Prediction Modelling for Gastroesophageal Variceal Bleeding in Patients With Chronic Hepatitis B Using Four-dimensional Flow MRI.

Background/Aims: In this study, we aim to develop a model for predicting gastroesophageal varices (GEV) bleeding in patients with chronic hepatitis B (CHB) by utilizing hemodynamic parameters obtained through four-dimensional flow MRI (4D flow MRI). Methods: This study conducted a prospective enrollment of CHB patients suspected of GEV from October 2021 to May 2022. The severity of varices and bleeding risk were evaluated using clinical findings and upper gastrointestinal endoscopy, and patients were classified into high-risk and non-high-risk groups. The study utilized serological examination, ultrasonographic examination, and 4D flow MRI. Relevant parameters were selected through univariate and multivariate analyses, and a prediction model was established using binary logistic regression analysis. The model was combined with the Baveno Ⅵ/Ⅶ and Expanded Baveno Ⅵ/Ⅶ criteria to evaluate diagnostic efficacy and the risk of avoiding endoscopic examination. Results: A total of 40 CHB patients were enrolled and categorized into the high-risk group (n = 15) and the non-high-risk group (n = 25). The spleen diameter and regurgitant fraction (R%) were independent predictors of variceal bleeding and a predictive model was established. The combination of this prediction model and the Baveno Ⅵ/Ⅶ criteria achieved high diagnostic efficiency, enabling 45.00% (18/40) of patients to be exempted from the unnecessary endoscopic procedure and the high-risk misclassification rate (0%) was less than 5%. Conclusion: The prediction model generated by 4D flow MRI has the potential to assess the likelihood of varices and can be supplemented by the Baveno VI/VII criteria to improve diagnostic accuracy in CHB patients.

The Impact of Gender and Race on Outcomes for Hospitalized Hepatitis A Patients Stratified by Liver Disease Severity.

Background: The incidence of hepatitis A virus (HAV) infection is on the rise, with a minority of patients at risk for poor outcomes. This study investigates the prognostic impacts of race and gender on hospital outcomes among admitted HAV-infected patients. Methods: Using the National Inpatient Sample from 2012 to 2017, patients admitted with HAV were selected and stratified by gender (male and female) and race (White, Black, Hispanic, Asian-Pacific Islander, Other). Propensity score-matching and statistical analysis were implemented with comparison to the controls ("Female" and "White"). Primary endpoints included mortality, length of stay (LOS), and hospitalization costs, while secondary endpoints consisted of hepatic-related medical complications such as ascites, hepatic encephalopathy, varices, and acute liver failure. Results: Females with compensated cirrhosis had increased odds of mortality (aOR 2.59, 95% CI: 1.14-5.91, P = 0.02). Otherwise, no other differences in mortality were detected between genders and races. Females had a shorter hospital LOS (aOR 0.97, 95% CI: 0.96-0.98, P < 0.001), lower adjusted cost ($12,241 vs. $13,510, aOR 0.92, 95% CI: 0.92-0.92, P < 0.001), lower odds of esophageal varices (aOR 0.74, 95% CI: 0.57-0.97, P = 0.03) and hepatic encephalopathy (aOR 0.67, 95% CI: 0.53-0.84, P < 0.001) compared to males. Black patients exhibited higher LOS (aOR 1.06, 95% CI: 1.04-1.08, P < 0.001) and adjusted costs ($13,392 vs $12,592, aOR 1.02, 95% CI: 1.02-1.03, P < 0.001). Hispanic patients exhibited higher rates of esophageal varices (aOR 2.19, 95% CI: 1.28-3.76, P = 0.005) and adjusted costs ($14,202 vs. $12,381, aOR 1.07, 95% CI: 1.07-1.07, P < 0.001), and Asian patients experienced higher adjusted costs ($18,426 vs. $13,137, aOR 1.10, 95% CI: 1.10-1.10, P < 0.001) compared to White patients. Conclusion: Various nuanced impacts of gender and race on hospitalization outcomes in HAV infection were observed, with only one subgroup analysis demonstrating a higher rate of mortality. Further research is warranted to better understand these findings and their implications.

Usability and acceptability of self-testing for hepatitis C virus exposure in a high-prevalence urban informal settlement in Karachi, Pakistan.

