Systemic crosstalk between liver and brain is associated with microplastic-induced neurobehavioral toxicity in zebrafish.

Acute liver failure (ALF) and acute-on-chronic liver failure (ACLF) are associated with high mortality, and therapeutic plasma exchange (TPE) is increasingly used as a bridging therapy. This retrospective observational study evaluated outcomes and predictors of response in 22 liver failure patients undergoing TPE. Demographic details, hepatic encephalopathy (HE) grade, timing of TPE initiation, laboratory parameters, and clinical outcomes were analyzed. Clinical improvement was defined as ≥ 1-grade HE improvement with hemodynamic stabilization and biochemical recovery. The mean age was 22.9 years, with alcohol-related liver failure and Wilson's disease being the most common indications. Patients with lower HE grades showed significantly better clinical improvement (p = 0.031). Earlier initiation of TPE (< 10 days) demonstrated a trend toward improved outcomes, although not statistically significant. Significant reductions in bilirubin, INR, ALT, and AST were observed following TPE. However, biochemical improvement did not always correlate with clinical recovery. Early TPE may improve clinical and biochemical recovery and potentially prevent progression to advanced encephalopathy; however, larger prospective studies and randomized controlled trials are needed to establish the optimal timing of TPE and evaluate its prophylactic role in preventing worsening HE.

Atractylenolide I ameliorates acute-on-chronic liver failure (ACLF) by promoting autophagy and preserving mitochondrial function through mTOR inhibition.

Factor XIII Deficiency and Measurement.

The increasing global burden of liver disease leads to more frequent encounters of anesthesiologists with these high-risk patients. This review summarizes current evidence on perioperative management of patients with liver disease, acute liver failure, and acute-on-chronic liver failure undergoing surgery. The etiology of liver disease is evolving with metabolic dysfunction on the rise creating new perioperative challenges. Patients with liver disease are particularly at risk of cardiovascular events, impaired glucose regulation, and delayed anesthetic recovery. Conventional coagulation assays inadequately reflect bleeding risk in patients with liver disease, whereas viscoelastic-guided coagulation strategies are associated with reduced transfusion requirements. Overall, 90-day mortality is about five-fold higher in patients with liver cirrhosis compared with the general population. Risk scores and clinical assessments are necessary to balance patient- and procedure-related risks during preoperative evaluation. Patients with liver disease undergoing surgery constitute one of the highest-risk surgical populations. Systematic preoperative assessment, individualized anesthetic drug selection, viscoelastic-guided coagulation management, and early multidisciplinary involvement are essential to improve outcomes. High-quality prospective evidence to guide anesthetic practice in patients with liver disease is urgently needed.

Rifaximin in cirrhosis: when therapeutic drift meets antimicrobial stewardship.

Autoantibodies in the follow-up of autoimmune hepatitis.

Acute and chronic liver diseases are often related to the disorder of liver regeneration. However, there is no drug specifically approved for promoting liver regeneration especially in acute-on-chronic liver failure (ACLF). According to recent studies, inhibition of mitogen-activated protein kinase kinase 4 (MKK4) protein is critical for promoting hepatocyte proliferation and liver regeneration. However, MKK4 is widely present in various parts of the body as well with the similar binding pocket as MKK7 for small molecular inhibitors, and non-specific inhibition of MKK4 expression may pose an off-target risk in clinical practice. Therefore, MKK4-siRNA (siMKK4) was designed and optimized as a therapeutic gene for specific knockdown of MKK4 and avoid the off-target binding to mitogen-activated protein kinase kinase 7 (MKK7). Moreover, N-acetylgalactosamine (GalNAc)-modified lipid nanoparticles (LNPs) were used as gene delivery carriers to construct a dual targeted gene therapy system GalNAc-LNP-siMKK4 with liver tropism and active targeting to hepatocyte. GalNAc-LNP-siMKK4 can be efficiently constructed by the reverse phase evaporation method, with uniform particle size, good stability, biocompatibility, hepatocyte targeting ability, and high gene silence effect on the expression of MKK4. In vitro and in vivo experiments demonstrated that GalNAc-LNP-siMKK4 had good efficacy of gene therapy on promoting liver regeneration, reducing hepatocytes apoptosis, and promoting liver function recovery. The constructed hepatocyte-targeted gene therapy system GalNAc-LNP-siMKK4 could hold promise for treating ACLF based on reducing protein expression of MKK4 to promote hepatocytes proliferation specifically mediated by the targeting moiety of GalNAc. GalNAc-LNP-siMKK4 has targeting ability to deliver therapeutic genes to liver and hepatocytes, achieving a highly efficient gene therapy for promotion of liver regeneration and providing new therapeutic strategies for ACLF.

