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Hepatitis E virus (HEV) is a foodborne virus transmitted through the faecal–oral route that causes viral hepatitis in humans worldwide. Ever since its discovery as a zoonotic agent, HEV was isolated from several species with an expanding range of hosts. HEV possesses several features of other RNA viruses but also has certain HEV‐specific traits that make its viral–host interactions inimitable. HEV leads to severe morbidity and mortality in immunocompromised people and pregnant women across the world. The situation in underdeveloped countries is even more alarming. Even after creating a menace across the world, we still lack an effective vaccine against HEV. Till date, there is only one licensed vaccine for HEV available only in China. The development of an anti‐HEV vaccine that can reduce HEV‐induced morbidity and mortality is required. Live attenuated and killed vaccines against HEV are not accessible due to the lack of a tolerant cell culture system, slow viral replication kinetics and varying growth conditions. Thus, the main focus for anti‐HEV vaccine development is now on the molecular approaches. In the current study, we have designed a multi‐epitope vaccine against HEV through a reverse vaccinology approach. For the first time, we have used viral ORF3, capsid protein and polyprotein altogether for epitope prediction. These are crucial for viral replication and persistence and are major vaccine targets against HEV. The proposed in silico vaccine construct comprises of highly immunogenic and antigenic T‐cell and B‐cell epitopes of HEV proteins. The construct is capable of inducing an effective and long‐lasting host immune response as evident from the simulation results. In addition, the construct is stable, non‐allergic and antigenic for the host. Altogether, our findings suggest that the in silico vaccine construct may be useful as a vaccine candidate for preventing HEV infections. [ABSTRACT FROM AUTHOR]

Hepatitis E virus (HEV) is a prevalent pathogen responsible for acute viral hepatitis, HEV genotypes 3 and 4 infections causing zoonotic infections. Currently, the nucleotide similarity analysis between humans and pigs for HEV genotype 4 is limited. In this study, stool samples from an HEV‐infected patient who is a pig farmer and from pigs were collected to obtain the near full‐length genome of HEV, phylogenetic trees were constructed for genotyping, and similarity of HEV sequences was analyzed. The results showed that HEV‐RNA was detected in the stool samples from the patient and six pigs (6/30, 20.0%). Both HEV subtype in the patient and pigs was 4b. Additionally, similarity analysis showed that the range was 99.875%–99.944% between the patient and pigs at the nucleotide level. Four isolates of amino acid sequences (ORFs 1–3) from pigs were 100% identical to the patient. Phylogenetic tree and similarity analysis of an additional nine HEV sequences isolated from other patients in this region showed that the HEV sequence from the pig farmer had the closest relationship with the pigs from his farm rather than other sources of infection in this region. This study provides indirect evidences for HEV subtype 4b can be transmitted from pigs to humans at the nucleotide level. Further research is needed to explore the characteristics of different HEV subtypes. [ABSTRACT FROM AUTHOR]

Background: This meta-analysis was dedicated to evaluating the effectiveness and safety of Atezolizumab plus Bevacizumab (Atez/Bev) and Lenvatinib (LEN) as first-line systematic therapy for unresectable hepatocellular carcinoma (u-HCC). Methods: The prospective protocol for this study was registered with the PROSPERO (Registration number: CRD42022356874). Literature searches were conducted in PubMed, EMBASE database Cochrane Library, and Web Science to determine all clinical controlled studies that reported Atez/Bev and LEN for treating u-HCC. We. evaluated as primary end-point overall survival (OS) and progression-free survival (PFS), as well as other outcomes such as tumor response and adverse events (AEs).Quality assessment and data extraction of studies were conducted independently by three reviewers. Mean difference (MD) and odds ratio (OR) with 95% confidence interval (CI) were calculated using a fixed-effects or random-effects model. The meta-analysis was performed with RevMan 5.3 software. Results: 12 retrospective cohort studies (RCSs) involving a total of 4948 patients were finally included. The results showed that compared with LEN, Atez/Bev can improve the patient's PFS (HR = 0.80, 95% CI: 0.72 ~ 0.88; p < 0.0001) and reduce the rate of overall AEs (OR = 0.46 95% CI: 0.38 ~ 0.55, p < 0.00001) and grade ≥ 3 AEs (OR = 0.43; 95% CI: 0.36 ~ 0.51, p < 0.00001), while there is no difference between OS and treatment responses rate (objective response rate, disease control rate, complete response, partial response, progressive disease, and stable disease) between two groups. In addition, the subgroup analysis shows that Atez/Bev can promote the OS of patients with viral hepatitis. (HR = 0.79, 95% CI: 0.67 ~ 0.95; p = 0.01), while LEN has an advantage in improving OS in patients with Child-Pugh grade B liver function (HR = 1.98, 95% CI: 1.50 ~ 2.63; p < 0.00001). Conclusion: Current evidence shows that compared with LEN, Atez/Bev has more advantages in PFS and safety in treating u-HCC and can improve the OS of patients with viral. LEN has advantages in improving the OS of patients with grade B liver function. However, more multicenter randomized controlled experiments are needed in the future to verify our results. [ABSTRACT FROM AUTHOR]

Gonorrhea is a widespread sexually transmitted infection; in 2022, China reported 96,313 cases of gonorrhea, making it the fourth most common notifiable infectious disease in the country after viral hepatitis, pulmonary tuberculosis, and syphilis. The rise in prevalence in antimicrobial-resistant strains, particularly the international spread of ceftriaxoneresistant clones, poses a formidable challenge to gonorrhea control. The China Gonococcal Resistance Surveillance Program (China-GRSP), established in 1987 and covering 19 of 34 provincial-level administrative units, continuously monitors gonococcal antimicrobial resistance. In 2022, 13 China-GRSP sentinel sites collected 2,804 gonococcal isolates, representing 2.9% of all cases reported in China, and 4.1% of cases reported in the 13 participating provinces. The prevalence of Neisseria gonorrhoeae resistance to ceftriaxone was 8.1%, approximately three times the 2017 rate of 2.9%; five provinces reported >10% ceftriaxone resistance. Resistance prevalences to cefixime, azithromycin, tetracycline, penicillin, and ciprofloxacin were 16.0%, 16.9%, 77.1%, 77.8%, and 97.6%, respectively. Only one case of spectinomycin resistance was reported. These data highlight a substantial increase in ceftriaxone resistance from 2017 to 2022. Effective diagnosis and treatment and appropriate management of sex partners are essential to protect the health of infected persons and prevent ongoing transmission of gonorrhea, including transmission of resistant strains. Identifying reasons for the spread of ceftriaxone-resistant N. gonorrhoeae in China could guide strategies, such as antibiotic stewardship, to mitigate the rising resistance rate and curb the spread of resistant strains. [ABSTRACT FROM AUTHOR]

Waterfowl astroviruses are mainly duck astroviruses and goose astroviruses, of which duck astroviruses (DAstV-3, -4), goose astroviruses (GoAstV-1, -2) are the four new waterfowl 21 astroviruses in recent years, which can lead to enteritis, viral hepatitis, gout and reduce the growth performance of waterfowl, affecting the healthy development of the waterfowl farming industry. Since no targeted drugs or vaccines on the market, studies on the epidemiology of the virus are necessary for vaccine development. In this study, we collected 1546 waterfowl samples from 13 provinces in China for epidemiological investigation. The results showed that 260 samples (16.8%) were positive. Four species of astrovirus were detected in 13 provinces except Fujian province. Among the four sites tested, the highest positive rates were found in farms and slaughterhouses. Cross-host and mixed infection were observed in four species of waterfowl astroviruses. The whole genome of 17 isolates was sequenced and compared with published sequences. Genetic evolution and homology analysis showed that the isolated strains had high similarity to their reference sequences. To assess the pathogenicity of GoAstV, 7-day-old goslings were inoculated with GoAstV-1 and GoAstV-2 by the intramuscular route, and infected geese showed similar clinical signs, such as anorexia, depression, and weight loss. Organ damage was seen after infection, with histopathological changes in the heart, liver, spleen, kidney, and intestine, and higher viral loads in throat and anal swabs. These findings increase our understanding of the pathogenicity of GoAstV-1 and GoAstV-2 in goslings and provide more references for future research. [ABSTRACT FROM AUTHOR]

