Introduction and Objective: Metabolic dysfunction-associated steatohepatitis (MASH) is highly prevalent among individuals with type 2 diabetes (T2D) and significantly increases the risk of liver-related events. Individuals with at-risk MASH (MASH+F2-4) are the main target for emerging therapies. We aimed to develop and validate a non-invasive model to identify at-risk MASH in adults with T2D. Methods: A multicenter derivation cohort undergoing liver biopsy (n=525) was used for model development. External validation was conducted in three transient elastography-based cohorts: a Chinese cohort (n=3,711), a Singapore cohort (n=422), and a US NHANES cohort (n=1,674). At-risk MASH was defined histologically in the derivation cohort and by the FibroScan-aspartate aminotransferase (FAST) score in validation cohorts. Performance was compared with the Fibrosis-4 index (FIB-4), non-alcoholic fatty liver disease fibrosis score (NFS), and AST/alanine aminotransferase (ALT) ratio (AAR). Results: The DiabetesMASH Index (DMI), which incorporates age, waist circumference, ALT, and hemoglobin A1c, showed satisfactory discrimination in the derivation cohort (AUROC 0.79; 95% CI 0.75 - 0.83) and validation cohorts (AUROC 0.91 [95% CI 0.89 - 0.94], 0.88 [0.80 - 0.96], and 0.90 [0.86 - 0.94]), outperforming the FIB-4, NFS, and AAR. Calibration analyses showed agreement between predicted and observed risks. Rule-out and rule-in thresholds were 0.184 (sensitivity 0.85; negative predictive value [NPV] 0.92) and 0.452 (specificity 0.90; PPV 0.57). The indeterminate zone accounted for 35.8% of patients in the derivation cohort and 19.9%, 24.8%, and 19.1% in validation cohorts. Conclusion: DMI is a validated, affordable, and accessible non-invasive tool for identifying at-risk MASH in T2D. Disclosure Y. Chen: None. B. Dong: None. C. Liu: None. Z. Li: None. M. Zheng: None. K. Chen: None. G. Goh: None. B. Ye: None. X. Liang: None. A. Hu: None. Y. Li: None. Q. Zeng: None. Y. Sun: None. W. Gou: None. H. Bian: None. J. Lv: None. J. Shen: None. X. Liang: None. X. Zhou: None. M. Huang: None. Q. Zhang: None. Y. Wang: None. X. Xiao: None. Y. Wang: None. Y. Qi: None. Y. Zhou: None. J. He: None. Z. Dai: None. X. Qi: None. Funding The Key Research and Development Program of Jiangsu Province (BE2023767a), the Health Research Program of Anhui (AHWJ2023A30169), and the Natural Science Foundation of Anhui Province (2508085QH314)
BACKGROUND & AIMS:The overlap between chronic hepatitis B (CHB) and metabolic dysfunction-associated steatotic liver disease (MASLD) has been growing. This study aimed to explore the impact of CHB and its clinical phases on liver fibrosis/cirrhosis in patients with MASLD. METHODS:We enrolled patients with MASLD who underwent vibration-controlled transient elastography (VCTE) or liver biopsy at 19 centers in China between 2004 and 2025. Logistic regression analyses were conducted to examine the association between CHB and liver fibrosis/cirrhosis. Propensity score matching was used to adjust for potential confounders. RESULTS:A total of 6682 patients with MASLD were included, comprising 3979 VCTE-based cases (351 with concurrent CHB) and 2703 biopsy-proven cases (1811 with concurrent CHB). In the VCTE cohort, patients with MASLD and CHB had higher proportions of significant fibrosis (50.1% vs 33.5%), advanced fibrosis (25.4% vs 10.8%), and cirrhosis (15.7% vs 5.4%) (all P < .001), with similar findings in the biopsy cohort. Multivariate analyses showed that concurrent CHB independently increased the risks of fibrosis/cirrhosis in both cohorts (odds ratios [ORs]: VCTE cohort: 1.98-3.73; biopsy cohort: 1.98-3.37; all P < .001). Under the 2018 American Association for the Study of Liver Diseases criteria, hepatitis B e-antigen-positive immune-active CHB had the highest odds of significant fibrosis, advanced fibrosis, and cirrhosis (OR, 3.27-11.18; P ≤ .001), with elevated odds also observed in gray-zone CHB (OR, 3.05-6.95; P ≤ .001); associations remained similar after propensity score matching and application of the 2025 European Association for the Study of the Liver classification. CONCLUSIONS:Concurrent CHB increased liver fibrosis/cirrhosis risk in MASLD not only in the immune-active phase but also in the gray-zone phase. Patients with MASLD and concomitant active/gray-zone CHB may warrant enhanced noninvasive monitoring and individualized management to mitigate fibrotic progression.
