OSPREY was a single-arm, open-label, phase 1b study that assessed whether reduction of viral antigens by the small-interfering RNA daplusiran/tomligisiran (DAP/TOM) could enhance HBV-specific T-cell and/or HBsAg responses to the DNA vaccine JNJ-64300535 (JNJ-0535) in participants with virologically suppressed, HBeAg-negative chronic hepatitis B. All participants received DAP/TOM (200 mg, Q4W) for 24 weeks and 4 doses of JNJ-0535 from Week (W)14 to W26. NA was given until W36 and continued to Follow-up W48, unless stopping criteria were met. Of 24 participants enrolled, 11 (45.8%) achieved the primary endpoint of ≥2 log10 HBsAg reduction at W36. JNJ-0535 vaccination enhanced core/polymerase-specific T-cell responses in 22% of participants by W28, and 39% during follow-up. Seven participants stopped NA based on W36 results and had more polyfunctional CD4 T-cells targeting ≥2 HBV antigens and a greater mean reduction in HBsAg at Follow-up W48 versus those who continued NA (2.42 log10 IU/mL vs 0.96 log10 IU/mL).

Chronic hepatitis C virus (HCV) infection remains a major global public health challenge. Despite the availability of highly effective therapies capable of curing the vast majority of patients, millions remain undiagnosed and often present for medical care at advanced stages of disease. This delay not only increases mortality and the burden of cirrhosis and hepatocellular carcinoma but also affects quality of life, productivity, and healthcare system costs. In this context, screening emerges as a cornerstone for achieving HCV elimination. It enables the identification of hidden cases, early treatment initiation, prevention of complications, and reduction of community transmission. At the population level, prioritizing individuals with the highest likelihood of transmitting infection produces a multiplier effect, while both universal and risk-based strategies have consistently proven cost-effective, generating medium-term savings. In Latin America, the epidemiological landscape is heterogeneous. While overall prevalence in the general population is relatively low, high endemicity persists in vulnerable groups such as people who inject drugs, incarcerated individuals, and patients undergoing hemodialysis. Major barriers include fragmented health systems, lack of clinical registries, stigma, and restricted access to diagnosis and therapy. Yet, the region also holds clear opportunities: simplified diagnostic pathways using rapid testing and reflex algorithms, micro-elimination in key populations, pooled procurement of antivirals through the Pan American Health Organization, and the integration of digital health and telemedicine. In conclusion, HCV screening constitutes both a public health necessity and an ethical obligation. Its organized and sustainable implementation is essential to translate therapeutic efficacy into collective benefit and to accelerate progress toward the elimination of hepatitis C.

BACKGROUND:Hepatitis C virus (HCV) disproportionately affects incarcerated individuals, and effective interventions are needed to improve HCV care within prisons to achieve global elimination targets. This review aimed to identify and synthesise evidence on interventions to improve HCV testing, linkage to care, and direct-acting antiviral (DAA) treatment initiation among people in prison and post-release. METHODS:We systematically searched MEDLINE (PubMed), Scopus, Web of Science, Cochrane CENTRAL, and PsycINFO for studies assessing non-pharmaceutical interventions with a comparator or control group. Outcomes were HCV antibody testing, HCV RNA testing, linkage to HCV care, and treatment initiation. Randomised controlled trials (RCTs) and controlled non-randomised studies were included; data were extracted and risk of bias assessed in duplicate using standard tools (RoB 2 and ROBINS-I). This analysis was restricted to studies of interventions evaluated in prison settings or among people recently released from prison. Searches had no date restriction and were updated November 2024. This review is registered in PROSPERO (CRD42020178035). FINDINGS:Of 20,643 unique records, 22 studies were included (19 non-randomised; three RCTs). Simplified testing modalities had the most evidence of impact on testing and treatment outcomes: dried blood spot (DBS) testing improved antibody testing uptake in three studies (two RCTs and one non-randomised study; OR 2.90, 95 % CI 1.43-5.86) and point-of-care RNA testing improved treatment initiation in three non-randomised studies (OR 9.60, 95 % CI 3.38-27.32). Simplified opt-out screening strategies also increased antibody testing uptake in three studies (OR 20.41, 95 % CI 1.88-221.19). Other interventions simplifying testing (e.g., reflex RNA testing, broadened testing criteria) were effective in individual studies, but pooled analyses for broadened testing criteria were not statistically significant due to high heterogeneity. Single studies also showed improvements in treatment initiation using DBS testing, nurse-led care, and no-cost coverage of HCV medications. INTERPRETATION:Several interventions, particularly those to enhance testing, may be successful in increasing HCV testing and treatment in prisons. However, the heterogeneity of interventions, methodological limitations of included studies, and limited number of studies underscore the need for further robust research, particularly RCTs, to optimise care in this setting.

