Estimating the key outcomes and hepatocellular carcinoma risk in patients in immune-tolerant phase of chronic hepatitis B virus infection: A systematic review and meta-analysis.

The question of whether patients in the immune-tolerant (IT) phase of chronic hepatitis B virus (HBV) infection should undergo antiviral therapy and determine the optimal regimen remains unclear. A comprehensive search of PubMed, Embase, MEDLINE, Cochrane Library, and Wanfang Data from inception to 5 December 2023, was conducted. Studies reporting on key outcomes such as HBV DNA undetectability, HBeAg loss or seroconversion, HBsAg loss or seroconversion, and hepatocellular carcinoma (HCC) incidence in patients in the IT phase of chronic HBV infection were included. In total, 23 studies were incorporated. Approximately 4% of patients in the IT phase achieved spontaneous HBeAg loss over 48 weeks of follow-up. Antiviral therapy demonstrated a favourable impact on HBV DNA negative conversion (Children: risk ratios [RR] = 6.83, 95% CI: 2.90-16.05; Adults: RR = 25.84, 95% CI: 6.47-103.31) and HBsAg loss rates (Children: RR = 9.49, 95% CI: 1.74-51.76; Adults: RR = 7.35, 95% CI: 1.41-38.27) for patients in the IT phase. Subgroup analysis revealed that in adult patients in the IT phase, interferon plus nucleos(t)ide analogues (NA)-treated patients exhibited a higher pooled rate of HBsAg loss or seroconversion than those treated with NA monotherapy (9% vs. 0%). Additionally, the pooled annual HCC incidence for patients in the IT phase was 3.03 cases per 1000 person-years (95% CI: 0.99-5.88). Adult patients in the IT phase had a significantly lower HCC incidence risk than HBeAg-positive indeterminate phase patients (RR = 0.46, 95% CI: 0.32-0.66), with no significant differences observed between IT and immune-active phases. Presently, there is insufficient evidence solely based on reducing the risk of HCC incidence, to recommend treating patients in the IT phase of chronic HBV infection. However, both adult and paediatric patients in the IT phase responded well to antiviral therapy, showing favourable rates of HBsAg loss or seroconversion.

Exploring the lack of continuity of care in older cancer patients under China's 'integrated health system' reform.

BACKGROUND: Continuity of care is essential to older patients' health outcomes, especially for those with complex needs. It is a key function of primary healthcare. Despite China's policy efforts to promote continuity of care and an integrated healthcare system, primary healthcare centres (PHCs) are generally very underused. OBJECTIVES: To explore the experience and perception of continuity of care in older cancer patients, and to examine how PHCs play a role in the continuity of care within the healthcare system in China. METHODS: A qualitative study using semi-structured interviews was conducted in two tertiary hospitals in Nantong city, Jiangsu province, China. A combination of deductive and inductive analysis was conducted thematically. RESULTS: Interviews with 29 patients highlighted three key themes: no guidance for patients in connecting with different levels of doctors, unmet patients' needs under specialist-led follow-up care, and poor coordination and communication across healthcare levels. This study clearly illustrated patients' lack of personal awareness and experience of care continuity, a key issue despite China's drive for an integrated healthcare system. CONCLUSION: The need for continuity of care at each stage of cancer care is largely unmeasured in the current healthcare system for older patients. PHCs offer benefits which include convenience, less burdened doctors with more time, and lower out-of-pocket payment compared to tertiary hospitals, especially for patients with long-term healthcare needs. However, addressing barriers such as the absence of integrated medical records and unclear roles of PHCs are needed to improve the crucial role of PHCs in continuity of care.

A Real-World Study on Safety and Efficacy of TAF Treatment in HBV Patients with High Risk of Osteoporosis or Osteopenia in China.