BACKGROUND:This study aimed to develop and validate a non-invasive model for screening advanced liver fibrosis and predicting liver-related outcomes in patients with type 2 diabetes mellitus (T2DM). METHODS:This study included patients with T2DM from five tertiary hospitals for the development and internal validation of a non-invasive model. Advanced liver fibrosis was defined as a liver stiffness measurement ≥12 kPa. An external validation cohort was obtained from the National Health and Nutrition Examination Survey (NHANES), and the model's predictive performance for hepatocellular carcinoma (HCC) and liver-related mortality was assessed in the UK Biobank. FINDINGS:In total, 28,197 patients with T2DM were enrolled. In the derivation cohort (n = 1,129), waist circumference, alanine aminotransferase, aspartate aminotransferase, platelet count, and albumin were identified as independent risk factors for advanced fibrosis and were fit to develop the "DiabetesLiver score." The area under the curve (AUC) was 0.835 (95% confidence interval [CI]: 0.781-0.890), significantly higher than the AUCs of non-invasive tests (all p < 0.01). It maintained high AUCs of 0.870 and 0.823 in the internal validation (n = 1,000), and NHANES cross-sectional (n = 1,432) cohorts, respectively. A dual cutoff of 2.39 and 3.99 with sensitivity ≥90% and specificity ≥90%, respectively, was used to classify patients into low-, middle-, and high-risk groups. In the UK Biobank cohort (n = 24,636), the high-risk group had an elevated risk of liver-related outcomes. CONCLUSIONS:The DiabetesLiver score demonstrated good performance in identifying advanced liver fibrosis and the development of liver-related events in the T2DM population. FUNDING:National Natural Science Foundation.
This study evaluated SARS-CoV-2 infection impacts on clinical characteristics, antibody levels, and immune responses in 100 malignant hematological tumor patients. Laboratory assessments included hematological, biochemical, and inflammatory markers. Multivariable analysis identified age (OR = 1.56, p = 0.004), chemotherapy cycles (OR = 1.86, p < 0.001), comorbidities (OR = 3.15, p = 0.015), WBC count (OR = 1.79, p = 0.016), CRP (OR = 2.07, p = 0.007), ferritin (OR = 1.22, p = 0.035), IL-6 (OR = 1.59, p = 0.001), IgG (OR = 2.28, p = 0.037), CD8+ T cells (OR = 2.97, p = 0.005), and NK cells (OR = 0.80, p = 0.019) as COVID-19 risk factors. COVID-19 patients showed significantly higher hospitalization (30.77% vs 10.42%, p = 0.007), ICU admission (23.08% vs 6.25%, p = 0.019), and lower 1-year survival (59.62% vs 87.50%, p = 0.002) versus controls. SARS-CoV-2 infection induces hematological/immune alterations and worsens clinical outcomes in hematological malignancy patients, emphasizing their heightened vulnerability.
Background and objectivesAlbumin is a major prognostic factor for patients with advanced liver disease, dependent on its concentration and biological activity. This study aimed to improve the method of active albumin detection and elucidate its predictive validity of albumin activity across hepatic disease progression and etiology.
Background Chronic liver diseases and type 2 diabetes mellitus (T2DM) frequently coexist and impact synergistically, and T2DM may be one of the strongest risk factors for non-alcoholic steatosis to advanced fibrosis. We aimed to investigate the prevalence of hepatic steatosis and fibrosis, and identify risk factors associated with compensated advanced chronic liver diseases (cACLD) among Chinese adults with T2DM in the community. Methods This is a prospective, large-scale, community-based study recruiting registered adults with T2DM in six cities in China between June 2021 and November 2022. The baseline demographics, comorbidities, and vibration-controlled transient elastography-defined hepatic steatosis and fibrosis, in terms of controlled attenuation parameter (CAP) and liver stiffness measurement (LSM), were collected for analysis. Results A total of 3,196 patients with T2DM in the community (age: 65±9 years; body mass index: 24.7±3.3 kg/m2) were included in the study. The prevalence of steatosis (CAP ≥248 dB/m) and cACLD (LSM ≥10 kPa) was 60% and 9%, respectively. Additionally, 12%, 7%, 7%, and 3% of patients had mild (F1), moderate (F2), severe (F3) fibrosis, and cirrhosis (F4), respectively. The distribution of mild (S1), moderate (S2), and severe (S3) steatosis was 14%, 8%, and 38%, respectively (IDDF2023-ABS-0072 Figure 1. Proportion of patients with T2DM screened in community having liver diseases (A) Proportion of subjects having NAFLD and cACLD (B) severity of fibrosis in subjects (C) Severity of S). Furthermore, 5% of patients with non-obesity (body mass index 50 years, body mass index, and the presence of hypertension were independent predictors of cACLD among patients with T2DM in the community. Conclusions We found a considerable prevalence of hepatic steatosis and fibrosis in community patients with T2DM. It is imperative to carry out screening to promote further intervention of T2DM patients.