Chronic hepatitis delta (CHD) is the most severe form of viral hepatitis and is associated with accelerated progression to cirrhosis and liver failure. Bulevirtide has shown promising results in trials, but real-world data on its effectiveness, safety and impact on patient-reported outcomes (PROs) remain limited. To evaluate the effectiveness, safety, and PROs (quality-of life-QoL; adherence) of bulevirtide therapy in CHD patients undergoing a dedicated pharmacist-led patient-education program (PEP). A prospective observational study enrolled 31 consecutive CHD patients receiving bulevirtide 2 mg daily at a tertiary referral centre. Virological, biochemical and combined responses were assessed at weeks 24, 48 and 60. QoL (through EQ-5D-5L questionnaire), adherence (proportion of days covered), and adverse events were monitored during follow-up. Bulevirtide significantly reduced HDV-RNA by week 24 (p < 0.01), with further reductions at week 48 (p = 0.05) and 60 (p < 0.01). Liver tests improved significantly from baseline to week 24 (p < 0.01) and remained stable. Combined response was achieved in 43.7% of patients by week 60. QoL improved significantly (p = 0.03), and adherence was excellent (≥ 90%). Adverse events were mostly mild and transient. In real-world clinical practice, bulevirtide achieved sustained virological and biochemical improvements with favourable safety and quality-of-life outcomes, confirming its effectiveness in routine management of CHD. While the 60-week data (n = 16) are exploratory due to the sample size, these findings confirm its effectiveness and safety in routine management of CHD.

Acetyl coenzyme A acetyltransferase 2 is a novel regulator of liver regeneration in mice.

Ameliorative potential of pomegranate juice against synthetic colorant (E124)-induced biochemical and histopathological changes in the rat brain and testes.

The inappropriate use of Traditional Chinese Medicine (TCM) poses significant health risks. Realgar (As4S4), an arsenic-containing mineral traditionally consumed during China's Dragon Boat Festival, may induce acute toxicity following ingestion. This case series describes 8 patients (age: 1 - 80 years), including 2 children, with clinically confirmed acute arsenic poisoning subsequent to Dragon Boat Festival ingestion of realgar-containing water. We systematically evaluated clinical manifestations, laboratory parameters, and environmental arsenic concentrations. Urinary arsenic quantification was performed in all cases, with intravenous 2,3-dimercaptopropane sulfonic acid (DMPS) sodium salt initiated as chelation therapy. All patients developed gastrointestinal manifestations (nausea, vomiting, and diarrhea) within 5 - 14 days post exposure, accompanied by biochemical evidence of hepatic dysfunction. Laboratory analyses confirmed elevated urinary arsenic concentrations (> 0.032 mg/L) and identified arsenic contamination in drinking water (> 0.01 mg/L), with both measures exceeding established safety thresholds. Multi-organ dysfunction syndrome (MODS) was observed in 3 patients. All cases demonstrated a favorable clinical response to intravenous DMPS sodium salt chelation therapy, achieving clinical improvements and subsequent discharge. This case series documented acute arsenic toxicity secondary to realgar consumption in both adults and children. The findings underscore the critical need for targeted public health education initiatives and enhanced regulatory oversight regarding traditional medicinal practices, particularly during cultural festivals. Furthermore, they emphasize the necessity for heightened clinical vigilance in the prompt diagnosis and management of arsenic poisoning associated with traditional cultural practices.

Extracellular histone H3 induces METosis in acute liver failure by regulating the NRF2/HO-1/NQO1 pathway-mediated oxidative stress.

