Canada has committed to eliminating hepatitis C virus (HCV) by 2030. Despite highly effective treatments, screening and treatment uptake remains suboptimal. Immigrants from HCV-endemic countries account for 35% of HCV cases and face distinct barriers to care. This study explored health care providers' perspectives on barriers and facilitators to providing HCV screening and treatment among immigrant populations. We conducted a qualitative descriptive study guided by the Theoretical Domains Framework (TDF). Semi-structured interviews were performed with health care providers in two Canadian cities. Transcripts were independently coded by two researchers, and key themes were identified. Twelve health care providers (7 female, 5 male) were interviewed, including eight family doctors, two infectious disease specialists, one nurse, and one social worker. Participants identified multiple barriers including limited familiarity with immigrants' specific clinical guidelines, low confidence in managing HCV, and difficulty addressing culturally sensitive issues. Providers perceived patient-related barriers, such as stigma, limited awareness, and competing life priorities, as factors that may hinder engagement with HCV care. Language and communication challenges frequently interfered with care. System-level issues, including fragmented services, long wait times, and shortages of family physicians, further constrained access. This study underscores the complex barriers health care providers face in delivering HCV care to immigrant populations in Canada. While some challenges reflect broader health care system gaps, they are compounded for immigrants by linguistic and cultural differences. Strengthening provider capacity, improving system coordination, and embedding culturally and linguistically responsive approaches are essential to advancing HCV elimination. Hepatitis C is a liver disease that can now be cured in more than 95% of cases with short courses of medication. However, many people with hepatitis C still go undiagnosed or untreated. Canada has promised to eliminate hepatitis C as a public health threat by 2030. About a third of individuals with hepatitis C in Canada are immigrants from countries in which hepatitis C is common. In this study, we wanted to understand the challenges health care providers (HCPs) face when providing hepatitis C testing and treatment to immigrants. We interviewed 12 HCPs including family doctors, specialists, a nurse, and a social worker in two Canadian cities, Ottawa and Montreal. Providers described several obstacles. Many felt unfamiliar with immigrant-specific guidelines or unsure about their role in delivering hepatitis C treatment. Some found it difficult to discuss the disease in culturally sensitive ways. They also perceived that stigma, low awareness, and competing life demands often made it harder for immigrants to prioritize hepatitis C care. Language barriers were a major challenge, with providers frequently relying on family or community members to translate because professional interpretation services were not available. System-level problems, such as shortages of family doctors, long wait times, and fragmented services, added to these difficulties. Our findings show that while many challenges reflect broader problems in Canada's health care system, they are especially difficult for immigrants who must also navigate language and cultural differences. To meet Canada's 2030 elimination goal, we need to support HCPs with clearer guidance and training, expand interpreter services, and create more coordinated, immigrant-friendly care pathways.
Hepatitis B surface antigen (HBsAg) clearance is regarded as the optimal therapeutic endpoint in patients with chronic hepatitis B (CHB). Pegylated interferon-α (PegIFNα) is currently one of the most effective strategies for achieving this goal. However, the impact of concurrent nonalcoholic fatty liver disease (NAFLD) on the PegIFNα treatment response in CHB patients remains controversial. The aim of this study was to investigate the impact of NAFLD on the antiviral efficacy of PegIFNα in patients with CHB and identify baseline predictors of HBsAg clearance. In this retrospective cohort study, 201 CHB patients receiving PegIFNα monotherapy or PegIFNα in combination with nucleos(t)ide analogs were enrolled and stratified into CHB-only (n = 125) and CHB + NAFLD (n = 76) groups based on the presence of hepatic steatosis. Baseline clinical, virological (including HBsAg levels), and histological characteristics were collected and compared. Cumulative HBsAg clearance, biochemical response, and virological response rates