This study examines the effects of hepatitis B virus on sex hormone levels, menopause, sleep, depression, anxiety, and quality of life in female hepatitis B patients under different alanine aminotransferase (ALT) conditions. A total of 306 female patients with chronic hepatitis B, exhibiting different viral loads and varying ALT statuses, were randomly selected for stratified sampling. The effects of hepatitis B virus on sex hormone levels, menopause, sleep, depression, anxiety, and quality of life were compared and analyzed across different ALT statuses. Among these, 110 female patients with chronic hepatitis B and ALT levels ≥ 2 times the upper limit of normal received antiviral treatment and were followed for 24 weeks. Changes in the above indicators before and after antiviral treatment were compared and analyzed. In the ALT-normal group and the group with ALT levels ≤ 2 times the upper limit of normal, there was no significant difference in the effects of different hepatitis B virus viral loads on sex hormone levels, menopause, sleep, depression, anxiety, or quality of life in female patients with chronic hepatitis B. However, in the group with ALT ≥ 2 times the upper limit of normal, as the viral load increased (from the low replication group to the high replication group), the estradiol concentration decreased from (84.20 ± 7.78) pg/mL to (64.60 ± 9.18) pg/mL, testosterone increased from (0.33 ± 0.02) ng/mL to (0.45 ± 0.04) ng/mL, follicle-stimulating hormone increased from (47.82 ± 7.62) mIU/mL to (59.68 ± 7.19) mIU/mL, the menopause rate increased from 55.56% to 86.11%, the Pittsburgh Sleep Quality Index increased from 11.02 ± 0.52 to 15.93 ± 0.71, the Self-Rating Anxiety Scale score increased from 46.06 ± 4.92 to 64.66 ± 6.18, the Self-Rating Depression Scale score increased from 44.14 ± 5.47 to 67.08 ± 4.57, and all dimensions of quality of life significantly decreased, with all differences being statistically significant (P < 0.05). After antiviral treatment in 110 female patients with ALT ≥ 2 times the upper limit of normal, estradiol significantly increased, testosterone and follicle-stimulating hormone significantly decreased, sleep indicators and depression and anxiety scores significantly decreased, and all quality of life indicators significantly increased (all P < 0.05). The impact of hepatitis B virus on female patients varies under different ALT conditions. For patients with ALT levels at or above twice the upper limit of normal, actively initiating antiviral treatment can significantly improve sex hormone levels and various physiological and psychological indicators in female patients, thereby enhancing their quality of life. 探讨在不同丙氨酸氨基转移酶(alanine aminotransferase, ALT)状态下乙型肝炎病毒对女性乙型肝炎(简称乙肝)患者性激素水平、绝经、睡眠、抑郁、焦虑及生活质量的影响。 分层随机选取不同ALT状态下不同病毒载量的女性慢性乙肝患者306例,分别比较分析在不同ALT状态下,乙型肝炎病毒对性激素水平、绝经、睡眠、抑郁、焦虑及生活质量的影响。并对ALT≥2倍正常上限的110例女性慢性乙肝患者进行抗病毒治疗,随访24周,对比分析抗病毒治疗前后患者上述指标的变化。 在ALT正常组及正常上限≤ALT<2倍正常上限组中不同病毒载量的乙型肝炎病毒对女性慢性乙肝患者性激素水平、绝经、睡眠、抑郁、焦虑及生活质量的影响无明显差异,而在ALT≥2倍正常上限组中,随病毒载量升高(低复制组→高复制组):雌二醇质量浓度从(84.20±7.78) pg/mL降至(64.60±9.18) pg/mL,睾酮质量浓度从(0.33±0.02) ng/mL升至(0.45±0.04) ng/mL,卵泡生成激素浓度从(47.82±7.62) mIU/mL升至(59.68±7.19) mIU/mL,绝经率从55.56%升至86.11%,匹兹堡睡眠质量指数从11.02±0.52升至15.93±0.71,焦虑自评量表评分从46.06±4.92升至64.66±6.18,抑郁自评量表评分从44.14±5.47升至67.08±4.57,生活质量各维度均显著下降,差异均有统计学意义(P<0.05)。对ALT≥2倍正常上限的110例女性患者行抗病毒治疗后,雌二醇明显增高,睾酮及卵泡生成激素明显下降,各项睡眠指标和抑郁、焦虑评分明显下降,而各项生活质量指标明显升高(均P<0.05)。 在不同ALT状态下乙型肝炎病毒对女性乙肝患者的影响机制不同,对于ALT≥2倍正常上限的患者积极进行抗病毒治疗可明显改善女性患者性激素水平及各项生理心理指标,从而提高生活质量。
Viral hepatitis remains a major global health threat, causing approximately 1.3 million deaths in 2022. Despite substantial advances in vaccination and clinical treatment, it continues to impose a heavy disease burden across China. Existing studies have largely focused on single hepatitis subtypes and national epidemiological trends, with limited evidence on provincial heterogeneity. To fill this research gap, this study aimed to conduct a refined, region-specific epidemiological assessment of viral hepatitis in China. Data were extracted from the Global Burden of Disease Study 2021 (GBD 2021) and the China Public Health Science Data Center to systematically analyze the epidemiological characteristics and spatiotemporal trends of viral hepatitis in China over the past three decades. The overall burden of viral hepatitis in China decreased substantially over the study period, with obvious regional heterogeneity. Acute hepatitis A, B and E, as well as chronic hepatitis B and C, all presented prominent downward trends. The fastest declines in incidence were observed in acute hepatitis B (estimated annual percentage change [EAPC] = -3.03) and chronic hepatitis B (EAPC = -4.74). Notably, males suffered a higher disease burden for nearly all outcomes, except for HCV-related hepatocellular carcinoma, which predominantly affected females. Furthermore, provincial-level analysis indicated marked regional disparities: Xizang maintained a high incidence rate, while Beijing exhibited low incidence accompanied by strikingly high hepatitis-related mortality, suggesting a notable decoupling between infection prevalence and mortality. China has achieved remarkable reductions in the overall burden of viral hepatitis, attributable to comprehensive public health interventions such as universal vaccination, standardized screening and improved sanitation conditions. Nevertheless, residual burdens in vulnerable populations and striking regional inequalities warrant targeted prevention and control strategies to reduce disease disparities nationwide.
