Acute liver failure is a rare but fatal condition characterized by rapid deterioration of liver function resulting in coagulopathy and altered mentation in patients without known liver disease. The three most common causes of liver failure in Korea are hepatitis B virus, exposure to certain herbs, and hepatitis A virus. Because the cause of liver failure is the most important prognostic factor, the etiology of liver failure should be evaluated as the initial step in the assessment of affected patients. Patients with acute liver failure should be intensively monitored and treated for various secondary conditions that may occur or have already developed, including cerebral edema, seizures, hemodynamic instability, renal failure, infection, bleeding, and metabolic disturbances. Although treatment with N-acetylcysteine has shown a survival benefit in patients with mild hepatic encephalopathy, the overall mortality rate associated with acute liver failure is high unless patients undergo liver transplantation, prompting patients and physicians to be prepared for transplantation. Therefore, patients who are suspected to have, or who have been diagnosed with, acute liver failure should be transferred to a transplant facility and be prepared for liver transplantation while they undergo intensive monitoring and medical treatment.
Acetylcysteine ; Brain Edema ; Diagnosis ; Hemodynamics ; Hemorrhage ; Hepatic Encephalopathy ; Hepatitis A virus ; Hepatitis B virus ; Humans ; Korea ; Liver ; Liver Diseases ; Liver Failure ; Liver Failure, Acute* ; Liver Transplantation ; Mortality ; Renal Insufficiency ; Seizures

Objective: To identify the predisposing factors, clinical characteristics, and risk factors of disease progression to establish a novel predictive survival model and evaluate its application value for hepatitis B virus-related acute-on-chronic liver failure. Methods: 153 cases of HBV-ACLF were selected according to the guidelines for the diagnosis and treatment of liver failure (2018 edition) of the Chinese Medical Association Hepatology Branch. Predisposing factors, the basic liver disease stage, therapeutic drugs, clinical characteristics, and factors affecting survival status were analyzed. Cox proportional hazards regression analysis was used to screen prognostic factors and establish a novel predictive survival model. The receiver operating characteristic curve (ROC) was used to evaluate predictive value with the Model for End-Stage Liver Disease (MELD) and the Chronic Liver Failure Consortium Acute-on-Chronic Liver Failure score (CLIF-C ACLF). Results: 80.39% (123/153) based on hepatitis B cirrhosis had developed ACLF. HBV-ACLF's main inducing factors were the discontinuation of nucleos(t)ide analogues (NAs) and the application of hepatotoxic drugs, including Chinese patent medicine/Chinese herbal medicine, non-steroidal anti-inflammatory drugs, anti-tuberculosis drugs, central nervous system drugs, anti-tumor drugs, etc. 34.64% of cases had an unknown inducement. The most common clinical symptoms at onset were progressive jaundice, poor appetite, and fatigue. The short-term mortality rate was significantly higher in patients complicated with hepatic encephalopathy, upper gastrointestinal hemorrhage, hepatorenal syndrome, and infection (P < 0.05). Lactate dehydrogenase, albumin, the international normalized ratio, the neutrophil-to-lymphocyte ratio, hepatic encephalopathy, and upper gastrointestinal bleeding were the independent predictors for the survival status of patients. The LAINeu model was established. The area under the curve for evaluating the survival of HBV-ACLF was 0.886, which was significantly higher than the MELD and CLIF-C ACLF scores (P < 0.05), and the prognosis was worse when the LAINeu score ≥ -3.75. Conclusion: Discontinuation of NAs and the application of hepatotoxic drugs are common predisposing factors for HBV-ACLF. Hepatic decompensation-related complications and infection accelerate the disease's progression. The LAINeu model can predict patient survival conditions more accurately.
Humans ; Hepatitis B virus ; Hepatic Encephalopathy/complications* ; Acute-On-Chronic Liver Failure/diagnosis* ; End Stage Liver Disease/complications* ; Severity of Illness Index ; Risk Factors ; ROC Curve ; Prognosis ; Retrospective Studies