Hepatitis delta virus (HDV) is a satellite RNA virus that requires the hepatitis B virus (HBV) for assembly and propagation. Individuals infected with HDV progress to advanced liver disease faster than HBV-monoinfected individuals. Recent studies have estimated the global prevalence of anti-HDV antibodies among the HBV-infected population to be 5-15%. This study aimed to better understand HDV prevalence at the population level in 25 countries/territories. We conducted a literature review to determine the prevalence of anti-HDV and HDV RNA in hepatitis B surface antigen (HBsAg)-positive individuals in 25 countries/territories. Virtual meetings were held with experts from each setting to discuss the findings and collect unpublished data. Data were weighted for patient segments and regional heterogeneity to estimate the prevalence in the HBV-infected population. The findings were then combined with The Polaris Observatory HBV data to estimate the anti-HDV and HDV RNA prevalence in each country/territory at the population level. After adjusting for geographical distribution, disease stage and special populations, the anti-HDV prevalence among the HBsAg+ population changed from the literature estimate in 19 countries. The highest anti-HDV prevalence was 60.1% in Mongolia. Once adjusted for the size of the HBsAg+ population and HDV RNA positivity rate, China had the highest absolute number of HDV RNA+ cases. We found substantially lower HDV prevalence than previously reported, as prior meta-analyses primarily focused on studies conducted in groups/regions that have a higher probability of HBV infection: tertiary care centers, specific risk groups or geographical regions. There is large uncertainty in HDV prevalence estimates. The implementation of reflex testing would improve estimates, while also allowing earlier linkage to care for HDV RNA+ individuals. The logistical and economic burden of reflex testing on the health system would be limited, as only HBsAg+ cases would be screened. There is a great deal of uncertainty surrounding the prevalence of hepatitis delta virus among people living with hepatitis B virus at the population level. In this study, we aimed to better understand the burden in 25 countries and territories, to refine techniques that can be used in future analyses. We found a lower prevalence in the majority of places studied than had been previously reported. These data can help inform policy makers on the need to screen people living with hepatitis B virus to find those coinfected with hepatitis delta virus and at high risk of progression, while also highlighting the pitfalls that other researchers have often fallen into. [Display omitted] • Previous studies have focused on the risk groups and regions that carry the highest HDV burden. • HDV prevalence among people living with HBV in 25 countries/territories was often (18/25) lower than previous estimates. • The highest prevalence was in Mongolia, but the largest absolute number of HDV-RNA+ individuals was in China. [ABSTRACT FROM AUTHOR]

The article presents a study which compared the prevalence of commonly screened infections in internationally adopted children as a distinct population seen at an international adoption clinic (IAC) by region of adoption. Topics discussed include demographics and testing results by region, overall rate of positive tuberculosis screening, and the decline in the number of children adopted from other countries since the global pandemic.

Hepatitis E virus (HEV) is the most common cause of acute viral hepatitis worldwide. In 2018–2022, we investigated the presence of HEV RNA in 1233 stool samples collected in the Qinghai‐Tibetan Plateau, including humans (16), Tibetan pigs (624), yaks (312), sheep (267), and dogs (14). HEV RNA was only detected in Tibetan pig faecal samples (18.27%, 114/624). To perform molecular characterization of HEV strains in Tibetan pigs, we obtained 21 complete HEV genome sequences between 2018 and 2022. Sequence comparisons showed that 21 HEV strains from Tibetan pigs shared the mean nucleotide identities with the reference HEV strains ranging between 82.9% and 94.9% and 89.3% and 92.1% similarities with human HEV strains. Phylogenetic analysis confirmed that all HEV strains were genotype 4, closely related to human HEV strains. Sequence recombinant analysis showed five potential recombinant strains identified in this study, of which SWU/D18/2018 (GenBank No. MK410044) was recombinant with human and swine HEV strains, located 6509–6878 nt from the recombination point. Based on the Bayesian evolutionary trees, we found that most HEV strains diverged later than human HEV (16 Tibetan pig HEV strains diverged later than 1979, and seven human HEV strains diverged earlier than 1979). Therefore, we speculated that the prevalence of HEV 4 in Tibetan pigs possibly originated from humans in the Qinghai‐Tibetan Plateau. [ABSTRACT FROM AUTHOR]

Simple Summary: Vertically transmitted duck viruses are viruses that are transmitted from a female duck to its offspring when it is an egg, which seriously threatens production in the duck breeding industry. In this study, we evaluated the distribution and genetic variation in four vertically transmitted duck pathogens, including DHBV, DuCV, DHAV-3, and ARV. This study found that DHBV was the most prevalent virus, followed by DuCV, and then ARV and DHAV-3. The genetic analysis results showed that all the identified duck viruses here had complex qualities. These findings will improve our knowledge of the evolution of DuCV, DHAV-3, and ARV and help choose suitable strains for vaccination. To investigate the distribution and genetic variation in four vertically transmitted duck pathogens, including duck hepatitis B virus (DHBV), duck circovirus (DuCV), duck hepatitis A virus 3 (DHAV-3), and avian reoviruses (ARV), we conducted an epidemiology study using PCR and RT-PCR assays on a duck population. We found that DHBV was the most prevalent virus (69.74%), followed by DuCV (39.48%), and then ARV (19.92%) and DHAV-3 (8.49%). Among the 271 duck samples, two, three or four viruses were detected in the same samples, indicating that the coinfection of vertical transmission agents is common in ducks. The genetic analysis results showed that all four identified DuCV strains belonged to genotype 1, the DHAV-3 strain was closely clustered with previously identified strains from China, and the ARV stain was clustered under genotype 1. These indicate that different viral strains are circulating among the ducks. Our findings will improve the knowledge of the evolution of DuCV, DHAV-3, and ARV, and help choose suitable strains for vaccination. [ABSTRACT FROM AUTHOR]

Background: It is uncertain how COVID-19 outbreak influences the hepatitis B epidemics. This study aims to evaluate the effects on hepatitis B owing to the COVID-19 outbreak and forecast the hepatitis B epidemiological trend in mainland China to speed up the course of the "End viral hepatitis Strategy". Methods: We estimated the causal impacts and created a forecast through adopting monthly notifications of hepatitis B each year from 2005 to 2020 in mainland China using the Bayesian structural time series (BSTS) method. Results: The hepatitis B epidemics fluctuates irregularly during the period 2005–2007(APC = 8.7, P = 0.246) and 2015–2020(APC = 1.7, P = 0.290), and there is a downturn (APC=-3.2, 95% CI -5.2 to -1.2, P = 0.006) from 2007 to 2015 in mainland China. The COVID-19 outbreak was found to have a monthly average reduction on the hepatitis B epidemics of 26% (95% CI 18–35%) within the first three months in 2020,17% (95% CI 7.7–26%) within the first six months in 2020, and 10% (95% CI19–22%) all year as a result of the COVID-19 outbreak, (probability of causal effect = 96.591%, P = 0.034) and the forecasts showed an upward trend from 2021 to 2025 (annual percentage change = 4.18, 95% CI 4.0 to 4.3, P < 0.001). Conclusion: The COVID-19 has a positive effect on the decline of hepatitis B cases. And the potential of BSTS model to forecast the epidemiological trend of the hepatitis B can be applied in automatic public health policymaking in mainland China. [ABSTRACT FROM AUTHOR]

The global pandemic of the new coronavirus infection (COVID-19), which began in December 2019 in Uhan (China), has spread worldwide. On 11 March 2020, the World Health Organization announced the outbreak of the SARS CoV-2 pandemic due to the constant number of cases outside China. Rapid and decisive measures are being taken in our country to effectively combat the coronavirus pandemic, which is spreading rapidly around the world. Particular attention is paid to such important aspects as preventing the spread of coronavirus infection, effective treatment of patients with the disease, and conducting laboratory tests. Patients with chronic liver diseases required increased attention of doctors during the epidemic, since against the background of an exacerbation of their diseases, not only the risk of contracting a viral infection of COVID - 19 increased, but also its aggravation. (Mekhtiev.S.N and co-author. 2020). Severe liver damage during the severe course of COVID - 19 is diagnosed with a severe course of the disease. Patients with COVID - 19, confirmed by serious liver damage, experience an increase in high biochemical indicators. At the height of the disease, thrombocytopenia is observed. An increase in serum aminotransferase, creatinkinase and lactatdegydrogenase activity is detected. Literature has shown that patients with severe covid - 19 manifestations are at higher ALT levels, lower platelet and albumin numbers, and higher risk of death. Data analysis shows that the frequency of cases of impaired liver function increases in proportion to the severity of COVID-19 flow. Apparently, an increase in alt, hypoalbuminemia and thrombocytopenia are unfavorable factors in the prognosis of the disease. Analysis of the clinical picture of COVID-19 has shown that SARSCoV-2 has significant effects for SJK (chronic liver diseases). Patients with viral etiology are more susceptible to liver damage, which is likely due to increased replication of hepatitis V and C viruses during SARSCoV-2 infection. The presence of an Associated side disease (diabetes, cardiovascular diseases) tends to develop a severe form of COVID-19 in patients. Today, there is no clear data on whether patients with chronic hepatitis C have a higher risk of contracting COVID-19 compared to other diseases. At the same time, serious complications, if it is not possible to prevent COVID-19 infection, then the disease develops rapidly in them. Even if hepatitis C has been successfully treated in particular, it increases the chances of severe covid-19 passing. Therefore, against the background of the COVID-19 pandemic, the problems of patients with chronic viral hepatitis C are unresolved and require study. In epidemic conditions, it is very important to effectively monitor patients with this pathology and continue to treat them health, as well as to carry out scientific research to reduce the problem in the health system and reduce the disease. [ABSTRACT FROM AUTHOR]

