Liver Failure Research Articles

Deficiency of myeloid NPC1 exacerbates liver injury and fibrosis by impairing macrophage efferocytosis.

Niemann-Pick C1 (NPC1), a lysosomal cholesterol transport protein, is required for efficient efferocytosis. Patients with Npc1 mutation are frequently accompanied with hepatic symptoms, including hepatomegaly, elevated liver transaminases, or even acute liver failure, but the pathogenic mechanism remains unknown. Our work aims to characterize the functional role of myeloid NPC1 in liver injury and elucidate its underlying mechanism. Analyses of injured livers from patients with liver diseases and mouse models were conducted to examine NPC1 expression. Myeloid cell-specific Npc1 knockout mice were constructed to determine the functional role of macrophage NPC1 in liver injury. Isolated macrophages were subjected to in vitro mechanistical assays. We found that NPC1 is mainly expressed in hepatic macrophages. Its mRNA and protein expression are significantly elevated in injured livers from both patients and mouse models. Tissue-specific deletion of myeloid Npc1 increased liver inflammation, levels of serum liver function enzymes, and liver fibrosis in mouse models of liver injury induced by carbon tetrachloride (CCl4) injection and methionine-and-choline-deficient (MCD) diets. Further analyses indicate that Npc1 deficiency in mouse models of liver injury resulted in increased levels of serum HMGB1 and mitochondrial DNA, promoted hepatic macrophage proinflammatory activation, M1 polarization, led to overproduction of hepatic inflammatory cytokines/chemokines, e.g. CCL2 and STING/NFκB pathway activation. In vitro mechanistical studies reveal that Npc1-deficient macrophages exhibited inefficient efferocytosis, partly due to impaired cargo degradation. These findings indicate that elevated expression of myeloid NPC1 in liver diseases protects liver from injury by promoting macrophage efferocytosis of damaged cells. Dysfunction of NPC1 aggravates liver injury, suggesting that NPC1 may be a potential therapeutic target for treating liver diseases.

Evaluation of a clinical decision support alert to identify hepatic dysfunction and need for medication therapy adjustment in hospitalized patients.

In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. To optimize the hepatic dysfunction alert tool at our institution to identify appropriate patients and minimize irrelevant alerts. This single-center, retrospective review included adults hospitalized over a 1-month period for whom a hepatic dysfunction alert fired for a medication order placed in the electronic health record. The existing alert determines hepatic dysfunction based on laboratory tests. The primary objective was to determine the proportion of patients with an alert that was deemed to be clinically relevant. Alerts were considered relevant if the patient had a Child-Pugh score in class B or C and were ordered a medication with a hepatic warning from FDA or LiverTox. The performance of 14 alternative models was evaluated. A total of 1,541 alerts fired for 309 patients. Of these patients, 155 were randomly selected for the analysis, and the alert was deemed relevant in 86 patients (55%). Patients with relevant alerts were more likely to have documented liver disease and worsening measures on liver function tests. Of the alternative models evaluated, a model that excluded INR and albumin resulted in a 27% decrease in the number of alerts fired, of which 73% were relevant; however, it failed to identify 30% of patients with relevant hepatic dysfunction. None of the other models performed better. The existing hepatic dysfunction clinical decision support tool correctly identifies patients with relevant hepatic dysfunction only 55% of the time. Alternative models were able to improve the rate of relevant results, but not without missing patients with relevant hepatic dysfunction.

Exploring the predictive value of serum lipids for short‐term prognosis in patients with acute‐on‐chronic liver failure

