Role of Early On-Treatment Serum HBV RNA Declines in Predicting Hepatocellular Carcinoma Risk in Patients With Chronic Hepatitis B.

BACKGROUND AND AIMS: Hepatocellular carcinoma (HCC) risk prediction models established in patients with chronic hepatitis B receiving a nucleos(t)ide analogue (NA) rarely include viral factors because of mediocre predictability of traditional viral markers. Here, we investigate the role of serum hepatitis B virus (HBV) RNA, a novel biomarker, in predicting HCC risk in NA-treated patients. METHODS: A total of 1374 NA-treated patients were enrolled from 2 prospective chronic hepatitis B cohorts. Serum HBV RNA was detected at baseline, year 1, 2 and 3 of treatment. Cox proportional-hazard model was used to investigate the association of HBV RNA kinetics with HCC risk. RESULTS: After a median follow-up of 5.4 years, 76 patients developed HCC. HBV RNA declines at year 1 (adjusted hazard ratio, 0.70, P = .009) and 2 (adjusted hazard ratio, 0.71; P = .016) were independently associated with HCC risk. Patients with less HBV RNA decline at year 1 (≤0.4 log10 copies/mL) or 2 (≤0.6 log10 copies/mL) had 2.22- and 2.09-folds higher HCC risk, respectively, than those with more declines. When incorporating these early on-treatment HBV RNA declines into existing HCC risk scores, including PAGE-B (age, sex, and platelets), modified PAGE-B (mPAGE-B) (age, sex, platelets, and albumin), and aMAP (age, sex, platelets, and albumin-bilirubin score) score, they could enhance their predictive performance (ie, C-index 0.814 vs 0.78 [model (PAGE-B + year-1 HBV RNA decline) vs PAGE-B score based on baseline parameters]). CONCLUSIONS: Serum HBV RNA declines at year 1 and 2 were significantly associated with on-treatment HCC risk. Incorporating early on-treatment HBV RNA declines into HCC risk prediction models can be useful tools to guide appropriate surveillance strategies in NA-treated patients.

acFibroMASH Index for the Diagnosis of Fibrotic MASH and Prediction of Liver-related Events: An International Multicenter Study.

BACKGROUND & AIMS: Metabolic dysfunction-associated steatohepatitis (MASH) and fibrotic MASH are significant health challenges. This multi-national study aimed to validate the acMASH index (including serum creatinine and aspartate aminotransferase concentrations) for MASH diagnosis and develop a new index (acFibroMASH) for non-invasively identifying fibrotic MASH and exploring its predictive value for liver-related events (LREs). METHODS: We analyzed data from 3004 individuals with biopsy-proven metabolic dysfunction-associated fatty liver disease (MAFLD) across 29 Chinese and 9 international cohorts to validate the acMASH index and develop the acFibroMASH index. Additionally, we utilized the independent external data from a multi-national cohort of 9034 patients with MAFLD to examine associations between the acFibroMASH index and the risk of LREs. RESULTS: In the pooled global cohort, the acMASH index identified MASH with an area under the receiver operating characteristic curve (AUROC) of 0.802 (95% confidence interval [CI], 0.786-0.818). The acFibroMASH index (including the acMASH index plus liver stiffness measurement) accurately identified fibrotic MASH with an AUROC of 0.808 in the derivation cohort and 0.800 in the validation cohort. Notably, the AUROC for the acFibroMASH index was 0.835 (95% CI, 0.786-0.882), superior to that of the FAST score at 0.750 (95% CI, 0.693-0.800; P < .01) in predicting the 5-year risk of LREs. Patients with acFibroMASH >0.39 had a higher risk of LREs than those with acFibroMASH <0.15 (adjusted hazard ratio, 11.23; 95% CI, 3.98-31.66). CONCLUSIONS: This multi-ethnic study validates the acMASH index as a reliable, noninvasive test for identifying MASH. The newly proposed acFibroMASH index is a reliable test for identifying fibrotic MASH and predicting the risk of LREs.

Machine-learning model comprising five clinical indices and liver stiffness measurement can accurately identify MASLD-related liver fibrosis.