Norovirus (NoV) and hepatitis A virus (HAV) pose a considerable health risk worldwide. In recent years, many cases of virus infection caused by virus‐contaminated strawberries have occurred worldwide. This study applied a critical control point system to analyze the main hazards during the production and marketing of strawberries imported into China and explore the key control points in the whole process. To further evaluate the risks in the supply chain, the established quantitative microbial risk assessment (QMRA) was used to determine the probability that residents would be infected with viruses after consuming imported strawberries. It was found that the risk of virus contamination from imported strawberries was low, and the virus contamination mainly results from water resources and personnel. This research helps the regulatory authorities formulate strategies to ensure the long‐term microbial safety of imported strawberries. In addition, the methods may prove useful in evaluating the risks of other agricultural produce. [ABSTRACT FROM AUTHOR]

The Science Popularization and Education Committee of the Academic Divisions of the Chinese Academy of Sciences (CASAD) invited the CAS Institutes of Science and Development (CASISD) and National Science Review (NSR) to organize a roundtable discussion of viral infectious diseases on 11 October 2022. During this extensive discussion, experts introduced the history and background of virus and viral infectious diseases. They explained the function of human's immune system. In addition, they answered frequently asked questions by the public such as the efficacy and safety of COVID vaccines, the cost of disease treatment and the threat of latest monkey pox outbreak. Chen Dong (董晨) Professor, director of Shanghai Immune Therapy Institute Fu-Sheng Wang (王福生) MD., director of the Department of Infectious Diseases, Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases George Fu Gao (高福) Professor, former director-general of Chinese Center for Disease Control and Prevention (China CDC) Zhonghe Zhou (周忠和, Chair) Associate director of the Science Popularization and Education Committee of CASAD, professor of CAS Institute of Vertebrate Paleontology and Paleoanthropology and associate editor-in-chief of NSR Yiming Shao (邵一鸣) Professor, deputy director of State Key Laboratory for Infectious Disease Control and Prevention, former chief expert on AIDS, China CDC [ABSTRACT FROM AUTHOR]

Background: Duck hepatitis A virus (DHAV) is a single-stranded, positive-strand small RNA virus that causes a very high mortality rate in ducklings. The DHAV-3 subtype incidence rate has recently increased in China, causing great economic losses to the waterfowl breeding industry. We analyzed the protection rate of DHAV vaccines used in mainland China from 2009 to 2021 and evaluated the effectiveness of vaccine prevention and control to reduce the economic losses caused by DHAV to the waterfowl breeding industry. We screened five electronic research databases and obtained 14 studies and patents on the protection efficiency of DHAV-1 and DHAV-3 vaccines. Results: Meta-analysis demonstrated that immunized ducklings produced higher antibody levels and had a significantly higher survival rate than non-immunized ducklings [relative risk (RR) = 12, 95% confidence interval (CI) 6–26, P < 0.01]. The age of the ducks and vaccine valence did not affect protection efficiency. Data source analysis of the vaccine protection rate demonstrated that the vaccines conferred immune protection for ducklings in both small-scale experiments and large-scale clinical conditions. The analysis results revealed that although the vaccines conferred protection, the immune protective effect differed between small-scale experimental conditions and large-scale clinical conditions. This might have been due to non-standard vaccination and environmental factors. Conclusions: Domestic DHAV vaccines can protect ducklings effectively. The subjects immunized (breeding ducks or ducklings) and vaccine valence had no effect on the protective effect. Both small-scale experiments and large-scale clinical conditions conferred immune protection on ducklings, but vaccine immunization under small-scale experimental conditions had slightly better protective effects than large-scale clinical immunization. [ABSTRACT FROM AUTHOR]

Object: The hepatitis C virus (HCV) is prevalent across China, with a distinctive genotypic distribution that varies by geographical region and mode of transmission. Yunnan is one such geographical region wherein the local population continues to experience a high level of HCV infection, severely straining public health resources. This high prevalence is likely due to the increased incidence of intravenous drug use in that region, as Yunnan is a major point of entry for illegal heroin into China. Methods: We investigated 510 individuals with chronic HCV infections in Yunnan Province from 2008 through 2018. Using reverse transcription PCR and Sanger sequencing to amplify and sequence samples. Bayesian analyses was performed to estimate the common ancestors and Bayesian skyline plot to estimate the effective viral population size. Molecular network was conducted to explore the characteristics of HCV transmission. Results: We successfully amplified and sequenced a total of 503 viral samples and genotyped each as either 3b (37.6%), 3a (21.9%), 1b (19.3%), 2a (10.5%), HCV6 (10.1%), or 1a (0.6%). Over this 11-year period, we observed that the proportion of 3a and 3b subtypes markedly increased and, concomitantly, that the proportion of 1b and 2a subtypes decreased. We also performed Bayesian analyses to estimate the common ancestors of the four major subtypes, 1b, 2a, 3a, and 3b. Finally, we determined that our Bayesian skyline plot and transmission network data correlated well with the changes we observed in the proportions of HCV subtypes over time. Conclusions: Taken together, our results indicate that the prevalence of HCV 3a and 3b subtypes is rapidly increasing in Yunnan, thus demonstrating a steadily growing public health requirement to implement more stringent preventative and therapeutic measures to curb the spread of the virus. [ABSTRACT FROM AUTHOR]

Introduction: To investigate the incidence, causes, and risk factors for unplanned readmission within 30 days of discharge in patients with pulmonary tuberculosis (TB). Methodology: The clinical data of 1,062 patients with confirmed pulmonary TB who were admitted to our hospital from October 2018 to October 2021 were analysed retrospectively. The subjects were divided into a readmission group (354 cases) and a non-readmission group (708 cases) according to whether there was an unplanned admission within 30 days of discharge. We analysed the risk factors for unplanned readmission within 30 days after discharge with pulmonary TB. Results: The incidence of unplanned readmission in patients with pulmonary TB was 5.2%. Being female (OR = 0.63, 95% CI: 0.434-0.942) and living in cities (OR = 0.218, 95% CI: 0.151-0.315) were protective factors for the readmission of patients with TB (p < 0.05). However, being = 65 years old (OR = 2.574, 95% CI: 1.709-3.870), being a smoker (OR = 2.773, 95% CI: 1.751-4.390), having chronic obstructive pulmonary disease (COPD) (OR = 3.373, 95% CI: 1.708-6.660), having viral hepatitis (OR= 2.079, 95% CI: 1.067-4.052), receiving nonstandard treatment (OR = 15.620, 95% CI: 10.413-23.431), having medical side effects (OR = 6.138, 95% CI: 3.798-9.922) and l unauthorised discharge (OR = 2.570, 95% CI: 1.509-4.376) were risk factors for the readmission to hospital of patients with TB (p < 0.05). Conclusions: Gender, age, place of residence, smoking, COPD, hepatitis, non-standard treatment, adverse drug reactions and unauthorised discharge were risk factors of TB for unplanned readmission. [ABSTRACT FROM AUTHOR]

Hepatitis A and hepatitis E are relatively common causes of liver disease. Both viruses are mainly transmitted through the faecal–oral route and, consequently, most outbreaks occur in countries with poor sanitation. An important role of the immune response as the driver of liver injury is also shared by the two pathogens. For both the hepatitis A (HAV) and hepatitis E (HEV) viruses, the clinical manifestations of infection mainly consist of an acute disease with mild liver injury, which results in clinical and laboratory alterations that are self-limiting in most cases. However, severe acute disease or chronic, long-lasting manifestations may occur in vulnerable patients, such as pregnant women, immunocompromised individuals or those with pre-existing liver disease. Specifically, HAV infection rarely results in fulminant hepatitis, prolonged cholestasis, relapsing hepatitis and possibly autoimmune hepatitis triggered by the viral infection. Less common manifestations of HEV include extrahepatic disease, acute liver failure and chronic HEV infection with persistent viraemia. In this paper, we conduct a non-systematic review of the available literature to provide a comprehensive understanding of the state of the art. Treatment mainly consists of supportive measures, while the available evidence for aetiological treatment and additional agents in severe disease is limited in quantity and quality. However, several therapeutic approaches have been attempted: for HAV infection, corticosteroid therapy has shown outcome improvement, and molecules, such as AZD 1480, zinc chloride and heme oxygenase-1, have demonstrated a reduction in viral replication in vitro. As for HEV infection, therapeutic options mainly rely on the use of ribavirin, and some studies utilising pegylated interferon-alpha have shown conflicting results. While a vaccine for HAV is already available and has led to a significant reduction in the prevalence of the disease, several vaccines for HEV are currently being developed, with some already available in China, showing promising results. [ABSTRACT FROM AUTHOR]