Abstract Chronic liver disease (CLD) has become a major health problem worldwide owing to its increased morbidity and mortality. Evaluation of the degree of liver injury is crucial for the clinical management and treatment of CLD patients. In the current clinical practice, liver biopsy with histological analysis is the clinical standard for assessing the degree of CLD injury. However, liver biopsy is an invasive procedure that is limited by sampling errors and interobserver variability and is insufficient for screening and monitoring. Advanced three‐dimensional magnetic resonance elastography (3D MRE) is a simple, fast, safe, and noninvasive technology. This offers comprehensive insight into increased liver stiffness beyond stage‐specific fibrosis. This technology exhibits considerable potential for comprehensively and simultaneously assessing early necroinflammation, discriminating necroinflammation from fibrosis, detecting nonalcoholic steatohepatitis severity, predicting cirrhosis complications, and identifying tumor recurrence. Nevertheless, the clinical application and promotion of this technology are currently required in China. 3D MRE should evolve towards better clinical convenience and satisfaction to provide an imaging basis to improve treatment selection in CLD patients and facilitate its widespread use.
With the advancement of technology, there are more and more information available and access to information. However, due to the clutter of official information, the public cannot obtain emergency knowledge and disaster information in a timely and effective manner. Early warning and popular science publicity of meteorological disasters through WeChat will be a new development direction. By analyzing the current status and defects of the disaster science popularization platform on the market, the functions of the disaster prevention science popularization system are analyzed and designed on the basis of sorting out and analyzing various disaster-related knowledge and protection information. Based on the official WeChat development platform, it adopts the Spring Cloud framework, develops using Java language, and uses databases and cloud functions for background data storage. The system can provide a wider platform for users to understand and browse disaster information, and facilitate the management of administrator background information.
BACKGROUND:Endoscopy plays an important role in the management of acute variceal bleeding (AVB) in patients with cirrhosis. This study aimed at determining the optimal endoscopy timing for cirrhotic AVB. METHODS:Patients with cirrhosis with AVB across 34 university hospitals in 30 cities from February 2013 to May 2020 who underwent endoscopy within 24 hours were included in this study. Patients were divided into an urgent endoscopy group (endoscopy <6 h after admission) and an early endoscopy group (endoscopy 6-24 h after admission). Multivariable analysis was performed to identify risk factors for treatment failure. Primary outcome was the incidence of 5-day treatment failure. Secondary outcomes included in-hospital mortality, need for intensive care unit, and length of hospital stay. A propensity score matching analysis was performed. In addition, we performed an analysis, in which we compared the 5-day treatment failure incidence and the in-hospital mortality among patients with endoscopy performed at <12 hours and 12-24 hours. RESULTS:A total of 3319 patients were enrolled: 2383 in the urgent endoscopy group and 936 in the early endoscopy group. After propensity score matching, on multivariable analysis, Child-Pugh class was identified as an independent risk factor for 5-day treatment failure (HR, 1.61; 95% CI: 1.09-2.37). The incidence of 5-day treatment failure was 3.0% in the urgent endoscopy group and 2.9% in the early group ( p = 0.90). The in-hospital mortality was 1.9% in the urgent endoscopy group and 1.2% in the early endoscopy group ( p = 0.26). The incidence of need for intensive care unit was 18.2% in the urgent endoscopy group and 21.4% in the early endoscopy group ( p = 0.11). The mean length of hospital stay was 17.9 days in the urgent endoscopy group and 12.9 days in the early endoscopy group ( p < 0.05). The incidence of 5-day treatment failure in the <12-hour group was 2.3% and 2.2% in the 12-24 hours group ( p = 0.85). The in-hospital mortality was 2.2% in the <12-hour group and 0.5% in the 12-24 hours group ( p < 0.05). CONCLUSIONS:The data suggest that performance of endoscopy within 6-12 or within 24 hours of presentation among patients with cirrhosis with AVB led to similar treatment failure outcomes.