BACKGROUND & AIMS:The rate of recompensation following alcohol-related hepatitis is unknown. The aims of this study were to assess the rate, predictors, and clinical impact of recompensation in survivors of alcohol-related hepatitis, and to develop adapted recompensation criteria. METHODS:Nationwide registry-based study including patients with alcohol-related hepatitis who were discharged between 2014 and 2021. Recompensation was defined according to: (1) Baveno VII criteria; or (2) expanded criteria for alcohol-related hepatitis in which alcohol abstinence was not required (alcohol-related hepatitis liberal-abstinence criteria); and was assessed at 1 and 3 years. A landmark analysis was used to evaluate the impact of recompensation on transplant-free survival. RESULTS:A total of 577 patients (85% with cirrhosis) were included. The rate of recompensation at 1 and 3 years was 9.9% and 8.8% (Baveno VII), and 11.4% and 14.3% (alcohol-related hepatitis liberal-abstinence). In patients with cirrhosis, rates were 8.2% and 9.0% at 1 and 3 years (Baveno VII). The absence of decompensation prior to alcohol-related hepatitis, higher baseline alkaline phosphatase levels and lower Child-Pugh score were independently associated with recompensation. In patients abstinent from alcohol at 1 year, the rate of recompensation at 1 and 3 years was 26.5% and 25.8%, respectively. Patients with recompensated disease had higher estimated 5-year transplant-free survival (84.9% vs 47.7% in decompensated disease; Plog-rank < .001). Survival estimates did not differ when classifying patients according to alcohol-related hepatitis liberal-abstinence criteria. Recompensation after alcohol-related hepatitis was a predictor of long-term survival. CONCLUSIONS:Recompensation in alcohol-related hepatitis is common, particularly following abstinence, and is associated with increased survival. Predicting recompensation in alcohol-related hepatitis can be valuable in decision-making, including the evaluation for liver transplantation.

Hepatitis B virus (HBV) and hepatitis C virus (HCV) remain public health threats in the WHO European region, where an estimated 29 million people live with chronic infection and viral hepatitis-related deaths now surpass those from HIV/AIDS and tuberculosis combined. Although effective prevention tools and antiviral treatments reduce the risk of complications, overall mortality has not declined. This Series paper reviews models of care (MoC) implemented between 2015 and 2025, drawing on scientific literature and policy documents to assess regional progress. Simplified testing and treatment, childhood and targeted adult HBV vaccination, harm-reduction programmes, and prison-based interventions have advanced elimination efforts. Pragmatic approaches, including point-of-care testing, decentralised services, and integrated models tailored to key populations demonstrate clear benefits. However, major challenges persist: large undiagnosed populations, regional disparities, inadequate healthcare worker knowledge, and inequities affect at-risk groups. Achieving elimination by 2030 will require accelerated case-finding, broader access to simplified treatment, stronger risk-tailored and vaccination strategies, improved data systems, and renewed commitment.