Concomitant administration refers to the receipt of two or more vaccines during a single healthcare encounter, which is an efficient way to increase vaccination coverage in children. However, the post-marketing safety studies of concomitant administration are scarce. Inactivated hepatitis A vaccine (Healive®) has been used widely in China and other countries for more than a decade. We aimed to explore the safety of Healive® co-administered with other vaccines compared to Healive® alone in children under 16 years old. We retrieved Adverse Events Following Immunization (AEFI) cases and vaccination doses of Healive® during 2020–2021 in Shanghai, China. The AEFI cases were divided into concomitant administration group and Healive® alone group. We used administrative data on vaccine doses as denominators to calculate and compare crude reporting rates between groups. We also compared baseline gender and age distribution, clinical diagnoses, and time interval from vaccination to onset of symptoms between groups. A total 319,247 doses of inactivated hepatitis A vaccine (Healive®) were used and 1,020 AEFI cases (319.50 per million doses) associated with Healive® were reported during 2020–2021 in Shanghai. There were 259,346 doses concomitantly administered with other vaccines and 830 AEFI cases (320.04 per million doses) were reported. There were 59,901 doses of Healive® that vaccinated alone, with 190 AEFI cases (317.19 per million doses). There was only one case with serious AEFI in concomitant administration group, with a rate of 0.39 per million doses. Reported rates of AEFI cases were similar between groups in general (p > 0.05). Concomitant administration of inactivated hepatitis A vaccine (Healive®) with other vaccines has a similar safe profile as Healive® alone. [ABSTRACT FROM AUTHOR]

Background: The clinical characteristics of primary liver cancer (PLC) patients are changing, maybe due to hepatitis viral vaccination and lifestyle changes, etc. The linkage between these changes and outcomes among these PLCs has not yet been fully elucidated. Methods: It was identified total of 1691 PLC cases diagnosed between 2000 ~ 2020. Cox proportional hazards models were utilized to determine the connections between the clinical presentations and their close risk factor(s) from PLC patients. Results: The average age of PLC patients increased gradually from 52.74 ± 0.5 years in 2000 ~ 2004 to 58.63 ± 0.44 years in 2017 ~ 2020, accompanied by an increased proportion of females from 11.11% to 22.46%, and non-viral hepatitisrelated PLC was raised from 1.5% to 22.35%. 840 (49.67%) PLC patients with alpha-fetoprotein (AFP) < 20ng/mL (AFP-negative). The mortality was 285 (16.85%) or 532 (31.46%) PLC patients with alanine transaminase (ALT) between 40 ~ 60 IU/L or ALT > 60 IU/L. The PLC patients with pre-diabetes/diabetes or dyslipidemia also increased from 4.29% or 11.1% in 2000 ~ 2004 to 22.34% or 46.83% in 2017 ~ 2020. The survival period of the PLC patients with normoglycemia or normolipidemic was 2.18 or 3.14 folds longer than those patients with pre-diabetes/diabetes or hyperlipidemia (P<0.05). Conclusions: It was gradually increased that age, the proportion of females, nonviral hepatitis-related causes, AFP-negative, and abnormal glucose/lipids among PLC patients. Proper control of glucose/lipids or ALT may improve the prognosis of PLCs. [ABSTRACT FROM AUTHOR]

Introduction: Viral hepatitis is a global public health problem, and China still faces great challenges to achieve the WHO goal of eliminating hepatitis. Methods: This study focused on hepatitis B and C, aiming to explore the longterm spatiotemporal heterogeneity of hepatitis B and C incidence in China from 2010 to 2018 and quantify the impact of socioeconomic factors on their risk through Bayesian spatiotemporal hierarchical model. Results: The results showed that the risk of hepatitis B and C had significant spatial and temporal heterogeneity. The risk of hepatitis B showed a slow downward trend, and the high-risk provinces were mainly distributed in the southeast and northwest regions, while the risk of hepatitis C had a clear growth trend, and the high-risk provinces were mainly distributed in the northern region. In addition, for hepatitis B, illiteracy and hepatitis C prevalence were the main contributing factors, while GDP per capita, illiteracy rate and hepatitis B prevalence were the main contributing factors to hepatitis C. Disussion: This study analyzed the spatial and temporal heterogeneity of hepatitis B and C and their contributing factors, which can serve as a basis for monitoring efforts. Meanwhile, the data provided by this study will contribute to the effective allocation of resources to eliminate viral hepatitis and the design of interventions at the provincial level. [ABSTRACT FROM AUTHOR]

Background: Chronic hepatitis B (CHB) is highly prevalent among adults in rural China and better management of those populations is of vital importance for viral hepatitis elimination. Adult immunization has been the subject of much controversy in previous studies. This study estimates the cost-effectiveness of population-based hepatitis B screening, treatment, and immunization strategy (comprehensive strategy) in rural areas with high prevalence under the national policy of sharp-drop drug prices. Methods: We constructed a Markov model comparing 4 strategies in a 30-year horizon from the healthcare payer perspective: (1) the conventional pattern; (2) screening and treating infected (treatment); (3) screening and immunizing susceptible individuals (immunization); and (4) the comprehensive strategy. Screening intensity ranged from 50% to 100%. Outcomes were measured by costs, quality-adjusted life-years (QALYs), incremental cost-effectiveness ratios (ICERs), and clinical outcomes. Results: The costs for the conventional pattern, treatment strategy, immunization strategy, and comprehensive strategy were US$ 341, 351, 318, and 323, respectively. In addition, effects were 17.45, 17.57, 17.46, and 17.58 QALYs, respectively. The ICER of the comprehensive strategy was US$ 35/QALY gained at 50% screening intensity and 420 US$/QALY gained at 100%. The net monetary benefit increased with increasing screening intensity and declined after 90%, with the highest value of US$40 693. All new infections and 52.5% mortality could be avoided from 2020 to 2049 if all patients were properly treated and all susceptible individuals were immunized. The results were stable within a wide range of parameters. Conclusion: It was cost-effective to implement the mass hepatitis B screening, treatment, and immunization strategy in areas of rural China with high prevalence, and the strategy gained the most net monetary benefit at a screening intensity of 90%. Although it was impractical to fulfill 100% coverage, efforts should be made to obtain more people screened. [ABSTRACT FROM AUTHOR]

Liver disease affects millions of people in the world, and China has the highest prevalence of liver disease in the world. Small ubiquitin-related modifier (SUMO) modification is a highly conserved post-translational modification of proteins. They are widely expressed in a variety of tissues, including the heart, liver, kidney and lung. SUMOylation of protein plays a key role in the occurrence and development of liver disease. Therefore, this study reviewed the effects of SUMO protein on non-alcoholic fatty liver disease (NAFLD), alcoholic liver disease (ALD), viral hepatitis, hepatic fibrosis (HF), hepatocellular carcinoma (HCC), and other liver diseases to provide novel strategies for targeted treatment of liver disease. [ABSTRACT FROM AUTHOR]

Since the first report from Cherry Valley ducks on a commercial duck farm in China (2008), duck astrovirus type 1(DAstV‐1)‐associated duck viral hepatitis (DVH) have been detected in several commercial duck flocks. A highly acute disease characterized by hepatitis broke out in ducklings in Shandong Province in March 2021, all diseased ducks have been immunized against the duck viral hepatitis vaccine. One DAstV‐1 strain, designated as DAstV‐SDWF, was isolated from a diseased duckling. Here, the isolation, cultivation, and characterization of DAstV‐1 isolate are described. The isolated astrovirus grew well in the LMH cell line. To determine the entire genomic of the DAstV‐SDWF isolate, the next‐generation sequencing (NGS) technique was conducted on the Illumina HiSeq platform. Complete genome sequence analysis revealed that DAstV‐SDWF isolate was 91.6%–98.6% homology with others DAstV‐1 deposited in Genbank. Similar clinical symptoms were successfully reproduced by an experimental infection study using the DAstV‐SDWF isolate. DAstV‐SDWF is the first DAstV‐1 strain whose experimental infection study has been conducted in China. Results of the above data demonstrated that DAstV‐1 could be one of the causative agents of the DVH occurring in China. The present works are likely to provide new insights into the pathogenicity and evolution of DAstV‐1 in ducks. [ABSTRACT FROM AUTHOR]