AbstractAimsAcute‐on‐chronic liver failure (ACLF) is defined as acute liver injury superimposed on chronic liver disease, resulting in a significantly increased short‐term mortality rate. Serum lipids are associated with the severity of liver disease and contribute to the prognostic assessment for cirrhosis and liver failure. However, the presentation of serum lipids varies in different studies, making it difficult to draw definitive conclusions. This study aimed to investigate the predictive value of serum lipids for short‐term prognosis in patients with ACLF.MethodsThis retrospective analysis was conducted using the clinical data of patients hospitalized for ACLF between January 2018 and December 2021. The collected data were subjected to Least Absolute Shrinkage and Selection Operator and logistic regression analyses to identify the independent predictors of 28‐day and 90‐day mortality. Separate regression models were developed for each identified serum lipid. These models were combined with the Model for End‐Stage Liver Disease (MELD), MELD combined with serum sodium concentration (MELD‐Na), Chronic Liver Failure Consortium Acute‐on‐chronic Liver Failure (CLIF‐C ACLF), and Chinese Group on the Study of Severe Hepatitis B‐ACLF (COSSH‐ACLF) scores to construct new models. The performance of these models was evaluated using the area under the receiver operating characteristic curve (AUC), Nagelkerke R2, Brier score, net reclassification index (NRI), and integrated discrimination improvement (IDI) to assess the prognostic ability of serum lipids.ResultsThis study included 266 patients with ACLF, of whom 25.9% (69/266) died within 28 days and 38.5% (102/265, with 1 lost to follow‐up) died within 90 days. The independent predictors of 28‐day mortality were age, the presence of overt hepatic encephalopathy at admission, high‐density lipoprotein cholesterol (HDL‐C) levels, and international normalized ratio (INR). The independent predictors of 90‐day mortality were age, albumin levels, serum creatinine levels, and INR. The comparative analysis revealed that the AUC of all other models exceeded that of HDL‐C (p < 0.001). The COSSH‐ACLF model demonstrated superior predictive ability compared with the MELD and HDL‐MELD models (p = 0.013 and 0.017, respectively). Furthermore, the HDL‐COSSH‐ACLF model exhibited a similar trend in predictive ability compared with the latter two models (p = 0.009). No significant differences were observed in the AUC performances of the other models. A comparison of NRI calculated using the cutoff values assigned by equal assignment revealed that the addition of HDL‐C improved the predictive ability of the MELD score by 4.6% (NRI = 0.0460, p = 0.036). The MELD‐Na score exhibited an 8.4% improvement (NRI = 0.0844, p = 0.047), while the COSSH‐ACLF score demonstrated a 14.4% improvement (NRI = 0.1443, p = 0.015). However, these changes did not significantly impact the capacity of the CLIF‐C ACLF score (NRI = 0.0350, p = 0.141). No significant differences were observed in the IDI comparisons between the models with different cutoff values (all p > 0.050).ConclusionsSerum HDL‐C is an independent predictor of 28‐day mortality in patients with ACLF. Although it has inferior predictive ability when considered alone, HDL‐C enhances the predictive capacity of MELD, MELD‐Na, and COSSH‐ACLF when incorporated into these models.

Abstract 4148085: Transfer to ‘Hub’ Hospitals and Outcomes in Cardiogenic Shock

Introduction: Patients with cardiogenic shock (CS) have high mortality. Many CS patients present to non-tertiary care centers. Limited data exist on outcomes for patients transferred to “hub” CS centers for both acute myocardial infarction (AMI) and non-AMI etiologies. This study sought to compare the characteristics and outcomes of transferred CS patients compared to patients presenting to a hub center. Methodology: Adults (≥18 years) with a primary or secondary diagnosis of CS were identified from the National Readmissions Database (2016-2020) and stratified by transfer status. Overlap propensity score (PS) weighting was performed to assess the association between in-hospital mortality, length of stay (LOS) and transfer status. Results: Of 314,098 CS patients (AMICS 27%, non-AMICS 73%), 30,630 (9.8%) were transferred. Compared to non-transferred patients, transferred patients were on average younger (65 [interquartile range {IQR} 55-73] vs. 68 [IQR 58-77] years), more likely to be female (34% vs. 37%), less frequently with Medicare as primary payor (55% vs. 62%), and with higher comorbidity (Elixhauser index 8 [IQR 6-9] vs. 6 [IQR 5-8]) (all p <0.001). Transferred patients had higher rates of respiratory failure (70% vs. 64%), renal failure (71% vs. 60%), hepatic failure (25% vs. 17%), bleeding complications (28% vs. 17%), and arrhythmias (59% vs. 52%) (all p <0.001). Transferred patients were also more likely to undergo percutaneous coronary intervention (22% vs. 19%), coronary artery bypass grafting (13% vs. 8%), pulmonary artery catheter insertion (36% vs.16%), placement of intra-aortic balloon pump (25% vs.13%), percutaneous left ventricular assist device (13% vs. 7%), and extracorporeal membrane oxygenation (7% vs. 2%), receive invasive mechanical ventilation (3% vs. 2%), and undergo hemodialysis (17% vs. 11%) (all p <0.001). In-hospital mortality was significantly lower in transferred patients – 39% vs. 47.1%; unadjusted odds ratio 0.71 (95% confidence interval 0.70-0.73); adjusted PS weighting odds ratio 0.73 (95% confidence interval 0.71-0.76), p <0.001. Transferred patients had a longer median LOS (13 [IQR 7-22] vs. 6 [IQR 3-11] days, p <0.001). Conclusion: Transferred CS patients had higher use of cardiovascular procedures and organ support therapies and lower in-hospital mortality suggesting patients were appropriately selected for transfer.