Objective: Long-term antiviral treatment is necessary for chronic hepatitis B (CHB) patients, and treatment safety is imperative for these patients. Previous studies showed tenofovir alafenamide (TAF) has shown efficacy non-inferior to that of tenofovir disoproxil fumarate (TDF) with improved renal and bone safety. However, there is still a lack of a rapid and convenient method to identify CHB patients at high risk of osteoporosis before initiating antiviral treatment. The International Osteoporosis Foundation (IOF) recommended a one-minute osteoporosis risk test to identify early high-risk patients. Our aim was to evaluate the feasibility of the one-minute osteoporosis risk test, along with evaluating the effectiveness and safety for virologically suppressed CHB patients switching to TAF. Methods: In this multicenter, prospective study, patients with chronic HBV infection who had been receiving TDF or Entecavir (ETV) for 48 weeks or more with HBV DNA less than 20 IU/mL for longer than 6 months were screened by one-minute osteoporosis risk test. Patients with a high risk of osteoporosis and then diagnosed with osteopenia or osteoporosis by dual-energy X-ray absorptiometry (DEXA) were enrolled. Safety in bone and bone turnover markers and antiviral efficacy of TAF were assessed respectively at 24 and 48 weeks. Results: 84.95% (175/206) CHB patients screened by one-minute osteoporosis risk test were at risk of osteoporosis.85.71% (150/175) were diagnosed with osteopenia by DEXA. The analysis included a total of 138 patients, of whom 92(62.3%) were male and 46 (37.7%) were female, with a mean age of 45 years old. HBV DNA was suppressed at 48 weeks at 88% (35/40) in the prior ETV group and 90% (88/98) at 48 weeks group in the prior TDF group. Bone mineral density (BMD) of the lumbar spine (L1-L4) from TDF switching to TAF was improved at 24 weeks (1.03±0.11 vs. 0.97±0.12, P = .001) than baseline. Propeptides of type I procollagen (PINP) and beta-C-terminal telopeptides of type 1 collagen (CTX) in serum at 24 weeks after switching from TDF to TAF declined compared with baseline (50.35±18.90 vs. 63.65±19.17, P = .016 and 0.21±0.13 vs. 0.32±0.10, P = .017). BMD, PINP, and CTX in ETV to TAF group remained stable during treatment. Conclusion: Attention should be paid to osteoporosis risk during lone-term nucleot(s)ide analogue treatment. One minute test of osteoporosis risk could rapidly identify most CHB patients at risk of osteoporosis. Given its convenience, we recommend using this test for early screening in CHB patients prior to initiating antiviral treatment. Our results further demonstrated that an improvement in bone safety after switching to TAF in virologically suppressed CHB patients with osteoporosis.

AhR may be involved in Th17 cell differentiation in chronic hepatitis B.

Th17 cells which are crucial for host immunity have been demonstrated to increase HBV infection. However, the mechanism of the Th17 cell increase is unknown. Hence, the mechanism of Th17 cell enhancement is important to provide a theoretical foundation for chronic hepatitis B immunotherapy. This study included 15 instances in the healthy control (HC) and 15 cohorts in the chronic hepatitis B (CHB). Their CD4+ T cells were isolated from their peripheral blood and then subjected to RNA transcriptome sequencing. Then, to identify target genes linked to Th17-cell differentiation, DEGs associated with CHB were convergent with the Th17-cell-associated genes from the KEGG database. Hub genes of DEG and target genes linked to Th17 cells were analysed for correlation. The AhR-related genes were located using the GeneMANIA database. To analyse the function of the genes, GO and KEGG pathways were employed. Protein-protein interaction network analysis employed the Metascape, STRING and Cytoscape databases. Finally, Western blotting and RT-qPCR were used to validate AhR. A total of 348 differential genes were identified in CHB patients. CytoHubba was used for screening five hub genes associated with CHB: CXCL10, RACGAP1, TPX2, FN1 and GZMA. This study aimed to determine the mechanism of elevated Th17 cells in CHB. As a result, further investigation using the convergence of DGEs and Th17 cell-related genes identified three target genes: AhR, HLA-DQA1 and HLA-DQB1, all of which were elevated in CHB. The three genes were primarily involved in immune response-related processes, according to the GO enrichment analysis. Correlation analysis of CXCL10, RACGAP1, TPX2, FN1 and GZMA genes with AhR, HLA-DQA1 and HLA-DQB1 revealed that AhR was positively associated with CXCL10 and GZMA genes, which best respond to the severity of CHB disease. Combined with the role of AhR in Th17 cell differentiation, the genes AhR was chosen for confirmation by RT-qPCR and WB in this study. The results showed that the CHB group had higher expression levels of AhR at both RT-qPCR and WB levels. Furthermore, this study's findings revealed that AhR may contribute to the development of CHB by affecting the differentiation of Th17 cells.