Rare diseases, also known as orphan diseases, are a group of diseases that affect a relatively small number of people. Low incidence rates, atypical symptoms, imperfect diagnosis criteria and few treatment options impose medical, psychological and financial stress on the local healthcare system. The spectrum of liver diseases in China has changed in the past decades due to successful control of once highly prevalent viral hepatitis B and C. Furthermore, the increased awareness and improved availability of specific laboratory tests have also facilitated the diagnosis of rare diseases such as autoimmune, cholestatic and genetic liver diseases. Finally, considering the huge population, the total number of many rare liver diseases in China is not as rare as once deemed. In this mini-review article, we will outline the current clinical and epidemiological profiles of some rare liver diseases that are no longer rare in China. [ABSTRACT FROM AUTHOR]

Matrine, an active component of Sophora flavescens Ait root extracts, has been used in China for years to treat cancer and viral hepatitis. In the present study, we explored the effects of matrine on hyperglycemia-treated cardiomyocytes. Cardiomyocyte function, oxidative stress, cellular viability, and mitochondrial fusion were assessed through immunofluorescence, quantitative real-time PCR (qRT-PCR), enzyme-linked immunosorbent assays, and RNA interference. Matrine treatment suppressed hyperglycemia-induced oxidative stress in cardiomyocytes by upregulating transcription of nuclear factor erythroid 2-like 2 and heme oxygenase-1. Matrine also improved cardiomyocyte contractile and relaxation function during hyperglycemia, and it reduced hyperglycemia-induced cardiomyocyte death by inhibiting mitochondrial apoptosis. Matrine treatment increased the transcription of mitochondrial fusion-related genes and thus attenuated the proportion of fragmented mitochondria in cardiomyocytes. Inhibiting mitochondrial fusion by knocking down mitofusin 2 (Mfn2) abolished the cardioprotective effects of matrine during hyperglycemia. These results demonstrate that matrine could be an effective drug to alleviate hyperglycemia-induced cardiomyocyte damage by activating Mfn2-induced mitochondrial fusion. [ABSTRACT FROM AUTHOR]

Wuzhi capsule (WZC), a preparation of Fructus Schisandra sphenanthera extract, has been used widely for the treatment of viral and drug‐induced hepatitis in China. This study aimed to determine the pharmacokinetic parameters of tacrolimus (TAC) when co‐administered with WZC and the dose‐effect of WZC on tacrolimus in healthy volunteers. The effect of an increased dosage of WZC (1, 2, 6, and 8 capsules once daily) on the relative oral exposure of tacrolimus was assessed to explore the dose–response relationship between WZC and tacrolimus using bioanalysis, pharmacokinetic, and genotypical analyses. The influence of CYP3A5 and MDR1 genetic polymorphisms on the WZC dose was elucidated by maintaining the Ctrough of tacrolimus in Chinese healthy volunteers. When co‐administered with WZC, the Tmax of tacrolimus was increased significantly while the apparent oral clearance was decreased. The plasma tacrolimus level in volunteers with high CYP3A5 expression was much lower than that in those with mutant CYP3A5. However, polymorphisms of MDR1 exon26 C3435T, exon21 G2677T/A, and exon12 C1236T were not associated with plasma tacrolimus levels. Our findings provide important information on interactions between modern medications and herbal products, thus facilitating a better usage of tacrolimus in patients receiving WZC. [ABSTRACT FROM AUTHOR]

Background: China has made substantial efforts aimed to promote the uptake of antiviral treatment of hepatitis B (HB). It is unclear whether these policies achieved the desired impact. This study adopted medicines procurement data from 31 provinces to generate the first evidence about the number of standard antiviral treatment of HB overtime at both national and provincial levels in China. Methods: We performed the panel data analyses and quasi‐experimental design with the time‐varying difference‐in‐difference method combined with the event study approach to estimate the uptake of HB antiviral treatment before and after national policy changes. Results: The overall trends in HB antiviral treatment at the national level increased incrementally during 2013–2020. There was 2.8862 million 12‐month (person‐year) antiviral standard treatment in 2020, which was only 8.93% of the eligible people estimated to need treatment. The number of monthly antiviral standard treatment increased by 42.4% (p =.001) overall following the nationwide adoption of the '4 + 7' pilot‐pooled procurement prices in 2019, which brought substantial price reduction of core antivirals. Conclusions: A low treatment rate is a critical issue in reaching the elimination of viral hepatitis as a public health threat in China. Affordability is an important but not the only factor that determines the uptake of hepatitis treatment. Further scaling up and acceleration of treatment uptake will need strategies improving public awareness of HB, strengthening diagnosis, linking people who are infected to chronic care, reducing loss to follow‐up, and ensuring people who are eligible get timely treatment. [ABSTRACT FROM AUTHOR]

Rare diseases, also known as orphan diseases, are a group of diseases that affect a relatively small number of people. Low incidence rates, atypical symptoms, imperfect diagnosis criteria and few treatment options impose medical, psychological and financial stress on the local healthcare system. The spectrum of liver diseases in China has changed in the past decades due to successful control of once highly prevalent viral hepatitis B and C. Furthermore, the increased awareness and improved availability of specific laboratory tests have also facilitated the diagnosis of rare diseases such as autoimmune, cholestatic and genetic liver diseases. Finally, considering the huge population, the total number of many rare liver diseases in China is not as rare as once deemed. In this mini‐review article, we will outline the current clinical and epidemiological profiles of some rare liver diseases that are no longer rare in China. [ABSTRACT FROM AUTHOR]

Approximately 80% of primary healthcare facilities in China were ready to deliver hepatitis care services by 2021. This study aimed to assess hepatitis B and C test uptake, identify the factors associated with testing and determine the predictors of hepatitis stigma among primary care patients. We conducted a cross‐sectional survey among patients seeking care in the family medicine and primary care unit of the University of Hong Kong‐Shenzhen Hospital, China. Participants were 30 years or older and had not tested for HBV and HCV in the preceding 12 months. Test uptake was defined as self‐reported previous HBV and HCV testing. Descriptive statistics, Chi‐square test, forward multivariable logistic regression and stepwise multiple linear regression were conducted, and a p‐value <.05 was deemed statistically significant. A total of 750 eligible patients completed the survey, and 54.5% (404 ± 0.9) were between 30 and 40 years old. Most participants were heterosexuals 98.0% (n = 735), female 57.5% (n = 431), married 78.3% (587) and earned ≤1500 USD per month 54.4% (n = 408). A 66.1% (n = 496) and 13.7% (n = 103) self‐reported previous HBV and HCV testing, respectively, and 62% (n = 468) were vaccinated. HCV testing was associated with HBV testing (aOR = 13.7, 95% CI:2.1–91.5); and HBV testing was associated with family history of HBV (aOR = 2.4, 95%CI:1.1–5.5). Overall hepatitis stigma was about average and decreased with family history of HBV (p =.017). In conclusion, HCV testing uptake among primary care patients was low and needs to be further promoted. Integrating HBV and HCV testing interventions and fostering family‐based support for disclosure could effectively improve testing uptake. [ABSTRACT FROM AUTHOR]

Despite the availability of hepatitis B virus (HBV) and hepatitis C virus (HCV) testing in primary care, testing rates in China remain low. Social media is an inexpensive means of disseminating information and could facilitate hepatitis testing promotion. We evaluated the capacity of digitally crowdsourced materials to promote HBV/HCV testing uptake via a randomized controlled trial (identifier: ChiCTR1900025771), which enrolled 750 Chinese primary care patients. We randomized patients (1:1) to receive crowdsourced HBV/HCV promotion materials through social media or facility-based care without promotional materials for four weeks. Exposure to all intervention materials was associated with increased odds of HBV (aOR = 1.79, 95% CI: 1.09–3.00) and HCV (aOR = 1.95, 95% CI: 1.29–2.99) testing compared to facility-based care. There was a significant reduction in hepatitis stigma among intervention group participants (HBV slope: −0.15, p < 0.05; and HCV slope: −0.13, p < 0.05). Digitally crowdsourced promotion messages could enhance hepatitis testing uptake and should be considered in hepatitis reduction strategies. Trial registration: Chinese Clinical Trial Registry (ChiCTR1900025771) on September 9, 2019. Available from: http://www.chictr.org.cn/showproj.aspx?proj=42788 [ABSTRACT FROM AUTHOR]