were assessed. Two Cox proportional hazards regression models were constructed to identify independent predictors of HBsAg clearance through univariable and multivariable analyses. No significant difference was observed in the 48-week cumulative HBsAg clearance rate between the CHB + NAFLD and CHB-only groups (18.42% vs 23.2%, P = 0.41), nor in the virological response rates. However, the biochemical response rate was significantly lower in the CHB + NAFLD group (13.79% vs 22.03%, P = 0.042). Multivariate Cox regression analysis identified baseline HBsAg levels (Model 2: HR = 0.36, 95% CI: 0.26-0.51, P < 0.001) and baseline hepatitis B virus (HBV) DNA levels (Model 2: HR = 0.79, 95% CI: 0.63-1.00, P = 0.049) as independent predictors of HBsAg clearance, while NAFLD comorbidity was not independently associated with HBsAg clearance (P = 0.58). In CHB patients receiving PegIFNα-based therapy, concurrent NAFLD did not significantly impair HBsAg clearance rates (18.42% vs 23.2% in week 48). However, it was associated with a reduced biochemical response rate. Baseline levels of HBsAg and HBV DNA served as independent predictors of HBsAg clearance.IMPORTANCEChronic hepatitis B (CHB) and nonalcoholic fatty liver disease (NAFLD) are two of the most common liver diseases worldwide, and their coexistence is increasingly frequent due to the rising prevalence of metabolic disorders. Achieving hepatitis B surface antigen clearance is a key therapeutic goal, and pegylated interferon-α (PegIFNα) remains one of the most effective treatments to achieve it. However, it remains unclear whether the presence of NAFLD influences the response to PegIFNα therapy. The study found that NAFLD does not impair the clearance or suppression of hepatitis B virus, but it is associated with delayed normalization of biochemical markers. Whether the hepatitis B surface antigen becomes negative depends mainly on baseline viral levels, rather than the presence of NAFLD. These findings provide important clinical insights for the management of patients with both CHB and NAFLD.
Hepatitis B virus (HBV) remains a leading cause of morbidity and liver-related mortality globally. Vulnerable migrant populations often experience challenges with accessing testing, vaccination and care, both before and after arrival. Asylum seekers and undocumented migrants hosted in six reception facilities in metropolitan Rome were prospectively offered screening for hepatitis B surface antigen (HBsAg), surface antibodies (anti-HBs) and core antibodies (anti-HBc). Individuals with HBsAg positivity were assisted in accessing a specialist referral service, with support available throughout the screen-and-link pathway to reduce administrative, linguistic and logistic barriers. Between February 2024 and August 2025, 435 individuals from 38 countries underwent screening (median age 28 years; 86.7% male). Most (273; 62.8%) were non-immune (HBsAg/anti-HBc/anti-HBs negative), 88 (20.2%) had prior infection (HBsAg negative/anti-HBc positive, usually with anti-HBs), and 51 (11.7%) had vaccine-induced immunity (anti-HBs positive only). HBsAg was detected in 23 (5.3%; 95% CI 3.6-7.8), including 16/149 (10.7%) participants from the African region and 7/160 (4.4%) from South-East Asia (all from Bangladesh); none had hepatitis delta, hepatitis C or HIV coinfection. Overall, 20/23 (87.0%) were successfully engaged in care; 5/20 (25%) met immediate treatment indications based on virological, biochemical and/or liver fibrosis criteria. This study highlights the dual public health challenge of chronic HBV infection and lack of HBV immunity among asylum seekers and undocumented migrants in Rome. The initially high linkage to care demonstrates the effectiveness of integrated screen-and-link approaches. Strengthened HBV testing, vaccination and care pathways should be proactively embedded within health services for vulnerable migrant populations.
Fibrosing cholestatic hepatitis (FCH) is a devastating complication that can occur when hepatitis C virus (HCV) recurs following liver transplantation. When it occurs, FCH typically develops between 1 and 6 months following transplant and is associated with markedly elevated HCV levels. With the advent of direct-acting antiviral therapy, FCH C is now a rare occurrence. Here, we describe a rare case of early-onset FCH that occurred when an HCV nucleic acid test (NAT) positive liver graft was transplanted into a hepatitis C naïve recipient. This case highlights the importance of initiation of antiviral therapy as soon as possible following transplantation of an HCV NAT-positive liver graft as recommended by current guidelines.