Hepatitis, a disease characterised by inflammation of the liver, is a leading global health challenge that contributes to over 1.3 million deaths annually, with hepatitis B and C accounting for many of these fatalities. Intensive care unit (ICU) management of patients is particularly challenging due to the complex clinical care and resource demands. Despite advancements in ICU predictive analytics, limited research has specifically addressed hepatitis patients, creating a gap in optimising care for this population. This study focuses on predicting ICU length of stay (LoS), hospital discharge outcomes and discharge location for ICU-admitted viral hepatitis patients using a comparative assessment of machine learning (ML) models. Leveraging data from the Medical Information Mart for Intensive Care-IV database, which includes around 94 500 ICU patient records, this study uses sociodemographic details, clinical characteristics and resource utilisation metrics to develop predictive models such as Random Forest, Logistic Regression, Gradient Boosting Machines and Generalised Additive Model with Negative Binomial Regression. Among 3875 ICU-admitted hepatitis patients, Random Forest classification outperformed Logistic Regression in predicting discharge outcomes, achieving higher accuracy (0.87 vs 0.82) and greater discriminative ability (area under the receiver operating characteristic curve 0.95 vs 0.89). For ICU LoS prediction, Random Forest regression applied to log-transformed LoS demonstrated strong performance (R² up to 0.82), while the generalised additive model with negative binomial distribution explained approximately 76% of LoS variance. Prediction of discharge location yielded moderate performance across Gradient Boosting and multinomial logistic regression models (accuracy 0.55 and 0.56), reflecting challenges associated with multi-class imbalance. Variable importance analyses across ML models consistently identified medication counts, procedure counts, comorbidity burden, age, race and total LoS as the most influential predictors of discharge outcomes and discharge location. This study demonstrates the value of ML models for predicting clinical outcomes for hepatitis patients, including ICU LOS and hospital discharge status. The results underscore the influence of factors like race and age, revealing disparities that must be addressed in predictive care strategies. While the models show promise, challenges such as variability in prolonged stays and limited multiclass prediction accuracy point to the need for ongoing refinement and research.
Chronic viral hepatitis caused by hepatitis B virus (HBV) and hepatitis C virus (HCV) remains a leading global public health burden, driving progressive liver fibrosis, cirrhosis, and hepatocellular carcinoma (HCC) through complex interactions between viral replication, host immune responses, and extracellular matrix (ECM) remodelling. Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases that serve as central regulators of ECM homoeostasis and immune modulation in the liver. While physiological MMP activity is essential for tissue repair and immune surveillance, dysregulation of the MMP/TIMP (tissue inhibitors of metalloproteinases) axis during viral hepatitis promotes hepatic fibrogenesis, immune evasion, and malignant transformation, positioning MMPs as both drivers of disease progression and promising therapeutic targets. This review comprehensively examines the molecular and cellular mechanisms governing MMP/TIMP dysregulation across the spectrum of viral hepatitis, with particular focus on HCV and HBV. We address the reciprocal interactions between these viruses and MMP/TIMP expression, the roles of MMPs in liver fibrosis, viral replication, hepatocarcinogenesis, and immunomodulation of the tumour microenvironment, and the accelerated fibrogenic mechanisms in HIV-HCV and HIV-HBV coinfection. The review also extends to acute viral hepatitis (HAV and HEV), where direct MMP/TIMP data remain scarce but mechanistic and indirect ECM evidence indicate significant involvement. Finally, we critically evaluate current and emerging MMP-targeted therapeutic strategies including selective inhibitors, nanoparticle delivery systems, and RNA-based approaches and highlight key unresolved questions to guide future research towards disease-tailored interventions against viral hepatitis-driven liver damage and malignant progression.
Viral hepatitis, particularly hepatitis B (HB) and hepatitis C (HC), has remained a major global health concern for decades due to its high infectivity and the liver damage it causes, which can lead to severe long-term complications. Thus, the development of diagnostic tools that enable rapid, cost-effective, and user-friendly detection of hepatitis infections is crucial. Here, we report label-free immunosensors for the detection of HB/HC biomarkers (Hepatitis B surface antigen, HBsAg, and Hepatitis C core antigen, HCcAg) using conventional electrolyte-gated organic field effect transistors (EGOFETs) as electrical transducers by modifying the gate contact with suitable antibodies. To enhance portability and enable point-of-care (PoC) operation, the EGOFETs were subsequently integrated into a lateral flow assay architecture (LF-EGOFET), where the antibodies are immobilized within a nitrocellulose membrane in contact with a coplanar gate electrode. The devices were evaluated as PoC diagnostic tests in buffer solutions and diluted artificial saliva, demonstrating high sensitivity, selectivity, and accuracy, with limits of detection (LoD) in the femtomolar range. Notably, the LF-EGOFET platform achieves a LoD over three orders of magnitude lower than those of commercial hepatitis lateral flow assays, while avoiding the use of labels and enabling the identification of discrete concentration ranges.