BACKGROUND & AIMS: aMAP score, as a hepatocellular carcinoma risk score, is proven to be associated with the degree of chronic hepatitis B-related liver fibrosis. We aimed to evaluate the ability of aMAP score for metabolic dysfunction-associated steatotic liver disease (MASLD; formerly NAFLD)-related fibrosis diagnosis and establish a machine-learning (ML) model to improve the diagnostic performance. METHODS: A total of 946 biopsy-proved MASLD patients from China and the United States were included in the analysis. The aMAP score, demographic/clinical indices and liver stiffness measurement (LSM) were included in seven ML algorithms to build fibrosis diagnostic models in the training set (N = 703). The performance of ML models was evaluated in the external validation set (N = 125). RESULTS: The AUROCs of aMAP versus fibrosis-4 index (FIB-4) and aspartate aminotransferase-platelet ratio (APRI) in cirrhosis and advanced fibrosis were (0.850 vs. 0.857 [P = 0.734], 0.735 [P = 0.001]) and (0.759 vs. 0.795 [P = 0.027], 0.709 [P = 0.049]). When using dual cut-off values, aMAP had a smaller uncertainty area and higher accuracy (26.9%, 86.6%) than FIB-4 (37.3%, 85.0%) and APRI (59.0%, 77.3%) in cirrhosis diagnosis. The seven ML models performed satisfactorily in most cases. In the validation set, the ML model comprising LSM and 5 indices (including age, sex, platelets, albumin and total bilirubin used in aMAP calculator), built by logistic regression algorithm (called LSM-plus model), exhibited excellent performance. In cirrhosis and advanced fibrosis detection, the LSM-plus model had higher accuracy (96.8%, 91.2%) than LSM alone (86.4%, 67.2%) and Agile score (76.0%, 83.2%), respectively. Additionally, the LSM-plus model also displayed high specificity (cirrhosis: 98.3%; advanced fibrosis: 92.6%) with satisfactory AUROC (0.932, 0.875, respectively) and sensitivity (88.9%, 82.4%, respectively). CONCLUSIONS: The aMAP score is capable of diagnosing MASLD-related fibrosis. The LSM-plus model could accurately identify MASLD-related cirrhosis and advanced fibrosis.

Developmental toxicity and mechanism of polychlorinated biphenyls 126 and nano-polystyrene combined exposure to zebrafish larvae.

3,3',4,4',5-Pentachlorobiphenyl (PCB126) is the most toxic congener of dioxin-like polychlorinated biphenyls (DL PCBs), while nanoplastics (NPs) have recently emerged as significant marine pollutants, both posing threats to aquatic organisms and human health. They coexist in the environment, but their comprehensive toxicological effects remain unclear. In this study, zebrafish embryos were simultaneously exposed to PCB126 and 80-nanometer nanoplastyrene (NPS). Researchers utilized fluorescence microscopy, qPCR, histopathological examination, and transcriptomic sequencing to investigate the developmental toxicity of different concentrations of PCB126 and NPS individually or in combination on zebrafish embryos and larvae. Results indicate that the chorion significantly impedes the accumulation of NPS (p < 0.05). It is noteworthy that this barrier effect diminishes upon simultaneous exposure to PCB126. In this experiment, the semi-lethal concentration of PCB126 for larvae was determined to be 6.33 µg/L. Exposure to PCB126 induces various deformities, primarily mediated through the aryl hydrocarbon receptor (AHR). Similarly, exposure to NPS also activates AHR, leading to developmental impairments. Furthermore, transcriptomic sequencing revealed similar effects of PCB126 and NPS on the gene expression trends in zebrafish larvae, but combined exposure to both exacerbates the risk of cancer and induces more severe cardiac toxicity. At this level, co-exposure to PCB126 and NPS adversely affects the development of zebrafish larvae. This study contributes to a deeper understanding of the in vivo accumulation of DL polychlorinated biphenyls and microplastics in actual aquatic environments and their impact on fish development.

Prognostic and therapeutic significance of microbial cell-free DNA in plasma of people with acute decompensation of cirrhosis.