BACKGROUND: Hepatitis C virus (HCV) antibody self-testing (HCVST) may help expand screening access and support HCV elimination efforts. Despite potential benefits, HCVST is not currently implemented in Pakistan. This study aimed to assess the usability and acceptability of HCVST in a high HCV prevalence informal settlement in Karachi, Pakistan. METHODS: We performed a cross-sectional study in a hepatitis C clinic from April through June 2023. Participants were invited to perform a saliva-based HCVST (OraSure Technologies, USA) while following pictorial instructions. A study member evaluated test performance using a standardized checklist and provided verbal support if a step could not be completed. Perceived usability and acceptability were assessed using a semi-structured questionnaire. The HCVST was considered successful if the participant was able to complete all steps and correctly interpret test results. Overall concordance and positive and negative agreement were estimated in comparison with the HCVST result read by the study member (inter-reader concordance and agreement) and result of a second rapid HCV test (Abbott Diagnostics Korea Inc, South Korea) performed by a trained user (inter-operator concordance and agreement). RESULTS: The study included 295 participants of which 97 (32%) were illiterate. In total, 280 (95%, 95% CI 92-97%) HCVSTs were successful. Overall, 38 (13%) people performed the HCVST without verbal assistance, 67 (23%) needed verbal assistance in one step, 190 (64%) in two or more. Assistance was most often needed in managing the test buffer and test reading times. The inter-reader concordance was 96% and inter-operator concordance 93%. Inter-reader and inter-operator positive percent agreement were 84 and 70%, respectively. All participants reported they would use HCVST again and would recommend it to friends and family. CONCLUSION: Saliva-based HCVST was very well accepted in this clinic-based setting. However, many people requested verbal support in several steps, highlighting the need for clear instructions for use and test devices that are simple to use, particularly in low literacy settings. Moderately low positive percent agreement with the results of a rapid test performed by a trained user highlights potential uncertainty in the accuracy of HCVST in the hands of lay users.

Use of passive samplers as sewage surveillance tool to monitor a hepatitis A outbreak at a school in Amsterdam, the Netherlands, Oct 2022 - March 2023.

BACKGROUND: Enteric hepatitis A virus (HAV) infections during childhood are often asymptomatic but may cause severe illness in adults. To improve public health surveillance we assessed the applicability of sewage monitoring during an HAV outbreak at a primary school. METHODS: Between October 19 and December 27, 2022, five symptomatic HAV cases were notified to the Public Health Service Amsterdam; all attended the same primary school. Passive samplers, small absorbent tools, were deployed in sewage near the school from November 14, 2022, to March 22, 2023. The absorbents were subjected to RNA extraction, HAV PCR testing, and, if positive, sequencing. PCR and sequencing were also performed on plasma and feces samples of HAV cases. RESULTS: In 22 out of 88 (25%) of sewage samples, HAV RNA was detected. All HAV-RNA-positive sewage samples until 8 February 2023 were subgenotype IB, matching the strain detected in all cases. Another strain of HAV (subgenotype IA) was detected in sewage from 15 February 2023 onwards, without associated cases. CONCLUSIONS: Passive sampler-based sewage monitoring is an effective method to rapidly detect HAV shedding linked to diagnosed cases. It detects unnoticed viral infections and allows monitoring of outbreaks. This suggests that passive sampler-based monitoring is a promising tool supporting the public health response during HAV and other outbreaks.

Hepatitis C virus attributable liver cancer in the country of Georgia, 2015-2019: a case-control study.