Chronic infection with hepatitis B virus (HBV) and hepatitis C virus (HCV) remains a major global public health problem, as many infected individuals remain undiagnosed. Emergency departments (ED) represent a strategic setting for opportunistic screening. This study aimed to evaluate implementation strategies of opportunistic screening in ED within the Girona Health Region in Spain. A prospective observational study was conducted in the ED of the Hospital Universitari de Girona Dr. Josep Trueta (HUGJT) and the Hospital Santa Caterina (HSC) between October 2023 and January 2024. Adults older than 18 years who required blood testing for clinical reasons were screened. In HUGJT screening was automated within the electronic system (opt-out strategy), while in HSC it was performed following a specific request from the attending physician. Comparisons of screening outcomes between hospitals and patient characteristics were evaluated using non-parametric tests. A total of 1695 patients from HUGJT (54.3% coverage) and 303 patients from HSC (6.9% coverage) with valid screening results were included. In HUGJT, antibodies to HCV were detected in 37 individuals (2.2%); while active infection was confirmed in 9 patients (0.5%) (50.0% were previously undiagnosed), being more frequent among individuals with a history of heroin (20.0%). Hepatitis B surface antigen was detected in 11 patients (0.6%) (60.0% had no prior diagnosis), being more common among individuals born outside Spain, particularly those from South-Saharan Africa (7.1%), North Africa (3.2%), and Eastern Europe (2.2%). Opt-out opportunistic screening in ED is effective for identifying undiagnosed infections and facilitating linkage to care.
Extracellular vesicles (EVs) are important mediators of intercellular communication in hepatitis B virus (HBV) and hepatitis C virus (HCV) infection. EVs released from infected hepatocytes can carry viral nucleic acids, proteins, and regulatory non-coding RNAs to immune and nonimmune cells, thereby influencing viral dissemination, immune regulation, and disease progression. In particular, EV-associated cargos modulate antiviral immunity by affecting interferon signaling, natural killer cell function, cytokine production, immune checkpoint pathways, and T-cell exhaustion. These effects may promote viral persistence and immune evasion, although some EV populations can also enhance innate antiviral responses, indicating context-dependent dual roles. EVs also contribute to fibrosis and hepatocarcinogenesis by regulating hepatic stellate cell activation, inflammatory signaling, and tumor microenvironment remodeling. In addition, EV-derived RNAs and proteins show potential as noninvasive biomarkers and therapeutic targets. This review summarizes current evidence on EVs in HBV and HCV infection, with emphasis on immune regulation, viral persistence, disease progression, and translational prospects, while also discussing key challenges such as EV heterogeneity and co-isolation with viral particles.
Chronic hepatitis B virus (HBV) infection poses a significant global public health challenge. Current therapies rarely achieve a functional cure, defined as the clearance of hepatitis B surface antigen (HBsAg) and fulfillment of other criteria. A critical unmet need is the development of agents that effectively suppress HBsAg production. Notably, serum HBsAg in patients predominantly originates from subviral particles (SVPs). To identify compounds inhibiting SVP production, we previously developed a cell model (HepG2-S-HiBiT) secreting HiBiT-tagged HBsAg, enabling high-throughput screening. Using this model, we screened a library comprising more than 5,000 compounds and identified a hit compound (Compound 2) that potently inhibited HBsAg production. Subsequent structural optimization yielded a lead derivative, designated D4. In vitro cellular assays confirmed that D4 suppresses HBsAg production through a transcription-dependent mechanism. Transcriptomic profiling further revealed that Transmembrane Protein 40 (TMEM40) is significantly upregulated following D4 exposure. Further mechanistic investigations established that TMEM40 exerts anti-HBV activity via activation of the JAK-STAT signaling pathway. Collectively, our findings demonstrate that D4 represents a promising lead scaffold for the development of novel anti-HBV therapeutics, exerting its antiviral effects by upregulating TMEM40 and subsequently activating the JAK-STAT pathway to suppress viral transcription.