The escalating frequency of environmental pollution incidents has raised significant concerns regarding the potential health impacts of pollutant fluctuations. Consequently, a comprehensive study on the role of pollutants in the prevalence of viral hepatitis is indispensable for the advancement of innovative prevention strategies. Monthly incidence rates of viral hepatitis from 2005 to 2020 were sourced from the Chinese Center for Disease Control and Prevention Infectious Disease Surveillance Information System. Pollution data spanning 2014-2020 were obtained from the National Oceanic and Atmospheric Administration (NOAA), encompassing pollutants such as CO, NO2, and O3. Time series analysis models, including seasonal auto-regressive integrated moving average (SARIMA), Holt-Winters model, and Generalized Additive Model (GAM), were employed to explore prediction and synergistic effects related to viral hepatitis. Spearman correlation analysis was utilized to identify pollutants suitable for inclusion in these models. Concurrently, machine learning (ML) algorithms were leveraged to refine the prediction of environmental pollutant levels. Finally, a weighted quantile sum (WQS) regression framework was developed to evaluate the singular and combined impacts of pollutants on viral hepatitis cases across different demographics, age groups, and environmental strata. The incidence of viral hepatitis in Beijing exhibited a declining trend, primarily characterized by HBV and HCV types. In predicting hepatitis prevalence trends, the Holt-Winters additive seasonal model outperformed the SARIMA multiplicative model ((1,1,0) (2,1,0) [12] ). In the prediction of environmental pollutants, the SVM model demonstrated superior performance over the GPR model, particularly with Polynomial and Besseldot kernel functions. The combined pollutant risk effect on viral hepatitis was quantified as βWQS (95% CI) = 0.066 (0.018, 0.114). Among different groups, PM 2.5 emerged as the most sensitive risk factor, notably impacting patients with HCV and HEV, as well as individuals aged 35-64. CO predominantly affected HAV patients, showing a risk effect of βWQS (95% CI) = - 0.0355 (- 0.0695, - 0.0016). Lower levels of PM 2.5 and PM 10 were associated with heightened risk of viral hepatitis incidence with a lag of five months, whereas elevated levels of PM 2.5 (100-120 μg/m 3 ) and CO correlated with increased hepatitis incidence risk with a lag of six months. The Holt-Winters model outperformed the SARIMA model in predicting the incidence of viral hepatitis. Among machine learning algorithms, SVM and GPR models demonstrated superior performance for analyzing pollutant data. Patients infected with HAV and HEV were primarily influenced by PM 10 and CO, whereas SO 2 and PM 2.5 significantly impacted others. Individuals aged 35-64 years appeared particularly susceptible to these pollutants. Mixed pollutant exposures were found to affect the development of viral hepatitis with a notable lag of 5-6 months. These findings underscore the importance of long-term monitoring of pollutants in relation to viral hepatitis incidence., (© 2024. The Author(s).)

Background: Viral hepatitis imposes a heavy disease burden worldwide and is also one of the most serious public health problems in China. We aimed to describe the epidemiological characteristics of hepatitis in China and to investigate the influencing factors., Methods: We first used the JoinPoint model to analyze the percentage change (APC) and average annual percentage change (AAPC) of hepatitis in Chinese provinces from 2002 to 2021. We then explored the influencing factors by using the time-series global principal component analysis (GPCA) and the panel fixed-effects model., Results: The disease burden varied across different provinces from 2002 to 2021. The AAPC of the total HAV incidence decreased by 10.39% (95% CI: [-12.70%, -8.02%]) from 2002 to 2021. Yet the AAPC of HBV, HCV, and HEV increased by 1.50% (95% CI: [0.23%, 2.79%]), 13.99% (95% CI: [11.28%, 16.77%]), and 7.10% (95% CI: [0.90%, 13.69%]), respectively. The hotspots of HAV, HBV, HCV, and HEV moved from the west to the center, from the northwest to the southeast, from the northeast to the whole country, and from the northeast to the southeast, respectively. Different types of viral hepatitis infections were associated with hygiene, pollutant, and meteorological factors. Their roles in spatial-temporal incidence were expressed by panel regression functions., Conclusions: Viral hepatitis infection in China showed spatiotemporal heterogeneity. Interventions should be tailored to its epidemiological characteristics and determinants of viral hepatitis., (© 2024. The Author(s).)

Background Liver diseases are the serious cause of death in China. We aim to describe the trends and disparities of major liver disease mortality rates and the loss of life expectancy (LLE) in China. Methods Annual percentage change (APC) and average APC (AAPC) were calculated using the Joinpoint regression model. LLE was calculated using cause eliminated life table. Results From 2006 to 2017, the overall age-standardized mortality rate (ASMR) of liver cirrhosis lightly declined (AAPC: −2.97%), whereas the ASMR of viral hepatitis and liver cancer remained stable. Viral hepatitis (AAPC: −4.36%) and liver cirrhosis (AAPC: −4.35%) ASMRs both declined for females. The highest ASMRs of viral hepatitis and liver cirrhosis were in the west region, while that of liver cancer was in the middle region. The ASMRs of liver cirrhosis in the middle region and liver cancer in the east region significantly decreased. The means of LLE on viral hepatitis, liver cirrhosis and liver cancer were 0.05, 0.1 and 0.46 years, respectively. Conclusions The burden of liver diseases is still severe and there are disparities between genders and different regions in China. Accurate early diagnostic approaches for high-risk populations should be established to eliminate the burden of liver diseases. [ABSTRACT FROM AUTHOR]

Several outbreaks of duck hepatitis A virus type 1 (DHAV-1), which were characterized by yellow coloration and hemorrhage in pancreatic tissues, have occurred in China. The causative agent is called pancreatitis-associated DHAV-1. The mechanisms involved in pancreatitis-associated DHAV-1 infection are still unclear. Transcriptome analysis of duck pancreas infected with classical-type DHAV-1 and pancreatitis-associated DHAV-1 was carried out. Deep sequencing with Illumina-Solexa resulted in a total of 53.9 Gb of clean data from the cDNA library of the pancreas, and a total of 29,597 unigenes with an average length of 993.43 bp were generated by de novo sequence assembly. The expression levels of D-3-phosphoglycerate dehydrogenase, phosphoserine aminotransferase, and phosphoserine phosphatase, which are involved in glycine, serine, and threonine metabolism pathways, were significantly downregulated in ducks infected with pancreatitis-associated DHAV-1 compared with those infected with classical-type DHAV-1. These findings provide information regarding differences in expression levels of metabolism-associated genes between ducks infected with pancreatitis-associated DHAV-1 and those infected with classical-type DHAV-1, indicating that intensive metabolism disorders may contribute to the different phenotypes of DHAV-1-infection. [ABSTRACT FROM AUTHOR]

Hepatitis B viral (HBV) load and hepatic enzymes play a critical role in hepatocellular carcinoma (HCC) development. However, the clinical significance of these in HBV‐related HCC patients after hepatectomy remains unclear. In this study, we analysed 1,940 HBV‐related HCC patients who underwent hepatectomy from four hospitals in west China. Risk classification was constructed based on baseline HBV‐DNA load and AST/ALT ratio. Based on the HBV‐DNA load and AST/ALT ratio classification, four types with distinguishable prognoses were established. Type 1 patients had the best prognosis with 5‐year overall survival (OS) of 69.8%, followed by type 2 and type 3 patients, whereas type 4 patients had the worst prognosis with 5‐year OS of 42.7%. Similarly, the four types had statistically different recurrence‐free survival. This classification was significantly associated with HCC recurrence (hazard ratio [HR]:1.492, p <.001) and long‐term survival (HR: 1.574, p =.001). Pathologically, type 4 correlated with more advanced tumours considering tumour size and microvascular invasion than those in type 1, 2, or 3. Moreover, type 4 patients had more severe hepatic inflammation in underlying liver. Conversely, type 1 patients had an active tumour immune microenvironment as indicated by more CD8+ T cell infiltration and less PD‐L1 expression. In conclusion, the classfication based on baseline HBV‐DNA load and AST/ALT ratio could effectively stratify HBV‐related HCC patients with distinguishable prognoses after hepatectomy. [ABSTRACT FROM AUTHOR]