Sarcopenia is a prevalent yet underdiagnosed complication in elderly patients with liver cirrhosis, associated with poor outcomes and increased frailty. In low-resource settings, the use of advanced imaging techniques for sarcopenia assessment is often limited. The Geriatric Nutritional Risk Index (GNRI) is a simple tool that may serve as a surrogate marker for sarcopenia, particularly in high-risk populations such as elderly cirrhotic patients with viral hepatitis. To evaluate the clinical utility of the GNRI in predicting sarcopenia and its severity in elderly Egyptian patients with viral hepatitis-related liver cirrhosis, and to explore its correlations with liver function scores and physical performance indices. This cross-sectional study included 90 elderly patients (aged ≥ 60 years) with viral hepatitis-related cirrhosis. Sarcopenia was diagnosed and staged according to EWGSOP2 criteria, incorporating measurements of muscle strength (handgrip), muscle mass (calf circumference), and physical performance (gait speed, KATZ index). GNRI was calculated using serum albumin and body weight. Liver disease severity was assessed using Child-Pugh and ALBI scores. Correlations between GNRI, sarcopenia components, and liver scores were analyzed, and diagnostic accuracy of GNRI and Child score in predicting severe sarcopenia was evaluated. The prevalence of sarcopenia in the cohort was 95.5%, with 42.2% classified as having severe sarcopenia. GNRI showed significant positive correlations with muscle strength (r = 0.536, p < 0.001), gait speed (r = 0.377, p = 0.001), and negative correlations with Child score (r = -0.240, p = 0.023) and ALBI score (r = -0.380, p < 0.001). A GNRI ≤ 87 was identified as an independent predictor of severe sarcopenia (OR = 4.15, p = 0.011). GNRI demonstrated high specificity (100%) but limited sensitivity (24.4%) for severe sarcopenia (AUC = 0.658). GNRI is a practical and cost-effective tool for predicting sarcopenia and functional decline in elderly patients with viral hepatitis-related liver cirrhosis. Its integration with functional performance assessments offers a comprehensive approach for early detection and risk stratification. GNRI may serve as a valuable screening tool, particularly in resource-limited hepatology settings.
This study aimed to evaluate the management of care regulation in the health care network and the process of elaboration and consensus of strategic actions to cope with viral hepatitis based on regional governance. This qualitative action research was carried out in a Mato Grosso Health Region, Brazil, with 45 professionals working in surveillance, care, regulation, management, and social control. The focus group enabled the joint analysis of coping strategies and the formulation of regional consensus and collegiate agreement. The results show the political-institutional absence of strategies to address care gaps, the centralization of regulation, and the fragility of computerization processes. Organizational difficulties in horizontal integration stand out, including a fragmented network and limited capacity for decentralized clinical support. Practices still show failures in intersectoral articulation, informality in care flows, and frail primary health care (PHC) in post-diagnosis monitoring. The consensual action plan included four strategic lines: expanding access to prevention actions, strengthening specialized care articulated with PHC, expanding laboratory diagnostic capacity, and consolidating health surveillance by inter-institutional agreements. Eliminating viral hepatitis requires systemic actions guided by social justice and the construction of collective solutions that meet regional needs and produce continuous monitoring to achieve the global goals by 2030. O estudo objetivou avaliar a gestão da regulação assistencial na rede de atenção à saúde, bem como o processo de elaboração e consenso de ações estratégicas pactuadas para o enfrentamento das hepatites virais, na perspectiva da governança regional. Trata-se de pesquisa-ação, de abordagem qualitativa, realizada em uma Região de Saúde de Mato Grosso, Brasil, com a participação de 45 profissionais atuantes na vigilância, cuidado, regulação, gestão e controle social. A realização de grupo focal possibilitou a análise conjunta das estratégias de enfrentamento, culminando na formulação de consenso regional e pactuação colegiada. Os resultados evidenciam, no nível político-institucional, a ausência de estratégias para enfrentar vazios assistenciais, a centralização da regulação e a fragilidade dos processos de informatização. No nível organizacional, destacam-se dificuldades de integração horizontal, com uma rede fragmentada e limitada capacidade de suporte clínico descentralizado. No nível das práticas, persistem falhas na articulação intersetorial, informalidade nos fluxos de cuidado e fragilidade da atenção primária à saúde (APS) no monitoramento pós-diagnóstico. O plano de ação consensuado contempla quatro linhas estratégicas: ampliar o acesso às ações de prevenção; fortalecer a atenção especializada articulada à APS; expandir a capacidade diagnóstica laboratorial; e consolidar a vigilância em saúde mediante pactuações interinstitucionais. A eliminação das hepatites virais demanda atuação sistêmica, orientada pela justiça social e pela construção de soluções coletivas que respondam às necessidades regionais, com monitoramento contínuo para o alcance das metas globais até 2030. Este estudio tuvo como objetivo evaluar la gestión de la regulación asistencial en la red de asistencia sanitaria, así como el proceso de elaboración y consenso de acciones estratégicas consensuadas para combatir las hepatitis virales desde la perspectiva de la gobernanza regional. Se trata de una investigación-acción, con enfoque cualitativo, realizada en una Región Sanitaria de Mato Grosso, Brasil, con la participación de 45 profesionales que trabajan en vigilancia, atención, regulación, gestión y control social. El grupo focal permitió el análisis conjunto de estrategias de afrontamiento, lo cual culminó en la formulación de consenso regional y acuerdo colegiado. Los resultados muestran, a nivel político-institucional, la ausencia de estrategias para enfrentar las brechas asistenciales, la centralización de la regulación y la fragilidad de los procesos de informatización. A nivel organizacional destacan las dificultades de integración horizontal, con una red fragmentada y limitada capacidad de apoyo clínico descentralizado. A nivel de prácticas persisten fallas en la articulación intersectorial, informalidad en los flujos asistenciales y fragilidad de la atención primaria de salud (APS) en el seguimiento posdiagnóstico. El plan de acción consensuado incluye cuatro líneas estratégicas: ampliar el acceso a las acciones de prevención; fortalecer la atención especializada articulada a la APS; ampliar la capacidad de diagnóstico de laboratorio; y consolidar la vigilancia de la salud mediante acuerdos interinstitucionales. La eliminación de las hepatitis virales requiere una acción sistémica guiada por la justicia social y la construcción de soluciones colectivas que respondan a las necesidades regionales, con un monitoreo continuo para alcanzar los objetivos globales para 2030.