A Novel Preoperative Classification System for Selecting Suitable Surgeries in Liver Transplant Patients with Portal Vein Cavernous Transformation

Background To evaluate the new preoperative Changgung classification (CC) system of portal vein thrombosis (PVT) in choosing suitable operative procedures to reconstruct portal veins during liver transplantation (LT) in patients with portal vein cavernous transformation (PVCT). Methods This retrospective observational study analyzed data from allograft LTs performed for various liver diseases Results The study included 22 males and 4 females with LT indications comprising cirrhosis (n = 9), hepatocellular carcinoma (n = 12), PVCT (n = 2), liver failure from fulminant hepatitis B (n = 1), dysfunction of transplanted liver (n = 1), and chronic rejection of transplanted liver (n = 1). Patients were classified according to Yerdel (21 Yerdel II and 5 Yerdel III) and CC (C1–C5). In total 16 simple operations were performed on C1–C3 cases and 9 complex operations on C4–C5 cases, with one additional simple operation. The distribution according to the Yerdel classification was 16 simple and 5 complex operations in Yerdel II cases and 1 simple and 4 complex operations in Yerdel III cases. The median follow-up time was 27.5 months with overall one-year and three-year OS rates of 88.1% and 83.9% for the cohort. Specifically, the one-year OS rates for patients classified as C1-3 vs. C4-5 were 93.3% and 80.0%, while the three-year OS rates were 86.7% and 80.0%, respectively (p = 0.526). Conclusion The CC proposed in this study shows comparable potential to the Yerdel classification in preoperatively identifying the need for complex surgical techniques in LT patients with PVCT and may also have predictive power for the survival benefits following LT.

Suspected hepatic hydrothorax secondary to cirrhosis in a dog

AbstractAn 8‐year‐old, entire, female labrador retriever presented with a 2‐week history of abdominal distension. Biochemistry identified hepatic dysfunction (elevated hepatobiliary markers, hypocholesterolaemia). Abdominal ultrasonography documented an irregular liver and a large volume of anechoic peritoneal effusion, which laboratory analysis confirmed as a protein‐poor transudate. Thoracic computed tomography identified a moderate volume of pleural effusion with a similar composition to the peritoneal fluid. Hepatic histopathology was consistent with cirrhosis secondary to chronic hepatitis and, in the absence of another cause for the pleural effusion, hydrothorax secondary to the hepatic disease was suspected. The patient was started on ciclosporin for treatment of the underlying liver disease, but developed signs consistent with disseminated intravascular coagulopathy 24 hours later and was humanely euthanased. As reported in humans, hydrothorax may therefore occur secondary to cirrhosis in dogs and should be considered as a differential diagnosis for pleural effusion in patients with advanced hepatic disease and concurrent peritoneal effusion.

Abstract 4140198: Impact of Non-ST-segment elevation Myocardial Infarction on outcomes of Diabetic Ketoacidosis in Hospitalized Patients: A National Inpatient Sample Analysis

