Iron overload-induced liver fibrosis involves interconnected pathological drivers: ferroptosis-like oxidative injury and dysregulated macrophage polarization. Although Caesalpinia sappan L. possesses well-characterized antioxidant and anti-inflammatory properties, its efficacy against this dual pathological axis has not been experimentally established. This study investigated the hepatoprotective effects of C. sappan wood extract (SWE) in an iron dextran-induced rat model of liver fibrosis. Male Wistar rats received intraperitoneal iron dextran (cumulative dose of 180 mg/kg BW over 39 days) to induce hepatic iron overload, followed by 28-day oral administration of SWE (25, 50, 75, or 100 mg/kg BW/day) or deferasirox (20 mg/kg BW/day). Hepatic iron concentration, liver function markers, oxidative stress parameters (MDA, SOD, and GPx4), macrophage polarization markers (CD86 and CD163), inflammatory and fibrogenic mediators (IL-6, IL-10, TGF-β1, and MMP-12), and fibrosis severity were assessed through biochemical, immunohistochemical, and histopathological analyses. SWE was standardized to 25.12% w/w brazilin by HPLC-PDA. SWE showed dose-related effects with optimal efficacy at intermediate doses, reducing hepatic iron burden, restoring GPx4 activity, suppressing lipid peroxidation, and enhancing antioxidant defense, collectively attenuating ferroptosis-like oxidative injury. Concurrently, SWE reduced M1 macrophage activation (decreased CD86 and IL-6) while promoting M2 polarization (increased CD163 and IL-10), suppressed TGF-β1-driven fibrogenesis, and restored MMP-12-mediated matrix remodeling, resulting in significant reductions in collagen deposition and fibrotic area. SWE performed comparably to deferasirox across most endpoints, with superior MMP-12 recovery. SWE simultaneously attenuates ferroptosis-like oxidative injury and restores macrophage polarization balance, establishing it as a mechanistically coherent multitarget candidate for iron overload-induced liver fibrosis with translational potential beyond that of iron chelation alone.
INTRODUCTION:Acute liver failure (ALF) is a rare and life-threatening condition characterized by rapid deterioration of liver function and often requires urgent liver transplantation (LT). This study aimed to evaluate donor and recipient factors associated with 30-day mortality after LT for ALF. METHODS:Medical records of patients who underwent LT for ALF at seven Brazilian transplant centers were reviewed. Patient data were obtained from electronic medical records. The primary outcome was 30-day mortality after LT. RESULTS:Ninety patients who underwent LT for ALF were included. Thirty-day mortality occurred in 46 of 90 patients (51%). In multivariable analysis, higher pretransplant serum creatinine levels (OR 3.49, 95% CI 1.69-8.72; p = 0.003) and the need for mechanical ventilation prior to transplantation (OR 5.46, 95% CI 1.21-28.9; p = 0.033) were independently associated with early mortality. Donor age ≥ 50 years and pretransplant vasoactive drug use were associated with mortality in univariate analysis. CONCLUSION:Higher pretransplant serum creatinine levels and the need for mechanical ventilation were independently associated with 30-day mortality, whereas donor age ≥ 50 years and pretransplant vasoactive drug use were associated with mortality only in the univariate analysis. These findings support improved pretransplant risk stratification and perioperative management in patients undergoing LT for ALF.
OBJECTIVES:To develop and validate a Chinese Physicians' Reactions to Uncertainty Scale for Endoscopy for assessing endoscopists' reactions to uncertainty in clinical practice. METHODS:Using a mixed-methods design, we translated the original Physicians' Reactions to Uncertainty scale and generated endoscopy-specific items through focus-group interviews. The draft scale was refined through Delphi consultation and then evaluated in an online survey of 360 digestive endoscopists from 204 hospitals in China. Item reduction was based on dispersion, critical ratio, and item-total correlation analyses. Construct validity was assessed using exploratory factor analysis and confirmatory factor analysis. Content validity was evaluated using item-level and scale-level content validity indices, and reliability was examined using Cronbach's alpha and split-half reliability. RESULTS:The final scale comprised 16 items across four dimensions: concerns about uncertainty and bad outcomes, disclosing uncertainty to patients, disclosing mistakes to physicians, and endoscopy-specific uncertainty responses and self-efficacy. In exploratory factor analysis, four factors explained 73.474% of the total variance. Confirmatory factor analysis supported an acceptable four-factor model fit (χ2/df = 2.778, RMSEA = 0.098, IFI = 0.908, TLI = 0.931). Cronbach's alpha was 0.818 for the overall scale and 0.801-0.932 for the subscales. Split-half reliability was 0.919. Item-level content validity indices ranged from 0.86 to 1.00, and the scale-level content validity index was 0.96. CONCLUSIONS:The Chinese Physicians' Reactions to Uncertainty Scale for Endoscopy is a reliable and valid instrument for assessing endoscopists' reactions to uncertainty in China.