BACKGROUND: Hepatitis C virus (HCV) infection can lead to a type of primary liver cancer called hepatocellular carcinoma (HCC). Georgia, a high HCV prevalence country, started an HCV elimination program in 2015. In addition to tracking incidence and mortality, surveillance for the HCV-attributable fraction of HCC is an important indicator of the program's impact. This study assesses HCV infection-attributable HCC in the Georgian population. METHODS: This case-control study utilized HCV programmatic and Georgian Cancer Registry data from 2015-2019. Bivariate logistic regression and age- and sex-stratified analyses assessed HCV and liver cancer association. HCV-attributable liver cancer proportions for the HCV-exposed and total population were calculated. A sub-analysis was performed for HCC cases specifically. RESULTS: The total study population was 3874 with 496 liver cancer cases and 3378 controls. The odds for HCV-infected individuals developing liver cancer was 20.1 (95% confidence interval [CI] 15.97-25.37), and the odds of developing HCC was 16.84 (95% CI 12.01-23.83) compared to the HCV-negative group. Odds ratios varied across strata, with HCV-infected older individuals and women having higher odds of developing both liver cancer and HCC. A large proportion of liver cancer and HCC can be attributed to HCV in HCV-infected individuals; however, in the general population, the burden of liver cancer and HCC cannot be explained by HCV alone. CONCLUSION: HCV was significantly associated with a higher risk of developing liver cancer and HCC in the Georgian population. In addition, given Georgia's high HCV burden, increased HCC monitoring in HCV-infected patients is needed.

Transmission network of Hepatitis C virus subtype 2a in Huazhou County, Shaanxi Province, China.

BACKGROUND: Huazhou County has one of the highest rates of hepatitis C virus (HCV) infection incidence and prevalence in Shaanxi Province, northwest China. Understanding the characteristics of HCV transmission patterns in this area could help guide targeted prevention strategies. This study employed phylogenetic analysis and the construction of a molecular transmission network of HCV-infected people in Huazhou County to describe the predominant strains of HCV and identify factors associated with onward transmission. METHODS: Whole blood samples were obtained from HCV RNA-positive individuals for sequencing of the non-structural protein 5B region. A maximum-likelihood (ML) phylogenetic tree was constructed to determine HCV subgenotypes, and Bayesian phylogenetic analysis was employed to estimate the evolutionary history. The transmission network was constructed using the ML phylogenetic tree and pairwise distances. Logistic regression was used to identify factors associated with clustering in the transmission network. RESULTS: ML phylogenetic analysis confirmed that the 61 sequences analyzed in the study belonged to subtype 2a. Bayesian phylogenetic analysis showed that the majority of subtype 2a sequences originated in the northwest of China and had descended approximately 8 to 20 years before sampling. Overall, 26.2% of participant sequences were grouped into phylogenetic network clusters. Multivariate logistic regression showed that individuals who had a history of blood transfusions and were living in Shi Village, Huazhou County, were more likely to form clusters within the transmission network. CONCLUSION: HCV transmission in Huazhou County was predominantly associated with subtype 2a. Having a history of blood transfusions and living in residential Shi Village, Huazhou County, were factors associated with a high risk of HCV infection transmission. Prioritizing targeted interventions for these patient groups may help to prevent further infections.

Economic Analysis of National Program for Hepatitis C Elimination, Israel, 20231.

In 2021, the Israel Ministry of Health began a national hepatitis C elimination program. Implementing a World Health Organization goal, Israel's program involved targeted screening, barrier minimization, workup simplification, awareness campaigns, and a patient registry. We evaluated program costs for testing and treatment. By May 15, 2023, the program had identified 865,382 at-risk persons, of whom 555,083 (64.3%) were serologically screened for hepatitis C virus (HCV), which was detected in 24,361 (4.4%). Among 20,928 serologically positive patients, viremia was detected in 13,379 (63.9%), of whom 10,711 (80%) were treated, and 4,618 (96.5%) of 4,786 persons receiving posttreatment HCV RNA testing had sustained virologic response. We estimated costs of ₪14,426 (new Israel shekel; ≈$3,606 USD) per person whose HCV infection was diagnosed and successfully treated. The program yielded screening and treatment in almost two thirds of the identified at-risk population. Although not eliminated, HCV prevalence will likely decrease substantially by the 2030 target.

Circovirus Hepatitis in Immunocompromised Patient, Switzerland.

We identified a novel human circovirus in an immunocompromised 66-year-old woman with sudden onset of self-limiting hepatitis. We detected human circovirus 1 (HCirV-1) transcripts in hepatocytes and the HCirV-1 genome long-term in the patient's blood, stool, and urine. HCirV-1 is an emerging human pathogen that persists in susceptible patients.

Implementing a new HCV model of care for people who use drugs.