Reported cases of hepatitis E have increased in Japan; however, the true burden of hepatitis E virus (HEV) infection is likely underestimated due to the high proportion of asymptomatic infections. We prospectively evaluated anti-HEV immunoglobulin G (IgG) seroprevalence, seroconversion-based incidence, and questionnaire-reported exposures in an occupational health-checkup cohort in Mie Prefecture, central Japan. A total of 608 individuals (189 men and 419 women) who underwent annual health checkups between fiscal years 2023 and 2025 were included. Serum anti-HEV IgG was measured. At baseline, participants completed a 10-item questionnaire on potential HEV-related exposures. Incident infection was evaluated by identifying IgG seroconversion during follow-up. Anti-HEV IgG was detected in 5 of 608 participants (0.82%), all of whom were men (5/189, 2.65% vs. 0/419 women, 0%; p = 0.0028). Age was not significantly associated with IgG seropositivity. As no women were seropositive, exploratory age-adjusted analyses were conducted among men only; no questionnaire item was significantly associated with IgG positivity. Sex differences were observed in reported consumption of pork liver/offal, pork tongue, and venison/wild boar meat. One participant seroconverted during follow-up, corresponding to an incidence of 138 per 100,000 (1/724; 95% CI, 3-770) person-years. The seroconverter reported frequent consumption of raw or undercooked pork products. Anti-HEV IgG seroprevalence was low in this relatively young, predominantly female cohort. However, prospective follow-up identified incident infections, with an incidence consistent with previous domestic estimates, suggesting that a substantial proportion of the Japanese population remains at risk of HEV infection.
To develop and validate a nomogram using routine admission indicators to predict total bilirubin on day 7 (TBil-Day7) in hepatitis B virus-related liver cirrhosis (HBV-LC) patients, enabling early identification of inadequate short-term TBil response and providing a reference for intensive treatment. We retrospectively enrolled 284 HBV-LC patients, randomly assigned 7:3 to training (n=198) and internal validation (n=86) cohorts. Candidate variables were clinical and laboratory parameters available within 24 hours of admission, with TBil-Day7 as the outcome. Predictors were selected via least absolute shrinkage and selection operator (LASSO) regression, and a multiple linear regression model was built and visualized as a nomogram. Model performance was evaluated using the coefficient of determination (R2), root mean square error (RMSE), mean absolute error (MAE), and the proportion of predicted values falling within ±20 μmol/L of the observed TBil-Day7 values. LASSO regression identified four predictors: admission TBil, direct bilirubin (DBil), aspartate aminotransferase (AST), and international normalized ratio (INR). The prediction equation was: TBil-Day7 (μmol/L) = -23.0159 + 0.5721×TBil + 0.5847×DBil + 0.0601×AST + 14.0707×INR. The training cohort had an R2 of 0.932. In the internal validation cohort, R2=0.75, RMSE=38.06 μmol/L, MAE=21.27 μmol/L, and 74.4% of predictions were within ±20 μmol/L of actual values. The calibration curve showed good agreement between predicted and observed TBil-Day7. This nomogram, incorporating four routine admission indicators (TBil, DBil, AST, INR), can predict TBil-Day7 in HBV-LC patients with reasonable accuracy. It facilitates early identification of high-risk patients with insufficient TBil decline and allows estimation of short-term treatment response at admission.
This cohort study compares hepatitis C care cascade outcome measures using laboratory and pharmacy data to document viral clearance and treatment initiation, respectively, among insured US adults.