Introduction: Diabetes Mellitus (DM) has a broad spectrum of complications and is one of the leading 5 causes of hospital admissions in the US. Decompensated DM is associated with high mortality in hospitalized patients. Cardiac ischemia and related events are proposed to be increasingly prevalent in hospitalized patients with decompensated diabetes. Numerous studies and reports have suggested that elevation in troponin levels is associated with high mortality in such patients. Notably, there have only been a few studies that assessed the prevalence of NSTEMI (Non-ST segment elevation myocardial infarction) and its effect on outcomes in patients hospitalized with Diabetes ketoacidosis (DKA). Methods: We aimed to compare the outcomes of DKA in hospitalized adults (age >18 years) with NSTMI with those without NSTEMI using the National Inpatient Sample (NIS) database from 2018 to 2020. NIS is the largest publicly available all-payer inpatient care database in the United States, containing data on more than seven million hospital stays. Results: There were a total of 1113295 hospitalizations identified with a diagnosis of DKA. Of these, 9860 (0.88%) patients had NSTEMI. The mean age of this subpopulation was 38.71 years. Among these patients, 48.59% were female, and 58.40% were male. We attempted to assess the impact of NSTEMI on the occurrence of complications such as cardiac arrest, acute renal failure (ARF), Acute liver failure (ALF), Acute heart failure (Acute HF), and acute respiratory failure in patients admitted with DKA. The results of this analysis are depicted in the table below. The cost of hospitalization for DKA with NSTEMI was $35878 higher and the length of stay was 50% longer compared to the patients with DKA without NSTEMI. The Odds ratio for mortality was 2.84 for patients with NSTEMI. Conclusions: Our analysis suggests that the occurrence of NSTEMI negatively impacts outcomes in DKA patients. The occurrence of primary outcomes assessed in this study (Cardiac arrest, ARF, ALF, Acute HF, and Acute respiratory failure) was significantly higher in DKA patients with concomitant diagnosis of NSTEMI. NSTEMI also increased the cost burden on hospitalizations for DKA.

Predicting post-hepatectomy liver failure in patients with hepatocellular carcinoma: nomograms based on deep learning analysis of gadoxetic acid-enhanced MRI.

This study aimed to develop nomograms for predicting post-hepatectomy liver failure (PHLF) in patients with hepatocellular carcinoma (HCC), using deep learning analysis of Gadoxetic acid-enhanced hepatobiliary (HBP) MRI. This retrospective study analyzed patients who underwent gadoxetic acid-enhanced MRI and hepatectomy for HCC between 2016 and 2020 at two referral centers. Using a deep learning algorithm, volumes and signal intensities of whole non-tumor liver, expected remnant liver, and spleen were measured on HBP images. Two multivariable logistic regression models were formulated to predict PHLF, defined and graded by the International Study Group of Liver Surgery: one based on whole non-tumor liver measurements (whole liver model) and the other on expected remnant liver measurements (remnant liver model). The models were presented as nomograms and a web-based calculator. Discrimination performance was evaluated using the area under the receiver operating curve (AUC), with internal validation through 1000-fold bootstrapping. The study included 1760 patients (1395 male; mean age ± standard deviation, 60 ± 10 years), with 137 (7.8%) developing PHLF. Nomogram predictors included sex, gamma-glutamyl transpeptidase, prothrombin time international normalized ratio, platelets, extent of liver resection, and MRI variables derived from the liver volume, liver-to-spleen signal intensity ratio, and spleen volume. The whole liver and the remnant liver nomograms demonstrated strong predictive performance for PHLF (optimism-corrected AUC of 0.78 and 0.81, respectively) and symptomatic (grades B and C) PHLF (optimism-corrected AUC of 0.81 and 0.84, respectively). Nomograms based on deep learning analysis of gadoxetic acid-enhanced HBP images accurately stratify the risk of PHLF. Question Can PHLF be predicted by integrating clinical and MRI-derived volume and functional variables through deep learning analysis of gadoxetic acid-enhanced MRI? Findings Whole liver and remnant liver nomograms demonstrated strong predictive performance for PHLF with the optimism-corrected area under the curve of 0.78 and 0.81, respectively. Clinical relevance These nomograms can effectively stratify the risk of PHLF, providing a valuable tool for treatment decisions regarding hepatectomy for HCC.