Chronic hepatitis B (CHB) refers to a global infectious disease caused by the hepatitis B virus. The treatment of CHB causes a heavy economic burden to society. To ensure the rational allocation of medical resources in the whole society and achieve the goal of patients' satisfaction and economy, this study aimed to evaluate the economics of de novo combination of tenofovir alafenamide fumarate (TAF) as the first-line nucleos(t)ide analogues (NAs) and peginterferon alfa-2b (PEG-IFNα-2b) versus PEG-IFNα-2b monotherapy of HBeAg-positive CHB in China. The Markov model was used to simulate the transition of HBeAg-positive CHB patients aged 30 in China under various health states using TreeAge Pro 2011 software. The cycle length was 1 year, and the cycle period of the model was 50 years. The model parameters included clinical efficacy, cost, transition probability and discount rate. Cost-effectiveness analysis was conducted through simulation of the total cost and quality adjusted life years (QALYs) of various treatment options through models. Simultaneously, one-way sensitivity analysis, probabilistic sensitivity analysis and scenario analysis were performed. De novo combination of TAF and PEG-IFNα-2b and PEG-IFNα-2b monotherapy resulted in 11.16 and 10.81 QALYs, with total costs of $55559.72 and $57670.23, respectively. De novo combination strategy for HBeAg-positive CHB patients can save costs and obtain more health outcomes. Sensitivity analyses showed the reliability of the results. From the perspective of the whole society, the de novo combination strategy of TAF and PEG-IFNα-2b for patients with HBeAg-positive CHB may be more cost-effective than PEG-IFNα-2b monotherapy.
OBJECTIVE: Despite advances in prevention and treatment, the burden of acute viral hepatitis (AVH) remains substantial yet understudied in the elderly. In this study, we used data from the Global Burden of Disease (GBD) 2021 database to analyze burden, inequality, and trends associated with acute hepatitis from 1990 to 2021 in individuals aged 60 years and above. METHODS: Data on AVH burden in the elderly were extracted from the GBD 2021 database for analysis of age-standardized prevalence rates (ASPR), age-standardized incidence rates(ASIR), age-standardized mortality rates(ASMR), age-standardized disability-adjusted life years [DALYs] rates(ASDR) and demographic factors (gender, age group). Analytical techniques included joinpoint regression, decomposition analyses, and predictive modeling to assess temporal trends and future projections. RESULTS: From 1990 to 2021, trends in global age-specific prevalence, incidence, mortality, and DALY rates (ASPR, ASIR, ASMR, and ASDR, respectively) were consistently downward. Specifically, low–Social Development Index (SDI) countries exhibited higher prevalence, incidence, and mortality rates and more DALYs. Frontier analysis showed that the AVH-related ASDR from 1990 to 2021 generally decreased with increasing SDI, indicating that higher levels of social development were associated with better health outcomes in the elderly. Generally, age analysis indicated declines in prevalence and incidence with age, with a valley around 85–89 years for most SDI regions, followed by a slight rise. By 2050, ASPR and ASIR were projected to show an upward trend, while ASMR and ASDR were expected to decline. CONCLUSIONS: This study highlighted a continuing, albeit declining, burden of AVH in the elderly, with stark regional disparities influenced by sociodemographic factors. Despite reductions in incidence and prevalence, mortality and DALYs remain high in low-SDI regions, underscoring the need for targeted interventions. These findings stress the importance of equitable healthcare strategies to address the specific needs of the elderly population worldwide and help achieve the hepatitis elimination goals of the World Health Organization. CLINICAL TRIAL NUMBER: Not applicable.
Peer-based models supporting testing and treatment for hepatitis C virus (HCV) infection have been explored, but peer-led testing is less common. We examined HCV testing and treatment following a mobile peer-led intervention integrating incentives, peer-delivered point-of-care HCV RNA testing, and linkage to care. Peers On Wheels is an observational study of peer-led mobile outreach integrating incentives, peer-delivered point-of-care HCV antibody and RNA testing, same-day receipt of test results, and peer-assisted linkage to care and treatment to people at HCV risk. Participants were recruited between July 2022 and May 2023 in New South Wales, Australia. The study was co-designed and implemented by a peer-based organisation representing people who use drugs. The primary outcomes were the number of tests performed and the proportion of people who initiated treatment within 12 weeks of testing. 674 participants received HCV point-of-care testing (median age, 45 years, 43% female), 48% injecting drug use ever, and 29% injecting in the previous 6 months. 84% (563 of 674) had no previous HCV treatment and received an antibody test, 20% (113 of 563) tested antibody positive, and 100% (113 of 113) received a reflex point-of-care RNA test. 16% (111 of 674) had previous HCV treatment and received immediate point-of-care RNA testing. HCV antibody prevalence was 33% (221 of 674) and was higher among people who had injected in the previous six months (73%, p < 0.001), and people who had injected, but not in the last six months (53%, p < 0.001) compared to people who had never injected drugs (3%). HCV RNA prevalence was 8% (53 of 674) and was higher among people who had injected in the previous six months (19%, p < 0.001), and people who had injected, but not in the last six months (10%, p < 0.001) compared to people who had never injected drugs (1%). Among people with current HCV, 19% (10 of 53) initiated treatment through the study. This peer-led mobile model facilitated testing and diagnosis, but a low proportion initiated HCV treatment. Further strategies should be explored to enhance linkage to treatment.