In treating Chronic Hepatitis B (CHB), tenofovir disoproxil fumarate (TDF) carries risks like renal toxicity and reduced bone mineral density (BMD). TAF, the next-generation prodrug of TFV, is more stable in plasma than TDF, requires a significantly lower dose (25 mg vs. 300 mg), and results in approximately 90% lower plasma TFV levels, contributing to a more favorable renal and bone safety profile. This study aimed to evaluate the efficacy and safety of tenofovir alafenamide fumarate (TAF) compared to TDF in CHB. We conducted a search on PubMed, Google Scholar, and the Cochrane Library. Only four RCTs that studied the comparison of efficacy and safety of TAF and TDF in treating CHB were included. The Primary outcome of interest was the proportion of patients with Hepatitis B virus (HBV) DNA below 15-29 IU/ml as all the RCT's included in this study report the same HBV DNA levels. We used a random-effects model to calculate the Risk Ratio (RR) and Mean Difference (MD) with 95% CI. This meta-analysis includes four eligible RCTs including 1,960 total patients. The comparison between TAF and TDF groups regarding HBV DNA level revealed no significant difference (RR = 1.00, 95% CI = 0.96 to 1.05; P = 0.82). Pooled data showed beneficial effects of TAF compared with TDF for ALT Normalization (RR = 1.38; 95% CI = 1.16 TO 1.64; p = 0.0002), Hip BMD (MD = 1.44, 95% CI = 0.98 to 1.91; P ‹ 0.00001), Spine BMD (MD = 1.93, 95% CI = 1.42 to 2.44; P ‹ 0.00001), serum creatinine concentration (MD= -0.02, 95% CI=-0.03 to -0.01; P ‹ 0.00001) and eGFR (MD = 3.55, 95% CI = 2.97 to 4.14; P ‹ 0.00001). However, the TAF group showed a significantly greater proportion of patients (46/1080 vs. 5/662) with LDL levels > 190 or 300 mg/dl than the TDF group (RR = 4.95, 95% CI = 1.21 to 20.29; P = 0.03). The TAF demonstrated improved BMD and renal function compared to TDF. There was no significant difference between TAF and TDF in achieving viral suppression. This was a systematic review and meta-analysis not a clinical trial. This systematic review and meta-analysis is registered at PROSPERO (CRD42023456006).
Since the onset of the COVID-19 pandemic, both SARS-CoV-2 infection and vaccination have been implicated as potential triggers for de novo autoimmune hepatitis (AIH). This review summarizes published cases, outlining clinical and biological features, treatment approaches, and outcomes. A PubMed search identified reports of new-onset AIH following SARS-CoV-2 infection or COVID-19 vaccination up to February 1, 2025. Inclusion criteria encompassed case reports, series, and reviews. Data were extracted on demographics, vaccine type, onset timing, laboratory findings, histology, treatments, and outcomes. A total of 74 post-vaccination AIH cases and 22 post-infection cases were included. Post-vaccination AIH predominantly affected older women (median age 62) and occurred mainly after mRNA vaccines, with a median onset of 14 days. Most patients showed marked transaminase elevation, high IgG, and positive ANA (74.3%). Liver biopsies (performed in 92% of cases) showed features compatible with AIH. A total of 80% of the 50 cases of our study with available serology and liver histology were classified as probable / definite AIH, according to the simplified AIH score. Corticosteroid therapy was effective in most cases (survival 95.9%). Post-infection AIH cases showed similar features but affected younger individuals (median age 47), with uniformly favorable responses to immunosuppression. New-onset AIH can occur following both SARS-CoV-2 infection or vaccination. Although these events remain rare, recognition of this association is essential for timely diagnosis and management.
The small envelope protein of hepatitis B virus (S-HBs) is the principal component of the spherical and filamentous noninfectious subviral particles (SVPs) produced by infected hepatocytes, likely functioning as immune tolerizing agents critical to the establishment and maintenance of chronic infection. The structural features of S-HBs in the context of SVPs have been recently elucidated by several groups using high resolution cryo-EM techniques. In this review, we resolve the commonalities and differences between these reports. The basic unit of SVPs is an S-HBs dimer which is stabilized by hydrophobic interactions between adjacent protomer helices (TH2/TH2 and TH1/EH4, nomenclature by Wang et al., 2024), forming a helical transmembrane core. The adjacent protomer cytosolic and antigenic loops (CYL and AGL, respectively) contribute to dimer stability through salt bridges and intermolecular disulfide bonds; the CYL likely features a zinc finger motif coordinated by C48, H60, C65 and C69, which were shown to be essential. Oligomerization of dimers into trimeric and multiple tetrameric arrangements of dimers during SVP morphogenesis is aided by conformational plasticity within the helical core. Taking previous cell biological studies into account, it is envisioned that in the ER membrane topology and dimerization of S-HBs occur co-translationally, initiating an SVP budding process that completes in the downstream ERGIC and/or Golgi compartments. We report on the identification of two possible non-symmetrical small-molecule binding pockets at the dimer interface, and one in the CYL zing finger region. The druggability of these pockets, as well as unresolved issues in SVP biology, are discussed.