BACKGROUND:PD-1 blockade has yet to achieve broad clinical success in colorectal cancer (CRC), with microsatellite-stable tumors proving especially resistant. At the same time, ferroptosis has emerged as a mechanistic link between redox control in tumor cells and the antitumor immune response. GPR39 is overexpressed in CRC, but its functional role in ferroptosis and immunotherapy resistance is currently unclear. METHODS:GPR39 expression was analyzed in human and mouse CRC cell lines. GPR39 knockdown, with or without the ferroptosis inhibitor liproxstatin-1, was performed to determine whether GPR39 regulates CRC cell proliferation and migration through ferroptosis. Ferroptosis was evaluated by measuring lipid peroxidation, glutathione (GSH) levels, ferrous iron (Fe2+) accumulation, and reactive oxygen species (ROS). Mechanistic involvement of the nuclear factor erythroid 2-related factor 2 (Nrf2)/solute carrier family 7 member 11 (SLC7A11) signaling axis was examined using Nrf2 overexpression. Subcutaneous implantation of MC38 cells with stable GPR39 knockdown was performed to evaluate whether GPR39 regulates tumor sensitivity to anti-PD-1 treatment in vivo in a ferroptosis-dependent manner. RESULTS:GPR39 was markedly upregulated in CRC cell lines. GPR39 knockdown induced ferroptosis, characterized by increased lipid peroxidation, Fe2+ accumulation, and oxidative stress and accompanied by suppression of the Nrf2/SLC7A11 pathway. Nrf2 overexpression reversed these changes. Functionally, silencing GPR39 inhibited the proliferative and migratory capacities of CRC cells, effects that were largely rescued by liproxstatin-1. In vivo, GPR39 knockdown significantly potentiated the antitumor activity of PD-1 blockade, as evidenced by suppressed tumor progression accompanied by enhanced infiltration of CD8+ T cells, whereas ferroptosis inhibition abrogated these effects. CONCLUSION:GPR39 suppresses ferroptosis in CRC via the Nrf2/SLC7A11 axis, thereby limiting PD-1 immunotherapy efficacy.
BACKGROUND:In patients with cirrhosis, prolonged international normalized ratio (INR) is primarily driven by liver synthetic dysfunction. Thromboelastography more accurately reflects coagulability and can also predict short-term mortality. Nevertheless, INR is used to define coagulation failure in the European Foundation for the Study of Chronic Liver Failure criteria for acute-on-chronic liver failure (ACLF). AIM:To evaluate the association between TEG parameters and mortality in critically ill patients with cirrhosis and to justify future investigation into TEG as a prognostic tool in ACLF. METHODS:We performed a retrospective study of 52 patients with cirrhosis admitted to the intensive care unit (ICU) who had TEG performed during their ICU admission prior to the administration of any blood products. We assessed the association between TEG parameters and 28-day mortality. RESULTS:Patients who did not survive beyond 28 days generally had more hypocoagulable TEG parameters (R time: 10.0 vs. 7.6, p = 0.03; K time: 3.4 vs. 2.2, p = 0.003; alpha angle: 53.1 vs. 63.5, p = 0.002; MA: 49.2 vs. 60.2, p = 0.001). Although global assessment of TEG demonstrated a state of rebalanced hemostasis among critically ill patients with cirrhosis, patients meeting diagnostic criteria for ACLF tended to have more hypocoagulable TEG parameters as compared to those who did not (coagulation index: 0.2 vs. 2.0, p = 0.004). As proof of concept, MA was incorporated into the definition of ACLF to replace INR as a marker of coagulation failure (TEG-ACLF). The area under the curve (AUC) for TEG-ACLF was 0.83 (0.72-0.95) compared to 0.8 (0.68-0.92) for the current ACLF-CLIF grading, with 9.6% (5/52) of patients being reclassified into a different ACLF grade. CONCLUSION:Hypocoagulable TEG parameters are associated with increased 28-day mortality in critically ill patients with cirrhosis, and incorporation of TEG parameters into a modified definition for ACLF may result in improved prediction of short-term mortality.