Background & Aims: An estimated 50 million individuals have chronic hepatitis C virus (HCV) infection worldwide and people who use drugs (PWUD) are disproportionately affected. Persistent stigma and discrimination make it challenging for PWUD to access healthcare, potentially hindering HCV elimination progress in this population. To mitigate healthcare access barriers in PWUD, an HCV care model that simplified screening and linkage to care pathways was developed and rolled out in the Balearic Islands, Spain. Methods: The prospective multicentre community model of care was implemented in 21 centres serving PWUD. This model involved: (1) participant recruitment and HCV antibody screening onsite via a point-of-care anti-HCV test, phlebotomy, or laboratory records; (2) HCV RNA, HBsAg and anti-HIV testing via a dried blood spot or phlebotomy; (3) linkage to specialist care and treatment prescription via telemedicine, when required; and (4) onsite monitoring of: (a) sustained virologic response (SVR) 4 and ≥12 weeks after treatment completion and; (b) potential new HCV infection or reinfection ∼1 year after phase 1 or SVR ≥12 monitoring. Care model acceptability was assessed. Results: Between April 2021 and April 2023, 1,423 participants were recruited, of whom 464 (33%) were anti-HCV+ and 170 (12%) had detectable HCV RNA. Of the latter, 147 (86%) initiated therapy, of whom 124 (84%) completed it. SVR ≥12 monitoring was performed in 95 (77%) of these, of whom 88 (93%) had undetectable HCV RNA. Upon re-screening, four HCV reinfections were detected. Over 90% accepted study participation and screening and treatment decentralisation. Conclusions: This adapted care model, which decentralised screening, diagnosis, and treatment, effectively increased healthcare access among PWUD, improving progress towards HCV elimination in this population in Spain. Impact and implications: People who use drugs (PWUD) are among the most affected by chronic hepatitis C virus (HCV) infection globally. A simplified model of care was implemented in 21 centres serving this population across the Balearic Islands, Spain, to offer HCV care to 1,423 PWUD in 2021-2023. This decentralised screening, diagnosis, and treatment model resulted in an HCV cure rate of 93% of those who both completed therapy and were monitored post treatment completion. The Hepatitis C Free Balears model can guide the HCV elimination efforts of regional health authorities and other stakeholders in the rest of Spain and other parts of the world.

The role of the hepatitis B virus genome and its integration in the hepatocellular carcinoma.

The integration of Hepatitis B Virus (HBV) is now known to be closely associated with the occurrence of liver cancer and can impact the functionality of liver cells through multiple dimensions. However, despite the detailed understanding of the characteristics of HBV integration and the mechanisms involved, the subsequent effects on cellular function are still poorly understood in current research. This study first systematically discusses the relationship between HBV integration and the occurrence of liver cancer, and then analyzes the status of the viral genome produced by HBV replication, highlighting the close relationship and structure between double-stranded linear (DSL)-HBV DNA and the occurrence of viral integration. The integration of DSL-HBV DNA leads to a certain preference for HBV integration itself. Additionally, exploration of HBV integration hotspots reveals obvious hotspot areas of HBV integration on the human genome. Virus integration in these hotspot areas is often associated with the occurrence and development of liver cancer, and it has been determined that HBV integration can promote the occurrence of cancer by inducing genome instability and other aspects. Furthermore, a comprehensive study of viral integration explored the mechanisms of viral integration and the internal integration mode, discovering that HBV integration may form extrachromosomal DNA (ecDNA), which exists outside the chromosome and can integrate into the chromosome under certain conditions. The prospect of HBV integration as a biomarker was also probed, with the expectation that combining HBV integration research with CRISPR technology will vigorously promote the progress of HBV integration research in the future. In summary, exploring the characteristics and mechanisms in HBV integration holds significant importance for an in-depth comprehension of viral integration.

Effectiveness and implementation of decentralized, community- and primary care-based strategies in promoting hepatitis B testing uptake: a systematic review and meta-analysis.