Acute hepatitis B (AHB), an acute manifestation triggered by hepatitis B virus infection, has emerged as a significant international public health concern, particularly endangering women of childbearing age (WCBA) who are prone to persistent infection, adverse pregnancy outcomes, and mother-to-child transmission threats. However, research on acute hepatitis B lags, mainly focusing on chronic cases or clinical treatments. This study aims to quantify its global disease burden from 1990 to 2021 among women of childbearing age and predict epidemiological trends to inform targeted prevention and control strategies. Data of AHB burden from 1990 to 2021were obtained from the GBD 2021 via Global Health Data Exchange (GHDx). Frontier analysis was utilized to find the unrealized health potential. The age-period-cohort model was applied to analyze trends across different age groups, periods, and birth cohorts. The joinpoint regression model was used to identify significant changes in data trends over time. The Bayesian age-period-cohort model was utilized for forecasting future epidemiological trajectories. A decreasing trend in age-standardized incidence rate (ASIR), age-standardized prevalence rate (ASPR), age-standardized mortality rate (ASMR), and disability-adjusted life-years rates (ASDR) was observed among the women of childbearing age worldwide from 1990 to 2021. The disease burden was disproportionately higher in low socio-demographic index (SDI) regions. The Bayesian age-period-cohort model revealed that by 2050, the ASIR and ASPR show similar downward trends, as do the ASMR and ASDR, but the latter decline less steeply than the former. The global disease burden of AHB in WCBA was declining, which is consistent with the vaccination and perinatal prevention, yet marked geographic disparities persist in low-resource regions. Modeling projections show that continued declines may contribute to progress toward the WHO viral hepatitis elimination goals, but vaccine coverage, safe injection and sufficient prevention of mother-to-child transmission remain essential. Not applicable.
American Indian and Alaska Native people have higher hepatitis C virus (HCV) incidence and mortality rates compared with other racial and ethnic groups. With the point-of-care HCV RNA diagnostic test recently approved for use in the US, the Cherokee Nation integrated diagnostic testing within existing community-based screening efforts to reach underserved community members. To describe the lessons learned from implementing community-based point-of-care HCV RNA testing, including same-day HCV treatment uptake, in a tribal health setting. This quality improvement study, conducted on the Cherokee Nation reservation in northeastern Oklahoma, collected quantitative data through paper-based surveys and electronic medical records from Cherokee Nation's Infectious Disease Department and harm reduction site, as well as qualitative data from staff meetings. Eligible participants included people aged 22 years or older who visited participating sites from October 30, 2024, to May 28, 2025, and provided informed consent. The Cherokee Nation Hepatitis C Engagement and Linkage Program. Test acceptance, completion, validity, and results; HCV treatment uptake; and implementation lessons learned. Of the 400 participants (mean [SD] age, 42.5 [12.6] years; 209 [52%] women), 247 of 377 (66%) had a high school degree or less, 309 of 374 (83%) had an annual income of $15 000 or less, and 149 of 385 (39%) reported ever injecting drugs. There were 405 point-of-care HCV RNA tests offered, and 348 (86%) accepted. Of these, 23 (7%) were not performed due to insufficient sample volume. An additional 51 samples (15%) tested were invalid. Of the 274 valid tests, 26 (10%) detected HCV. Of the samples with HCV, 12 (46%) were from American Indian and Alaska Native participants and 14 (54%) were not. Nine participants (35%) with detectable HCV initiated treatment, 6 (67%) the same day, and all who initiated treatment were American Indian and Alaska Native. Most invalid tests occurred within 2 months of implementation. Test validity increased after introducing techniques to improve volume collection. In this quality improvement study conducted in a tribal clinic and harm reduction site, point-of-care HCV RNA testing was feasible and effective, with high acceptance and same-day treatment among American Indian and Alaska Native participants. Staff training, addressing logistical barriers, and broadening the population reached supported equitable access to testing. This study supports expanding point-of-care HCV RNA testing and integrated treatment to advance HCV elimination.
BackgroundLiver cancer (LivCa) is one of the most prevalent malignancies globally, and can result from viral hepatitis, non-alcoholic steatohepatitis (NASH), and alcohol use. LivCa is of increasing concern in Asia, but the burden of etiology-specific LivCa and future projections remain to be elucidated.MethodsWe extracted the incidence, mortality, and disability-adjusted life years (DALYs) of LivCa across Asia and in 34 Asian countries in 1990-2021 from the Global Burden of Disease Study 2021 (GBD 2021). We then calculated their estimated annual percentage change (EAPC) and percentage variation to quantify the changes in the burden of LivCa. The association of the level of social development with LivCa burden was explored using the sociodemographic index (SDI). Moreover, the trend of the epidemiology of LivCa burden in Asia from 2022 to 2040 was predicted using the Bayesian age-period-cohort (BAPC) model.ResultsOverall, the age-standardized incidence, mortality, and DALYs rates of LivCa in Asia showed a general declining trend, with EAPCs of -0.47, -0.73, and -1.14, respectively. Notably, hepatitis B virus remained the predominant cause. However, the burdens attributed to non-alcoholic steatohepatitis and alcohol use increased significantly, while that of hepatoblastoma decreased. Regarding demographic distribution, the highest disease burden was observed among males and the elderly population aged 85-94 years. Geographically, Nepal, Taiwan (Province of China), India, and Malaysia contributed most substantially to the increasing burden. In terms of risk factors, high BMI and alcohol use were prominent in Central Asia, whereas smoking was a key factor in East and Southeast Asia. Additionally, a positive correlation was observed between the SDI and the burden of LivCa. Finally, projections from the BAPC model indicated a persistent decline in the burden of LivCa from 2022 to 2040.ConclusionsDespite the overall decreasing trend, targeted strategies addressing etiology-specific risks and regional disparities are urgently needed to further reduce the future burden of LivCa in Asia.