Correlation analysis of lung mucosa-colonizing bacteria with clinical features reveals metastasis-associated bacterial community structure in non-small cell lung cancer patients.

BACKGROUND: Microbes colonizing lower airways can regulate the host immune profile and consequently participate in lung disease. Increasing evidence indicate that individual microbes promote lung cancer progression and are involved in metastasis incidence. To date, however, no study has revealed the community structure of lung bacteria in metastatic non-small cell lung cancer (NSCLC) patients. METHODS: We prospectively enrolled 50 healthy subjects and 57 NSCLC patients. All healthy subjects and NSCLC patients underwent bronchoscope procedures for brush specimen collection. The 16 S ribosomal RNA gene was sequenced to characterize the community structure of lung mucosa-colonizing bacteria. The peripheral blood of NSCLC patients was also measured for leukocytes and cancer markers. RESULTS: The lung bacteria of healthy subjects and NSCLC patients were divided into four communities. All community 2 members showed increased abundance in NSCLC patients compared with healthy subjects, and most community 2 members showed increased abundance in the metastatic NSCLC patients compared with the non-metastatic group. These bacteria were significantly and positively correlated with eosinophils, neutrophils and monocytes in the metastatic NSCLC group. In addition, the correlation between lung bacteria and cancer markers differed between the metastatic and non-metastatic NSCLC patients. Furthermore, bronchoalveolar lavage fluid from lung adenocarcinoma patients directly promoted NSCLC cell migration. CONCLUSIONS: The community structure of lung mucosa-colonizing bacteria was relatively stable, but changed from the healthy population to NSCLC patients, especially the metastatic group. This distinct community structure and specific correlation with immune cells and cancer markers could help to distinguish NSCLC patients with or without metastasis.

Effectiveness of integrating primary healthcare in aftercare for older patients after discharge from tertiary hospitals-a systematic review and meta-analysis.

BACKGROUND: Quality of aftercare can crucially impact health status of older patients and reduce the extra burden of unplanned healthcare resource utilisation. However, evidence of effectiveness of primary healthcare in supporting aftercare, especially for older patients after discharge are limited. METHODS: We searched for English articles of randomised controlled trials published between January 2000 and March 2022. All-cause hospital readmission rate and length of hospital stay were pooled using a random-effects model. Subgroup analyses were conducted to identify the relationship between intervention characteristics and the effectiveness on all-cause hospital readmission rate. RESULTS: A total of 30 studies with 11,693 older patients were included in the review. Compared with patients in the control group, patients in the intervention group had 32% less risk of hospital readmission within 30 days (RR = 0.68, P < 0.001, 95%CI: 0.56-0.84), and 17% within 6 months (RR = 0.83, P < 0.001, 95%CI: 0.75-0.92). According to the subgroup analysis, continuity of involvement of primary healthcare in aftercare had significant effect with hospital readmission rates (P < 0.001). Economic evaluations from included studies suggested that aftercare intervention was cost-effective due to the reduction in hospital readmission rate and risk of further complications. CONCLUSION: Integrating primary healthcare into aftercare was designed not only to improve the immediate transition that older patients faced but also to provide them with knowledge and skills to manage future health problems. There is a pressing need to introduce interventions at the primary healthcare level to support long-term care.

Effectiveness of Computerized Cognitive Training in Delaying Cognitive Function Decline in People With Mild Cognitive Impairment: Systematic Review and Meta-analysis.