Hepatic Failure in Pancreonecrosis and the Development of Abdominal Sepsis

It is well known that acute destructive pancreatitis, pancreonecrosis is accompanied by severe endogenous intoxication, often leading to the development of multiple organ failure syndrome, liver failure is one of the important links in this process. The mortality rate of patients with pancreonecrosis related to liver failure is as high as 83%, and approximately 5% of patients with pancreonecrosis have fulminant liver failure. Proven: liver function is closely related to the progression of purulent-necrotic complications in patients with acute destructive pancreonecrosis. The authors present the data of literature on the importance of liver failure in the course and prognosis of acute destructive pancreatitis. The pathogenetic role of lipid peroxidation processes are especially emphasized. The controversial issues of portal and systemic bacteremia and toxemia in the development of pancreatogenic abdominal sepsis are discussed, as well as the involvement of the lymphatic system. The authors’ research aims to analytically dissect and summarize the processes underlying the clinical manifestations of liver failure in pancreatic necrosis and their underlying mechanisms, which may provide new insights for further understanding and better management of liver failure in patients with pancreatic necrosis and abdominal sepsis.

Hepatitis E as a trigger for Acute-on-Chronic Liver Failure.

Acute hepatitis E virus (HEV) infection is typically self-limiting and has a favourable prognosis. However, certain populations such as patients with pre-existing chronic liver disease may experience severe manifestations, including progression to acute-on-chronic liver failure (ACLF). Among viral hepatitis types, hepatitis A, E, and B are major causes of ACLF. Active screening and early diagnosis of HEV infection in patients with cirrhosis, especially those who develop ACLF, can improve management and enable timely antiviral therapy. Preventive measures, including HEV vaccination for high-risk groups, could reduce the morbidity and mortality associated with hepatitis E.

Impact of ascites grading and non-selective β-blockers on 1-year prognosis of Acute-on-chronic liver failure

Objective: To investigate the influence of ascites grading and non-selective β- blockers (NSBBs) on the 1-year prognosis of patients with acute-on-chronic liver failure (ACLF). Methods: A total of 1 386 patients with ACLF were graded for ascites and followed up for one year. Kaplan-Meier Log-rank test and Cox regression were used for multivariate regression to analyze the effects of ascites grading and NSBBs on the 1-year prognosis of ACLF. Results: The incidence of ascites in 1 836 patients with ACLF was 77.56% on admission. Ascites grade was related to the 1-year prognosis of ACLF [log rank (Mantel-Cox) χ2=21.384, p=0.000]. Cox stepwise regression analysis showed that ascites grade, age, gastrointestinal bleeding, pulmonary infection, acute kidney injury, prothrombin time activity(PTA), urea, MELD-Na score, and application of NSBBs were closely related to the 1-year prognosis of ACLF. The result of Kaplan-Meier Log-rank test for patients treated with NSBBs in the grade 2/3 ascites group suggest that NSBBs can improve the 1-year survival rate of ACLF patients with grade 2 and grade 3 ascites ( log rank (Mantel-Cox) χ2=6.113, p=0.013). Conclusions: Ascites grading and application of NSBBs can affect the 1-year prognosis of ACLF. NSBBs may be beneficial to the long-term prognosis of ACLF. Patients treated with NSBBs before the onset of ACLF should continue NSBBs treatment.

Plasma Exchange as a Viable Therapeutic Option in a Patient With Alcohol-Related Acute-on-Chronic Liver Failure: A Case Report

Plasma Exchange as a Viable Therapeutic Option in a Patient With Alcohol-Related Acute-on-Chronic Liver Failure: A Case Report

CTNI-12. TIRABRUTINIB FOR RECURRENT/REFRACTORY PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA –A SINGLE-INSTITUTION RETROSPECTIVE ANALYSIS–

Abstract BACKGROUND Tirabrutinib is a second-generation, highly selective oral Bruton’s tyrosine kinase inhibitor and approved for the treatment of recurrent/refractory primary central nervous system lymphoma (PCNSL) in Japan. We reviewed our single institution experiments of tirabrutinib. MATERIALS AND METHODS Our institutional review board approved this retrospective study. Twenty-eight patients with recurrent or refractory PCNSL treated with tirabrutinib at our institution between 2020 and 2024 were included. Information regarding the patient’s age, gender, imaging findings, pathological results, including immunostaining findings, and treatment information, including chemotherapy and radiation therapy, was obtained from medical records. RESULTS Tirabrutinib was administered to 14 patients with recurrent cases (20-85 years old, median 69.5 years old, 9 males and 5 females), 14 with refractory cases (59-87 years old, median 74 years old, 9 males and 5 females). Three male patients received rechallenge with tirabrutinib against re-relapsed. We assessed the effectiveness of tirabrutinib and observed complete response (CR) in 12 cases, partial response (PR) in 1 case, and progressive disease (PD) in 1 case among refractory patients. In recurrent cases, we observed CR in 8 cases, PR in 1 case, stable disease (SD) in 3 cases, and PD in 2 cases. In rechallenge for re-relapsed cases, we observed CR in 2 cases and PD in 1 case. The progression-free survival following beginning of tirabrutinib was 12.95 months for refractory cases and 8.2 months for recurrent cases. The overall survival was 25 months for refractory cases and 12.8 months for recurrent cases. One patient each experienced CTCAE grade 3 interstitial pneumonia or liver failure, both of which improved after discontinuing the medication. Four patients exhibited grade 1-2 skin rashes. CONCLUSIONS Tirabrutinib demonstrates efficacy and high tolerability for the treatment of recurrent/refractory PCNSL in real-world settings.