BACKGROUND & AIMS: Although the effect of bacterial infection on cirrhosis has been well-described, the effect of non-hepatotropic virus (NHV) infection is unknown. This study evaluated the genome fragments of circulating microorganisms using metagenomic next-generation sequencing (mNGS) in individuals with acute decompensation (AD) of cirrhosis, focusing on NHVs, and related the findings to clinical outcomes. METHODS: Plasma mNGS was performed in 129 individuals with AD of cirrhosis in the study cohort. Ten healthy volunteers and 20, 39, and 81 individuals with stable cirrhosis, severe sepsis and hematological malignancies, respectively, were enrolled as controls. Validation assays for human cytomegalovirus (CMV) reactivation were performed in a validation cohort (n = 58) and exploratory treatment was instituted. RESULTS: In the study cohort, 188 microorganisms were detected in 74.4% (96/129) of patients, including viruses (58.0%), bacteria (34.1%), fungi (7.4%) and chlamydia (0.5%). A NHV signature was identified in individuals with AD, and CMV was the most frequent NHV, which correlated with the clinical effect of empirical antibiotic treatment, progression to acute-on-chronic liver failure, and 90-day mortality. The NHV signature in individuals with acute-on-chronic liver failure was similar to that in those with sepsis and hematological malignancies. CMV was detected in 24.1% (14/58) of patients in the validation cohort. Of the 14 cases with detectable CMV by mNGS, nine were further validated by real-time PCR or pp65 antigenemia testing. Three patients with CMV reactivation received ganciclovir therapy in an exploratory manner and experienced clinical resolutions. CONCLUSIONS: The results of this study suggest that NHVs may play a pathogenic role in complicating the course of AD. Further validation is needed to define whether this should be incorporated into the routine management of individuals with AD of cirrhosis. IMPACT AND IMPLICATIONS: A non-hepatotropic virus (NHV) signature, which was similar to that in individuals with sepsis and hematological malignancies, was identified in individuals with acute decompensation of cirrhosis. The detected viral signature had clinical correlates, including clinical efficacy of empirical antibiotic treatment, progression to acute-on-chronic liver failure and short-term mortality. Cytomegalovirus reactivation, which is treatable, may adversely affect clinical outcomes in some individuals with decompensated cirrhosis. Routine screening for NHVs, especially cytomegalovirus, may be useful for the management of individuals with acute decompensation of cirrhosis.

Baveno VII algorithm outperformed other models in ruling out high-risk varices in individuals with HBV-related cirrhosis.

BACKGROUND & AIMS: The Baveno VII consensus recommends that spleen stiffness measurement (SSM) ≤40 kPa is safe for ruling out high-risk varices (HRVs) and avoiding endoscopic screening in patients who do not meet the Baveno VI criteria. This study aimed to validate the performance of the Baveno VII algorithm in individuals with HBV-related cirrhosis. METHODS: Consecutive individuals with HBV-related cirrhosis who underwent liver stiffness measurement (LSM) and SSM - using a 50 Hz shear wave frequency, spleen diameter measurement, and esophagogastroduodenoscopy (EGD) were prospectively enrolled from June 2020. A 100 Hz probe has been adopted for additional SSM assessment since July 2021. RESULTS: From June 2020 to January 2022, 996 patients were screened and 504 were enrolled for analysis. Among the 504 patients in whom SSM was assessed using a 50 Hz probe, the Baveno VII algorithm avoided more EGDs (56.7% vs. 39.1%, p <0.001) than Baveno VI criteria, with a comparable missed HRV rate (3.8% vs. 2.5%). Missed HRV rates were >5% for all other measures: 11.3% for LSM-longitudinal spleen diameter to platelet ratio score, 20.0% for platelet count/longitudinal spleen diameter ratio, and 8.8% for Rete Sicilia Selezione Terapia-hepatitis. SSM@100 Hz was assessed in 232 patients, and the Baveno VII algorithm with SSM@100 Hz spared more EGDs (75.4% vs. 59.5%, p <0.001) than that with SSM@50 Hz, both with a missed HRV rate of 3.0% (1/33). CONCLUSIONS: We validated the Baveno VII algorithm, demonstrating the excellent performance of SSM@50 Hz and SSM@100 Hz in ruling out HRV in individuals with HBV-related cirrhosis. Furthermore, the Baveno VII algorithm with SSM@100 Hz could safely rule out more EGDs than that with SSM@50 Hz. CLINICAL TRIAL NUMBER: NCT04890730. IMPACT AND IMPLICATIONS: The Baveno VII guideline proposed that for patients who do not meet the Baveno VI criteria, SSM ≤40 kPa could avoid further unnecessary endoscopic screening. The current study validated the Baveno VII algorithm using 50 Hz and 100 Hz probes, which both exhibited excellent performance in ruling out HRVs in individuals with HBV-related cirrhosis. Compared with the Baveno VII algorithm with SSM@50 Hz, SSM@100 Hz had a better capability to safely rule out unnecessary EGDs. Baveno VII algorithm will be a practical tool to triage individuals with cirrhosis in future clinical practice.

Metabolic biomarkers significantly enhance the prediction of HBV-related ACLF occurrence and outcomes.