• We investigated the toxicity and adverse reactions of the combined HAV-EV71 vaccine. • SD rats that received one dose of the HAV-EV71 combined vaccine showed no toxicity. • Restored phagocytosis of basophilic granules was observed with three doses. • Guinea pigs showed no allergic reactions following multiple intramuscular injection. Since 2007, Hepatitis A (HAV) vaccination has been a part of the National Immunization Program of China. Recognizing enterovirus 71 (EV71) as the most important pathogen in severe hand, foot and mouth disease, an inactivated EV71 vaccine was successfully marketed in 2015. Based on the concept of one vaccine preventing two diseases and owing to similarities in vaccine preparation and the overlap of the eligible population, a combination of the inactivated HAV vaccine and inactivated EV71 vaccine is theoretically feasible and desirable. However, the optimal vaccination schedule for this combination vaccine has yet to be optimized. Use of this combined vaccine would not only decrease the number of vaccinations, but also lower associated cost. This study aimed to investigate the toxicity and adverse reactions of the combined HAV-EV71 vaccine under Good Laboratory Practice conditions to provide a reference for clinical studies/applications in the future. CD®(Sprague Dawley) IGS rats were employed for single-dose toxicity testing using a high dose, and repeated-dose toxicity testing using high, as well as low doses. Animals that received only a single dose showed no obvious clinical symptoms nor abnormal body weight, and no significant gross pathological change at the experimental endpoint at necropsy. In the rats injected with three doses, phagocytosis of basophilic granules by macrophages was observed in the inguinal, mesenteric, and local lymph nodes, besides irritation at the administration site. At 56 days after the last dose, no significant histopathological change was observed in the lymph nodes, and local irritation gradually faded. Further, systematic allergy testing was performed in guinea pigs. After systemic sensitization and challenge with the HAV-EV71 vaccine, animals showed normal weight gain and no allergic reactions. This study, therefore, confirmed a good safety profile of the inactivated HAV and EV71 combined vaccine. [ABSTRACT FROM AUTHOR]

Hepatitis E virus (HEV) infection is a worldwide disease and the primary cause of acute viral hepatitis with an estimated 3.3 million symptomatic cases every year and 44,000 related deaths. It is a waterborne infection in the developing countries. In these countries, HEV genotypes 1 and 2 cause large outbreaks and affect young subjects resulting in significant mortality in pregnant women and patients with cirrhosis. In developed countries, HEV genotypes 3 and 4 are responsible for autochthonous, sporadic hepatitis and transmission is zoonotic. Parenteral transmission by the transfusion of blood products has been identified as a potential new mode of transmission. HEV can also cause neurological disorders and chronic infections in immunocompromised patients. The progression of acute hepatitis E is usually asymptomatic and resolves spontaneously. Diagnosis is based on both anti‐HEV IgM antibodies in serum and viral RNA detection in blood or stools by PCR in immunocompetent patients, while only PCR is validated in immunocompromised individuals. Ribavirin is the only validated treatment in chronic infection. A vaccine has been developed in China. [ABSTRACT FROM AUTHOR]

Duck hepatitis A virus (DHAV) causes a highly contagious and acute disease in ducklings younger than 3 weeks of age and spreads rapidly by horizontal transmission to all susceptible ducklings in the flock. To date, there is no evidence of vertical transmission of DHAV‐1. In a previous study, we identified a novel DHAV type 1 (DHAV‐1) isolate that could infect adult ducks and induce laying drop. In this study, 30 non‐embryonated duck eggs and 60 17‐day‐old embryos were collected from three breeding duck flocks with egg drop syndrome caused by DHAV‐1 in China, and 30 17‐day‐old embryos were randomly selected from the 60 embryos and allowed to hatch. DHAV‐1 RNA was detected by RT‐PCR in 10 of 30 non‐embryonated eggs, 9 of 30 17‐day‐old embryos, 5 of 7 dead embryos and 5 of 23 newly hatched ducklings. Overall, 29 of 90 (32.2%) eggs and embryos were positive for DHAV‐1. Three DHAV‐1 strains were isolated from the dead duck embryos of the three breeding duck flocks, respectively. Pathogenicity studies showed that the three DHAV‐1 isolates had median embryo lethal doses but were highly pathogenic to healthy ducklings. Compared with the DHAV reference strains, there were two specific amino acid mutation sites (F169 and S220) in VP1 of the three isolates. To the best of our knowledge, this is the first report that DHAV‐1 is isolated from duck embryos. The findings provide evidence of possible vertical transmission of DHAV‐1 from breeding ducks to ducklings. [ABSTRACT FROM AUTHOR]

Matrine, an active component of Sophora flavescens Ait root extracts, has been used in China for years to treat cancer and viral hepatitis. In the present study, we explored the effects of matrine on hyperglycemia-treated cardiomyocytes. Cardiomyocyte function, oxidative stress, cellular viability, and mitochondrial fusion were assessed through immunofluorescence, quantitative real-time PCR (qRT-PCR), enzyme-linked immunosorbent assays, and RNA interference. Matrine treatment suppressed hyperglycemia-induced oxidative stress in cardiomyocytes by upregulating transcription of nuclear factor erythroid 2-like 2 and heme oxygenase-1. Matrine also improved cardiomyocyte contractile and relaxation function during hyperglycemia, and it reduced hyperglycemia-induced cardiomyocyte death by inhibiting mitochondrial apoptosis. Matrine treatment increased the transcription of mitochondrial fusion-related genes and thus attenuated the proportion of fragmented mitochondria in cardiomyocytes. Inhibiting mitochondrial fusion by knocking down mitofusin 2 (Mfn2) abolished the cardioprotective effects of matrine during hyperglycemia. These results demonstrate that matrine could be an effective drug to alleviate hyperglycemia-induced cardiomyocyte damage by activating Mfn2-induced mitochondrial fusion. [ABSTRACT FROM AUTHOR]

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Hepatitis E virus (HEV) is an important cause of enterically transmitted viral hepatitis and a significant contributor to maternal mortality in endemic regions around the world, yet the global response has been limited. HEV is a disease of poverty, and the populations experiencing the greatest burden of HEV-associated illness are not benefitting from existing interventions, including WASH strategies and immunization. Though a vaccine exists (HEV 239, Hecolin®, Xiamen Innovax Biotech, China), it is only licensed and available in the private market in China and has yet to be prequalified by the WHO for use in endemic settings and outbreaks. This review of the current state of HEV disease and subsequent recommendations for a coordinated public health response are intended to guide the global health community towards breaking the current 'vicious cycle,' in which a lack of data prevents actions that would improve health outcomes. Vaccine implementation in future outbreaks, targeted studies assessing vaccine effectiveness and immunogenicity in endemic regions and populations, improved understanding of the global burden, and improvements in diagnostic and epidemiologic tools are urgently needed. Strategies for implementing routine vaccination programs, improving water, sanitation, and hygiene in endemic regions. [ABSTRACT FROM AUTHOR]

Background: The aim of this study is to quantify the burden caused by viral hepatitis in China from 1990 to 2016.Methods: Data from the GBD 2016 study were extracted to calculate incidence, prevalence and disability-adjusted life years (DALYs). Trends in DALYs were assessed in 33 provinces/regions.Results: From 1990 to 2016, the total incidence of hepatitis decreased by 88.5%. However, the prevalence of hepatitis (counts in thousands), increased by 37.6% from 153,856 (95% UI: 136,047-172,319) in 1990 to 211,721 (95% UI: 179,776-240,981) in 2016, with age-standardized prevalence rates changing slightly. The number and age-standardized rates of prevalence increased by 35.9 and 1.6% for hepatitis B, respectively, and by 81.8 and 30.4% for hepatitis C. Guangxi, Guangdong and Hainan had the highest age-standardized prevalence rates (≥16,500 per 100,000). Tibet, Qinghai and Gansu had the highest age-standardized DALYs rates (≥40 per 100,000). The largest absolute number of DALYs was observed in the 15-49 year age group in 2016. The highest rate of DALYs occurred in males aged 50-69 years and in females aged ≧70 years.Conclusion: The incidence and DALYs of viral hepatitis decreased dramatically from 1990 to 2016. However, the prevalence still remains at a high level, which may result in heavy burdens in the future. [ABSTRACT FROM AUTHOR]

To explore the epidemic mode of COVID-19, we made an epidemiological investigation, set up hypothetical models, and compared them with hepatitis A virus (HAV) age-specific epidemic characteristic. In the epidemiological investigation, we reported the first familial COVID-19 silent infection in the world. A 19-year-old healthy female COVID-19 virus carrier without any symptoms caused two mild and one severe pneumonia. In hypothetical models, the silent infection rate ranges from 60% to 80% based on 3 sources: China mainland, evacuation of 4 nationals, and the ship "Diamond Princess," respectively. In comparison with HAV, COVID-19 shows the same infection mode in children (aged 0–9 years), but significant difference in young adults (aged 10–44 years) and the elderly (aged 45 years or older). Therefore, we prejudged that COVID-19 is a silent infection pandemic mainly in young adults but threatens the elderly. [ABSTRACT FROM AUTHOR]