BACKGROUND & AIMS:Hepatitis delta virus (HDV) is the most aggressive form of chronic viral hepatitis. As new therapies emerge, a clearer understanding of its natural history - particularly in early disease stages - is needed. We assessed real-world outcomes of HDV-infected patients with mild-to-moderate fibrosis and identified predictors of progression to cirrhosis. METHODS:We performed a multicenter, international, retrospective study including adult patients with active HDV infection (HDV-RNA positive) and no advanced fibrosis at baseline, confirmed by histology or liver stiffness measurement (TE-LSM) within the first year of diagnosis. Demographic, clinical, biochemical, and virological variables were collected at baseline and annually thereafter. The primary outcome was development of cirrhosis; secondary outcomes included liver-related events and longitudinal changes in fibrosis markers. RESULTS:The cohort included 168 patients (median age 37.5 [31-45] years; 53% male; 56% Caucasian). Fewer than 15% had HIV/HCV coinfection or metabolic/alcohol-related risk factors. At baseline, 36% had ALT ≥2 × the upper limit of normal and median TE-LSM was 7.6 (6-9) kPa. Over a median follow-up of 62 (40-94) months, 37 patients (22%) developed cirrhosis. Two developed ascites (one required liver transplantation), and one developed hepatocellular carcinoma and died. HDV clearance occurred in 32 patients (19%), either spontaneously (n = 14) or after antiviral therapy (n = 18). In the multivariate analysis, only TE-LSM ≥7 kPa independently predicted progression (HR 6.02 [1.76-20.6]; p = 0.004). FIB-4 ≥1.45 also identified higher-risk patients when TE-LSM was unavailable (HR 3.51 [1.68-7.34]; p <0.01). Neither antiviral therapy nor changes on HDV RNA or ALT overtime remained as independent predictors. CONCLUSIONS:Despite mild-to-moderate baseline fibrosis, over 20% of patients progressed to cirrhosis within 5 years. Baseline non-invasive markers effectively stratify risk and may inform prioritization of emerging HDV therapies. IMPACT AND IMPLICATIONS:Patients with HDV and mild-to-moderate fibrosis remain at substantial risk of progression, with more than 20% developing cirrhosis during a median follow-up of 5 years. Liver stiffness measured by transient elastography (TE-LSM) was the strongest predictor of progression. FIB-4 may have a prognostic value when TE-LSM is not available, whereas ALT levels and HDV-RNA, both at baseline and during follow-up, did not influence fibrosis outcomes. These findings support improved early risk stratification and may help clinicians identify which patients with apparently early-stage disease warrant closer monitoring or timely treatment intervention.

INTRODUCTION:the comprehensive diagnosis of viral hepatitis is an advance towards its elimination, but not all Spanish hospitals performed this diagnosis in 2022. Our objective was to evaluate the situation of the comprehensive diagnosis after the publication of the guidelines and evaluate the degree of implementation in the centers that responded to both surveys. METHODS:a descriptive cross-sectional study was conducted among 79 hospitals that had participated in the initial survey. They were reinvited to respond via Google Forms (sent 23/12/2024). RESULTS:the response rate was 91 % (72/79). Compared to the previous year, reflex testing increased by 3 %, with notable increases for hepatitis B virus (HBV) (33 %), hepatitis C virus (HCV) (2 %), hepatitis D virus (HDV) (45 %) and dual HBV-HDV (79 %). Anti-HDV and HDV-RNA testing increased by 18 % and 21 %, respectively. Alerts to specialist physicians rose by 24.1 % for HBV and 52.9 % for HDV. Automated appointment systems and referral mechanisms also expanded. Hepatitis A virus (HAV) testing was integrated in 38 % of centers, human immunodeficiency virus (HIV) testing in 50 %, and sexually transmitted infections (STI) testing in 56 %. CONCLUSIONS:awareness and implementation of integrated diagnostics, particularly for hepatitis D, have improved. Nonetheless, further progress is needed to ensure broader coverage and to contribute towards World Health Organization (WHO) elimination goals.

Hepatitis B virus (HBV), hepatitis C virus (HCV), and hepatitis D virus (HDV), together with HIV and bacterial sexually transmitted infections (STIs), account for a rising toll of more than one million deaths annually and overlap within shared behavioral and social networks, yet are still diagnosed through separate, pathogen-specific pathways. This narrative review synthesizes contemporary evidence on the convergence between viral hepatitis, HIV, and high-risk STI groups—men who have sex with men, pre-exposure prophylaxis (PrEP) users, people practicing chemsex, people who inject drugs, incarcerated populations, and migrants from endemic regions—and characterizes the diagnostic technologies and linkage-to-care models available to address it. Despite effective antivirals, the diagnostic cascade remains the principal bottleneck: most people with chronic HCV are undiagnosed, and HDV—with a pooled anti-HDV seroprevalence of approximately 4.5% among HBsAg-positive individuals—is its clearest expression, as most carriers are never tested. Reflex algorithms, multiplex panels, point-of-care assays, dried blood spots, and electronic health record alerts are validated but unevenly implemented. We argue that, alongside persistent resource, political, and equity-related constraints, a substantial share of the remaining barriers is operational rather than purely technological, and propose a practical, STI-clinic-centered framework integrating reflex testing, population-specific periodicity, and explicit linkage pathways toward the WHO 2030 elimination targets.