BACKGROUND: With no current cure for mild cognitive impairment (MCI), delaying its progression could significantly reduce the disease burden and improve the quality of life for patients with MCI. Computerized cognitive training (CCT) has recently become a potential instrument for improvement of cognition. However, the evidence for its effectiveness remains limited. OBJECTIVE: This systematic review aims to (1) analyze the efficacy of CCT on cognitive impairment or cognitive decline in patients with MCI and (2) analyze the relationship between the characteristics of CCT interventions and cognition-related health outcomes. METHODS: A systematic search was performed using MEDLINE, Cochrane, Embase, Web of Science, and Google Scholar. Full texts of randomized controlled trials of CCT interventions in adults with MCI and published in English language journals between 2010 and 2021 were included. Overall global cognitive function and domain-specific cognition were pooled using a random-effects model. Sensitivity analyses were performed to determine the reasons for heterogeneity and to test the robustness of the results. Subgroup analyses were performed to identify the relationship between the characteristics of CCT interventions and cognition-related effectiveness. RESULTS: A total of 18 studies with 1059 participants were included in this review. According to the meta-analysis, CCT intervention provided a significant but small increase in global cognitive function compared to that in the global cognitive function of the control groups (standardized mean difference=0.54, 95% CI 0.35-0.73; I2=38%). CCT intervention also resulted in a marginal improvement in domain-specific cognition compared to that in the control groups, with moderate heterogeneity. Subgroup analyses showed consistent improvement in global cognitive behavior in the CCT intervention groups. CONCLUSIONS: This systematic review suggests that CCT interventions could improve global cognitive function in patients with MCI. Considering the relatively small sample size and the short treatment duration in all the included studies, more comprehensive trials are needed to quantify both the impact of CCT on cognitive decline, especially in the longer term, and to establish whether CCT should be recommended for use in clinical practice. TRIAL REGISTRATION: PROSPERO International Prospective Register of Systematic Reviews CRD42021278884; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=278884.

The global burden of hepatitis E outbreaks: a systematic review.

Hepatitis E virus (HEV) is responsible for repeated water-borne outbreaks since the past century, representing an emerging issue in public health. However, the global burden of HEV outbreak has not been comprehensively described. We performed a systematic review of confirmed HEV outbreaks based on published literatures. HEV outbreaks have mainly been reported from Asian and African countries, and only a few from European and American countries. India represents a country with the highest number of reported HEV outbreaks. HEV genotypes 1 and 2 were responsible for most of the large outbreaks in developing countries. During the outbreaks in developing countries, a significantly higher case fatality rate was observed in pregnant women. In fact, outbreaks have occurred both in open and closed populations. The control measures mainly depend upon improvement of sanitation and hygiene. This study highlights that HEV outbreak is not new, yet it is a continuous global health problem.

[Gut flora and gut-derived endotoxin in minimal hepatic encephalopathy].

OBJECTIVE: To investigate the relationship of gut flora and gut-derived endotoxin with minimal hepatic encephalopathy (MHE). METHODS: Patients with hepatitis B virus-related liver cirrhosis (HBV-LC) were screened for MHE using the number connect test-A (NCT-A) and digital symbol test (DST) and divided into the following groups: HBV-LC with (+) MHE (n = 26) and HBV-liver cirrhosis without (-) MHE (n = 25); in addition, one healthy immediate family member of each patient in the HBV-LC + MHE group was enrolled as a control. Each participant provided fecal and blood samples. PCR amplification and 454 pyrosequencing were used to detect bacterial 16S rRNA in feces. Turbidimetric Limulus amebocyte lysate assay was used to detect level of endotoxin in serum. The significance of inter-group differences was assessed by one-way ANOVA or Student's t-test. RESULTS: The three groups showed different distributions of gut flora. The differences in the microbial communities' members and distributions were related to disease or health status, but not to the patient's genetic makeup or diet. In particular, the HBV-LC + MHE patients showed significantly lower amounts of different bacterial species and abundance of these species than the other two (non-MHE) groups (P less than 0.05). The healthy control family members had a richer diversity of gut flora than their counterparts with HBV-LC + MHE (P less than 0.05). The HBV-LV + MHE patients also had higher serum levels of endotoxin. CONCLUSION: Development of minimal hepatic encephalopathy in patients with HBV-LC may be related to a gut flora disorder or higher levels of endotoxin in serum.

Microbial genotoxin-elicited host DNA mutations related to mitochondrial dysfunction, a momentous contributor for colorectal carcinogenesis.

Gut microbe dysbiosis increases repetitive inflammatory responses, leading to an increase in the incidence of colorectal cancer. Recent studies have revealed that specific microbial species directly instigate mutations in the host nucleus DNA, thereby accelerating the progression of colorectal cancer. Given the well-established role of mitochondrial dysfunction in promoting colorectal cancer, it is reasonable to postulate that gut microbes may induce mitochondrial gene mutations, thereby inducing mitochondrial dysfunction. In this review, we focus on gut microbial genotoxins and their known and potential targets in mitochondrial genes. Consequently, we propose that targeted disruption of genotoxin transport pathways may effectively reduce the rate of mitochondrial gene mutations and yield substantial benefits for the prevention of colorectal carcinogenesis.