Evolution and Impact of Hepatitis A Epidemiology in Europe-Systematic Literature Review of the Last 20 Years.

While globally hepatitis A (hepA) infections occur in 150 million people annually, European high-income countries now have a low endemicity. However, this results in a more susceptible adult population which is prone to severe illness. To determine current epidemiological characteristics, we performed a systematic literature review to assess the severity of hepA disease in the past two decades in 11 European countries (i.e., Denmark, France, Germany, Greece, Hungary, Italy, the Netherlands, Spain, Sweden, Switzerland and the United Kingdom). Literature search was performed using PubMed and Embase between 1 January 2001 and 14 April 2021. Search terms included the disease (hepA), the 11 selected countries, the term 'outbreaks' and its synonyms, outcomes and terms for hepA virus circulation. In total, 43 records reported data on hepA disease outcomes. Hospitalisation rates varied between the countries, with annual rates exceeding 50% at least once in seven countries. The lowest hospitalisation rates were reported for the Netherlands (≤ 32%) and the highest for Greece (≥ 81%). Liver failure, haemorrhagic and other complications were rarely reported, and case fatality rates were low (0.03%-0.26%). Our findings are consistent with the trends observed globally. This systematic literature review highlights the need to increase awareness of hepA risks and to strengthen prevention strategies. Continuous monitoring of epidemiological data is crucial to assess which populations would most benefit from prevention, mainly with respect to future vaccination recommendations.

Ultrasound-Defined Sarcopenia Independently Predicts Acute Decompensation in Advanced Chronic Liver Disease.

It has been shown that in patients with liver cirrhosis, sarcopenia is a predictor of acute decompensation (AD), acute-on-chronic liver failure (ACLF) and death. However, computer tomography (CT), as a suggested standard method for diagnosing sarcopenia, is resource intensive and involves radiation exposure. Therefore, in this study, we evaluate the muscle thickness of quadriceps femoris measured by ultrasound (US) as a prognostic parameter for AD and all-cause mortality in chronic liver disease. Sixty-three patients with chronic liver disease and signs of portal hypertension were analysed in this prospective monocentric study for the occurrence of acute decompensation such as hepatic encephalopathy, ascites, haemorrhage and liver-related death within 1 year. We assessed muscle thickness at three different heights in terms of suitability as a predictor. Among all 63 patients, 15 patients experienced acute decompensation, and 9 patients died due to liver-related death. We found the upper third of the muscle, measured without applying pressure with the transducer, to be the most significant for predicting AD/ACLF [AUC 0.739 (confidence interval (CI) 0.604-0.874, p = 0.006]. A cut-off value of US-defined muscle thickness standardized per height for identifying sarcopenia was determined (1.83 cm/m). Patients with US-defined sarcopenia showed significantly higher rates of AD (38.9% vs. 3.7%, p = 0.001) and all-over 1-year mortality (27.8% vs. 3.7%, p = 0.013). The mean AD free survival time is 8.3 months (95% CI 6.6-9.9) for sarcopenic patients and 11.8 months (95% CI 11.0-12.6) for the non-sarcopenic cohorts. Corresponding CT analysis displayed similar results for AD free survival for both groups (40% AD rate in the sarcopenic group vs. 7% AD rate in the non-sarcopenic group, p = 0.001). The risk for AD was significantly higher in the sarcopenic cohort compared with those without sarcopenia in both US and CT (US: HR 16.6; p = 0.009; 95% CI 2.0-136.0; CT: HR 8.7; p = 0.017; 95% CI 1.5-51.0). CT and US displayed a moderate agreement (p = 0.006; κ = 0.379). Sarcopenia classification based on US measurements is shown to be an independent predictor of AD occurrence within 1 year. This pilot study is the first to suggest that screening for sarcopenia by ultrasonography may be useful for risk assessment in patients with chronic liver disease and signs of portal hypertension.