Thanks to the emergence of direct-acting antiviral agents, Hepatitis C (hepatitis C virus (HCV)) elimination is a real possibility. In 2016, the World Health Organization established a global strategy with the aim of achieving HCV elimination by 2030. However, the actual implementation of this strategy within healthcare systems worldwide has proven challenging, and the COVID-19 pandemic nearly completely halted HCV elimination programs. Seroprevalence studies in the general population attending health centers in Spain place us as a low-prevalence country, but recent reports have shown that the Emergency Department and hospital population show significantly higher prevalence rates, suggesting that studies in the general population may underestimate the true prevalence, especially in vulnerable people. Thus, HCV screening should be implemented through a combination of approaches: population-based programs, self-referral options, and opportunistic testing during any healthcare encounter. Here, we summarize the main updates to the measures adopted in the Strategy for the Elimination of Hepatitis C in Cantabria, a region in northern Spain, so that they can serve as inspiration for other regions. The update prespecifies primary operational and virological endpoints (coverage, linkage‑to‑care, time‑to‑treatment, and sustained virological response 12 (SVR12)), and secondary clinical outcomes, and it includes a pragmatic economic assessment (cost per diagnosis/SVR and budget impact).

Introduction and Objectives Viral hepatitis remains a leading cause of cirrhosis and hepatocellular carcinoma globally. Implementation of the WHO 2030 elimination agenda across Latin America and the Caribbean (LAC) remains heterogeneous. REVIRAL-LATAM was conducted under the auspices of the Latin American Association for the Study of the Liver (ALEH) to evaluate policies, clinical practices, structural barriers, and implementation gaps in viral hepatitis elimination across the region. Patients and Methods Multinational cross-sectional study using a REDCap-based questionnaire adapted from the Hep-CORE framework (171 variables across ten thematic domains—including governance, diagnosis, treatment, screening, micro-elimination, surveillance, and innovation). Data were collected between May–September 2025, with country-level stratification and construction of a Global Elimination Index (IGE). Results A total of 475 valid responses from 19 LAC countries were analyzed; awareness of national elimination plans was reported for HCV - 67.6% respondents, HBV - 59.1%, and HDV - 11.0%. Test-and-treat implementation remained limited (HCV 19.5%, HBV 13.7%, HDV 3.2%), despite broad availability of simplified HCV treatment (81.5%). Leading barriers included public misinformation(93.1%), insufficient healthcare professional training(86.0%), territorial inequalities(84.8%), lack of prescribing training(81.3%), and hospital-centered care models (77.3%). Coverage was particularly low for indigenous populations(21.8%), migrants(25.5%), and homeless individuals(29.4%). Telemedicine(25.6%), and re-linkage programs(11.4%) remained isolated initiatives. The IGE revealed marked regional heterogeneity(23.7%–55.6%). Conclusions The principal regional gap is implementation capacity, not therapeutic availability—particularly in decentralized diagnosis, surveillance, vulnerable populations, and integrated care. HDV remains the most neglected elimination component. Reflex-testing, simplified treatment pathways, and micro-elimination strategies should be prioritized toward WHO 2030 targets.

The REVIRAL project proposes a comprehensive and tailored strategy for the elimination of viral hepatitis in Latin America, drawing inspiration from successful models in other countries. Despite global advances, the region faces specific barriers, including the lack of universal screening programs, disparities in access to direct-acting antiviral treatments, the presence of fragmented health systems, and the social stigma associated with these infections. These factors hinder progress towards elimination, necessitating collaborative responses tailored to the epidemiological and socioeconomic realities of each country. The project’s structure is organized into three fundamental phases: The first phase involves an initial assessment, where the epidemiological situation of each country will be analyzed, specifically the prevalence and incidence data of viral hepatitis and the response capacity of each country’s health systems. This phase will also identify specific barriers, allowing interventions to be adjusted to local needs. The second phase will focus on the implementation of intervention programs, promoting universal screening, strengthening healthcare personnel training, and implementing health models that enhance linkage-to-care. The third phase will concentrate on monitoring and evaluating results through a global elimination marker, designed to measure and compare progress across countries. The success of REVIRAL will largely depend on the commitment of local governments and international cooperation. If implemented correctly, the project could transform the public health response to viral hepatitis in Latin America and serve as a replicable model for other regions with similar challenges advancing toward the WHO’s global elimination goals set for 2030.