Liver failure is a serious clinical syndrome in which multiple pathogenic factors exceed the liver's self-repair capability, resulting massive hepatocellular necrosis, rapid disease progression and high mortality. Liver transplantation is the most effective method for the treatment of liver failure, but it has disadvantages, such as insufficient liver donor and high cost. The clinical efficacy of mesenchymal stem cells in liver failure have been validated, but its application has been limited to certain extent. Cell-free-based therapies, especially mesenchymal stem cell-derived exosomes, has become a research hotspot in recent years. This paper reviews the research advances in the treatment of liver failure with the use of mesenchymal stem cell-derived exosomes.
Cell- and Tissue-Based Therapy ; Exosomes ; Hepatic Insufficiency ; Humans ; Liver Failure/therapy* ; Liver Failure, Acute/therapy* ; Mesenchymal Stem Cells

Objective: To investigate the ABC prognostic classification and the updated version of Model for End-stage Liver Disease (MELD) score 3.0 and Chinese Group on the Study of Severe Hepatitis B ACLF Ⅱ score (COSSH-ACLF Ⅱ score) to evaluate the prognostic value in acute-on-chronic liver failure (ACLF). Methods: ABC classification was performed on a 1 409 follow-up cohorts. The area under the receiver operating characteristic curve (AUROC) was used to analyze MELD, MELD 3.0, COSSH-Ⅱ and COSSH-Ⅱ score after 3 days of hospitalization (COSSH-Ⅱ-3d). The prognostic predictive ability of patients were evaluated for 360 days, and the prediction differences of different classifications and different etiologies on the prognosis of ACLF were compared. Results: The survival curve of 1 409 cases with ACLF showed that the difference between class A, B, and C was statistically significant, Log Rank (Mantel-Cox) χ²=80.133, P<0.01. Compared with class A and C, χ²=76.198, P<0.01, the difference between class B and C, was not statistically significant χ²=3.717, P>0.05. AUROC [95% confidence interval (CI)] analyzed MELD, MELD 3.0, COSSH-Ⅱ and COSSH-Ⅱ-3d were 0.644, 0.655, 0.817 and 0.839, respectively (P<0.01). COSSH-Ⅱ had better prognostic predictive ability with class A ACLF and HBV-related ACLF (HBV-ACLF) for 360-days, and AUROC (95% CI) were 0.877 and 0.881, respectively (P<0.01), while MELD 3.0 prognostic predictive value was not better than MELD. Conclusion: ACLF prognosis is closely related to ABC classification. COSSH-Ⅱ score has a high predictive value for the prognostic evaluation of class A ACLF and HBV-ACLF. COSSH-Ⅱ score has a better prognostic evaluation value after 3 days of hospitalization, suggesting that attention should be paid to the treatment of ACLF in the early stage of admission.
Humans ; Acute-On-Chronic Liver Failure ; Prognosis ; End Stage Liver Disease/complications* ; Retrospective Studies ; Severity of Illness Index