Survival of Patients with Alcohol-Related Liver Disease Cirrhosis—Usefulness of the New Liver Mortality Inpatients Prognostic Score

Background/Objectives: Alcohol can directly damage the liver, causing steatosis, steatohepatitis, cirrhosis, and hepatocellular cancer. The aim of this study was to examine 28-day survival in hospitalized patients with alcohol-related liver disease (ALD) cirrhosis, as well as to develop and validate a new survival prediction model. Methods: A total of 145 patients with ALD cirrhosis were included; 107 were diagnosed with acute decompensation (AD) and 38 with acute-on-chronic liver failure (ACLF). The new liver mortality inpatients (LIV-IN) score was calculated using the following variables: hepatic encephalopathy (HE), hepatorenal syndrome (HRS), ascites, systemic inflammatory response syndrome (SIRS), community-acquired infection (CAI), and fibrinogen. The diagnostic accuracy of the LIV-IN score was tested, along with the model for end-stage liver disease (MELD), model for end-stage liver disease-sodium (MELD-Na), albumin-bilirubin (ALBI), neutrophil-to-lymphocyte ratio (NLR), chronic liver failure consortium-C acute decompensation (CLIF-C AD), and chronic liver failure consortium-acute-on-chronic liver failure (CLIF-C ACLF). Results: Lethal outcome occurred in 46 (31.7%) patients. The mortality rate was higher in the ACLF group (n = 22, 57.9%) compared to the AD group (n = 24, 22.4%) (p < 0.01). The highest predictive power for short-term mortality was observed for the LIV-IN score (AUC 73.4%, p < 0.01). In patients with AD, the diagnostic accuracy of the CLIF-C AD score was better than for the LIV-IN score (AUC 0.699; p = 0.004, AUC 0.686; p = 0.007, respectively). In patients with ACLF, only the LIV-IN score had statistically significant discriminative power in predicting 28-day survival. Conclusions: The liver mortality inpatients prognostic score is a new, reliable prognostic model in predicting 28-day mortality.

Accumulation of polyunsaturated lipids fuels ferroptosis to promote liver failure after extended hepatectomy in mice

Background Post-hepatectomy liver failure (PHLF) is a fatal complication of hepatectomy. However, the mechanism of hepatocyte injury in PHLF remains elusive. Methods PHLF was induced by extended 86% hepatectomy (eHx) in mice. Lipidomics was performed to investigate the eHx-induced lipid alteration in the residual liver. Ferroptosis was assessed to screen the hepatocyte injury induced by eHx. The therapeutic effects of ferrostatin-1 (Fer-1) on PHLF were evaluated. Results PHLF was induced by eHx with elevation in markers of hepatocyte injury and mortality in mice within 48 h after surgery. eHx-induced hepatocyte injury was manifested by hepatocyte enlargement and hepatocyte death with glycogen depletion and lipid accumulation. Lipidomics revealed that eHx induced the accumulation of ferroptosis-favored polyunsaturated lipids. Ferroptosis was found to mediate the eHx-induced hepatocyte death in the residual liver during the development of PHLF. Fer-1 could attenuate the eHx-induced ferroptotic hepatocyte death and PHLF in mice. Conclusions Ferroptosis partly mediates the eHx-induced hepatocyte injury during the development of PHLF. Accumulation of polyunsaturated lipids in hepatocytes may promote eHx-induced ferroptosis, and targeting lipid peroxidation is a potential therapeutic strategy for PHLF.