Background & Aims: Bepirovirsen, an antisense oligonucleotide, induces sustained reductions in hepatitis B surface antiger (HBsAg) and HBV DNA to below the lower limit of quantification (

Several dynamic models predict mortality and corticosteroid response in alcohol-associated hepatitis (AH), yet no consensus exists on the most effective model. This study aimed to assess predictive models for corticosteroid response and short-term mortality in severe AH within a global cohort. We conducted a multi-national study of patients with severe AH treated with corticosteroids for at least 7 days, enrolled between 2009 and 2019. Dynamic models-Lille-4, Lille-7, trajectory of serum bilirubin (TSB), and neutrophil-to-lymphocyte ratio (NLR)-were used to estimate 30- and 90-day mortality. Lille-7 demonstrated the highest accuracy for both 30- and 90-day mortality.

BACKGROUND:Severe alcohol-associated hepatitis (sAH) is a well-characterized disease with high short-term mortality. However, there is limited research on those with a "less severe condition" (moderate AH). This study aims to characterize in-depth patients with moderate AH (mAH), including the performance of mortality scoring systems, key prognostic factors, and survival over time. METHODS:A multicenter retrospective cohort study (2009-2019) included patients with mAH (MELD score ≤20 at admission). Cox regression and receiver operating characteristic curves with AUC were used for analysis. RESULTS:We included 1845 patients with AH (20 centers, 8 countries) between 2009 and 2019. mAH was defined as a MELD score ≤20 at admission. Twenty-four percent met the criteria for an mAH episode. Patients with mAH tend to be older and have a higher proportion of females, with a median MELD of 17 (15-19), Maddrey discriminant function (mDF) of 33 (22-40), the trajectory of serum bilirubin of 0.83 (0.60-1.21), and neutrophil-to-lymphocyte ratio (NLR) of 5 (2.96-8.60). The primary causes of death in mAH included multiple organ failure (34.1%) and infections (16.6%). The cumulative survival rates at 30, 90, and 180 days were 94.3%, 90.4%, and 88.2%, respectively. In multivariable analysis, age was the only significant predictor of 30-day mortality (HR 1.49, 95% CI: 1.27-1.76, p<0.001). Mortality prediction models showed poor performance, with AUC for MELD (0.671), mDF (0.726), trajectory of serum bilirubin (0.733), and NLR (0.697). CONCLUSIONS:Patients with moderate AH exhibited a mortality of 11.8% at 6 months, primarily driven by multiple organ failure and infections. These patients also exhibit a different clinical profile compared to those with sAH. Tailored models and therapeutic strategies are needed to improve long-term outcomes in mAH.

Viral hepatitis constitutes a major health burden among people living in prison globally. There is poor access to prison-based viral hepatitis services, and people living in prison are rarely prioritised for care, undermining global elimination efforts. This Review is a narrative summary of the first Global Guidelines for Viral Hepatitis Service Delivery in Prisons, which included a systematic review and an expert-led GRADE process to develop best practice recommendations for viral hepatitis management in prisons. 703 articles were included, underpinning the development of 30 recommendations across eight domains: policy, testing, treatment, continuity of care, prevention and harm reduction, education, minority populations and special considerations, and monitoring and evaluation. Quality of evidence and strength of recommendations were rated as A1 (n=5), B1 (n=7), C1 (n=10), D1 (n=7), and expert opinion (n=1). The guidelines aim to standardise a global approach to prison-based viral hepatitis elimination efforts with consistent policy, practice, and reporting.

The transition from non-alcoholic fatty liver disease (NAFLD) to metabolic dysfunction-associated steatotic liver disease (MASLD) represents a significant evolution in the nomenclature of steatotic liver disease. This updated terminology emphasizes metabolic dysfunction as a central criterion, offering greater precision and improved risk stratification. MASLD broadens the scope of liver disease classification by incorporating individuals with diverse metabolic profiles, including lean patients with hepatic steatosis, and aligns clinical practice with the multifactorial nature of this condition. The global adoption of MASLD creates opportunities for standardization in clinical and research settings, facilitating multicenter collaborations and enhancing the development of diagnostic tools and therapeutic strategies. However, the adoption of this new nomenclature poses challenges, including potential confusion during implementation, cultural and linguistic barriers, the integration of MetALD, and the need for educational initiatives targeting healthcare providers and patients. Further efforts are required to refine diagnostic criteria, address implementation challenges, and seamlessly incorporate MASLD into international coding systems. This review evaluates the key advantages and ongoing challenges associated with MASLD, providing a comprehensive analysis of its impact on clinical practice, research, and global health strategies.