BACKGROUND & AIMS: Acute-on-chronic liver failure (ACLF) is a clinical syndrome associated with high short-term mortality in patients with chronic liver disease. Chronic hepatitis B is the main cause of ACLF (HBV-ACLF) in China and other Asian countries. To improve disease management and survival for patients with ACLF, we aimed to discover novel biomarkers to enhance HBV-ACLF diagnosis and prognostication. METHODS: We performed a metabolomics profiling of 1,024 plasma samples collected from patients with HBV-related chronic liver disease with acute exacerbation at hospital admission in a multi-year and multi-center prospective study (367 ACLF and 657 non-ACLF). The samples were randomly separated into equal halves as a discovery set and a validation set. We identified metabolites associated with 90-day mortality in the ACLF group and the progression to ACLF within 28 days in the non-ACLF group (pre-ACLF) using statistical analysis and machine learning. We developed diagnostic algorithms in the discovery set and used these to assess the findings in the validation set. RESULTS: ACLF significantly altered the plasma metabolome, particularly in membrane lipid metabolism, steroid hormones, oxidative stress pathways, and energy metabolism. Numerous metabolites were significantly associated with 90-day mortality in the ACLF group and/or pre-ACLF in the non-ACLF group. We developed algorithms for the prediction of 90-day mortality in patients with ACLF (area under the curve 0.87 and 0.83 for the discovery set and validation set, respectively) and the diagnosis of pre-ACLF (area under the curve 0.94 and 0.88 for the discovery set and validation set, respectively). To translate our discoveries into practical clinical tests, we developed targeted assays using liquid chromatography-mass spectrometry. CONCLUSIONS: Based on novel metabolite biomarkers, we established tests for HBV-related ACLF with higher accuracy than existing methods. CLINICAL TRIAL NUMBER: NCT02457637 and NCT03641872. IMPACT AND IMPLICATIONS: Acute-on-chronic liver failure (ACLF) is a clinical syndrome associated with high short-term mortality affecting 25% of patients hospitalized with cirrhosis. Chronic hepatitis B is the main etiology of ACLF in China and other Asian counties. There is currently no effective therapy. Early diagnosis and accurate prognostication are critical for improving clinical outcomes in patients with ACLF. Based on novel metabolite biomarkers, we developed liquid chromatography-mass spectrometry tests with improved accuracy for the early diagnosis and prognostication of HBV-related ACLF. The liquid chromatography-mass spectrometry tests can be implemented in clinical labs and used by physicians to triage patients with HBV-related ACLF to ensure optimized clinical management.

Risk factors associated with recurrent febrile urinary tract infection in children with neurogenic bladder who perform clean intermittent catheterization.

OBJECTIVE: To identify the clinical and urodynamic risk factors associated with the development of recurrent febrile urinary tract infections (FUTIs) in children with neurogenic bladder (NB) who perform clean intermittent catheterization (CIC). METHODS: Children with NB receiving CIC were prospectively enrolled from January to December 2019 and followed up prospectively for 2 years. All data were compared between occasional (0-1 FUTI) and recurrent FUTIs (≥2 FUTI) groups. In addition, the risk factors for recurrent FUTIs in children were evaluated. RESULTS: Complete data from 321 children were analyzed. Occasional FUTIs occurred in 223 patients, and 98 patients experienced recurrent FUTIs. Univariate and multivariate analyses, showed late-initiation and low-frequency CIC, vesicoureteral reflux (VUR), small bladder capacity and low compliance, and detrusor overactivity were associated with an increased risk of recurrent FUTIs. Children with high-grade VUR (grades IV-V) had a higher risk of recurrent FUTIs than those with low-grade VUR (grades I-III) (odds ratio [OR]: 26.95 vs. OR: 4.78, p < 0.001). CONCLUSIONS: Our study suggests that late-initiation and low-frequency CIC, VUR, small bladder capacity and low compliance, and detrusor overactivity were associated with recurrent FUTIs in patients with NB. In addition, high-grade VUR is a crucial risk factor for recurrent FUTIs.

Portal vein thrombosis compromises the performance of MELD and MELD-Na scores in patients with cirrhosis.