Background and Aims: The Baveno VI and expanded-Baveno VI criteria has been validated as single-use screening for varices needing treatment (VNT) in patients enriched with hepatitis C virus and alcoholic-related compensated cirrhosis. Here, we aimed to develop and validate novel CHESS model for single-use screening and dynamic monitoring of VNT in patients with predominantly hepatitis B virus (HBV)-related compensated cirrhosis. Methods: A total of 3,470 patients with compensated cirrhosis from China, Singapore and India were included in the international multicenter study with six cohorts as follows: real-world cohort; multicenter validation cohort; international validation cohort; multicenter HBV cohort; dynamic monitoring longitudinal cohort; multicenter, clinical practice cohort. Primary outcomes were the rates of VNT missed and spared esophagogastroduodenoscopy (EGD).Results: In the real-world cohort (65%HBV), implementing Baveno VI criteria would have spared 30% of EGDs and missed 3·6% of VNT. Expanded-Baveno VI criteria had an unacceptable VNT missed rate of 6·2%. Using the new CHESS model (platelets>110×109/L and liver stiffness<19kPa) would have spared 46% of EGDs (p<0.001 vs. Baveno VI criteria) and missed 4·9% of VNT. In the multicenter cohort (75%HBV), international cohort (14%HBV) and HBV cohort, CHESS model would also have spared more EGDs (all p<0·001) than Baveno VI criteria. Notably, employing CHESS model in dynamic monitoring cohort would have safely spared 41% and 54% of EGDs for primary and secondary monitoring, respectively. In the prospective clinical practice cohort, 75% of EGDs were spared according to CHESS model, with a VNT rate of 36% in patients dissatisfied CHESS model who underwent EGD.Conclusion: CHESS model were superior to Baveno VI criteria and expanded-Baveno VI criteria for the screening and monitoring of varices in patients with HBV-dominated compensated cirrhosis.Funding Information: None. Declaration of Interests: None.Ethics Approval Statement: All procedures were performed in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008. The study was approved by the Ethics Committees of all the involved centers. The committees waived the need for written informed consent from subjects in two retrospective cohorts because de-identified secondary data were analyzed. Written informed consent was obtained from all patients prior to inclusion in the prospective cohorts.
Background: Screening tools for identifying patients with high-risk varies (HRV) including esophagogastroduodenoscopy (EGD) and Baveno VI criteria (noninvasive) have been recommended to be performed in clinical practice in order to prevent the first episode of variceal hemorrhage. In this study, we aimed to examine the cost-effectiveness of the tools to support clinical decision making.Methods: A decision analytic model was developed, in which Markov models were embedded, to simulate the clinical pathway and possible health outcomes of compensated cirrhotic patients who undergo screening for preventing variceal hemorrhage. Clinical data were derived from published literature and meta-analysis, while medical costs were collected from multilevel hospitals. Deterministic and probabilistic sensitivity analyses were followed. Our model was calculated over a decade and the health system perspective was adopted.Findings: Patients categorized into the no screening scenario had the highest total cost of $1451 (¥9431) per patient and the lowest quality-adjusted life years (QALYs) of 4·79 years. Screening conducted by Baveno VI criteria had the cheapest medical cost of $1118 (¥7264) per patient, and patients who underwent EGD obtained the highest QALYs of 5·52 years. Compared to the Baveno VI criteria strategy, the incremental cost-effectiveness ratio (ICER) of the EGD strategy was $87·25 (¥567) per QALY. The results were sensitive to the probability of HRV diagnosed by EGD in patients who were treated with nonselective beta-blockers and the cost of endoscopy. In terms of ICER, the strategies of EGD and Baveno VI criteria were both cost-effective compared to no screening scenario according to the willingness-to-pay but EGD had a 90·3% chance of being the optimal option. Baveno VI criteria strategy becomes preferred strategy compared to EGD strategy when willingness-to-pay is lower than $3077 (¥20000) per QALY.Interpretation: Primary prophylaxis of variceal hemorrhage is cost-effective and should be performed as soon as possible. Baveno VI criteria gained the highest QALY among all strategies at the first year when it was implemented. The consideration of spared endoscopy rate and dynamic follow-up will improve the screening value of Baveno VI criteria in routine practice.Funding Information: This study was funded by the Gansu Science Fund for Distinguished Young Scholars.Declaration of Interests: We declare no competing interests.