Background: Expanding chronic hepatitis B (CHB) testing through effective implementation strategies in primary- and community-care setting is crucial for elimination. Our study aimed to determine the effectiveness of all available strategies in the literature and evaluate their specifications and implementation outcomes, thereby informing future programming and policymaking. Methods: We conducted a systematic review and meta-analysis (PROSPERO CRD42023455781), searching Scopus, Embase, PubMed, and CINAHL databases up to June 05, 2024, for randomized controlled trials investigating primary- and community-care-based implementation strategies to promote CHB testing. Studies were screened against a priori eligibility criteria, and their data were extracted using a standardized protocol if included. ROB-2 was used to assess the risk of bias. Implementation strategies' components were characterized using the Behavior Change Wheel (BCW) framework. Random-effect models were applied to pool the effectiveness estimate by strategy. Mixed-effect meta-regression was employed to investigate if effectiveness varied by the number of strategy's BCW components. Findings: 7146 unique records were identified. 25 studies were eligible for the review, contributing 130,598 participants. 19 studies were included in the meta-analysis. No studies were conducted in low-and-middle-income countries. Implementation outcomes were reported in only ten studies (40%). Community-based strategies included lay health workers-led education (Pooled Risk Difference = 27.9% [95% Confidence Interval = 3.4-52.4], I2 = 99.3%) or crowdsourced education on social media (3.1% [-2.2 to 8.4], 0.0%). Primary care-based strategies consisted of electronic alert system (8.4% [3.7-13.1], 95.0%) and healthcare providers-led education (HCPs, 62.5% [53.1-71.9], 27.5%). The number of BCW-framework-driven strategy components showed a significant dose-response relationship with effectiveness. Interpretation: HCPs-led education stands out, and more enriched multicomponent strategies had better effectiveness. Future implementation strategies should consider critical contextual factors and policies to achieve a sustainable impact towards hepatitis B elimination targets. Funding: Tran Dolch Post-Doctoral Fellowship in Hepatology, Johns Hopkins University School of Medicine, Baltimore MD, USA.

Advances in the study of the mechanism of action of miR­22 in liver lesions (Review).

Globally, nearly 2 million deaths annually are attributed to the development of liver diseases, with liver cancer and cirrhosis being particularly prominent, which makes liver disease a significant global health concern. Cirrhosis is closely linked to the evolution of hepatitis, hepatic fibrosis and fatty liver. However, most liver diseases have an insidious onset, are challenging to treat and the prognosis and efficacy of current therapies are unsatisfactory, which can result in irreversible functional damage to the liver. Therefore, there is an urgent need to explore the molecular mechanisms underlying liver disease and identify new biomarkers and therapeutic targets. In previous years, microRNAs (miRs), a class of short non-coding RNAs comprising 17-25 nucleotides, have attracted attention for their roles in various types of liver diseases. Among them, miR-22 serves a unique role in mediating multiple pathway mechanisms and epigenetic modifications and can act both as an inhibitor of liver cancer and a metabolic blocker. Given its close association with the liver, several studies have reported that the differential expression of miR-22 regulates the metabolic process of liver cancer and is involved in the evolution of hepatic fibrosis and steatohepatitis, making it a potential target for early diagnosis and treatment. The present manuscript aimed to comprehensively review the key role of miR-22 in the evolution of liver diseases and offer valuable references and guidance for subsequent studies by identifying its specific mechanism of action and future development prospects.

Ensemble for evaluating diagnostic efficacy of non-invasive indices in predicting liver fibrosis in untreated hepatitis C virus population.