BACKGROUND AND AIMS: The accuracy of model for end-stage liver disease (MELD) and MELD with sodium (MELD-Na) scores in reflecting the clinical outcomes of patients with cirrhosis and portal vein thrombosis (PVT) remains unclear. This study aimed to evaluate the performance of scores in predicting 90-day mortality in patients with cirrhosis and PVT. METHODS: Post hoc analysis was performed in two prospective cohorts (NCT02457637 and NCT03641872). The correlation between the MELD/MELD-Na score and 90-day liver transplantation (LT)-free mortality was investigated in patients with cirrhosis with and without PVT. RESULTS: In this study, 2826 patients with cirrhosis were included, and 255 (9.02%) had PVT. The cumulative incidence of 90-day LT-free mortality did not significantly differ between patients with and without PVT (log-rank P = 0.0854). MELD [area under the receiver operating curve (AUROC), 0.649 vs. 0.842; P = 0.0036] and MELD-Na scores (AUROC, 0.691 vs. 0.851; P = 0.0108) were compared in patients with and without PVT, regarding the prediction of 90-day LT-free mortality. In MELD < 15 and MELD-Na < 20 subgroups, patients with PVT had a higher 90-day LT-free mortality than those without PVT (7.91% vs. 2.64%, log-rank P = 0.0011; 7.14% vs. 3.43%, log-rank P = 0.0223), whereas in MELD ≥ 15 and MELD-Na ≥ 20 subgroups, no significant difference was observed between patients with and without PVT. CONCLUSIONS: The performance of MELD and MELD-Na scores in predicting 90-day LT-free mortality of patients with cirrhosis was compromised by PVT. MELD < 15 or MELD-Na < 20 may underestimate the 90-day LT-free mortality in patients with PVT.

A novel prognostic nomogram for older patients with acute-on-chronic liver diseases (AoCLD): a nationwide, multicentre, prospective cohort study.

BACKGROUND: the incidence of acute-on-chronic liver disease (AoCLD) is increasing. OBJECTIVE: to investigate the clinical features and risk factors of AoCLD and construct an effective prognostic nomogram model for older patients with AoCLD. METHODS: data from 3,970 patients included in the CATCH-LIFE study were used, including 2,600 and 1,370 patients in the training and validation sets, respectively. Multivariate Cox regression analyses were performed to identify predictive risk factors in older individuals, and an easy-to-use nomogram was established. Performance was assessed using area under the curve, calibration plots and decision curve analysis (DCA). RESULTS: of the 3,949 patients with AoCLD, 809 were older with a higher proportion of autoimmune-related abnormalities, hepatitis C viral infection and schistosomiasis. In the older patient group, the incidence of cirrhosis, hepatic encephalopathy (HE), infection, ascites and gastrointestinal bleeding; neutrophil-to-lymphocyte ratio (NLR), aspartate-to-alanine transaminase ratio (AST/ALT), creatinine and blood urea nitrogen levels were higher, whereas incidence of acute-on-chronic liver failure, white blood cell, platelet and haemoglobin levels; albumin, total bilirubin (TB), AST and ALT levels; international normalised ratio (INR), estimated glomerular filtration rate and blood potassium levels were lower than in the younger group. The final nomogram was developed based on the multivariate Cox analysis in training cohort using six risk factors: ascites, HE grades, NLR, TB, INR and AST/ALT. Liver transplantation-free mortality predictions were comparable between the training and validation sets. DCA showed higher net benefit for the nomograph than the treat-all or treat-none strategies, with wider threshold probabilities ranges. CONCLUSIONS: our analysis will assist clinical predictions and prognoses in older patients with AoCLD.

Severe anemia is associated with increased short-term and long-term mortality in patients hospitalized with cirrhosis.

INTRODUCTION AND OBJECTIVES: The relationship between anemia and the outcome of patients with cirrhosis is not completely clear. Therefore, we performed this large-scale epidemiological study to investigate the prevalence and severity of anemia in patients with cirrhosis and acute decompensation or liver injury and how anemia impacts short-term and long-term outcomes. PATIENTS AND METHODS: Patients with cirrhosis and acute decompensation (AD) or acute liver injury (ALI) were enrolled in the Chinese AcuTe on CHronic LIver FailurE (CATCH-LIFE) studies, which consisted of two large, multicenter, prospective, observational cohorts between January 2015 and December 2016 and July 2018 and January 2019. We conducted data analysis on the prevalence of anemia and determined the relationship between anemia and prognosis. RESULTS: Among 1979 patients, 1389 (70.2%) had anemia, among whom 599 (41.3%) had mild anemia, 595 (15.8%) had moderate anemia and 195 (2.4%) had severe anemia. A linear association between hemoglobin level and 90-day or 1-year LT-free mortality was shown, and a 10 g/L decrease in hemoglobin level was associated with a 6.8% extra risk of 90-day death and a 5.7% extra risk of 1-year death. Severe anemia was an independent risk factor for 90-day [HR=1.649 (1.100, 2.473), p=0.016] and 1-year LT-free mortality [HR=1.610 (1.159, 2.238), p=0.005]. Multinomial logistic regression analysis further identified that severe anemia was significantly associated with post-28-day mortality but not within-28-day mortality. CONCLUSIONS: Anemia is common in patients with cirrhosis admitted for acute events. Severe anemia was associated with poor 90-day and 1-year prognoses in these patients.

