[Expert recommendations on screening, testing and management for hepatitis B virus infection in adults].

The prevalence of hepatitis B represents a significant public health concern with a heavy disease burden. In China, there is still a big gap between the current diagnosis and treatment rates of hepatitis B and the goal of eliminating viral hepatitis as a public health threat by 2030 set by the World Health Organization (WHO). In order to achieve the WHO goal and the goal of 2030 Healthy China Outline, the Chinese Preventive Medicine Association organized domestic experts in the fields of clinical medicine, public health and clinical laboratory medicine to develop the Expert Recommendations on Screening, Testing and Management for Hepatitis B Virus Infection in Adults after several rounds of discussion based on comprehensive review of relevant domestic and international guidelines and literatures, the purpose is to facilitate universal screening of hepatitis B virus(HBV)infection in adults and provide practical guidance on disease assessment, treatment and long-term follow-up management of people infected with HBV and vaccination for people susceptible to HBV infection,thus promoting the elimination of the threat of hepatitis B.

[Expert recommendations on hepatitis B vaccination in adults].

In order to achieve the target of eliminating viral hepatitis as a public health threat by 2030 and to prioritize the role of hepatitis B vaccination in reducing new hepatitis B virus infections, the Chinese Preventive Medicine Association commissioned experts to develop the Expert Recommendations on Hepatitis B Vaccination in Adults to scientifically guide adult hepatitis B vaccination,build the herd immunity in population, and reduce the hepatitis B virus infection rate and incidence of hepatitis B.

Intermediate hepatitis C virus (HCV) endemicity and its genotype distribution in Myanmar: A systematic review and meta-analysis.

BACKGROUND: Comprehensive details on Hepatitis C virus (HCV) infection in Myanmar are lacking. This study determined the prevalence of HCV antibodies and ribonucleic acid (RNA) and the distribution of HCV genotypes across different populations in Myanmar from 1990 to 2023. MATERIAL AND METHODS: A systematic search in PubMed, Web of Science, Scopus, and local journals identified studies reporting on HCV antibodies, RNA, and genotypes, excluding clinical research related to liver disease prognosis. Screening and data extraction was done by two authors and study populations were categorized into low-risk, high-risk, liver disease patients, and refugees outside the country. The pooled prevalence was performed by Dersimonian and Laird method using the R program. The publication bias was shown by funnel plot, the Egger test was used to assess the symmetry of the plot, and the heterogeneity was examined by the Cochran Q test and I2 index. RESULTS: Out of 135 reports screened for eligibility, 35 reports comprising 51 studies were included in which 33 studies provided data on HCV seroprevalence in 685,403 individuals, 8 studies reported HCV RNA prevalence in 25,018 individuals, and 10 studies examined HCV genotypes in 1,845 individuals. The pooled seroprevalence of HCV among low-risk, high-risk, liver disease patients and refugees were 2.18%, 37.07%, 33.84%, and 2.52% respectively. HCV RNA-positive rates in these groups were 1.40%, 5.25%, 24.96%, and 0.84% respectively. Seroprevalence studies showed publication bias (Egger test, p = 0.0001), while RNA studies did not (Egger test, p = 0.8392). HCV genotype 3 was predominant in all sub-groups in Myanmar. CONCLUSION: Our study shows Myanmar has intermediate HCV endemicity with lowest HCV prevalence of 2.18% in low-risk groups and highest prevalence of 37.07% in high- risk groups. However, the findings highlight the need for further epidemiological studies to understand actual disease burden and implement effective countermeasures to achieve the WHO's goal of HCV elimination by 2030.

Visualizing in-field detection of HCV using a one-pot RT-RAA-CRISPR/Cas12a platform.

Hepatitis C, one of the major infectious diseases posing a serious threat to human health, contributes a significant disease burden to global public health governance. Low diagnostic rates are a major barrier to eliminating hepatitis C in resource-constrained countries. As a result, the development of rapid, accurate, ultra-sensitive, and user-friendly POCT assays is desperately needed to improve the diagnostic rate and control of HCV. Here, we present a Visual One-Pot RT-RAA-Cas12a (HCV-VOpRCas12a) platform, which performed RT-RAA and CRISPR-based detection in a single tube by physical separation, and low-cost, readily accessible hand warmers were used as incubators. A visualization device was built to achieve the visual readout. The LoD of the HCV-VOpRCas12a platform was as low as 100 copies per µL and only took about 15 min to achieve HCV-RNA diagnosis. In the validation of 101 clinical serum samples, the detection sensitivity and specificity of the visualization device were 95% and 100%. The VOpRCas12a platform holds enormous potential in achieving a global strategy to eliminate the public threat of HCV infection by 2030 and in the next generation of real-time molecular diagnostics.