OBJECTIVE:To investigate the link between smoking and fatty liver, particularly the influence of different smoking patterns on its prevalence, aiming to provide insights for public health policies. PATIENTS AND METHODS:We conducted a cross-sectional analysis of data from 6140 adults participating in the NHANES between 2017 and 2020. Participants were categorized into nonsmoking, secondhand smoke exposure, and active smoking groups based on serum cotinine levels. Multivariable regression models were used to assess the associations between smoking status and fatty liver, controlling for potential confounders. RESULTS:Active smokers showed a significantly higher prevalence of fatty liver compared to nonsmokers, especially among obese subgroups. In obese populations, both active smoking and secondhand smoke exposure remarkably increased the risk of fatty liver (OR = 2.51, p = 0.014). In contrast, a negative but statistically nonsignificant association was found between smoking and fatty liver in nonobese individuals. CONCLUSION:Therefore, smoking, particularly among obese individuals, is a significant contributor to fatty liver. Raising public awareness of the risks associated with smoking could help enhance liver health and overall quality of life.
BACKGROUND:Hepatic encephalopathy (HE) remains a major cause of hospitalization and readmission in cirrhosis and is closely linked to hyperammonemia, microbial dysbiosis, impaired short-chain fatty acid (SCFA) output, barrier dysfunction, and altered mucosal immunity. We evaluated whether adding a multistrain probiotic to rifaximin was associated with greater neurometabolic improvement and coordinated gut-liver-brain axis changes. METHODS:In this prospective, 6-month, randomized, open-label, assessor-blinded, three-arm controlled study, 61 adults with cirrhosis-related HE received standard care alone (Con, n = 20), standard care plus rifaximin 550 mg twice daily (Rif, n = 20), or rifaximin plus a multistrain probiotic (1 × 10^9 CFU three times daily; Rif + Pro, n = 21). The main prespecified biochemical readout was serum ammonia at Month 6. A composite HE index incorporating mental status, flapping tremor, number connection test, and ammonia grade was analyzed as a prespecified exploratory neurometabolic score. A predefined mechanistic subset underwent 16S rRNA microbiome profiling, serum SCFA measurement, and fecal secretory IgA (SIgA) testing. RESULTS:Baseline characteristics did not differ across arms. Post-treatment serum ammonia decreased in a graded pattern (Con 177 ± 43.2, Rif 143 ± 37.5, Rif + Pro 117 ± 34.3 μmol/L), with parallel improvement in the exploratory HE index (10.0 ± 4.9, 5.3 ± 4.7, and 3.7 ± 4.1, respectively). In the mechanistic subset, the microbial community structure differed by treatment (PERMANOVA p = 0.006). Rif + Pro was associated with higher serum propionate, increased Lactobacillus salivarius-associated signal, reduced Bacteroides ovatus-associated signal, and marked fecal SIgA elevation compared with standard care or rifaximin alone. The SIgA-propionate relationship was interpreted as exploratory. CONCLUSIONS:Rifaximin plus multistrain probiotics was associated with greater improvement in serum ammonia and exploratory HE severity readouts than rifaximin alone, accompanied by coordinated microbial, metabolic, and mucosal immune changes. These findings support confirmation in adequately powered event-driven trials with strain-resolved profiling and targeted metabolomics.
OBJECTIVE:To analyze spatiotemporal distribution, health inequalities, and future trends of nonalcoholic fatty liver disease (NAFLD) burden in Asia from 1990 to 2023. METHODS:Using Global Burden of Disease (GBD) 2023 data, age-standardized prevalence rates (ASPRs), incidence rates (ASIR), mortality rates (ASMR), and disability-adjusted life years (DALYs) rates (ASDR) were calculated. Joinpoint regression analyzed temporal trends, age-period-cohort models evaluated multidimensional effects, and Das Gupta decomposition explored contributions from population, aging, and epidemiological factors. Data envelopment analysis (DEA) assessed relationships with Human Development Index (HDI), while slope index of inequality (SII) and concentration index (CI) analyzed health inequalities. Bayesian age-period-cohort (BAPC) model projected 2024-2038 trends. RESULTS:In 2023, Asia carried 797.20 million prevalent cases (95% UI 693.74-910.71), 30.61 million incident cases, 27,083 deaths, and 760,383 DALYs. ASPR and ASIR had increased since 1990 (EAPC +0.851% and +0.696%), while ASMR (-0.903%) and ASDR (-0.895%) had fallen. Country dispersion was extreme: Kuwait's ASPR exceeded Japan's more than fourfold, and Central Asia's ASMR was an order of magnitude above East Asia's. Decomposition attributed 69.75% of prevalence-burden change to population growth and 29.00% to epidemiologic factors; East Asia was uniquely dominated by aging (47.24%). DEA flagged efficiency gaps in several upper-HDI states, including Kazakhstan and the Gulf countries. SII rose from 4.882 to 8.864 (81.6%), while CI remained negative throughout, signaling widening absolute inequality and persistent concentration of burden among lower-HDI populations. Projections to 2038 suggested gradual decline in all four indicators. CONCLUSION:Asia's NAFLD trajectory is not a uniform rise. Morbidity is expanding while prognosis improves, and efficiency and equity gaps are growing. One-size-fits-all continental strategies will underdeliver; development-stage-specific responses are required.