BACKGROUND: Hepatitis C virus (HCV) infection progresses through various phases, starting with inflammation and ending with hepatocellular carcinoma. There are several invasive and non-invasive methods to diagnose chronic HCV infection. The invasive methods have their benefits but are linked to morbidity and complications. Thus, it is important to analyze the potential of non-invasive methods as an alternative. Shear wave elastography (SWE) is a non-invasive imaging tool widely validated in clinical and research studies as a surrogate marker of liver fibrosis. Liver fibrosis determination by invasive liver biopsy and non-invasive SWE agree closely in clinical studies and therefore both are gold standards. AIM: To analyzed the diagnostic efficacy of non-invasive indices [serum fibronectin, aspartate aminotransferase to platelet ratio index (APRI), alanine aminotransferase ratio (AAR), and fibrosis-4 (FIB-4)] in relation to SWE. We have used an Artificial Intelligence method to predict the severity of liver fibrosis and uncover the complex relationship between non-invasive indices and fibrosis severity. METHODS: We have conducted a hospital-based study considering 100 untreated patients detected as HCV positive using a quantitative Real-Time Polymerase Chain Reaction assay. We performed statistical and probabilistic analyses to determine the relationship between non-invasive indices and the severity of fibrosis. We also used standard diagnostic methods to measure the diagnostic accuracy for all the subjects. RESULTS: The results of our study showed that fibronectin is a highly accurate diagnostic tool for predicting fibrosis stages (mild, moderate, and severe). This was based on its sensitivity (100%, 92.2%, 96.2%), specificity (96%, 100%, 98.6%), Youden's index (0.960, 0.922, 0.948), area under receiver operating characteristic curve (0.999, 0.993, 0.922), and Likelihood test (LR+ > 10 and LR- < 0.1). Additionally, our Bayesian Network analysis revealed that fibronectin (> 200), AAR (> 1), APRI (> 3), and FIB-4 (> 4) were all strongly associated with patients who had severe fibrosis, with a 100% probability. CONCLUSION: We have found a strong correlation between fibronectin and liver fibrosis progression in HCV patients. Additionally, we observed that the severity of liver fibrosis increases with an increase in the non-invasive indices that we investigated.

Acute Hemorrhagic Leukoencephalitis in a Patient With Hepatitis B.

Acute hemorrhagic leukoencephalitis (AHLE), also known as Weston-Hurst syndrome or Hurst disease, is a rare and rapidly progressive form of acute disseminated encephalomyelitis. It is characterized by severe inflammation, hemorrhage, and necrosis within the white matter of the brain. AHLE often follows an upper respiratory infection or other systemic illnesses, suggesting a potential post-infectious autoimmune mechanism. The disease is associated with a high mortality rate and significant disability among survivors. We present the case of a 46-year-old Indian woman with a history of chronic hepatitis B (HBV) who presented with an insidious onset of right-sided limb weakness and bi-frontal headaches. Initial brain MRIs showed features of tumefactive demyelination. Despite aggressive treatment with intravenous (IV) methylprednisolone, IV immunoglobulin, and anti-edema measures, the patient's condition rapidly deteriorated, leading to a diagnosis of AHLE following the emergence of hemorrhagic white matter lesions on repeat MRI. Remarkably, with continued treatment, the patient survived and showed gradual neurological improvement, although she remained significantly debilitated at the time of discharge. AHLE represents one of the most severe forms of demyelinating diseases, often resulting in rapid neurological decline and high mortality. This case highlights the potential link between chronic HBV infection with a high viral load and the onset of AHLE. The patient's recovery underscores the importance of early recognition and aggressive treatment in improving outcomes, even in conditions with traditionally poor prognosis. Clinicians should maintain a high index of suspicion for AHLE in patients with chronic viral infections presenting with neurological symptoms. Prompt and aggressive management can be life-saving, and ongoing research is needed to better understand the pathogenesis and optimal treatment strategies for this rare but devastating condition.

Targeting NTCP for liver disease treatment: A promising strategy.

The sodium taurocholate co-transporting polypeptide (NTCP), a bile acids transporter, has been identified as a new therapeutic target for the treatment of liver disease. This paper thoroughly investigates the function of NTCP for regulating bile acid regulation, its correlation with hepatitis B and D infections, and its association with various liver diseases. Additionally, in this review we examine recent breakthroughs in creating NTCP inhibitors and their prospective applications in liver disease treatment. While this review emphasizes the promising potential of targeting NTCP, it concurrently underscores the need for broader and more detailed research to fully understand the long-term implications and potential side effects associated with NTCP inhibition.

[Hepatotoxicity due to albendazole: safe alternatives for echinococcosis therapy]. / Hepatotoxizität durch Albendazol: sichere Alternativen bei Echinokokkosetherapie.

Infection with Echinococcus multilocularis leads to the clinical manifestation of alveolar echinococcosis. This is characterized by the formation of alveolar liver tumours, which usually disintegrate necrotically in the course of the disease. Pseudocysts are formed. Especially in the early stages, curative resection followed by long-term treatment with albendazole is recommended. However, the majority of patients are not amenable to curative surgery. In these cases, albendazole therapy is the first-choice treatment. We present a rare case of albendazole-associated hepatitis in a patient with inoperable Echinococcus multilocularis infection, with a favourable outcome following a change in treatment to mebendazole.