This JAMA Patient Page describes characteristics of acute and chronic hepatitis B and provides information on risk factors, diagnosis, treatment, and prognosis.
Very early recurrence (within one year) after curative hepatectomy significantly impairs long-term survival in patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). Accurately predicting this risk preoperatively is crucial for adjusting clinical decision-making. This study aimed to develop and externally validate a robust machine learning model using exclusively routinely available preoperative clinical data to predict very early recurrence. We retrospectively analyzed 943 patients with HBV-related HCC from two centers. To capture complex, non-linear clinical interactions, we systematically evaluated seven feature selection strategies in combination with seven machine learning algorithms. Sequential Forward Selection (SFS) and SHapley Additive exPlanations (SHAP) were applied to identify core predictive features and interpret variable importance. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC) across training, validation, and external test sets, and compared with conventional benchmark models. X-tile was used for risk stratification, followed by Kaplan-Meier survival analyses. The cohort comprised a training-validation set (n = 754) and an external test set (n = 189). The Random Forest (RF) model demonstrated the most stable and superior predictive accuracy, achieving AUCs of 0.864 (95% CI: 0.832-0.897), 0.814 (95% CI: 0.758-0.870), and 0.843 (95% CI: 0.786-0.899) in the training, validation, and external test sets, respectively, significantly outperforming conventional statistical models. The model effectively stratified patients into high- and low-risk cohorts with significantly distinct disease-free survival (DFS) across all datasets (all P < 0.001). A parsimonious set of eight core preoperative features-comprehensively reflecting tumor biology (tumor size, number, capsule, and AFP) and the underlying liver condition (age, total bilirubin, PALBI grade, and FIB-4 index)-was integrated into an accessible web-based calculator. By systematically integrating key characteristics of tumor aggressiveness and the liver microenvironment, this RF-based preoperative model reliably predicts very early recurrence after hepatectomy. The user-friendly web tool empowers clinicians to preoperatively identify high-risk patients, potentially preventing rushed upfront surgeries in favor of tailored neoadjuvant therapies to optimize survival outcomes.
Hepatitis E virus (HEV) seroprevalence varies by age and geography. Data on HEV seroprevalence across age groups and among people living with HIV (PLWH) in South Africa is scarce. We conducted a prospective multi-site assessment of anti-HEV IgG seroprevalence on 859 South African participants enrolled at three clinical research centres including Newtown Clinical Research Centre in Johannesburg, Be Part Research in Mbekweni, Western Cape, and Mecru Clinical Research Unit in Garankuwa, Pretoria. Participants comprised adults aged 18-45 years (PLWH, n = 178 and HIV-negative, n = 232), and children aged 2-17 years (n = 449). Anti-HEV IgG serostatus and antibody titer were measured using a commercial ELISA kit and a WHO reference standard. Seroprevalence was assessed by site, age group, sex, and HIV status. Overall anti-HEV IgG seroprevalence was 18.0% (95% CI: 15.6-20.8). Adults had the highest seroprevalence (27.3% among all adults; 29.2% among PLWH and 25.9% in HIV-negative adults), while adolescents aged 12-17 years had the lowest (6.9%), and young children aged 6-11 years and 2-5 years had 10.3% and 13.0%, respectively. Adults had significantly higher odds of seropositivity than children (aOR 2.8, 95% CI: 1.5-5.5, p = 0.002). A significant site-specific variation was also observed among healthy adults and adolescents: Newtown Clinical Research Centre (23.0% and 14.0%) and Be Part Research (34.5% and 7.3%) had higher seroprevalence compared with those from Mecru Clinical Research Unit (17.2% and 1.5%, p = 0.0499 and 0.0262, respectively). Higher mean antibody titer observed in younger children aged 2-5 years (5.06 IU/mL), compared with adults (0.88 IU/mL among PLWH and 0.68 IU/mL among HIV-negative adults), and older children (2.02 IU/mL in those aged 6-11 years and 0.67 IU/mL in those aged 12-17 years). HEV seroprevalence in South Africa was highly heterogeneous, varying markedly by age group and study site. These findings highlight the need for strengthened, integrated HEV surveillance to better define transmission patterns and to inform evidence-based considerations for prevention of infection. ClinicalTrials.gov: NCT06306196; Registration date: 2024-02-18. South African National Clinical Trials Register (SANCTR): DOH-27-032024-8165; Registration Date 2024-03-04.
