among the 423 AMA-positive subjects, 77 (18.2%) developed PBC, for a mean duration of 1.757 years. Compared with AMA-positive subjects, PBC patients had similar concurrent chronic hepatitis B (CHB) rates (2.7% versus 4.3%, p = 0.197) but lower chronic hepatitis C (CHC) rates (3.69% versus 15.60%, p < 0.01). PBC was more prevalent than AMA-positive subjects, and PBC patients had a higher female-to-male ratio than AMA-positive subjects, of whom 18.2% developed PBC (mean lag: 1.757 years). Upward trends in prevalence rates and downward trends in incidence rates were noted for both AMA-positive subjects and PBC. CHB was rare, CHC was more prevalent among PBC patients than the general population, and CHC was less prevalent among PBC than among AMA-positive subjects.

Clinical significance of CDT1 mRNA expression in chronic hepatitis C or liver cirrhosis.

We have previously reported that chromatin licensing and DNA replication factor 1 (CDT1) is associated with the postoperative recurrence of hepatocellular carcinoma (HCC). Based on this fact, we verified whether CDT1 mRNA expression is also associated with HCC development from chronic hepatitis C (CHC) and liver cirrhosis (LC). There were 142 cases with CHC or LC who underwent liver biopsy. Detection of CDT1 mRNA in liver was performed by RT-qPCR using frozen liver biopsy tissues. We examined the association between the CDT1 mRNA expression and clinical conditions and long-term outcome. We then examined the association between serum cytokine/chemokine levels and CDT1 mRNA expression in 58 cases. The cumulative incidence rates of HCC development in cases with CDT1 mRNA in the low expression group showed significantly lower than those in the high expression group (p = 0.0391). A significant correlation was found between CDT1 mRNA expression and the extent of proliferation of atypical hepatocytes in hematoxylin and eosin-stained sections (p<0.0001). CDT1 mRNA expression has been associated with cytokines involved in tumorigenesis in experimental and human cancers. We found that cases with high CDT1 mRNA expression were at risk for developing HCC, even if they were CHC or LC.