Criminal legal system-involved individuals face barriers to care after release from carceral settings. Elevated SARS-CoV-2 risk while incarcerated, together with living in congregate settings post-incarceration, increase the risk of respiratory viral infection transmission. This study evaluated a community health worker-led point-of-care SARS-CoV-2 testing and education intervention in a re-entry-focused community-based organisation compared with standard referrals. This non-blinded, parallel group, randomised controlled trial, conducted in partnership with a community-based organisation in New York City (NYC), NY, USA, enrolled clients who were released from incarceration in the previous 90 days, fluent in English or Spanish, and residing within NYC for the study duration. Participants were randomly assigned (1:1) via computer-generated randomisation to onsite point-of-care testing and education or standard of care referral to offsite testing sites over 12 months. All participants were advised to test every 3 months. The study was not masked due to the nature of the intervention. The primary outcome was the proportion of patients with at least one SARS-CoV-2 test performed with results received during the 12-month period. Primary analyses were done by intention-to-treat using logistic or Poisson regression modelling. This trial was registered with ClinicalTrials.gov, NCT04878328, and is completed. Between April 14, 2022, and May 22, 2024, 572 formerly incarcerated individuals were assessed for study eligibility. After the exclusion of 247 individuals, and a further 75 who did not attend enrolment, 250 participants were randomly assigned to the two study groups (125 to onsite point-of-care testing and education and 125 to standard of care). 216 (86%) participants were cisgender men, 30 (12%) were cisgender women, two (1%) were transgender women, and two (1%) were non-binary; 120 (48%) were Black and 82 (33%) were Hispanic; mean age was 42·0 years (SD 11·8). 109 (87%) of the 125 participants in the onsite point-of-care testing and education group and 67 (54%) of 125 participants in the standard of care group had at least one complete SARS-CoV-2 test (odds ratio 5·9 [95% CI 3·1-11·1]; p<0·0001). The absolute difference was 34 percentage points (95% CI 23-44; p<0·0001). The incidence rate ratio of complete SARS-CoV-2 tests was 2·4 times (95% CI 1·9-3·0, p<0·0001) as high among participants in the intervention group versus those in the standard of care group. No serious adverse events occurred. Community-health worker-led testing and education at a re-entry-focused community-based organisation could potentially increase uptake of SARS-CoV-2 testing among formerly incarcerated individuals. Although further, larger trials are required, trusted community health workers can provide onsite point-of-care testing and health education, which has relevance for respiratory viral infections such as SARS-CoV-2 and might potentially be applicable to other infectious diseases such as HIV and hepatitis C virus. US National Institutes of Health.
Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death in patients with cirrhosis. Although advancements in surgical, locoregional, and systemic therapies have improved outcomes for patients with early-stage HCC, most cases are diagnosed at later stages due to both the limitations of currently recommended surveillance modalities and their underuse, with fewer than 1 in 4 patients with cirrhosis receiving surveillance for this tumor. Current guidelines recommend semiannual surveillance with ultrasound and α-fetoprotein, but this strategy has suboptimal sensitivity, and alternative imaging techniques (eg, computed tomography and magnetic resonance imaging) have their own risks and challenges with implementation. HCC surveillance has established benefits in certain at-risk populations, including patients with cirrhosis (of any etiology) and selected patients with chronic hepatitis B virus. The burden of HCC is rising most rapidly among patients with nonviral liver diseases, including metabolic dysfunction-associated steatotic liver disease and alcohol-associated liver disease, among whom the annual incidence rate of HCC is significantly lower than was previously observed in patients with viral hepatitis. This underscores the need for better biomarker and risk-stratification tools to detect HCC earlier and improve surveillance efficiency, although integrating them into routine clinical practice presents a significant challenge. This American Gastroenterological Association (AGA) Clinical Practice Update aims to provide Best Practice Advice on emerging strategies for HCC risk stratification and surveillance. This Expert Review was commissioned and approved by the AGA Institute Clinical Practice Updates Committee and the AGA Governing Board to provide timely guidance on this topic of high clinical importance to the AGA membership and underwent internal peer review by the Clinical Practice Updates Committee and external review procedures through the standard review process for Gastroenterology. These Best Practice Advice statements were drawn from a review of the published literature and from expert opinion. Because a systematic review was not performed, these Best Practice Advice statements do not carry formal ratings of the quality of available evidence or the strength of the presented advice. Best Practice Advice Statements BEST PRACTICE ADVICE 1: The best strategy for reducing hepatocellular carcinoma morbidity and mortality is to prevent cirrhosis. These strategies include vaccination and treatment of viral hepatitis (eg, hepatitis C virus and hepatitis B virus), recognizing and treating alcohol use disorder, managing metabolic syndrome, and addressing liver diseases at early stages. BEST PRACTICE ADVICE 2: The preferred current surveillance strategy for patients at risk of hepatocellular carcinoma is semiannual ultrasound and α-fetoprotein in combination. The benefits of surveillance include a higher likelihood of detecting early-stage hepatocellular carcinoma, access to curative therapy, and improved survival. BEST PRACTICE ADVICE 3: Among patients without cirrhosis, only a subset of those with chronic hepatitis B virus should undergo hepatocellular carcinoma surveillance; surveillance is not advised for those without cirrhosis from other etiologies due to the low annual incidence rate. BEST PRACTICE ADVICE 4: Although the benefits of hepatocellular carcinoma surveillance are well established, it is important for clinicians to consider the potential physical, psychological, and financial harms associated with the process. BEST PRACTICE ADVICE 5: Several novel blood-based biomarkers, such as GALAD, and radiologic biomarkers are undergoing clinical validation. Some are already commercially available, but evidence is insufficient to support their use in routine hepatocellular carcinoma surveillance. These assays should not replace guideline-recommended tests, although their accessibility and potential cost-effectiveness may support broader use once sufficiently validated. BEST PRACTICE ADVICE 6: Multicancer blood-based biomarker detection panels should not be used in the screening or surveillance of patients at risk for hepatocellular carcinoma. BEST PRACTICE ADVICE 7: Many hepatocellular carcinoma risk-stratification scores exist for patients with cirrhosis. However, few scores have undergone sufficient validation to support their use in clinical practice. BEST PRACTICE ADVICE 8: Among patients with chronic hepatitis B virus infection without cirrhosis, PAGE-B and REAL-B scores can stratify patients based on their future risk of hepatocellular carcinoma.