OBJECTIVE:This research aimed to investigate the disparities in improving the model for end-stage liver disease (MELD) score and plasma volume consumption between standard-volume plasma exchange (SVPE) and low-volume plasma exchange (LVPE) combined with the double plasma molecular adsorption system (DPMAS) in adult patients with acute liver failure (ALF). METHODS:This multicenter cohort study retrospectively enrolled adult patients with ALF who were admitted to the designated hospitals and received conventional drug treatment along with one or more sessions of SVPE or LVPE combined with DPMAS during hospitalization. According to the different therapeutic plasma exchange (TPE) methods received during hospitalization, the enrolled patients were subsequently classified into the SVPE group and the LVPE combined with DPMAS group. Thereafter, the aforementioned demographic characteristics, laboratory parameters, their change rates, and plasma consumption were compared between different groups or before and after TPE. RESULTS:In this multicenter retrospective cohort study, 97 adult patients with ALF were recruited, with a male-to-female ratio of 1.06: 1. Subsequently, they were classified into the SVPE group (n = 48) and the LVPE combined with DPMAS group (n = 49). During hospitalization, they received a total of 97 sessions of SVPE and 91 sessions of LVPE combined with DPMAS. There were significant differences in multiple laboratory parameters before the first SVPE or LVPE combined with DPMAS between different groups, yet the MELD score was not involved. The change rates of multiple laboratory parameters, including the MELD score, and plasma consumption displayed significant differences between the SVPE group and the LVPE combined with DPMAS group. CONCLUSION:In terms of improving the MELD score of patients with ALF and reducing the plasma volume, the combined use of LVPE and DPMAS is more effective than SVPE.
AIMS:Steatotic liver disease (SLD) is highly prevalent, yet large-scale identification remains challenging because imaging is not always available and existing noninvasive indices perform heterogeneously across subgroups. We developed and validated sex- and age-stratified laboratory-based indices for simplified SLD identification. METHODS:We analyzed 2085 adults from NHANES III (1988-1994). An exposure-wide association study (EWAS) of 119 clinical features informed sex- and age-stratified logistic models to derive two SLD lab data indices (SLDLD1-2) and simplified categorical versions (SSLDLD1-2). Discrimination (AUROC) was compared with FLI, HSI, NAFLD-LFS, and US-FLI using paired DeLong tests. Bootstrap internal validation, comparison with a pooled nonstratified model, and decision curve analysis were additionally performed. External validation was performed for SSLDLD1 in NHANES 2017-2018 and the Taiwan MJ Health database. SLDLD2/SSLDLD2 were not externally validated because C-peptide was unavailable in both datasets. RESULTS:Central adiposity and insulin-resistance markers were key predictors, whereas β-carotene showed an inverse association and contributed to discrimination, particularly in men. Across strata, SLDLD1 achieved AUROCs of 0.71-0.79 in derivation. The stratified framework outperformed a pooled nonstratified model in the overall cohort, in men, and in women aged < 55 years. SLDLD1 also outperformed FLI and HSI across strata and showed superior or comparable performance versus NAFLD-LFS and US-FLI, with stratum-dependent differences. External validation of SSLDLD1 yielded AUROCs of 0.71-0.80 across datasets. Feature-reduction analysis and an MJ-variables-only implementation of SSLDLD1 showed only small absolute AUROC changes overall, supporting simplified implementation when nonroutine biomarkers such as β-carotene and insulin are unavailable, although fixed NHANES III-derived thresholds were not fully transferable to the MJ cohort. CONCLUSION:The stratified SLDLD framework provides a practical toolbox for SLD identification, supporting high-throughput research and implementation in settings where advanced imaging is not readily available. SSLDLD1 showed acceptable external discrimination across U.S. and Taiwanese datasets and may be more feasible for settings without nonroutine biomarkers, although local recalibration and validation of decision thresholds are needed before implementation across populations. ABBREVIATIONS:AASLD, American Association for the Study of Liver Diseases; AIC, Akaike information criterion; ALP, alkaline phosphatase; ALT, alanine aminotransferase; AST, aspartate aminotransferase; AUROC, area under the