Optical Coherence Tomography Angiography in Vogt-Koyanagi-Harada Patients: A Systematic Review and Meta-Analysis.

PURPOSE: To describe the choroidal retinal microvascular system in Vogt-Koyanagi-Harada (VKH) subjects and furnish additional proof for the early authentication and treatment of VKH suffers. METHODS: From the beginning to July 2023, a comprehensive search for issued articles on optical coherence tomography angiography (OCTA) among VKH sufferers was implemented in Embase, PubMed, and Web of Science databases. This meta-analysis included 9 eligible studies. Primary endpoints included four kinds of vascular densities, such as superficial capillaris plexus (SCP), deep capillaris plexus (DCP), and choriocapillary (CC). In addition to these, there were foveal avascular zone (FAZ), central retinal thickness (CT), best-corrected distance visual acuity (BCVA log MAR), and subfoveal choroidal thickness (SFCT). RESULTS: SCP and DCP vessel densities in maculas were both smaller in VKH sufferers in the active stage than those normal and remission examinees (SCP vessel density, p < 0.00001, DCP vessel density, p < 0.00001). Compared to remission, CC vascular density was lower during the active phase. (p < 0.00001). SFCT and CT in the active phase exceeded those in normal and remission examinees (all of them p < 0.00001). In terms of the patients with remission, their FAZ was bigger than that in normal subjects. (MD =0.04, p < 0.0001). CONCLUSIONS: Retinal and choroidal microvasculatures are characteristically changed in active VKH patients, which suggests that OCTA can be used as a tool for VKH follow-up.

Eliciting Older Cancer Patients' Preferences for Follow-Up Care to Inform a Primary Healthcare Follow-Up Model in China: A Discrete Choice Experiment.

BACKGROUND AND OBJECTIVES: Increasing longevity and advances in treatment have increased the cancer burden in the elderly, resulting in complex follow-up care needs; however, in China, little is known about the follow-up care preferences of these patients. This study quantified older cancer patients' preferences for follow-up care and examined the trade-offs they are willing to make to accept an alternative follow-up model. METHODS: A discrete choice experiment was conducted among inpatients aged over 60 years with breast, prostate, or colorectal cancer, at two large tertiary hospitals in Nantong, China. Preference weights for follow-up care were estimated using mixed logit analysis. Subgroup analysis and latent class analysis were used to explore preference heterogeneity. RESULTS: Complete results were obtained from 422 patients (144 with breast cancer, 133 with prostate cancer, 145 with colorectal cancer), with a mean age of 70.81 years. Older cancer patients stated a preference for follow-up by specialists over primary healthcare (PHC) providers ( ß = -1.18, 95% confidence interval -1.40 to -0.97). The provider of follow-up care services was the most valued attribute among patients with breast cancer (relative importance [RI] 37.17%), while remote contact services were prioritized by patients with prostate (RI 43.50%) and colorectal cancer (RI 33.01%). The uptake rate of an alternative care model integrating PHC increased compared with the baseline setting when patients were provided with preferred services (continuity of care, individualized care plans, and remote contact services). CONCLUSION: To encourage older cancer patients to use PHC-integrated follow-up care, alternative follow-up care models need to be based on patients' preferences before introducing them as a routine option.

Adherence to the Mediterranean diet is associated with reduced chronic pancreatitis risk: a longitudinal cohort study.