Overview of microplastic pollution and its influence on the health of organisms.

Microplastic pollution has gradually become a major global concern, due to the widespread use of plastics. Microplastics enter the environment and are degradated, while also being ingested by organisms, affecting various physiological functions and adversely affecting the health of organisms. Microplastic pollution is currently a wide concern, but data on the impact on organisms is still not sufficient. Therefore, this review summarizes the research on microplastic pollution in marine, soil and fresh water, and its impact on organisms, focusing on the effects of microplastics on organisms' feeding behavior and oxidative stress responses, intestinal microbes and reproductive function, and the combined effects of microplastic pollutants on organisms. We also summarized the various possible ways of microplastics entering into the human body, and posing a potential threat to human health, which still needs further research.

Association of Serum Hepatitis B Virus RNA With Hepatocellular Carcinoma Risk in Chronic Hepatitis B Patients Under Nucleos(t)ide Analogues Therapy.

BACKGROUND: Whether serum hepatitis B virus (HBV) RNA associates with hepatocellular carcinoma (HCC) development in chronic hepatitis B (CHB) patients has not been fully elucidated. METHODS: We enrolled 2974 patients receiving nucleos(t)ide analogues (NAs) from a prospective, observational CHB cohort to investigate the effect of serum HBV RNA, measured at study entry (baseline), on HCC development, using Cox regression analyses. RESULTS: During median follow-up of 4.4 years, 90 patients developed HCC. Patients with detectable baseline HBV RNA (n = 2072) exhibited significantly higher HCC risk than those with undetectable level (5-year HCC incidence estimated by Kaplan-Meier method: 4.1% versus 1.8%, P = .009; adjusted hazard ratio [aHR] = 2.21, P = .005). HBV RNA levels of 609-99 999 and ≥100 000 copies/mL were associated with incrementally increasing HCC risk (aHR = 2.15 and 3.05, respectively; P for trend = .003), compared to undetectable level (<609 copies/mL). Moreover, patients with single-detectable either HBV DNA or RNA and double-detectable DNA and RNA had 1.57- and 4.02-fold higher HCC risk, respectively, than those with double-undetectable DNA and RNA (P for trend = .001). CONCLUSIONS: High-level HBV RNA is associated with increased HCC risk in NAs-treated patients. Achieving undetectable HBV RNA may contribute to better clinical outcomes, indicating it could be a valuable endpoint of anti-HBV treatment.

MELD score < 18 rule out 28-day ACLF development among inpatients with hepatitis B-related previous compensated liver disease.

The acute-on-chronic liver failure (ACLF) development is highly dynamic. Currently, no satisfactory algorithm identifies patients with HBV at risk of this complication. The aim of the study was to characterize ACLF development in hospitalized HBV-related patients without previous decompensation and to test the performance of traditional prognostic models in ruling out ACLF development within 28 days on admission we conducted a cohort study. Two multi-center cohorts with hospitalized HBV-related previous compensated patients were analyzed. Performances of MELD, MELD-Na, CLIF-C AD, and CLIF-C ACLF-D in ruling out ACLF development within 28 days were compared and further validated by ROC analyses. In the derivation cohort (n = 892), there were 102 patients developed ACLF within 28 days, with profound systemic inflammatory levels and higher 28-day mortality rate (31.4% vs. 1.0%) than those without ACLF development. The MELD score (cut-off = 18) achieved acceptable missing rate (missed/total ACLF development) at 2.9%. In the validation cohort (n = 1656), the MELD score (<18) was able to rule out ACLF development within 28 days with missing rate at 3.0%. ACLF development within 28 days were both lower than 1% (0.6%, derivation cohort; 0.5%, validation cohort) in patients with MELD < 18. While in patients with MELD ≥ 18, 26.6% (99/372, derivation cohort) and 17.8% (130/732, validation cohort) developed into ACLF within 28 days, respectively. While MELD-Na score cut-off at 20 and CLIF-AD score cut-off at 42 did not have consistent performance in our two cohorts. MELD < 18 was able to safely rule out patients with ACLF development within 28 days in HBV-related patients without previous decompensation, which had a high 28-day mortality.