receiver-operating. characteristic curve; BMI, body mass index; CAP, controlled attenuation parameter; CI, confidence interval; CMRF, cardiometabolic risk factor; DM, diabetes mellitus; EWAS, exposure-wide association study; FLI, fatty liver index; FSI, Framingham steatosis index; FPG, fasting plasma glucose; GGT, gamma-glutamyl transferase; HbA1c, glycated hemoglobin; HCC, hepatocellular carcinoma; HDL, high-density lipoprotein; HOMA-IR, homeostasis model assessment of insulin resistance; HSI, hepatic steatosis index; IR, insulin resistance; LDL, low-density lipoprotein; MCHC, mean corpuscular hemoglobin concentration; MJ, MJ Health (Taiwan); NAFLD, nonalcoholic fatty liver disease; NAFLD-LFS, nonalcoholic fatty liver disease liver fat score; NHANES, National Health and Nutrition Examination Survey; NPV, negative predictive value; PPV, positive predictive value; SLD, steatotic liver disease; SLDLD, steatotic liver disease lab data; SLDLD1/SLDLD2, steatotic liver disease lab data indices 1/2; SSLDLD, simplified steatotic liver disease lab data; SSLDLD1/SSLDLD2, simplified steatotic liver disease lab data indices 1/2; TG, triglyceride; US-FLI, US fatty liver index; VCTE, vibration-controlled transient elastography; WC, waist circumference; WHR, waist-to-hip ratio.
BackgroundFucosyltransferase 2 (FUT2) deficiency exacerbates inflammation, a known risk factor for colon cancer. However, the precise role and underlying mechanism of FUT2 in regulating colon cancer cell differentiation remain unclear. Although olfactomedin-4 (OLFM4) has been known to have a tumor-suppressive effect, its functional interaction with FUT2 in colon cancer remains unexplored.MethodsFUT2 expression levels were assessed using TCGA and cBioPortal databases and in different colon cancer cell lines. ALP assays were performed to evaluate the effect of FUT2 on cancer cell differentiation. Transwell invasion assays, scratch assays, and tumor sphere formation assays were used to investigate the functional effects of FUT2 on colon cancer cells. N-glycosylation proteomics and UEA-I chromatography were used to identify the regulatory effect of FUT2 on OLFM4 fucosylation.ResultsFUT2 expression was associated with the differentiation degree of colon cancer cell lines. Based on their endogenous FUT2 expression, we overexpressed FUT2 in SW480 cells (low baseline) and knocked it down in HT29 cells (high baseline). Overexpressing FUT2 promoted the differentiation of SW480 cells and inhibited their migration, invasion, EMT, and stemness. Conversely, knockdown of FUT2 in HT29 cells reduced its degree of differentiation and increased its malignancy. N-glycosylation proteomics analysis and UEA-I chromatography indicated OLFM4 as a downstream target of FUT2. FUT2-mediated fucosylation of OLFM4 is positively correlated with the degree of cancer cell differentiation. Knockdown of OLFM4 attenuated differentiation in FUT2-overexpressing SW480 cells, while overexpression of OLFM4 produced opposite effects.ConclusionFUT2 promotes colon cancer cell differentiation by mediating OLFM4 fucosylation, suggesting that FUT2 may serve as a therapeutic target for colon cancer.
BACKGROUND:Hepatocellular carcinoma (HCC) is a lethal cancer. Early recurrence, i.e., recurrence within two years of curative treatment, is a major determinant of ultimate survival. MATERIALS AND METHODS:We included 625 patients with newly diagnosed early-stage HCC, i.e., Barcelona Clinic Liver Cancer (BCLC) Stage 0 or A, and Child-Pugh Class A liver disease who underwent percutaneous radiofrequency ablation (RFA) between 2011 and 2021 at our institution with a follow-up period of > 2 years. The patients were divided into Group 1 (patients who developed nonlocal recurrence or died within two years after RFA; n = 300 [48.0%]) and Group 2 (patients who developed local recurrence within two years or were recurrence-free and were alive for two years after RFA; n = 325 [52.0%]). RESULTS:Multivariate analysis showed that a Model for End-Stage Liver Disease (MELD) score of > 9, anti-hepatitis C virus (HCV) positivity, the presence of image-defined cirrhosis, treatment with antiviral therapies for hepatitis B virus or HCV, alpha-fetoprotein ≥ 20 ng/mL, multiple tumors, and larger tumor size were independent factors associated with Group 1. A nomogram was developed based on these variables to predict Group 1, with a concordance index of 68.3% (95% CI = 64.1%-72.5%). The 10-year overall survival of Group 1 was 28%, and that of Group 2 was 64%. CONCLUSION:We developed a nomogram to predict true early recurrence (i.e., nonlocal recurrence) of HCC after RFA.