Safety of in vivo gene therapy in children: mechanisms and management of liver injury.

Animal models are essential for investigating disease pathogenesis and progression. Acute liver injury (ALI) precedes acute liver failure (ALF), establishing a crucial and close relationship between these conditions. Appropriate animal models are required in order to develop successful treatments for ALF. However, the inability to construct appropriate animal models that accurately represent the pathophysiological features of ALF has impeded research progress. The present review examined the pathophysiological mechanisms of ALF, evaluated the strengths and limitations of commonly used model organisms, and highlighted the advantages of mouse models in simulating the onset and progression of ALF. Furthermore, the review systematically summarized the varying drug and chemical dosages used in the development of drug‑induced and chemical‑induced ALF models in mice. In addition, whether ALI/ALF models constructed with different drug dosages accurately reflect disease progression has been a topic of critical discussion. Therefore, the present review proposed specific drug and chemical dosages for ALF model development and described future directions for developing optimal ALF animal models.

To retrospectively review the indications, timing, outcomes, and complications of membrane-based therapeutic plasma exchange (mTPE) in critically ill children at a single-center pediatric intensive care unit (PICU). Retrospective observational study. A tertiary-care PICU at All-India Institute of Medical Sciences (AIIMS), Raipur. A total of 106 patients aged 1 month to 18 years who underwent mTPE between January 2022 and December 2024. Patients had a median age of 144 months (IQR: 13-216). Renal and hepatic diseases were the most common indications. Overall, 61.3% of patients recovered and were discharged. Complications (inclusive of minor and line-related events) were observed in 35.8% of patients. Logistic regression analysis identified fluid-refractory shock at admission (p < 0.001), elevated Pediatric Risk of Mortality (PRISM-3) scores (p = 0.007), and concurrent continuous renal replacement therapy (CRRT) (p = 0.016) as statistically significant predictors of mortality. In the subgroup of patients with liver disease, time to mTPE initiation was an independent, significant predictor of mortality (p = 0.013). Membrane-based therapeutic plasma exchange is a safe and feasible adjunct therapy in critically ill children. While mTPE is most effective for conditions classified as American Society for Apheresis (ASFA) category I, its outcomes are highly variable and are significantly influenced by the underlying condition and the timing of the intervention, particularly for acute liver failure.

Type 2 diabetes mellitus (T2DM) has evolved into a global health crisis, driving a silent yet progressive hepatic pathological cascade that advances from nonalcoholic fatty liver disease to fibrosis and ultimately to cholangiocarcinoma with a high probability. However, the covert nature and gradual progression of this pathological cascade pose significant challenges for early detection and continuous monitoring. Herein, we design a multiparameter magnetic resonance imaging (MRI) strategy for visually monitoring T2DM-associated hepatic dysfunction across disease stages in vivo, based on dual-modality NaGdF4 nanoprobes. Owing to the long tumbling time (τR), NaGdF4 nanoprobes can enhance longitudinal relaxivity (r1) to brighten T1-weighted signals, while the regular arrangement of Gd3+ in the crystal induces magnetic anisotropy, creating local static magnetic field heterogeneity that generates negative signals in susceptibility-weighted imaging (SWI) sequences. The multiparametric MRI strategy combined with pathological analysis comprehensively characterized hepatic disease progression in a T2DM mouse model and confirmed the association between T2DM-induced liver injury and precancerous biliary transformation. With the NaGdF4 nanoprobes, key imaging features were successfully identified, including impaired hepatic metabolic capacity with prolonged contrast retention, hypoxia-induced neovascularization, and biliary tract lesions progressing from intermediate reactive hyperplasia to advanced cholangiocarcinoma. This multiparameter MRI approach provides noninvasive, high-resolution insights into hepatic metabolic dysfunction, vascular remodeling, and biliary pathology, offering a powerful tool for early diagnosis and prognostic assessment of T2DM-associated liver complications.

ASO Author Reflections: A Practical Prediction Model for Clinically Relevant Post-Hepatectomy Liver Failure After Major Liver Resection for HCC.