Rapid detection for infected ascites in cirrhosis using metagenome next-generation sequencing: A case series.

Empirical antibiotic therapy in patients with spontaneous bacterial peritonitis (SBP) is common as pathogen(s) are identified in only 5%-20% patients using conventional culture-based techniques. Metagenome next-generation sequencing (mNGS) test is a promising approach for the diagnosis of infectious disease. The clinical application of mNGS for infected ascites in cirrhotic patients is rarely reported. Here, we describe three cases to preliminarily explore the potential role of mNGS for microbiological diagnosis of ascites infection in an exploratory manner. The clinical performance of ascites mNGS in cirrhotic patients remains to be further evaluated.

Effects of Environmental and Spatial Variables on Bacteria in Zhanjiang Mangrove Sediments.

The bottom mud of mangroves contains numerous microbial groups that play an important role in the main ecological functions of the mangrove ecosystem. The diversity and functional and environmental factors related to microbial communities, in terms of the assembly process and in environmental adaptation of the abundance and rare bacterial communities in the mangrove ecosystem, have not been fully explored. We used 16S high-throughput sequencing and operational taxonomic unit analysis to compare the diversity and composition of bacterial communities in different tidal zones in the sediments of the Zhanjiang Gaoqiao Mangrove Nature Reserve, compare the ecological adaptation thresholds and phylogenetic signals of bacterial communities under different environmental gradients, and examine the factors affecting the composition of the bacterial community. The diversity of microbial species and structure and function of the mangrove sediments were affected by the environment, showing the trend: mid tide zone > climax zone > low tide zone. Organic matter content, oxygen content, pH, and total phosphorus were identified as important environmental factors determining the functional diversity of bacterial communities and survival, while pH influences species evolution. The abundant taxa showed a wider response threshold and stronger phylogenetic signals of ecological preference across environmental gradients compared to rare taxa. The abundant bacterial groups have broader environmental adaptability than rare bacterial groups, and different environmental factors affect different communities and functions in the mangrove ecological environment. These results elucidate the mechanism underlying the generation and maintenance of bacterial diversity in response to global environmental changes.

Interactions between C8orf37 and FAM161A, Two Ciliary Proteins Essential for Photoreceptor Survival.

Mutations in C8orf37 cause Bardet-Biedl syndrome (BBS), retinitis pigmentosa (RP), and cone-rod dystrophy (CRD), all manifest in photoreceptor degeneration. Little is known about which proteins C8orf37 interacts with to contribute to photoreceptor survival. To determine the proteins that potentially interact with C8orf37, we carried out a yeast two-hybrid (Y2H) screen using C8orf37 as a bait. FAM161A, a microtubule-binding protein localized at the photoreceptor cilium required for photoreceptor survival, was identified as one of the preys. Double immunofluorescence staining and proximity ligation assay (PLA) of marmoset retinal sections showed that C8orf37 was enriched and was co-localized with FAM161A at the ciliary base of photoreceptors. Epitope-tagged C8orf37 and FAM161A, expressed in HEK293 cells, were also found to be co-localized by double immunofluorescence staining and PLA. Furthermore, interaction domain mapping assays identified that the N-terminal region of C8orf37 and amino acid residues 341-517 within the PFAM UPF0564 domain of FAM161A were critical for C8orf37-FAM161A interaction. These data suggest that the two photoreceptor survival proteins, C8orf37 and FAM161A, interact with each other which may contribute to photoreceptor health.

Effects of Microplastics on Microbial Community in Zhanjiang Mangrove Sediments.

Microplastics are easily consumed by marine animals, thereby entering the food chain and endangering animal health. However, there are few studies focusing on the effects of microplastics in mangrove sediments on microbial communities. In order to study the influence of microplastics on microorganisms, microplastics and microorganisms were extracted from Zhanjiang (Guangdong Province, China) mangrove sediments and analyzed. The results showed that there were differences in Shannon and Simpson indices of the microbial community in microplastics (p < 0.05), and there were also differences between JG30_KF_CM45 and Natranaerovirga at the genus level, indicating that microplastics may affect the diversity and composition of microorganisms in sediments. In addition, FAPROTAX function prediction analysis showed that microplastics may affect the nitrification of microbial communities. The results from this study indicate that microplastics affected the diversity and richness of microorganisms in mangrove sediments, which provides an experimental basis for the relationship between microplastics and microorganisms.