Although there are various treatment modalities available for hepatocellular carcinoma (HCC), HCC is still among the most common causes of cancer-related death globally. Identifying independent biomarkers of poor prognosis in HCC patients remains a critical goal to allow timely intervention and ameliorate patient survival. MicroRNAs (miRNAs), the most widely investigated small noncoding RNAs to date, play a crucial role in regulating the initiation and progression of HCC. The expression of numerous miRNAs is altered in tumor tissues and blood specimens of HCC patients, underscoring their potential as promising prognostic biomarkers. This review offers an exhaustive overview of the current literature examining tissue- and circulation-derived miRNAs as single or combined independent prognostic biomarkers in HCC patients.
BACKGROUND:Inflammatory bowel disease (IBD) encompasses chronic gastrointestinal disorders that significantly impact patients' quality of life (QoL). While clinical trials support the efficacy and safety of vedolizumab, real-world data linking its effectiveness to QoL-related patient-reported outcomes remain limited. This prospective observational study assessed the effects of 14-week vedolizumab induction therapy on QoL (i.e., fatigue, mood, and sleep disturbances), clinical response, safety, and predictors of response. METHODS:A total of 257 patients with ulcerative colitis (UC; n = 205) and Crohn's disease (CD; n = 52) received 14-week vedolizumab induction therapy. Disease activity, QoL (assessed using the total Inflammatory Bowel Disease Questionnaire [IBDQ]), fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue [FACIT-Fatigue]), mood and sleep disturbances (PROMIS Depression and Sleep Disturbance scales), and selected biomarkers were evaluated. Clinical response was assessed using the Mayo score for UC and Crohn's Disease Activity Index (CDAI) score for CD. RESULTS:At Week 14, clinical response was observed in 82% of UC patients and 82.7% of CD patients. Median total IBDQ scores increased by 45.0 points in UC and 31.5 points in CD (p < 0.001). Median prorated FACIT-Fatigue scores increased by 5.0 points in both groups (p < 0.001), while median prorated PROMIS Sleep Disturbance and Depression T-scores decreased (p < 0.05). Improvement in QoL was moderately correlated with clinical response (r = 0.5). In logistic regression analysis, baseline patient characteristics indicative of advanced disease were associated with a reduced likelihood of clinical and QoL response to treatment. A total of 28 adverse events were reported, including 11 serious events and four treatment-related events. CONCLUSIONS:Vedolizumab reduced disease activity and led to a rapid improvement in QoL during the 14-week induction therapy in patients with IBD. Clinical response was positively correlated with QoL improvement. Predictors of reduced response were consistent with features of advanced disease.
BACKGROUND:Upper gastrointestinal bleeding (UGIB) is a significant cause of cirrhosis decompensation; however, there is still controversy on risk factors for poor outcomes. This study aims to explore the impact of additional variables, such as liver disease etiology and intensive care unit (ICU) accessibility, on mortality, rebleeding, and infection rates. METHODS:Cox regression analysis was employed to identify predictors associated with mortality and rebleeding, while Poisson regression analysis was utilized to assess associations with infections. RESULTS:A total of 228 patients were included, with the majority classified as Child-Pugh B and C. Among them, 96 patients (42.1%) had alcohol-associated liver disease (ALD), of which 45 (46.9%) were in alcohol abstinence. One hundred and ninety-five patients (85.5%) survived, while 33 (14.5%) died. Intubation was required for 31 patients (13.6%), and 28 were transferred to the ICU. Antibiotic prophylaxis was administered to 219 patients (96%), and 55 (24.1%) developed infections. Both orotracheal intubation and transfusions were associated with high mortality, whereas ALD was linked to a lower risk of death (p < 0.001, 0.029, and 0.005, respectively). Intubation was also correlated with an increased risk of rebleeding, while transfer to ICU reduced this complication (p = 0.012 and 0.045, respectively). The Child-Pugh score and length of hospitalization were associated with the occurrence of infections (p = 0.037 and < 0.001, respectively). CONCLUSIONS:Intubation, transfusions, liver disease etiology, and ICU accessibility are critical predictors following UGIB in cirrhosis. Additionally, the Child-Pugh score and duration of hospitalization are directly proportional to the risk of infections in this context. TRIAL REGISTRATION:ClinicalTrials.gov identifier: NCT04662918.