Long-term outcomes data of chronic hepatitis B (CHB) patients treated with high-genetic barrier nucleos(t)ide analogues (NA) beyond year-10 are scarce. We assessed the incidence and predictors of such long-term outcomes. The long-term PAGE-B cohort included 1644 Caucasians with CHB treated with entecavir/tenofovir. Cumulative incidence was estimated using Kaplan-Meier or cumulative incidence function accounting for competing events. Incidence rates (IR) per 100 person-years (/100 PYs) were estimated. Of 1644 patients, 903 were followed beyond year-10 (mean:14±2 years). The 10- and 15-year cumulative incidence of hepatocellular carcinoma (HCC) was 10.9% and 13.2%, respectively, and the HCC IR was 1.25 before and 0.55/100 PYs after year-10 (P<0.001), with similar findings after inverse probability weighting. The IR of death or liver transplantation (LT) was relatively lower before than after year-10 (1.50 vs 1.95/100 PYs, P=0.069) and similar for liver-related death/LT in the two periods (0.74 vs 0.70/100 PYs, P=0.840). HCC development and baseline platelets were independently associated with LT-free liver-related or overall survival, which was also associated with older age and diabetes. The 10- and 15-year cumulative incidence of HBsAg loss on NA(s) was 8.3% and 14.3%, respectively; the IR of HBsAg loss was 0.94 before year-10 increasing to 1.42/100 PYs after year-10 (P=0.025). HBsAg loss was independently associated with older age and baseline HBeAg-positive. NA therapy was discontinued in 125 (7.6%) patients remaining HBsAg-positive. Despite >10 years of NA therapy, CHB patients remain at risk for HCC, but the incidence rate declines significantly. HCC remains the main determinant of mortality. HBsAg loss rate increases after year-10, but it remains low being higher in older, initially HBeAg-positive patients.
Real-time monitoring of viral replication is essential for infectious disease diagnosis and antiviral drug development. The G-quadruplex (G4), a conserved regulatory element within viral genomes, represents a significant endogenous biomarker for tracking viral activity. However, imaging viral G4s in deep tissues remains a challenge for current optical technologies due to severe photon attenuation and autofluorescence. Herein, we report Lumin680, the first near-infrared (NIR) chemiluminescent probe directly activated by conserved viral G4 conformations. Its chemiluminescence was triggered by parallel G4, emitting in the NIR optical window (680 nm) with a 104.6-fold signal enhancement. Notably, the luminescence of Lumin680 could penetrate up to 1.2 cm of biological tissue, outperforming traditional G4 fluorescent probe. In vivo, Lumin680 enabled the rapid visualization of orthotopic hepatitis C virus (HCV) genome RNA-presenting mini-organ within 5 min post-intravenous administration. Furthermore, the chemiluminescent intensity of Lumin680 quantitatively mapped the therapeutic efficacy of clinical direct-acting antivirals (DAAs) at both the cellular and whole-animal levels, exhibiting high concordance with the gold-standard quantitative RT-PCR (qPCR). This study not only provides a powerful G4 specific chemiluminescent tool but also establishes a novel paradigm for the non-invasive, in situ diagnosis and precise therapeutic monitoring of viral infections.