Background: The role of diet on the risk of chronic pancreatitis (CP) is understudied. The health benefits of the Mediterranean diet (MedDiet) pattern have long been recognized, but its association with CP risk is unclear. We aimed to investigate the association between adherence to MedDiet and the incidence of CP in a large-scale cohort. Methods: 190 790 participants from the UK Biobank were involved, all free of CP and with typical diet recall data at recruitment. The diagnosis of CP was ascertained by the combination of hospital inpatient data, primary care data, and death registry data. Multivariable Cox regression models were used to evaluate the associations between MedDiet adherence, measured by the Mediterranean Diet Adherence Screener (MEDAS) continuous score, and the incidence of CP. The mediating role of inflammation (assessed by C-reactive protein) and metabolic status between MedDiet adherence and CP risk was also investigated. Results: During a mean of 10.8 years of follow-up, 214 participants developed CP. Individuals with the highest adherence to MedDiet, defined by continuous MEDAS scores, exhibited significantly lower risk of developing CP (hazard ratio [HR] = 0.57, 95% confidence interval [CI]: 0.40-0.82; p = 0.002) compared to those in the lowest tertiles. Metabolic status mediated 4.74% of the association between MedDiet adherence and CP risk, while the mediating role of C-reactive protein was not significant. Conclusion: Greater Mediterranean diet adherence is associated with reduced chronic pancreatitis risk.

Global, regional, and national burden and quality of care of multiple myeloma, 1990-2019.

Background: Multiple myeloma (MM) is the second most common haematologic malignancy, presenting a great disease burden on the general population; however, the quality of care of MM is overlooked. We therefore assessed gains and disparity in quality of care worldwide from 1990 to 2019 based on a novel summary indicator - the quality of care index (QCI) - and examined its potential for improvement. Methods: Using the Global Burden of Disease 2019 data set, we calculated the QCI of MM for 195 countries and territories. We used the principal component analysis to extract the first principal component of ratios with the combinations of mortality to incidence, prevalence to incidence, disability-adjusted life years to prevalence, and years of life lost to years lived with disability as QCI. We also conducted a series of descriptive and comparative analyses of QCI disparities with age, gender, period, geographies, and sociodemographic development, and compared the QCI among countries with similar socio-demographic index (SDI) through frontier analysis. Results: The age-standardised rates of MM were 1.92 (95% uncertainty interval (UI) = 1.68, 2.12) in incidence and 1.42 (95% UI = 1.24, 1.52) in deaths per 100 000 population in 2019, and were predicted to increase in the future. The global age-standardised QCI increased from 51.31 in 1990 to 64.28 in 2019. In 2019, New Zealand had the highest QCI at 99.29 and the Central African Republic had the lowest QCI at 10.74. The gender disparity of QCI was reduced over the years, with the largest being observed in the sub-Saharan region. Regarding age, QCI maintained a decreasing trend in patients aged >60 in SDI quintiles. Generally, QCI improved with the SDI increase. Results of frontier analysis suggested that there is a potential to improve the quality of care across all levels of development spectrum. Conclusions: Quality of care of MM improved during the past three decades, yet disparities in MM care remain across different countries, age groups, and genders. It is crucial to establish local objectives aimed at enhancing MM care and closing the gap in health care inequality.

Alterations of pathogen transmission patterns and attenuated immune stimulation might be the cause of increased adult respiratory infections cases in 2023, results from a multi-center study in mainland China.

Background: Several respiratory infections outbreaks have been observed in mainland China after reduction of non-pharmaceutical interventions. Other countries have seen increases in respiratory infections outside typical seasons post-COVID-19, warranting investigation into underlying causes. Methods: We established monitoring networks for suspected respiratory infection in 14 tertiary hospitals nationwide. PCR for SARS-CoV-2, influenza A and B were performed on 3708 respiratory specimens and deep sequencing were conducted to identify co-infections or newly emerging microbes in 2023. Viral evolutionary analysis was completed. We retrospectively detected serum antibody level for various respiratory pathogens from 4324 adults without respiratory infections over 7 years to observe its dynamic curves. Findings: SARS-CoV-2 and influenza A were the main pathogens during outbreaks in 2023, bacterial-virus and bacterial-bacterial co-infections were most detected, but community co-infections didn't significantly increase pneumonia incidence. Different SARS-CoV-2 and influenza variants were present in different outbreaks, and no novel pathogens were found. The epidemiological patterns of influenza A, COVID-19 and etc. were altered, exhibiting characteristics of being "staggered" compared to most global regions, and potentially led to "overlapping prevalence". Binding antibody testing showed regular fluctuation, without significant decrease against common respiratory pathogens in adults. Influenza A antibody stimulation was attenuated during the 2023 outbreak. Conclusions: "Misaligned" alteration in seasonal respiratory disease patterns possibly caused combined epidemics, leading to cases spike in China, 2023. In adults, antibody levels didn't show significant decline, but reduced immune response to influenza during 2020-2023 emphasizes the need for consistent vaccination during pandemics.