The Status of Polychlorinated Biphenyls (PCBs) Extract from Zhanjiang Mangrove Sediments and the Effects on Tissue Structure and Inflammatory Cytokines in Zebrafish Liver.

Polychlorinated biphenyls (PCBs) are released into the environment from a wide range of sources. The aim of the present study was to investigate the effect of the PCBs extracted from the Zhanjiang mangrove sediments on the immune function of zebrafish. The sediments were collected from 3 mangrove forest points in Zhanjiang (Guangdong Province, China), and the results showed that PCB153 was detected in the sediments of the Guangdong Zhanjiang Mangrove National Nature Reserve (MNNR) and Gaoqiao Mangrove Reserve (GMR), while PCB101, PCB112, PCB155, and PCB198 were detected in the sediments of the Leizhou Peninsula (LP). The zebrafish were exposed to different concentrations of PCBs, i.e., control group, positive control group (Aroclor1254; 10 µg/L), low dose group (LD; 0.6 µg/L), medium-dose group (MD; 3.0 µg/L) and high dose group (HD; 15 µg/L) for 14 days. As compared to the control group, the liver index increased significantly in all PCB treated groups. The liver tissue structure was destroyed in all PCB-treated groups as compared to the control group. In addition, the relative mRNA expression of the target genes (IL-1ß, IL-8, and TNF-α) was significantly expressed in each concentration group. Therefore, these findings suggest that exposure of zebrafish to PCBs can destroy the liver histology and increase the liver index and mRNA expression of inflammatory cytokines in a dose and time-dependent manner.

Baveno VI criteria and spleen stiffness measurement rule out high-risk varices in virally suppressed HBV-related cirrhosis.

BACKGROUND & AIMS: There are no data validating the performance of spleen stiffness measurement in ruling out high-risk varices in patients with HBV-related cirrhosis under maintained viral suppression. Thus, we aimed to prospectively validate the performance of spleen stiffness measurement (cut-off 46 kPa) combined with Baveno VI criteria in ruling out high-risk varices in these patients. METHODS: Patients with cirrhosis were enrolled from April to December 2019 at the hepatology unit of the Nanfang Hospital, China. Liver and spleen transient elastography and esophagogastroduodenoscopy were performed at enrollment. Antiviral regimen(s) and virological responses, evaluated every 3-6 months, were recorded. RESULTS: Overall 341 patients with HBV-related cirrhosis under maintained viral suppression were enrolled, and the prevalence of high-risk varices was 20.5% (70/341). Baveno VI criteria spared 37.0% (126/341) esophagogastroduodenoscopies and no high-risk varices were missed (0/70). Eight cases of high-risk varices (8/70, 11.4%) were misclassified in patients (208/341, 61.0%) within the expanded Baveno VI criteria. The spleen stiffness measurement cut-off (≤46.0 kPa) was shown to safely rule out high-risk varices in these patients (the percentage of missed high-risk varices was 4.3%). Over half (61.6%, 210/341) of patients met the combined model (Baveno VI criteria and spleen stiffness measurement cut-off ≤46 kPa) and 4.3% (3/70) of high-risk varices cases were misclassified. This combined model exhibited a sensitivity of 95.71%, specificity of 76.38%, negative predictive value of 98.57%, and negative likelihood ratio of 0.06 for ruling out high-risk varices. CONCLUSIONS: We validated the excellent performance of Baveno VI criteria combined with spleen stiffness measurement (cut-off 46 kPa) for safely ruling out high-risk varices in patients with HBV-related cirrhosis under viral suppression; more than half of esophagogastroduodenoscopy procedures were spared using this combination. CLINICAL TRIAL NUMBER: NCT04123509 LAY SUMMARY: Esophageal varices have important prognostic implications in patients with cirrhosis. Thus, their timely identification is important so that treatment can be initiated early. Herein, we validated the excellent performance of the combination of Baveno VI criteria with spleen stiffness measurement (cut-off 46 kPa) for ruling out high-risk esophageal varices in patients with HBV-related cirrhosis under maintained viral suppression (with antiviral treatment). This combined model was able to safely rule out high-risk varices (missed/total <5%) and over half (61.6%) of esophagogastroduodenoscopy procedures were spared.