Control of Hepatitis B Virus with Imdusiran, a Small Interfering RNA Therapeutic.

Chronic hepatitis B is a global health concern with a high risk of end-stage liver disease. Current standard-of-care agents have low cure rates, and new therapies are needed. Small interfering RNAs (siRNAs) that target viral RNAs fulfill a gap not addressed by standard-of-care agents and may contribute to a functional cure. Here, we describe the preclinical characterization of imdusiran (AB-729), a novel, pan-genotypic siRNA therapeutic that effectively reduces HBsAg, viral antigens, and viral replication in chronic hepatitis B patients and is currently in Phase 2 clinical studies. In hepatitis B virus (HBV) cell-based systems, imdusiran possessed pan-genotypic nanomolar potency and retained activity against HBV target site polymorphisms. Imdusiran was active against nucleos(t)ide analogue- and capsid assembly modulator-resistant HBV isolates, and combination with standard-of-care agents was additive. In an HBV adeno-associated virus mouse model, HBsAg was reduced up to 3.7 log10 after a single imdusiran dose, with sustained suppression for 10 weeks. Imdusiran did not intrinsically stimulate cytokine release in healthy donor human whole blood, supportive of its mechanism of action as a direct acting RNA interference antiviral. Taken together, these data support imdusiran in combination treatment approaches toward chronic hepatitis B functional cure.

Is there still hope for the prophylactic hepatitis C vaccine? A review of different approaches.

Despite remarkable progress in the treatment of hepatitis C virus (HCV) infection, it remains a significant global health burden, necessitating the development of an effective prophylactic vaccine. This review paper presents the current landscape of HCV vaccine candidates and approaches, including more traditional, based on inactivated virus, and more modern, such as subunit protein, vectored, based on nucleic acids (DNA and mRNA) and virus-like particles. The concept of the HCV vaccine is first put in the context of viral genetic diversity and adaptive responses to HCV infection, an understanding of which is crucial in guiding the development of an effective vaccine against such a complex virus. Because ethical dimensions are also significant in vaccine research, development, and potential deployment, we also address them in this paper. The road to a safe and effective vaccine to prevent HCV infection remains bumpy due to the genetic variation of HCV and its ability to evade immune responses. The progress in cell-culture systems allowed for the production of an inactivated HCV vaccine candidate, which can induce cross-neutralizing antibodies in vitro, but whether this could prevent infection in humans is unknown. Subunit protein vaccine candidates that entered clinical trials elicited HCV-specific humoral and cellular responses, though it remains to be shown whether they translate into effective prevention of HCV infection or progression of infection to a chronic state. Such responses were also induced by a clinically tested vector-based vaccine candidate, which decreased the viral HCV load but did not prevent chronic HCV infection. These disappointments were not readily predicted from preclinical animal studies. The vaccine platforms employing virus-like particles, DNA, and mRNA provide opportunities for the HCV vaccine, but their potential in this context has yet to be shown. Ensuring the designed vaccine is based on conserved epitope(s) and elicits broadly neutralizing immune responses is also essential. Given failures in developing a prophylactic HCV vaccine, it is crucial to continue supporting national strategies, including funding for screening and treatment programs. However, these actions are likely insufficient to permanently control the HCV burden, encouraging further mobilization of significant resources for HCV vaccine research as a missing element in the elimination of viral hepatitis as a global public health.

Results from a retrospective case finding and re-engagement exercise for people previously diagnosed with hepatitis C virus to increase uptake of directly acting antiviral treatment.