Background and AimsEmergency endoscopy is recommended for patients with acute esophageal variceal bleeding (EVB) and their prognosis has improved markedly over past decades due to the increased specialization of endoscopic practice. The study aimed to compare outcomes following emergency endoscopic injection sclerotherapy (EIS) and endoscopic variceal ligation (EVL) in cirrhotic patients with acute EVB. MethodsCirrhotic patients with acute EVB who underwent emergency endoscopy were retrospectively enrolled from 2013 to 2020 across 34 university hospitals from 30 cities. The primary outcome was the incidence of 5-day rebleeding after emergency endoscopy. Subgroup analysis was stratified by Child-Pugh class and bleeding history. A 1:1 propensity score matching (PSM) analysis was performed. ResultsA total of 1,017 and 382 patients were included in EIS group and EVL group, respectively. The 5-day rebleeding incidence was similar between EIS group and EVL group (4% vs. 5%, P = 0.45). The result remained the same after PSM (P = 1.00). Among Child-Pugh class A, B and C patients, there were no differences in the 5-day rebleeding incidence between the two groups after PSM (P = 0.25, 0.82, and 0.21, respectively). As for the patients with or without bleeding history, the differences between EIS group and EVL group were not significant after PSM (P = 1.00 and 0.26, respectively). ConclusionThe nationwide cohort study indicates that EIS and EVL are both efficient emergency endoscopic treatment strategies for acute EVB. EIS should not be dismissed as an economical and effective emergency endoscopic treatment strategy of acute EVB. ClincialTrials.gov number NCT04307264.
Purpose:To determine whether combinations of antifungal drugs are effective and safe for patients in intensive-care units.Methods:This study compared the efficacy and safety of caspofungin (CAS), voriconazole (VOR), amphotericin B liposome (L-AmB), CAS+VOR, and CAS+L-AmB as empirical, preemptive, and targeted therapies for invasive fungal infection (IFI).Results:Comparing the CAS, VOR, and CAS+VOR groups revealed that there were no differences in response rates between all therapy types, IFI-associated death within 90 days was less common in the CAS+VOR group (1.8%) than the VOR group (14.3%), and there were more adverse events in the VOR group than in the CAS group (P < 0.05). For empirical or preemptive therapy, the CAS group had a better response rate (80.0%) than the CAS+VOR group (47.1%), and there were more adverse events in the VOR group than in the CAS group (P < 0.05). For targeted therapy, no differences were found for efficacy and safety. There were no differences among the CAS, L-AmB, and CAS+L-AmB groups in efficacy and safety.Conclusion:Patients who received CAS monotherapy as an empirical or preemptive therapy could achieve good outcomes. Patients who received CAS+VOR or CAS+L-AmB achieved almost the same outcomes when compared with those who received CAS, VOR, and L-AmB monotherapy as targeted therapies, but those who received CAS+VOR had a lower IFI mortality rate than did those who received VOR monotherapy.
Background & Aims: The development of COVID-19 vaccines has progressed with encouraging safety and efficacy data. Concerns have been raised about SARS-CoV-2 vaccine responses in the large population of patients with non-alcoholic fatty liver disease (NAFLD). The study aimed to explore the safety and immunogenicity of COVID-19 vaccination in NAFLD. Methods: This multicenter study included patients with NAFLD without a history of SARS-CoV-2 infection. All patients were vaccinated with 2 doses of inactivated vaccine against SARS-CoV-2. The primary safety outcome was the incidence of adverse reactions within 7 days after each injection and overall incidence of adverse reactions within 28 days, and the primary immunogenicity outcome was neutralizing antibody response at least 14 days after the whole-course vaccination. Results: A total of 381 patients with pre-existing NAFLD were included from 11 designated centers in China. The median age was 39.0 years (IQR 33.0-48.0 years) and 179 (47.0%) were male. The median BMI was 26.1 kg/m(2) (IQR 23.8-28.1 kg/m(2)). The number of adverse reactions within 7 days after each injection and adverse reactions within 28 days totaled 95 (24.9%) and 112 (29.4%), respectively. The most common adverse reactions were injection site pain in 70 (18.4%), followed by muscle pain in 21 (5.5%), and headache in 20 (5.2%). All adverse reactions were mild and self-limiting, and no grade 3 adverse reactions were recorded. Notably, neutralizing antibodies against SARS-CoV-2 were detected in 364 (95.5%) patients with NAFLD. The median neutralizing antibody titer was 32 (IQR 864), and the neutralizing antibody titers were maintained. Conclusions: The inactivated COVID-19 vaccine appears to be safe with good immunogenicity in patients with NAFLD. Lay summary: The development of vaccines against coronavirus disease 2019 (COVID-19) has progressed rapidly, with encouraging safety and efficacy data. This study now shows that the inactivated COVID-19 vaccine appears to be safe with good immunogenicity in the large population of patients with nonalcoholic fatty liver disease. (C) 2021 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.