New progress in HBV control and the cascade of health care for people living with HBV in China: evidence from the fourth national serological survey, 2020.

Background: Since 1992, when recombinant hepatitis B vaccine was introduced in China, government health officials have used nationally representative serological surveys to monitor progress in prevention and control of hepatitis B. In 2020, we conducted the fourth seroepidemiological survey, which for the first time included medical evaluation of the clinical status of HBsAg positive subjects over the age of 15 and their medical management. We report survey results in comparison with the three previous surveys. Methods: Consistent with previous national surveys, the 2020 survey used a stratified, three-stage cluster random sampling method to select for evaluation 1-69-year-olds in 120 national disease surveillance points. Blood samples were tested for HBsAg, anti-HBV surface antigen (anti-HBs), and anti-HBV core antigen (anti-HBc) in the National Hepatitis Laboratory of the Institute for Viral Disease Control and Prevention of China CDC. HBsAg positive subjects aged ≥15-year were evaluated for evidence of liver disease, and through face-to-face questionnaire-based survey, we determined the healthcare management cascade of HBV-infected individuals. Findings: HBsAg prevalence in 1-69-year-olds was 5.86%; in children 1-4 years of age, seroprevalence was 0.30%; 75 million people were living with HBV nationwide. Among HBsAg-positive individuals 15 years and older, expert medical examination found that 78.03% were HBsAg carriers with no evidence of liver damage, 19.63% had chronic HBV with liver enzyme abnormalities, 0.84% had evidence of cirrhosis, and 0.15% had evidence of liver cancer. 59.78% of HBsAg + individuals were aware that they were positive before the survey, 30 million were unaware; 38.25% of those who knew they were positive (17 million) had medical indications for antiviral treatment, and 17.33% of these individuals (3 million) were being treated with antivirals. Interpretation: The decline in HBsAg prevalence in the general population, from 9.72% in 1992 to 5.86% in 2020, and in 1-4-year-olds from 9.67% in 1992 to 0.30% in 2020, shows progress that continues on track toward WHO targets for prevention of new infections. Implementation of acceptable strategies to identify infected individuals and offer long-term medical monitoring and management will be important to prevent complications from hepatitis B infection and for meeting WHO cascade-of-care targets. Funding: The study was funded by the Major Science and Technology Special Project of China's 13th 5-Year Plan (grant no. 2017ZX10105015); Central finance-operation of public health emergency response mechanism of Chinese Center for Disease Control and Prevention (131031001000200001, 102393220020010000017).

Isolation and pathogenicity of a fowl adenovirus 8b (FAdV-8b) strain in Cherry Valley ducks.

AbstractInclusion body hepatitis (IBH) is an economically important viral disease primarily affecting the poultry industry. In this study, we isolated a strain of FAdV-8b (strain SDYT) from naturally infected ducks and the hexon and fiber gene sequences were analysed by polymerase chain reaction (PCR) amplification. In order to study the pathogenicity of FAdV-8b on Cherry Valley ducks, we inoculated 10- and 20-day-old ducks with 0.3 ml of FAdV-4 virus (TCID50 of 105.5/0.1 ml) either orally or intramuscularly. Clinical signs, gross lesions and histopathological changes, cytokines, viral load and antibody levels were noticed and recorded within 15 days after infection.Pathomorphological investigations revealed that ducks in the experimental group exhibited hepatitis symptoms. Histopathology showed multiple-organ damage, including serious liver and kidney lesions. Furthermore, elevated levels of inflammatory cytokines and antibodies was noticed, due to the infection and innate immune response. At later stage of infection immunosuppression occurred, resulting in decreased levels of cytokines. Determination of viral load indicated that the virus was present in several organs, with the highest viral DNA load found in the liver, followed by the kidney. Compared to birds infected orally, the intramuscular group exhibited the highest viral load. In summary, this study increases our understanding of the pathogenicity of FAdV-8b in ducks and establishes a model that will inform antiviral drug testing and vaccine evaluation for IBH, thereby preventing and reducing the spread of IBH in the poultry industry.