BACKGROUND: Direct acting antivirals (DAAs) for the Hepatitis C virus (HCV) have shifted the World Health Organisation global strategic focus to the elimination of HCV by 2030. In England, the UK Health Security Agency (UKHSA) led a national 'patient re-engagement exercise', using routine surveillance data, which was delivered through the HCV Operational Delivery Networks (ODNs) with support from National Health Service England (NHSE), to help find and support people with a positive HCV PCR test result to access treatment. We report a quantitative evaluation of outcomes of this exercise. METHODS: Individuals with a recorded positive HCV antibody or PCR result between 1996 and 2017 were identified using UKHSA's records of HCV laboratory diagnosis. Linkage with established health-care datasets helped to enhance patient identification and minimise attempts to contact deceased or previously treated individuals. From September to November 2018 each ODN was provided with a local list of diagnosed individuals. ODNs were asked to perform further data quality checks through local systems and then write to each individual's GP to inform them that the individual would be contacted by the ODN to offer confirmatory HCV PCR testing, assessment and treatment unless the GP advised otherwise. Outcomes of interest were receipt of treatment, a negative PCR result, and death. Data were collected in 2022. RESULTS: Of 176,555 individuals with a positive HCV laboratory report, 55,329 individuals were included in the exercise following linkage to healthcare datasets and data reconciliation. Participants in the study had a median age of 51 years (IQR: 43, 59), 36,779 (66.5%) were males, 47,668 (86.2%) were diagnosed before 2016 and 11,148 (20.2%) lived in London. Of the study population, 7,442 (13.4%) had evidence of treatment after the re-engagement exercise commenced, 6,435 (11.6%) were reported as PCR negative (96% had no previous treatment records), 4,195 (7.6%) had prescription data indicating treatment before the exercise commenced or were reported to have been treated previously by their ODN, and 2,990 (5.4%) had died. The status of 32,802 (59.3%) people remains unknown. CONCLUSIONS: A substantial number of those included had treatment recorded after the exercise commenced, however, many more remain unengaged. Evaluation of the exercise highlighted areas that could be streamlined to improve future exercises.

Prevalence, trends, and distribution of hepatitis C virus among the general population in sub-Saharan Africa: A systematic review and meta-analysis.

BACKGROUND AND AIMS: Although the evidence is uncertain, existing estimates for hepatitis C virus (HCV) in sub-Saharan Africa (SSA) indicate a high burden. We estimated HCV seroprevalence and viraemic prevalence among the general population in SSA. METHODS: We searched Medline, Embase, Web of Science, APA PsycINFO, and World Health Organization Africa Index Medicus for community-based studies. Study quality was assessed using the Joanna Briggs Institute critical appraisal tool, and heterogeneity using the index of heterogeneity (I2). Two approaches were deployed. First, we used random-effects meta-analysis to pool prevalence. Second, to derive representative estimates, we weighted each country's HCV seroprevalence using 2021 United Nations country population sizes. RESULTS: We synthesized 130 studies. Overall, SSA HCV seroprevalence from the random-effects model was 4.17% (95% confidence interval [CI]: 3.71-4.66, I2 = 99.30%). There were no differences between males (4.31%) and females (4.03%). Seroprevalence was 2.25%, 3.31%, and 16.23% for ages ≤20, 21-64, and ≥65 years, respectively, and was higher in rural (6.63%) versus urban (2.93%). There was indication of decrement overtime from 5.74% to 4.35% to 3.03% in the years 1984-2000, 2001-2014, and 2015-2023, respectively. The weighted overall SSA HCV seroprevalence was estimated to be 2.30% (95% CI: 1.59-3.00) with regional variation: Africa-Southern (.79%), Africa-Central (1.47%), Africa-Eastern (2.71%), and Africa-Western (2.88%). HCV viremia among HCV seropositives was 54.77% (95% CI: 47.80-61.66). CONCLUSIONS: HCV seroprevalence in SSA remains high. Populations aged ≥65 years, rural communities, Africa-Western, and some countries in Africa-Central and Africa-Eastern appear disproportionately affected. These results underline the need for governmental commitment to achieve the 2030 global HCV elimination targets.

Novel mechanistic insights - A brand new Era for anti-HBV drugs.