BackgroundMetabolic dysfunction-associated steatohepatitis (MASH), the progressive phenotype of metabolic dysfunction-associated steatotic liver disease (MASLD), is well recognized for its increased risk of progressing to cirrhosis and hepatocellular carcinoma (HCC). However, early diagnosis and identification of the MASH patients with a tendency toward malignancy HCC remain a significant challenge.MethodIn previous studies, we established a novel conditional inducible HRAS gene expression murine model with normal diet and lifestyle conditions, which exhibited 100% HCC incidence and recapitulated the four major progression stages of MASH to HCC: MASH, fibrosis, cirrhosis, and HCC. Based on this model, we revealed the potential markers of MASH prone to HCC characteristics of malignant MASH through RNA-Seq and bioinformatics analysis, and further confirmed by pathological biopsy, biochemical tests, inflammatory cytokines measurement, Oil O red staining, and immunohistochemical examination.ResultsFor MASH, the initial stage of HCC, we observed evidence of hyperlipidemia and insulin resistance in the HRAS mouse model based on blood morphology, biochemical parameters, and insulin tolerance test. Furthermore, the pathological features of MASH were confirmed by the presence of hepatocellular fatty vacuolar changes, lipid droplet accumulation, and inflammation. Then, RNA-Seq analysis revealed the molecular signatures of malignant MASH and revealed three novel potential markers associated with adverse progression of MASH to HCC: Klk1b4, Alox5, and Pla2g2e.ConclusionBased on a stable and novel murine model of MASH prone to HCC, we, for the first time, presented a comprehensive molecular signature and identified novel potential adverse progression markers of MASH prone to malignant HCC, which contributed possibly to early clinical diagnosis and prognostic assessment, even becoming potential therapeutic target.
Background and Aim: Since the stage of liver fibrosis is closely associated with mortality in nonalcoholic fatty liver disease (NAFLD) and metabolic dysfunction-associated steatotic liver disease (MASLD), it is essential to identify patients at risk of fibrosis progression. Basal metabolic rate (BMR) has gained attention in weight management for individuals with obesity. This study aimed to assess the accuracy of BMR in predicting the severity of fibrosis in patients with NAFLD or MASLD. Methods: Data from the National Health and Nutrition Examination Survey (NHANES) 2017-2020.03 were analyzed. Noninvasive diagnosis of liver steatosis was performed using the controlled attenuation parameter (CAP) measured by FibroScan. BMR calculated using the Harris-Benedict equation (BMRh) and the Mifflin-St Jeor equation (BMRm) was included in the analysis. Results: A total of 4184 individuals with MASLD were included, of whom 639 (15.27%) had significant fibrosis. Among 1577 individuals with NAFLD, 223 (14.14%) had significant fibrosis. Participants with significant fibrosis were older and had higher CAP, BMRh, and BMRm values (all p < 0.05). Multivariate analysis identified BMR as an independent risk factor for significant fibrosis. In obesity participants with MASLD or NAFLD, both BMRh and BMRm were positively correlated with BMI, CAP, and liver stiffness measurement (all p < 0.01). For obesity participants with MASLD or NAFLD, both BMRh- or BMRm-incorporating models had higher AUROCs than aspartate transaminase-to-platelet ratio index, fibrosis-4, and gamma-glutamyl transpeptidase to platelet ratio in predicting significant fibrosis (all p < 0.001). Conclusion: BMR is elevated in individuals with NAFLD or MASLD and significant liver fibrosis. The novel model combining age, male gender, BMR, aspartate transaminase, white blood cell counts, platelet counts, and diabetes outperformed conventional noninvasive scoring systems in predicting significant fibrosis in individuals with MASLD and obesity.