Emergency departments (EDs) are well positioned to screen for hepatitis C virus (HCV), particularly among persons experiencing homelessness who are at increased risk for HCV and are traditionally underserved in health care settings. We examined associations between homelessness and HCV test offer, acceptance, seropositivity, and viremia as part of ED screening. We performed a secondary analysis of data from Denver Health Medical Center (Denver, Colorado), one site in the DETECT Hep C Screening Trial, a multicenter randomized pragmatic clinical trial of nontargeted versus targeted screening in EDs. Stratified by the 2 screening strategies, we performed multivariable log binomial regression while adjusting for demographics, clinical severity, arrival method, payor, and, in targeted screening, HCV risk factors. A total of 67,223 visits were included, with 13.5% persons experiencing homelessness (n=4,539/33,626) in the nontargeted group and 13.7% persons experiencing homelessness (n=4,614/33,597) in the targeted group. Compared to housed patients, persons experiencing homelessness more commonly accepted testing (21.7% [n=895/4,122] versus 15.7% [n=4,044/25,752] in nontargeted and 30.2% [n=540/1,788] versus 23.2% [n=1,600/6,895] in targeted) and were more commonly HCV seropositive (14.2% [n=91/643] versus 2.6% [n=65/2,479] in nontargeted and 17.6% [n=76/432] versus 6.0% [n=72/1,198] in targeted). In multivariable regression, homelessness was not associated with test offer in either screening group. In nontargeted screening, homelessness was associated with test acceptance (adjusted risk ratio [aRR] 1.31, 95% confidence interval [CI] 1.22 to 1.41), but this association was not observed in targeted screening (aRR 1.05, 95% CI 0.97 to 1.14). In both nontargeted and targeted screening, homelessness was associated with HCV seropositivity (aRR 2.91 [95% CI 2.06 to 4.13] and aRR 2.07 [95% CI 1.46 to 2.93], respectively) and viremia (aRR 3.33 [95% CI 2.12 to 5.24] and aRR 3.70 [95% CI 2.14 to 6.39], respectively). Compared to housed individuals, persons experiencing homelessness were more likely to agree to nontargeted HCV screening and equally likely to agree to targeted HCV screening, suggesting that nontargeted HCV screening in the ED may better support HCV detection among persons experiencing homelessness. Furthermore, persons experiencing homelessness had higher risk of HCV seropositivity and viremia regardless of screening strategy and HCV risk factors.
Hepatitis C virus (HCV) infection is associated with adverse outcomes among patients with end-stage kidney disease (ESKD) receiving dialysis. Although direct-acting antivirals (DAAs) achieve high cure rates in patients with ESKD, real-world evidence regarding their long-term clinical benefits remains limited. We evaluated the association between direct-acting antiviral (DAA) therapy and long-term outcomes among dialysis patients with HCV infection. We conducted a multicenter retrospective cohort study using the TriNetX research network. Adults (≥18 years) with ESKD receiving dialysis and confirmed HCV infection between 2015 and 2025 were included. Patients were classified as DAA-treated or untreated. The primary outcome was all-cause mortality; secondary outcomes included kidney transplantation, incident cirrhosis, and hepatocellular carcinoma. Propensity score matching (1:1) was performed to balance baseline covariates. Outcomes were analyzed using Cox proportional hazards models with up to 5 years of follow-up. Among 7660 patients (1482 DAA-treated and 6178 untreated), 1458 matched pairs were included in the analysis. DAA therapy was associated with lower mortality (HR, 0.68; 95% CI, 0.59-0.77; P < .001) and a higher likelihood of kidney transplantation (hazard ratio [HR], 1.42; 95% confidence interval [CI], 1.12-1.80; P = .004). No significant differences were observed in incident cirrhosis or hepatocellular carcinoma during follow-up. Findings were generally consistent across prespecified subgroups. Among patients with ESKD receiving dialysis and HCV infection, DAA therapy was associated with improved long-term survival and a higher likelihood of kidney transplantation. These findings provide real-world evidence supporting the clinical benefits of antiviral therapy and highlight the importance of expanding HCV treatment in dialysis populations.