Hepatitis B Virus (HBV) remains a critical global health issue, with substantial morbidity and mortality. Current therapies, including interferons and nucleoside analogs, often fail to achieve complete cure or functional eradication. This review explores recent advances in anti-HBV agents, focusing on their innovative mechanisms of action. HBV entry inhibitors target the sodium taurocholate cotransporting polypeptide (NTCP) receptor, impeding viral entry, while nucleus translocation inhibitors disrupt key viral life cycle steps, preventing replication. Capsid assembly modulators inhibit covalently closed circular DNA (cccDNA) formation, aiming to eradicate the persistent viral reservoir. Transcription inhibitors targeting cccDNA and integrated DNA offer significant potential to suppress HBV replication. Immunomodulatory agents are highlighted for their ability to enhance host immune responses, facil-itating better control and possible eradication of HBV. These novel approaches represent significant advancements in HBV therapy, providing new strategies to overcome current treatment limitations. The development of cccDNA reducers is particularly critical, as they directly target the persistent viral reservoir, offering a promising pathway towards achieving a functional cure or complete viral eradication. Continued research in this area is essential to advance the effectiveness of anti-HBV therapies.

Tenofovir versus entecavir on the prognosis of hepatitis B virus-related hepatocellular carcinoma: a reconstructed individual patient data meta-analysis.

Background: Hepatitis B, often leading to Hepatocellular carcinoma (HCC), poses a major global health challenge. While Tenofovir (TDF) and Entecavir (ETV) are potent treatments, their comparative effectiveness in improving recurrence-free survival (RFS) and overall survival (OS) rates in HBV-related HCC is not well-established. Methods: We conducted an individual patient data meta-analysis using survival data from randomized trials and high-quality propensity score-matched studies to compare the impact of Tenofovir (TDF) and Entecavir (ETV) on RFS and OS in HBV-related HCC patients. Data from six databases and gray literature up to 30 August 2023, were analyzed, utilizing Kaplan-Meier curves, stratified Cox models, and shared frailty models for survival rate assessment and to address between-study heterogeneity. The study employed restricted mean survival time analysis to evaluate differences in RFS and OS between TDF-treated and ETV-treated patients. Additionally, landmark analyses compared early (<2 years) and late (≥2 years) tumor recurrence in these cohorts. Results: This study incorporated seven research articles, covering 4,602 patients with HBV-related HCC (2,082 on TDF and 2,520 on ETV). Within the overall cohort, TDF recipients demonstrated significantly higher RFS (p = 0.042) and OS (p < 0.001) than those on ETV. The stratified Cox model revealed significantly improved OS for the TDF group compared to the ETV group (hazard ratio, 0.756; 95% confidence interval, 0.639-0.896; p = 0.001), a result corroborated by the shared frailty model. Over a follow-up period of 1-8 years, no significant difference was noted in the mean time to death between the TDF and ETV groups. The rates of early recurrence did not significantly differ between the groups (p = 0.735). However, TDF treatment was significantly associated with a reduced risk of late recurrence compared to ETV (p < 0.001). In the HCC resection subgroup, the disparities in OS, early, and late recurrence rates between the two treatments paralleled those seen in the overall cohort. Conclusion: Compared to ETV, TDF may enhance OS and reduce late tumor recurrence risk in HBV-related HCC patients receiving curative treatment. However, there was no statistically significant distinction in the timing of tumor recurrence and mortality between patients administered TDF and those prescribed ETV. Systematic Review Registration: http://www.crd.york.ac.uk/prospero/.

Inherent symmetry and flexibility in hepatitis B virus subviral particles.

Chronic hepatitis B virus (HBV) infection poses a major global health challenge with massive morbidity and mortality. Despite a preventive vaccine, current treatments provide limited virus clearance, necessitating lifelong commitment. The HBV surface antigen (HBsAg) is crucial for diagnosis and prognosis, yet its high-resolution structure and assembly on the virus envelope remain elusive. Utilizing extensive datasets and advanced cryo-electron microscopy analysis, we present structural insights into HBsAg at a near-atomic resolution of 3.7 angstroms. HBsAg homodimers assemble into subviral particles with D2- and D4-like quasisymmetry, elucidating the dense-packing rules and structural adaptability of HBsAg. These findings provide insights into how HBsAg assembles into higher-order filaments and interacts with the capsid to form virions.

Hepatitis C elimination: amplifying the role of primary care nurses in Australia.

