Development and Validation of a New Prognostic Model for Predicting Survival Outcomes in Patients with Acute-onchronic Liver Failure

Background and Aims:Early determination of prognosis in patients with acute-on-chronic liver failure(ACLF)is crucial for optimizing treatment options and liver allocation.This study aimed to identify risk factors associated with ACLF and to develop new prognostic models that accurately predict patient outcomes.Methods:We retrospectively selected 1,952 hospitalized patients diagnosed with ACLF between January 2010 and June 2018.This cohort was used to develop new prognostic scores,which were subsequently validated in external groups.Results:The study included 1,386 ACLF patients and identified six independent predictors of 28-day mortality through multivariate analysis(all p<0.05).The new score,based on a multivariate regression model,demonstrated superior predictive accuracy for both 28-day and 90-day mortalities,with Areas under the ROC curves of 0.863 and 0.853,respectively(all p<0.05).This score can be used to stratify the risk of mortality among ACLF patients with ACLF,showing a significant difference in survival between patients categorized by the cut-off value(log-rank(Mantel-Cox)χ^(2)=487.574 and 606.441,p=0.000).Additionally,the new model exhibited good robustness in two external cohorts.Conclusions:This study presents a refined prognostic model,the Model for end-stage liver disease-complication score,which accurately predicts short-term mortality in ACLF patients.This model offers a new perspective and tool for improved clinical decision-making and short-term prognostic assessment in ACLF patients.

Roles of organelle-specific autophagy in hepatocytes in the development and treatment of non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease(NAFLD)is a disorder of lipid metabolism.The lipotoxic intermediates of lipid metabolism cause mitochondrial dysfunction and endoplasmic reticulum stress.Organelle-specific autophagy is responsible for the removal of dysfunctional organelles to maintain intracellular homeostasis.Lipophagy contributes to lipid turnover by degrading lipid droplets.The level of autophagy changes during the course of NAFLD,and the activation of hepatocyte autophagy might represent a method of treating NAFLD.

The Role of Macrophage-Derived Exosomes in Liver Diseases

Exosomes(exos)widely distributed in a variety of biological fluids,including blood,urine,saliva,sputum,breast milk,cerebrospinal fluid,and ascites,contain specific bioactive contents which are involved in physiological and pathological processes,such as signal molecular transfer,substance metabolism,gene regulation,and immune regulation.Macrophages are important innate immune cells which usually act as the first line of defense against infection,and can switch between different functional phenotypes in response to the changes around the microenvironment.Evidence suggests that macrophage-derived exos exert a crucial effect on infection,inflammation,regeneration,tumors,fibrosis,and other lesions in multiple human diseases.However,the role and mechanism of macrophage-derived exos in liver diseases remain to be explored.This review summarizes the current researches on the role and possible mechanism of macrophage-derived exos in liver diseases,with the purpose of providing new potential targets and directions for diagnostic biomarker and clinical treatment of liver diseases.

Clinical Course and Outcome Patterns of Acute-on-chronic Liver Failure:A Multicenter Retrospective Cohort Study

Background and Aims:Acute-on-chronic liver failure(ACLF)is acute decompensation of liver function in the setting of chronic liver disease,and characterized by high short-term mortality.In this study,we sought to investigate the clinical course of patients at specific time points,and to propose dynamic prognostic criteria.Methods:We assessed the clinical course of 453 patients with ACLF during a 12-week follow-up period in this retrospective multicenter study.The clinical course of patients was defined as disease recovery,improvement,worsening or steady patterns based on the variation tendency in prothrombin activity(PTA)and total bilirubin(TB)at different time points.Results:Resolution of PTA was observed in 231 patients(51%)at 12 weeks after the diagnosis of ACLF.Among the remaining patients,66(14.6%)showed improvement and 156(34.4%)showed a steady or worsening course.In patients with resolved PTA,the clinical course of TB exhibited resolved pattern in 95.2%,improved in 3.9%,and steady or worse in 0.8%.Correspondingly,in patients with improved PTA,these values for TB were 28.8%,27.3%,and 43.9%,respectively.In patients with steady or worsening PTA,these values for TB were 5.7%,32.3%,and 65.6%,respectively.Dynamic prognostic criteria were developed by combining the clinical course of PTA/TB and the clinical outcomes at 4 and 12 weeks after diagnosis in ACLF patients.Conclusions:We propose the following dynamic prognostic criteria:rapid progression,slow progression,rapid recovery,slow recovery,and slow persistence,which lay the foundation for precise prediction of prognosis and the improvement of ACLF therapy.

UGT1A1-related Bilirubin Encephalopathy/Kernicterus in Adults

Background and Aims:Bilirubin encephalopathy/kernicterus is very rare in adults.This study is aimed to investigate the clinical manifestations and genetic features of two patients with UGT1A1-related kernicterus.Methods:Sanger sequencing analysis was performed to identify UGT1A1 gene mutations in the patients and their families.Bioinformatics analysis was used to predict the potential functional effects of novel missense mutations.Clinical manifestations and biochemical parameters were collected and analyzed.Results:Two patients with Crigler-Najjar syndrome type II(CNS2)developed kernicterus in adulthood.Sanger sequencing identified a compound heterozygous mutation in the UGT1A1 gene in patient 1,which was inherited from his mother(G71R)and his father(c.-3279T>G;S191F).Patient 2 carried three heterozygous mutations,namely G71R,R209W and M391K;among which,the M391K mutation has not been reported before.Multiple prediction software showed that the M391K mutation was pathogenic.Symptoms were relieved in the two patients after phenobarbital and artificial liver support treatment.Patient 1 also underwent liver transplantation.Conclusions:Adults with CNS2 are at risk for kernicterus.Phenobarbital treatment is beneficial for maintaining bilirubin levels and preventing kernicterus.