Comparative Transcriptome Analysis Reveals the Impact of a High-Fat Diet on Hepatic Metabolic Function in Tilapia (Oreochromis niloticus)

Hepatic steatosis is prevalent among cultured fish, yet the molecular mechanisms remain incompletely understood. This study aimed to assess changes in hepatic metabolic function in tilapia and to explore the underlying molecular mechanisms through transcriptomic analyses. Tilapia were allocated into two groups: a normal control (Ctr)-fed group and a high-fat diet (HFD)-fed group. Serum biochemical analyses revealed that HFD feeding led to liver damage and lipid accumulation, characterized by elevated levels of glutamic-pyruvic transaminase (GPT), glutamic-oxaloacetic transaminase (GOT), triglycerides (TGs), and total cholesterol (TC). Transcriptome analysis showed that 538 genes were significantly downregulated, and 460 genes were significantly upregulated in the HFD-fed fish. Gene Ontology (GO) enrichment analysis showed that these differentially expressed genes (DEGs) were apparently involved in the lipid metabolic process and monocarboxylic acid metabolic process. Meanwhile, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis indicated significant alterations in pathways of steroid biosynthesis, porphyrin metabolism, terpenoid backbone biosynthesis, and retinol metabolism after HFD feeding. Additionally, results from Gene Set Enrichment Analysis (GSEA) revealed that gene expression patterns in pathways including oxidative phosphorylation, protein export, protein processing in the endoplasmic reticulum, and ribosome biogenesis were positively enriched in the HFD-fed tilapia. These findings provide novel insights into the mechanisms underlying HFD-induced hepatic dysfunction in fish, contributing to the optimization of feeding strategies in aquaculture.

Preliminary Exploration of the Protective Mechanism of Eugenol Against Acute Liver Injury Induced by Thioacetamide Based on Metabolomics

Acute liver injury (ALI) is a significant global public health issue that can rapidly develop into acute liver failure, seriously endangering the safety of patients. Eugenol has various pharmacological effects such as antioxidant, anti-inflammatory, antibacterial, and neuroprotective properties. Through pathological section observation, eugenol can alleviate the degree of liver damage caused by thioacetamide. Based on metabolomics, a total of 87 metabolites were found to have differences in content between the control group and the thioacetamide group. Compared with the control group, the contents of 42 metabolites had increased and 45 metabolites had decreased in the thioacetamide group. These differential expressed metabolites mainly indicate inflammatory damage, oxidative damage, and abnormal energy metabolism. There were 269 metabolites with differences in content between the eugenol intervention group and the thioacetamide group. Compared with the thioacetamide group, there were 101 metabolites with increased content and 168 metabolites with decreased content in the eugenol intervention group. These differential expressed metabolites suggest that eugenol intervention can correct inflammation damage, oxidative damage, and energy metabolism abnormalities caused by TAA. This study found through pathological section observation and metabolomics that eugenol has a protective effect on acute liver injury caused by thioacetamide, and the protective mechanism may be related to the antioxidant and anti-inflammatory effects of eugenol.

Screening of Herbs with Potential Modulation of NLRP3 Inflammasomes for Acute Liver Failure: A Study Based on the Herb-Compound-Target Network and the ssGSEA Algorithm.

NLRP3 inflammasomes are considered to be key factors in the pathogenesis of Acute Liver Failure (ALF). Some Traditional Chinese Medicines (TCMs) have shown protective and therapeutic effects against ALF by inhibiting NLRP3 inflammasomes. However, the inhibitory effects of most TCMs on ALF remain to be further elucidated. This study aimed to screen potential herbs that can treat ALF based on the inhibition of NLRP3 inflammasomes. Initially, we constructed the target set for 502 herbs. Subsequently, based on the target set and the gene set related to the NLRP3 inflammasome, using the ssGSEA algorithm, we evaluated herb scores and NLRP3 scores in the ALF expression matrix and performed a preliminary herb screening based on score correlations. Through bioinformatics approaches, we identified the key targets for candidate herbs and determined core herbs based on the herb-compound-target network. Furthermore, molecular docking and molecular biology methods validated the screening results of the herbs. A total of 18 crucial targets associated with the inhibition of the NLRP3 inflammasome were identified, which included ALDH2, HMOX1, and VEGFA. Subsequently, based on these key targets, a set of 10 primary herbs was chosen, notably Qinghao, Duzhong, and Gouteng. Moreover, the results were verified through molecular docking and molecular dynamic simulation. Ten key herbs have been identified as potential inhibitors of the NLRP3 inflammasome, offering insights into ALF therapy for drug development.