Background Australia's commitment to eliminate hepatitis C by 2030 is underpinned by the mobilisation of the primary care sector. Primary care nurses are well placed to contribute to achieving elimination given their unique access to people with/at risk of hepatitis C and their person-centred approach to care delivery. This study examines the enablers to primary care nurse involvement in elimination efforts. Methods Primary care nurses involved in the care of people with/at risk of hepatitis C were recruited through two national nursing organisations. Participants provided verbal consent to participate in an electronically recorded, semi-structured interview. Interview data were transcribed verbatim, coded and analysed using a thematic analysis. Results Sixteen interviews were conducted with nurses working in general practice, community health, alcohol and other drug services, and custodial settings, with the findings framed using a social-ecological model. The study identified individual attributes, such as empathy and advocacy for clients deemed 'too hard for everyone else'. Interpersonal enablers included participants' ability to effectively communicate with clients and colleagues, and using trusted professional relationships to improve client access to care. Public policy that addressed community factors, including stigma and confidentiality, were seen as supportive. Conclusions This study identified the critical and varied role primary care nurses play in hepatitis C elimination. Effective scale up of hepatitis C care involves recognising the pivotal role of primary care nurses, which will help to create an enabling environment that supports nurses to work to their full scope of practice and enhance their contribution to the elimination response.

Integrated network pharmacology and metabolomics to study the potential mechanism of Jiawei Yinchenhao decoction in chronic hepatitis B.

Chronic hepatitis B infection (CHB) is a major risk factor for the development of hepatocellular carcinoma (HCC) globally and continues to pose a significant global health challenge. Jiawei Yinchenhao decoction (JWYCH) is a modified version of Yinchenhao decoction (YCHD), which is widely used to treat liver diseases including icteric hepatitis, cholelithiasis, and hepatic ascites. However, the effectiveness and underlying mechanism of JWYCH on CHB are still unclear. This study aimed to investigate the impact of JWYCH on CHB and explore the underlying mechanism via network pharmacology and metabolomics. C57BL/6 mice were administered rAAV-HBV1.3 via hydrodynamic injection (HDI) to establish the CHB model. The infected mice were orally administered JWYCH for 4 weeks. HBsAg, HBeAg, HBV DNA, the serum liver function index, and histopathology were detected. In addition, network pharmacology was used to investigate potential targets, whereas untargeted metabolomics analysis was employed to explore the hepatic metabolic changes in JWYCH in CHB mice and identify relevant biomarkers and metabolic pathways. JWYCH was able to reduce HBeAg levels and improve liver pathological changes in mice with CHB. Additionally, metabolomics analysis indicated that JWYCH can influence 105 metabolites, including pipecolic acid, alpha-terpinene, adenosine, and L-phenylalanine, among others. Bile acid metabolism, arachidonic acid metabolism, and retinol metabolism are suggested to be potential targets of JWYCH in CHB. In conclusion, JWYCH demonstrated a hepatoprotective effect on a mouse model of CHB, suggesting a potential alternative therapeutic strategy for CHB. The effect of JWYCH is associated mainly with regulating the metabolism of bile acid, arachidonic acid, and retinol. These differentially abundant metabolites may serve as potential biomarkers and therapeutic targets for CHB.

Effects and Costs of Hepatitis C Virus Elimination for the Whole Population in China: A Modelling Study.

BACKGROUND AND OBJECTIVE: China has the highest number of hepatitis C virus (HCV) infections in the world. However, it is unclear what levels of screening and treatment are needed to achieve the WHO 2030 hepatitis C elimination targets. We aimed to evaluate the impact of scaling up interventions on the hepatitis C epidemic and determine how and at what cost these elimination targets could be achieved for the whole population in China. METHODS: We developed a compartmental model incorporating HCV transmission, disease progression, and care cascade for the whole population in China, calibrated with data on demographics, injecting drug use, HCV prevalence, and treatments. Five different scenarios were evaluated for effects and costs for 2022-2030. All costs were converted to 2021 US dollar (USD) and discounted at an annual rate of 5%. One-way sensitivity analyses were conducted to assess the robustness of the model. RESULTS: Under the status quo scenario, the incidence of hepatitis C is projected to increase from 60.39 (57.60-63.45) per 100,000 person-years in 2022 to 68.72 (65.3-73.97) per 100,000 person-years in 2030, and 2.52 million (1.94-3.07 million) infected patients are projected to die between 2022 and 2030, of which 0.76 (0.61-1.08) million will die due to hepatitis C. By increasing primary screening to 10%, conducting regular rescreening (annually for PWID and every 5 years for the general population) and treating 90% of patients diagnosed, the incidence would be reduced by 88.15% (86.61-89.45%) and hepatitis C-related mortality by 60.5% (52.62-65.54%) by 2030, compared with 2015 levels. This strategy would cost USD 52.78 (USD 43.93-58.53) billion. CONCLUSIONS: Without changes in HCV prevention and control policy, the disease burden of HCV in China will increase dramatically. To achieve the hepatitis C elimination targets, China needs to sufficiently scale up screening and treatment.