Large-scale survey of gut microbiota associated with MHE Via 16S rRNA-based pyrosequencing.

OBJECTIVES: Elucidating the minimal hepatic encephalopathy (MHE)-associated gut microbiome may help in predicting and lowering the high risk for MHE in patients with cirrhosis. METHODS: Twenty-six MHE patients were recruited and screened from among those with liver cirrhosis without overt hepatic encephalopathy as defined by abnormality seen on two test modalities: number connection test part A and the digit symbol test. Using 26 MHE-matched normal relatives and 25 cirrhotic patients without MHE as controls, by means of 16S ribosomal RNA (rRNA)-based pyrosequencing, we examined and analyzed 241,622 bacterial 16S rDNA gene sequences from feces of 77 subjects. RESULTS: Using multiple comparative analyses, our results found the continuous overrepresentation of two bacterial families, Streptococcaceae and Veillonellaceae, in cirrhotic patients with and without MHE, compared with normal individuals. In addition, we also discovered an MHE-unique interplay pattern of gut microbiota largely influenced by the members of those two families. Following these findings, we further revealed that gut urease-containing bacteria Streptococcus salivarius was absent in the normal group but was present in cirrhotic patients with and without MHE. The abundance of S. salivarius was significantly higher in cirrhotic patients with MHE than in those without (P=0.030), and the change in the amount of this bacteria was positively correlated with ammonia accumulation (R=0.58, P=0.003) in cirrhotic patients with MHE but not in those without. CONCLUSIONS: Gut microbiota dysbiosis may be associated with the presence of MHE in cirrhotic patients, in particular with ammonia-increasing phenotype in MHE. Gut ammonia-increasing bacteria S. salivarius might be expected to be a potential biomarker of ammonia-lowering therapies in cirrhotic patients with MHE.

The incidence of hepatocellular carcinoma and clearance of hepatitis B surface for CHB patients in the indeterminate phase: a systematic review and meta-analysis.

Background: Nearly 30%-40% of patients with chronic hepatitis B do not fall into any of the traditional natural history classification and thus are classified as indeterminate. However, it is unclear whether patients in the indeterminate phase (IP) are at a higher risk for hepatocellular carcinoma (HCC) than those in the defined phases (DP) and would benefit from antiviral therapy. We performed a systematic review and meta-analysis of HCC incidence and HBsAg clearance among patients in the IP versus DP. Methods: We defined the clinical phases as per the AASLD 2018 hepatitis B guidance. We searched PubMed, Embase, Medline, and Web of Science for relevant studies that reported HCC incidence or HBsAg clearance in IP versus DP patients published between January 2007 and March 2023. Annual HCC incidence and HBsAg clearance rates were pooled using a random/common-effects model. Results: We analyzed data from 14 studies, comprising 7798 IP patients (222 patients developed HCC and 239 achieved HBsAg clearance) and 10,725 DP patients. The pooled annual HCC incidence was 2.54 cases per 1,000 person-years (95% CI, 1.14-4.39) and HBsAg clearance rate was 12.36 cases per 1,000 person-years (95% CI, 10.70-14.13) for the IP patients. IP patients were associated with significantly higher HCC incidence risk (RR = 1.64, 95% CI, 1.34-2.00) and slightly lower annual HBsAg clearance rate (RR = 0.83, 95% CI, 0.70-0.99) than the DP patients. In addition, HBeAg-negative IP patients (2.31%; 95% CI, 0.87-4.45) showed a significantly higher HCC incidence than those who were HBeAg positive (0.00%; 95% CI, 0.00-0.99) (p< 0.001). The Asia-Pacific region IP patients (4.30%; 95% CI, 2.07-7.27) were also associated with a higher HCC incidence versus Europe (0.05%; 95% CI, 0.00-1.39) (p< 0.001). However, there were no significant differences between different strategies (treated vs. untreated: 2.56%; 95% CI, 1.01-4.63 vs. 1.61%; 95% CI, 0.00-5.81, p = 0.09), and heterogeneity was substantial across the studies (I2 = 89%). Conclusion: The systematic review and meta-analysis showed a high HCC incidence and low HBsAg clearance among patients in the IP, especially for HBeAg-negative patients and the Asian population. We emphasize that future multicenter prospective cohort studies or randomized trials are needed to verify if expanding antiviral therapy for patients in the IP is associated with reduced HCC risk or good treatment outcomes.