Globally, alcohol consumption contributes to more than 3 million deaths each year. While much of its ramifications is preventable, a coherent public health discourse on how to limit alcohol-related harm has been overdue. By synthesizing information from national and global databases, we show in this analysis that alcohol consumption level and alcohol-attributable burden of diseases, particularly alcoholic liver disease (ALD), are intimately linked to national income distribution, cultural norms, religion, sex, age, and health status. Prevalence and burden of ALD are positively associated with economic standing in most countries, which necessitate active governmental control via cost-effective policies, such as the best buys proposed by the World Health Organization. To date, a number of critical questions remain unanswered over the molecular mechanisms underlying ALD pathophysiology; the insights gained thereof should provide new opportunities for the advancement of novel diagnostic and management strategies. In comparison with other prevailing liver diseases (e.g., viral hepatitis and nonalcoholic fatty liver disease), governmental support to ALD investigation has been sluggish in most Western countries and China, resulting in a dearth of breakthroughs on both the basic and clinical research fronts in the past decades. Emerging foci of clinical trials for ALD therapy include empirical use of probiotics, antioxidants, growth factors, monoclonal antibodies against key inflammatory mediators, and technology-enhanced behavioral interventions. In this article, we seek to provide a comprehensive analysis on the progress and challenges in tackling ALD as a global health problem, with particular emphasis on global disease burden, socioeconomic influences, research trends, government roles, and future therapies. [ABSTRACT FROM AUTHOR]

Hepatitis E virus (HEV) is associated with acute hepatitis disease, which may lead to chronic disease in immunocompromised individuals. The disease is particularly severe among pregnant women (20–30% mortality). The only licensed vaccine against HEV, which is available in China, is the Escherichia coli purified recombinant virus-like particles (VLPs) encompassing the 368–660 amino acids (aa) of the viral ORF2 protein. The viral capsid is formed by the ORF2 protein, which harbors three glycosylation sites. Baculo virus expression system has been employed to generate a glycosylated VLP, which encompasses 112–608aa of the ORF2 protein. Here, we sought to produce a recombinant VLP containing 112–608aa of the ORF2 protein in Pichia pastoris (P. pastoris) expression system. The cDNA sequence encoding 112–608aa of the ORF2 protein was fused with the α-mating factor secretion signal coding sequence (for release of the fusion protein to the culture medium) and cloned into the yeast vector pPICZα. Optimum expression of recombinant protein was obtained at 72 h induction in 1.5% methanol using inoculum density (A600) of 80 and at pH-3.0 of the culture medium. Identity of the purified protein was confirmed by mass spectrometry analysis. Further studies revealed the glycosylation pattern and VLP nature of the purified protein. Immunization of BALB/c mice with these VLPs induced potent immune response as evidenced by the high ORF2 specific IgG titer and augmented splenocyte proliferation in a dose dependent manner. 112–608aa ORF2 VLPs produced in P. pastoris appears to be a suitable candidate for development of diagnostic and prophylactic reagents against the hepatitis E. [ABSTRACT FROM AUTHOR]

Hepatitis E Virus (HEV) infection is a worldwide disease and the primary cause of acute viral hepatitis in the world with an estimated 20 million cases every year and 70 000 deaths. Hepatitis E is a waterborne infection in the developing countries. In these countries, HEV genotypes 1 and 2 cause large outbreaks and affect young subjects, resulting in significant mortality in pregnant women and patients with cirrhosis. In the developed countries, HEV genotypes 3 and 4 are responsible for autochthonous, sporadic hepatitis and transmission is zoonotic. Parenteral transmission by the transfusion of blood products has been identified as a potential new mode of transmission. The prevalence of positive HEV viraemia in blood donors in Europe ranges from 1/600 to 1/2500 in highly endemic European countries. HEV can cause neurological disorders and chronic infections in immunocompromised patients. The progression of acute hepatitis E is usually asymptomatic and resolves spontaneously. Diagnostic tools include anti‐HEV IgM antibodies in serum and/or viral RNA detection in the blood or the stools by PCR. Ribavirin is used to treat chronic infection. A vaccine has been developed in China. [ABSTRACT FROM AUTHOR]

Stigma against people with hepatitis B virus (HBV) is a barrier to prevention, diagnosis and treatment of HBV in China. Our study examined an innovative intervention to reduce HBV stigma among men who have sex with men (MSM) in China. We extracted data from a randomized controlled trial conducted in May 2018, where the intervention consisted of crowdsourced images and videos to promote viral hepatitis testing and reduce HBV stigma. HBV stigma was assessed using a 20‐item scale at baseline and four weeks post‐enrolment. Participants were divided into three groups based on their exposure to intervention: full exposure, partial exposure and no exposure. Linear regression was used to determine associations between baseline stigma and participant characteristics. Data from 470 MSM were analysed. Mean participant age was 25 years old and 56% had less education than a college bachelor's degree. Full exposure to intervention was associated with significant stigma reduction (adjusted beta = −3.49; 95% CI = −6.11 to −0.87; P =.01), while partial exposure led to stigma reduction that was not statistically significant. The mean stigma score was 50.6 (SD ± 14.7) at baseline, and stigma was most prominent regarding physical contact with HBV carriers. Greater HBV stigma was associated with not having a recent doctor's visit (adjusted beta = 4.35, 95% CI = 0.19 to 8.52; P =.04). In conclusion, crowdsourcing can decrease HBV stigma among MSM in China and may be useful in anti‐stigma campaigns for vulnerable populations in low‐ and middle‐income countries. [ABSTRACT FROM AUTHOR]

Duck hepatitis A virus (DHAV) is one of the pathogens that cause fatal duck viral hepatitis (DVH) in ducklings, which is an acute and contagious disease with a high mortality rate. Despite a continuing official duck vaccination program, DHAV infection remains a major threat to the duck industry. Considerable changes were observed in the epidemiology of DHAV-1/-3 in China over time. Therefore, comparing the pathogenicity of different DHAV serotypes can provide a theoretical basis for the diagnosis and prevention of DVH. In this study, we systematically investigated the effects of infection with DHAV-1/-3 field strains on clinical signs, gross lesions, histopathological changes, viral RNA detection, enzymatic systems, and metabolite concentrations. The results demonstrated that the major macroscopic and microscopic lesions in ducks infected with DHAV-1/-3 in the liver, brain, spleen, pancreas, and kidneys exhibited no significant differences. After 24 h of infection, DHAV quickly appeared in blood and major organs. Significant changes in clinical chemical markers together with histopathological lesions and viral RNA detection indicated that the liver is the major target organ for both viruses, resulting in impaired of liver integrity and function. In addition, we found that both viruses were able to invade both central and peripheral immune organs. Also lipase plasma activity was substantially affected by DHAV-1/-3, indicating that the integrity and function of the pancreas was compromised. However, there was no significant difference in pathogenicity between DHAV-1 and -3. The results of this study provide new insights into the pathogenesis of DHAV-1/3, two viruses that cause serious depression, metabolic disorders, and immunosuppression. [ABSTRACT FROM AUTHOR]

Both live attenuated (HA-L) and inactivated (HA-I) hepatitis A vaccine were licensed for routine use in China. Although phase 1, 2 and 3 clinical studies of both vaccines have been completed, further systematic evaluation of their immunogenicity and immunological persistence under phase 4 clinical studies in a wide range of conditions and involving large populations is necessary. A phase IV clinical trial (NCT02601040) was performed in 9000 participants over 18 months of age. Geometric mean concentrations (GMCs) and seroconversion rates (SRs) were compared at five time points during 3 years for 1800 individuals among them. The SRs of HA-L and HA-I were 98.08% (95% CI 95.59%–99.38%) and 99.64% (95% CI 98.93%–100.00%) respectively 28 days after administration of the first dose, and remained at 97.07% (95% CI 94.31%–98.73%) or above and 96.73% (95% CI 94.07%–98.42%) or above respectively during the following 3 years. The GMCs for both the HA-L and HA-I groups showed that both vaccines elicited high anti-HAV titres, considerably more than the threshold of protection needed against HAV infection in humans, and these titres were sustained. Hence, both HA-I and HA-L vaccines could provide an excellent long-term protective effect, and supported the routine use of both vaccines. [ABSTRACT FROM AUTHOR]