Dia Mundial de combate à Hepatite: OPAS incentiva a ampliação do acesso a diagnóstico e tratamento

Antecipando o Dia Mundial de Combate à Hepatite (28 de julho), a Organização Pan-Americana da Saúde (OPAS) está incentivando os países a expandirem o acesso ao teste e tratamento para hepatite viral, que afeta mais de dez milhões de pessoas nas Américas, das quais apenas 23% são diagnosticadas.

Purification and characterization of soluble recombinant Crimean-Congo hemorrhagic fever virus glycoprotein Gc expressed in mammalian 293F cells.

BACKGROUND: Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne zoonotic disease that presents with severe hemorrhagic manifestations and is associated with significant fatality rates. The causative agent, Crimean-Congo Hemorrhagic Fever Virus (CCHFV), is a high-priority pathogen identified by the World Health Organization with no approved vaccine or specific treatment available. In addition, there is a critical need for enhanced diagnostic tools to improve public health awareness, prevention measures, and disease control strategies. METHODS: We designed plasmids to enable the purification of soluble CCHFV glycoprotein Gc expressed in mammalian 293 F cells, followed by purification using affinity and size exclusion chromatography. The purified antigen was analyzed by SDS-PAGE and Western blotting to confirm its reactivity to antibodies from CCHF survivors. Additionally, an in-house indirect ELISA was developed using the purified Gc as a coating antigen. RESULTS: The optimized expression system successfully produced soluble and pure Gc antigen after affinity chromatography. The protein showed specific reactivity with CCHFV-positive serum antibodies in Western blot analysis. The indirect ELISA assay demonstrated high efficacy in distinguishing between CCHFV-positive and -negative serum samples, indicating its potential as a valuable diagnostic tool. Size exclusion chromatography further confirmed the presence of aggregates in our protein preparation. CONCLUSIONS: The purified Gc antigen shows promise for developing direct diagnostic assays for CCHFV. The antigen's suitability for subunit vaccine development and its application as bait for monoclonal antibody isolation from survivors could be investigated further. This work lays the foundation for future research into the development of rapid diagnostic tests for field deployment.

Global temporal trends and projections of acute hepatitis E incidence among women of childbearing age: Age-period-cohort analysis 2021.

BACKGROUND & AIMS: Acute hepatitis E (AHE) poses a significant threat to global public health, particularly among women of childbearing age (WCBA), who are at heightened risk for severe pregnancy-related complications. This study aimed to delineate the temporal trends and project future incidence of AHE in WCBA, providing insights crucial for targeted prevention and control strategies. METHODS: Data on AHE incidence from the Global Health data 2021. The age-period-cohort (APC) model was applied to analyze trends across different age groups, periods, and birth cohorts, and the Bayesian APC model was utilized for forecasting future epidemiological trajectories. RESULTS: Globally, AHE incidence numbers among WCBA rose from 2,831,075 in 1992 to 3,420,786 in 2021, while the age-standardized incidence rate (ASIR) declined from 194.66 to 179.54 per 100,000 with a global net drift of -0.28%. However, high SDI regions showed a contrasting trend with a positive net drift of 0.02%. The age effect was consistent across SDI regions and globally, showing a decrease with advancing age, while unfavorable period and cohort effects were exhibited in high-SDI region. At the national level, locations exhibited varying trends of change. The BAPC model predicted a total of 3,759,384 AHE global cases in WCBA by 2030, with an expected mild increase in the ASIR. The outlook for the management and containment of AHE is grim in certain countries, including India. CONCLUSIONS: The study revealed a complex epidemiological landscape of AHE in WCBA, with increasing global incidence numbers juxtaposed against a declining ASIR. The AHE burden by 2030 remain severe among WCBA. Young WCBA and high SDI region merit particular attention. The findings underscore the need for region-specific strategies to curb the projected rise in AHE incidence and align with the 2030 WHO goals.