[A case of liver failure caused by fatal amanita poisoning was successfully treated by open cholecystostomy drainage].

The fatality rate of liver failure caused by fatal amanita poisoning is high, and there are no effective antidote drugs in China. On July 30, 2020, the department of infectious diseases and liver diseases of the First People's Hospital of Yunnan Province admitted a 67-year-old female patient with liver failure caused by fatal amanita poisoning. The patient went to the emergency department for treatment due to abdominal pain, vomiting and diarrhea after eating 350-400 g of amanita mushroom for 2 days, accompanied by fatigue for 1 day. There was no abnormality in physical examination. Laboratory indexes: alanine aminotransferase (ALT) 4 798 U/L, aspartate aminotransferase (AST) 10 030 U/L, activated partial thromboplastin time (APTT) 57.5 s, prothrombin time (PT) 72.1 s, international normalized ratio (INR) 8.66, prothrombinactivity (PA) 10%. Based on the patient's medical history, clinical manifestations and laboratory data, the diagnosis was amanita peptide mushroom poisoning and acute liver failure. According to the mechanism of amanita toxin poisoning as enterohepatic circulation, endoscopic retrograde cholangiopancreatography and ultrasound-guided gallbladder puncture and drainage for drainage of bile to discharge toxins were performed to interrupt the enterohepatic circulation of toxins. However, both methods failed, so open cholecystostomy was performed. Because the patient's coagulation function was very poor, artificial hepatic plasma exchange was given to improve coagulation function before open cholecystostomy, and eventually bile was drained successfully. After a total of 19 days of comprehensive medical treatment, the patient was cured and discharged from the hospital, and no sequelae was found after 1 year of follow-up. For such patients, early identification of the disease is required, and blocking the enterohepatic circulation of toxins as soon as possible according to the characteristics and toxicological mechanism of toxins may be the key treatment for rescuing patients with liver failure poisoned by amanita toxin, and it is necessary to combine comprehensive treatments such as active fluid replacement and blood purification to further improve the survival rate.

Gut microbe and hepatic macrophage polarization in non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is a common chronic hepatic disorder with the potential to progress to hepatic fibrosis, hepatic cirrhosis, and even hepatocellular carcinoma. Activation of hepatic macrophages, important innate immune cells predominantly composed of Kupffer cells, plays a pivotal role in NAFLD initiation and progression. Recent findings have underscored the regulatory role of microbes in both local and distal immune responses, including in the liver, emphasizing their contribution to NAFLD initiation and progression. Key studies have further revealed that gut microbes can penetrate the intestinal mucosa and translocate to the liver, thereby directly influencing hepatic macrophage polarization and NAFLD progression. In this review, we discuss recent evidence regarding the translocation of intestinal microbes into the liver, as well as their impact on hepatic macrophage polarization and associated cellular and molecular signaling pathways. Additionally, we summarize the potential mechanisms by which translocated microbes may activate hepatic macrophages and accelerate NAFLD progression.

Gut microbes in central nervous system development and related disorders.

The association between gut microbiota and central nervous system (CNS) development has garnered significant research attention in recent years. Evidence suggests bidirectional communication between the CNS and gut microbiota through the brain-gut axis. As a long and complex process, CNS development is highly susceptible to both endogenous and exogenous factors. The gut microbiota impacts the CNS by regulating neurogenesis, myelination, glial cell function, synaptic pruning, and blood-brain barrier permeability, with implication in various CNS disorders. This review outlines the relationship between gut microbiota and stages of CNS development (prenatal and postnatal), emphasizing the integral role of gut microbes. Furthermore, the review explores the implications of gut microbiota in neurodevelopmental disorders, such as autism spectrum disorder, Rett syndrome, and Angelman syndrome, offering insights into early detection, prompt intervention, and innovative treatments.