Despite increasing access to HIV treatment and care, HIV-associated deaths remain high. We aimed to summarize global and regional trends in risk and causes of death among people living with HIV (PLHIV) admitted to hospital. We conducted a systematic search across eight databases on 23 April 2023, identifying studies that reported cause of hospital admission or death among hospitalized PLHIV from first January 2014 onwards. We extracted data on age, geographical region, type of ward, antiretroviral treatment use, CD4 cell count, risk of death, cause of death and method of ascertainment of cause of death. We grouped studies into mutually exclusive groups: adults in medical wards by world region; adults in intensive care; and children. We used a Bayesian multilevel meta-regression model to pool data on causes of death. We additionally estimated temporal trends in risk of death among hospitalized PLHIV between 2000 and 2023. We identified 67 studies (59,013 participants) reporting risk of death among hospitalized PLHIV between 2014 and 2023. The overall risk of in-hospital death was 16% (95% credible interval [CrI]: 8%-27%). Mortality risk was highest among adults in Africa (19%, 95% CI: 15%-24%) and adults in intensive care units (44%, 95% CI: 34%-55%). Among 40 studies reporting cause of death in 6,838 participants, AIDS-related conditions predominated (72% of deaths, 95% CrI: 57%-85%), including tuberculosis deaths (27% of deaths, 95% CrI: 15%-40%). Bacterial infections were the second leading cause of death (25% of deaths, 95% CrI: 9%-47%). There was no strong evidence of risk of death changing between 2000 and 2023 (-2.2 percentage point decrease, 95% CrI -16.1 to +17.0 percentage points). Despite advances in HIV treatment, AIDS-related illnesses and bacterial infections remain the leading causes of in-hospital death among PLHIV. Our analysis reveals that in most regions, the risk of death for hospitalized PLHIV has remained largely unchanged in the past 23 years. These findings underscore the critical need to prioritize high-quality hospital care for opportunistic infections to reduce AIDS-related deaths.
Quantitative detection of human immunodeficiency virus-type 1 (HIV-1) and hepatitis C virus (HCV) RNA plays a crucial role in the diagnosis, monitoring of the therapy and evaluation of the treatment response. The ELITe BeGenius® platform (ELITechGroup, Turin, Italy) is a fully automated sample-toresult molecular system integrating extraction, amplification and detection within a single workflow. The HIV-1 ELITe MGB® and HCV ELITe MGB® assays are real-time polymerase chain reaction tests designed for plasma viral-load quantification. This study aimed to verify their analytical performance under routine clinical laboratory conditions. Verification included assessments of accuracy, intra- and inter-assay precision, linearity and method correlation. A total of 70 plasma samples for HIV-1 RNA and 52 for HCV RNA were analyzed using previously tested and stored patient specimens, reference materials, and external quality controls. Results were compared with established reference assays used in accredited laboratories. Statistical analyses included positive, negative, and overall percent agreement (PPA, NPA, OPA), coefficients of variation (CV%), correlation and regression analyses and Bland-Altman bias estimation. For HIV-1 RNA, 19 of 20 positive and all 20 negative plasma samples were correctly identified by the ELITe MGB® assay, yielding a PPA of 95.0%, NPA of 100.0% and OPA of 97.5% (κ= 0.95). Intra-assay precision showed strong repeatability, with CVs of <1-3.9% for low-positive, 0.4-6.4% for medium-positive and <2% for high-positive specimens. Inter-assay reproducibility was consistent with CVs of 12.8% at low, 2.4% at medium, and 1.4% at high viral loads. Correlation analysis showed excellent concordance with the reference assay (p= 0.975, p< 0.001; R²= 0.95) and a mean bias of -0.40 log10 copies/mL in Bland-Altman analysis. Linearity was strong (R²= 0.97), confirming accurate quantification across the dynamic range with minor underestimation at higher dilutions. For HCV RNA, all 14 positive and 14 negative samples were correctly classified (PPA, NPA, and OPA= 100%; κ= 1.00). Intra-assay precision was excellent, with CVs around 2% for both low- and medium-positive samples, confirming consistent repeatability within a single run. Inter-assay reproducibility was equally robust, with CVs of 0.4-3.3% for low positives, 1.0-2.5% for medium and <1.1% for high-titer specimens. Correlation with the comparator method was strong (r= 0.956, p< 0.001; R²= 0.91) with a mean bias of -0.38 log10 IU/mL. Linearity analysis confirmed high proportionality between expected and measured concentrations (R²= 0.96). Deviations were negligible at low titers and slightly elevated at high loads but remained within acceptable limits. The HIV-1 and HCV ELITe MGB® assays on the BeGenius® platform demonstrated high accuracy, reproducibility and linearity, showing excellent correlation with reference methods. These results confirm that the ELITe BeGenius® system provides reliable and clinically valid viral-load measurements suitable for routine diagnostic use. Comprehensive laboratory verification of molecular assays under real-world conditions is crucial to ensure consistent performance, cross-platform comparability and reliable viral-load monitoring.