BACKGROUND AND AIMS:Metabolic dysfunction-associated steatotic liver disease (MASLD) is highly prevalent, and smoking is associated with greater disease severity. We investigated whether documented smoking cessation attempts among adults with MASLD were associated with liver-related outcomes, cardiovascular outcomes, and all-cause mortality. METHODS:We performed a retrospective cohort study using the TriNetX Research Network. Adults (≥ 18 years) with MASLD and documented smoking history were included. A smoking cessation attempt was defined by cessation counseling and/or cessation pharmacotherapy; comparators had no documented cessation attempt. Patients with depressive disorders and competing liver etiologies were excluded. Cohorts were matched 1:1 using propensity scores, and outcomes were analyzed using Cox proportional hazards models. Sensitivity analyses were performed at fixed follow-up horizons of 6 months, 1 year, and 2 years. RESULTS:Among 418,784 eligible patients, 85,639 had a documented cessation attempt and 333,145 did not; after matching, 83,315 patients remained in each cohort. In the matched cohort, cessation attempt was associated with lower hazards of cirrhosis progression (1.7% vs. 2.1%; HR 0.87, 95% CI 0.81-0.93), hepatocellular carcinoma (0.2% vs. 0.3%; HR 0.58, 95% CI 0.48-0.70), portal hypertension (0.8% vs. 1.1%; HR 0.77, 95% CI 0.70-0.86), and MASH progression (2.2% vs. 2.9%; HR 0.76, 95% CI 0.71-0.81). The cessation attempt was also associated with higher hazards of MACE (13.6% vs. 11.4%; HR 1.24, 95% CI 1.20-1.28), peripheral artery disease (4.1% vs. 3.2%; HR 1.33, 95% CI 1.26-1.40), and all-cause mortality (8.5% vs. 7.3%; HR 1.23, 95% CI 1.18-1.27). Fixed-horizon analyses showed similar patterns over time. CONCLUSIONS:In adults with MASLD and smoking history, documented smoking cessation attempts were associated with lower hazards of several liver outcomes but higher cardiovascular event rates and mortality, findings likely influenced by residual confounding and clinical risk clustering in patients receiving cessation interventions.
Background Esophageal variceal bleeding (EVB) is a serious complication of cirrhosis and a major cause of upper gastrointestinal hemorrhage, carrying substantial risks of mortality and treatment failure. Prognostic scores are essential for guiding management. This study evaluated and compared the predictive accuracy of the ABC and MAP(ASH) scores with established models in cirrhotic patients with EVB. Methods We retrospectively analyzed 278 cirrhotic patients admitted for EVB at Da Nang Hospital, Vietnam, between January 2022 and January 2025 who underwent endoscopic variceal ligation. Data were collected for ABC, MAP(ASH), AIMS65, and Glasgow-Blatchford scores. Primary outcomes were in-hospital mortality and 5-day treatment failure. Predictive performance was assessed using AUROCs and statistical comparisons. Results The ABC score achieved the highest AUROC for predicting in-hospital mortality (0.88), significantly surpassing the MAP(ASH), GBS, and AIMS65 scores (p < 0.001 for all pairwise comparisons). A similar trend was observed for predicting 5-day treatment failure, where the ABC score again demonstrated the highest AUROC (0.79), outperforming both the GBS and AIMS65 scores; however, it showed comparable performance to MAP(ASH) (p = 0.19). In addition, the ABC score's risk stratification (low, medium, and high) accurately differentiated patients with varying mortality and treatment failure rates. Conclusion The ABC score is a highly effective and reliable tool for predicting in-hospital mortality and early treatment failure in cirrhotic patients with EVB. While the MAP(ASH) score remains valuable for predicting early treatment failure, the ABC score offers superior overall prognostic accuracy. These findings suggest that the ABC score can guide clinical decisions, particularly in resource-limited settings.
BACKGROUND & AIMS:Prophylactic use of antibiotics was found to decrease mortality in patients with cirrhosis and acute variceal bleeding (AVB). Patients with Child A cirrhosis have a low risk of treatment failure and mortality. The present study was designed to investigate the association between antibiotics and Child-Pugh A patients with AVB. METHODS:This retrospective analysis was conducted on Child-Pugh class A cirrhotic patients presenting with AVB at West China Hospital between January 2016 and November 2022. The outcome indicators evaluated in this study include the rate of treatment failure within five days, mortality within 6 weeks, incidence of nosocomial infections, and 1-year cumulative mortality. RESULTS:This study ultimately enrolled 237 patients. The day of patients' admission was defined as Day 0. A total of 117 patients received prophylactic use of antibiotics on Days 0-1 (Group A), and 120 patients did not receive antibiotics on Days 0-1 (Group B). Baseline characteristics were well-balanced between the two groups. The 5-day treatment failure was 8.5% in Group A and 6.7% in Group B (p = 0.63). The 6-week mortality was 1.71% in Group A and 0% in Group B (p = 0.24). The incidence of nosocomial infection (5.98% vs. 6.67%, p = 1.00) and 1-year cumulative mortality (4.81% vs. 1.89%, p = 0.40) was comparable between the two groups. CONCLUSIONS:The antibiotics' prophylactic use was not associated with 5-day treatment failure or 6-week mortality. Prophylactic use of antibiotics may not be routinely necessary in patients with Child A cirrhosis and AVB.