Global surgical volumes continue to rise, yet postoperative morbidity and mortality remain substantial, particularly among geriatric patients. The scarcity of multi-center prospective perioperative cohorts with active follow-up and large-scale, high-quality data limits the understanding of risk profiles and hinders individualized perioperative management in this population. To address this gap, the PeRiOperative sTress risk assEssment and Clinical decision cohorT (PROTECT) was established by creating a dedicated perioperative data platform for geriatric patients. This cohort profile specifically describes the study design, recruitment strategy, data structure, and current status of PROTECT. PROTECT is an ongoing, ambispective, real-world observational cohort across three tertiary medical centers. The study continuously enrolls inpatients aged ≥ 65years undergoing surgery under anesthesia. Preoperatively, standardized pre-anesthesia assessments are conducted to collect comprehensive medical information. Intraoperatively, anesthetic and surgical data, along with high-frequency biosignals are recorded. Postoperative outcomes are evaluated at 48hours, 7days, and 30days. Descriptive analyses were performed to summarize baseline characteristics and postoperative outcomes. The first participant was enrolled in August 2019. As of May 2025, 61,289 participants aged 65-100years have been included. The median age is 71years, and 44.4% are female. 52.2% are classified as American Society of Anesthesiologists physical status III or higher. The most common surgeries are abdominal (42.8%) and orthopedic (19.9%). Since October 2023, postoperative follow-up response rates have reached 96.5% at 48hours, 77.7% at 7days, and 72.1% at 30days. The 30-day all-cause mortality rate is 0.7%. The most frequent postoperative adverse outcomes are pulmonary infection (13.0%), nausea (11.9%), hepatic dysfunction (9.9%), and intensive care unit admission (8.6%). Leveraging the PROTECT dataset, several prediction models for major postoperative complications have already been developed and implemented in clinical practice. PROTECT provides one of the largest and most comprehensive perioperative datasets for geriatric population. It enables detailed characterization of risk profiles, morbidity, and mortality in geriatric patients, supports identification of contributors to adverse outcomes, and offers a robust platform for developing perioperative risk assessment tools and multivariable models to support clinical decision-making. Future expansions will include extending follow-up to 90, 180, and 365days and recruiting additional participating centers. Registered at chictr.org.cn on 15/10/2025 (ChiCTR2500110517).

This study aimed to evaluate the association between metabolic syndrome (MetS) and clinical outcomes in patients hospitalized for acute-on-chronic liver failure (ACLF), and to establish a prognostic prediction model incorporating MetS. A retrospective cohort study was conducted involving 303 ACLF patients admitted to a tertiary hospital between May 2023 and May 2025. Patients were categorized into two groups based on their MetS status (MetS group vs. non-MetS group). The primary outcome was 90-day all-cause mortality. Propensity score matching (PSM) was employed to balance baseline characteristics. The association was assessed using multivariable Cox regression and logistic regression analyses after adjusting for confounders. Based on the results of the multivariable analysis, a nomogram model for predicting 90-day mortality was constructed. The model's discriminative ability, calibration, and clinical utility were evaluated in both the training and testing sets using receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). After PSM, 206 patients (103 in the MetS group and 103 in the non-MetS group) were included in the final analysis. The 90-day mortality rate was significantly higher in the MetS group than in the non-MetS group (49.51% vs. 27.18%, p < 0.001). Multivariate Cox regression analysis showed that MetS, age, alanine aminotransferase (ALT), artificial liver support system (ALSS), transfusion times (TT), international normalized ratio (INR), C-reactive protein (CRP) and hepatocellular carcinoma (HCC) were independent predictors of 90-day death risk in patients with ACLF. The nomogram prediction model constructed based on these variables demonstrated excellent discriminative ability in both the training set (area under the curve, AUC = 0.877) and the testing set (AUC = 0.820). The calibration curve showed a high consistency between the predicted probabilities and the actual observations. Decision curve analysis confirmed the model's favorable net clinical benefit. MetS is an independent predictor of poor short-term prognosis in patients with ACLF, significantly increasing the risk of mortality. This study established a nomogram prediction model that integrates MetS, which can accurately assess patients' short-term mortality risk and may assist clinicians in early risk stratification.