To achieve hepatitis B virus (HBV) elimination in Australia, a shift from hospital to community-based care is needed. This study aimed to describe the prevalence of chronic HBV and uptake of the cascade of care in primary care patients. This prospective cohort study was conducted in 76 urban and regional primary care clinics across Victoria, Australia between 1/7/2020 and 30/6/2023. Anonymised socio-demographic, clinical and laboratory data from general practice (GP) clinics' electronic medical records (EMR) were extracted. Descriptive analysis of the cohort of clinic clients with HBV was performed. A total of 346,927 individuals attended appointments across the study period. Of these, 25,212 had records indicating HBV-related testing. 491 (0.14%) individuals had evidence of current HBV infection defined as HBV surface antigen (HBsAg) positive and/or HBV DNA positive. 469 attended the clinics during the study period, among whom 239 (51%) were female. In the GP EMR, only 59 (13%) had evidence of at least one HBV DNA test and at least one ALT test ordered. Fourteen patients (3%) had record of being reviewed for HBV management by the clinic nurse or GP and 78 (17%) reviewed by a viral hepatitis specialist. Ninety-two (20%) were on treatment for HBV. Of people receiving treatment, 23 (25%) had a record of linkage to specialist care. Our data show that significant gaps in the cascade of care remain for people with chronic HBV in primary care settings, with a low proportion of patients having evidence of participating in all stages of the HBV cascade of care.
Strategies are needed to overcome barriers to hepatitis C virus (HCV) care in marginalised populations. This study evaluated an intervention integrating peer- and nurse-based outreach, financial incentives, point-of-care HCV antibody and RNA testing, and linkage to specialist assessment to increase testing and treatment initiation among people who have used drugs or experienced homelessness. REACH_U is a historically controlled study comparing HCV RNA testing and treatment during a control phase consisting of referral to hospital-based testing and treatment (October 2018-March 2020) to an intervention phase to decentralise testing (April 2021-December 2024) in Lisbon, Portugal. During the control phase, point-of-care HCV antibody testing was performed with antibody-positive participants referred for hospital-based HCV RNA testing and treatment. During the intervention phase, a peer and nurse-based outreach team performed incentivised point-of-care HCV antibody and RNA testing in the community with referral to decentralised specialist assessment and treatment. Endpoints included the proportion receiving HCV RNA testing and initiating HCV therapy. Among 814 participants (control, n = 120; intervention, n = 694), mean age (42 vs. 45), proportion female (18% vs 24%), and homelessness (67% vs. 60%) were similar, but ever (51% vs 25%) and recent injecting drug use (48% vs 12%) was higher in the control. The proportion receiving HCV RNA testing (standard of care, 17 of 51; intervention, 135 of 148; 33% vs 91%, P < 0.001) and the proportion initiating treatment (standard of care, 4 of 15; intervention, 34 of 57; 27% vs 60%, P = 0.023) was higher in the intervention compared to the control phase. After adjusting for recent injecting drug use and current homelessness, the intervention phase was associated with greater odds of initiating treatment (aOR, 4.58; 95% CI 1.16-18.07). This decentralised model with linkage to a university hospital led to increased HCV RNA testing and treatment among people who have used drugs or experienced homelessness, providing a model that could be explored in other settings.
We evaluated impact of hepatitis C treatment adherence support among people who inject drugs (PWID) in India using a precision trial design. Treatment naïve participants with a history of drug injection were recruited from community-based clinics across 7 cities. All received sofosbuvir/velpatasvir once/day for 12 weeks. Failure risk was defined a priori using a prognostic score including age, sex, income, homelessness, injection frequency, depressive symptoms, quality of life indicators and sexual partners. Elevated risk were randomized 3:2:1 to high (patient navigation [PN]+flexible directly observed therapy [≥1 dose/week observed]), medium (PN contact ≥every 2 weeks) or low intensity support. Minimal risk were randomized 1:2:3 to high, medium and low intensity support. Primary outcome was sustained virologic response (SVR; HCV RNA <LLOQ 24 weeks post-randomization; intention to treat). 3000 were randomized (1/2021-12/2022; 2048 minimal, 952 elevated risk), 2798 (93.3%) completed SVR assessment. In minimal risk participants, SVR was 62.6%, 60.8% and 68.3% in low, medium and high intensity support, respectively. In elevated risk participants, SVR was 48.4%, 45.5% and 50.8%. 51 experienced a serious adverse event (35 deaths). In minimal risk participants, we observed superiority of high intensity (adjusted relative risk vs. low [aRR] 1.09; 95% confidence interval [CI]: 1.00-1.19; p=0.04) not medium intensity (aRR 0.97; 95% CI: 0.90-1.05) support. In elevated risk participants, there was no impact (low vs. high 0.96; 95% CI: 0.80-1.15; medium vs. high 0.89; 95% CI: 0.77-1.04). Every 10% decrease in prognostic score was associated with 1.06 increase in SVR (95% CI: 1.04-1.08). Prognostic scores could help target interventions more efficiently; greater adherence support and/or novel interventions are needed to improve SVR for the highest risk. ClinicalTrials.gov NCT04652804. This trial represents one of the largest trials to date of hepatitis C treatment. Our results, which demonstrate limited impact of adherence support interventions and sub-optimal sustained virologic response (SVR) among community-based people who inject drugs (PWID), suggest that more intensive or different tools and or strategies will be needed to support HCV elimination in populations like PWID. At the same time, these results provide strong evidence for the use of prognostic scores in trials as well as potentially in the delivery of interventions particularly when resources are scarce.