Objective: To compare the impact of different prognostic scores in patients with acute-on-chronic liver failure (ACLF) in order to provide treatment guidance for liver transplantation. Methods: The information on inpatients with ACLF admitted at Beijing You'an Hospital Affiliated to Capital Medical University and the First Affiliated Hospital of Zhejiang University School of Medicine from January 2015 to October 2022 was collected retrospectively. ACLF patients were divided into liver transplantation and non-liver transplantation groups, and the two groups prognostic conditions were followed-up. Propensity score matching was carried out between the two groups on the basis of liver disease (non-cirrhosis, compensated cirrhosis, and decompensated cirrhosis), the model for end-stage liver disease incorporating serum sodium (MELD-Na), and ACLF classification as matching factors. The prognostic condition of the two groups after matching was compared. The difference in 1-year survival rate between the two groups was analyzed under different ACLF grades and MELD-Na scores. The independent sample t-test or rank sum test was used for inter-group comparison, and the χ (2) test was used for the comparison of count data between groups. Results: In total, 865 ACLF inpatients were collected over the study period. Of these, 291 had liver transplantation and 574 did not. The overall survival rates at 28, 90, and 360 days were 78%, 66%, and 62%, respectively. There were 270 cases of matched ACLF post-liver transplantation and 270 cases without ACLF, in accordance with a ratio of 1:1. At 28, 90, and 360 days, patients with non-liver transplantation had significantly lower survival rates (68%, 53%, and 49%) than patients with liver transplantation (87%, 87%, and 78%, respectively; P < 0.001). Patients were classified into four groups according to the ACLF classification criteria. Kaplan-Meier survival analysis showed that the survival rates of liver transplantation and non-liver transplantation patients in ACLF grade 0 were 77.2% and 69.4%, respectively, with no statistically significant difference (P = 0.168). The survival rate with an ACLF 1-3 grade was significantly higher in liver transplantation patients than that of non-liver transplantation patients (P < 0.05). Patients with ACLF grades 1, 2, and 3 had higher 1-year survival rates compared to non-liver transplant patients by 50.6%, 43.6%, and 61.7%, respectively. Patients were divided into four groups according to the MELD-Na score. Among the patients with a MELD-Na score of < 25, the 1-year survival rates for liver transplantation and non-liver transplantation were 78.2% and 74.0%, respectively, and the difference was not statistically significant (P = 0.149). However, among patients with MELD-Na scores of 25-30, 30-35, and≥35, the survival rate was significantly higher in liver transplantation than that of non-liver transplantation, and the 1-year survival rate increased by 36.4%, 54.9%, and 62.5%, respectively (P < 0.001). Further analysis of the prognosis of patients with different ACLF grades and MELD-Na scores showed that ACLF grades 0 or 1 and MELD-Na score of < 30 had no statistically significant difference in the 1-year survival rate between liver transplantation and non-liver transplantation (P > 0.05), but in patients with MELD-Na score≥30, the 1-year survival rate of liver transplantation was higher than that of non-liver transplantation patients (P < 0.05). In the ACLF grade 0 and MELD-Na score of≥30 group, the 1-year survival rates of liver transplantation and non-liver transplantation patients were 77.8% and 25.0% respectively (P < 0.05); while in the ACLF grade 1 and MELD-Na score of≥30 group, the 1-year survival rates of liver transplantation and non-liver transplantation patients were 100% and 20.0%, respectively (P < 0.01). Among patients with ACLF grade 2, the 1-year survival rate with MELD-Na score of < 25 in patients with liver transplantation was 73.9% and 61.6%, respectively, and the difference was not statistically significant (P > 0.05); while in the liver transplantation patients group with MELD-Na score of ≥25, the 1-year survival rate was 79.5%, 80.8%, and 75%, respectively, which was significantly higher than that of non-liver transplantation patients (36.6%, 27.6%, 15.0%) (P < 0.001). Among patients with ACLF grade 3, regardless of the MELD-Na score, the 1-year survival rate was significantly higher in liver transplantation patients than that of non-liver transplantation patients (P < 0.01). Additionally, among patients with non-liver transplantation with an ACLF grade 0~1 and a MELD-Na score of < 30 at admission, 99.4% survived 1 year and still had an ACLF grade 0-1 at discharge, while 70% of deaths progressed to ACLF grade 2-3. Conclusion: Both the MELD-Na score and the EASL-CLIF C ACLF classification are capable of guiding liver transplantation; however, no single model possesses a consistent and precise prediction ability. Therefore, the combined application of the two models is necessary for comprehensive and dynamic evaluation, but the clinical application is relatively complex. A simplified prognostic model and a risk assessment model will be required in the future to improve patient prognosis as well as the effectiveness and efficiency of liver transplantation.
Humans ; Acute-On-Chronic Liver Failure ; Prognosis ; Retrospective Studies ; End Stage Liver Disease ; Severity of Illness Index

Acute-on-chronic liver failure (ACLF) is increasingly recognized as a distinct disease entity associated with acute deterioration of liver function in patients with chronic liver disease. Although no widely accepted diagnostic criteria for ACLF are yet available, the definitions of the Asian-Pacific Association for the Study of the Liver (APASL) ACLF Research Consortium (AARC) and the European Association for the Study of the Liver (EASL) Chronic Liver Failure Consortium (CLIF-C) are commonly employed. However, the AARC and CLIF-C criteria are based on fundamentally different features, rendering among-study comparisons difficult. The areas of uncertainty include the definition and extent of heterogeneity of ACLF, ambiguities in terms of the underlying liver disease, and whether infection or sepsis may precipitate the condition. Although the detailed pathogenesis of ACLF remains to be elucidated, changes in host responses to injury, infection, and uncontrolled inflammation play important roles. The “predisposition, infection/inflammation, response, organ failure” (PIRO) concept used to evaluate sepsis may be valuable when it is sought to describe the pathophysiology and clinical features of ACLF. Currently, treatment is limited to organ support but a better understanding of the pathophysiology is likely to lead, in future, to the discovery of novel biomarkers and the development of new therapeutic strategies.
Acute-On-Chronic Liver Failure* ; Biomarkers ; End Stage Liver Disease ; Humans ; Inflammation ; Liver ; Liver Cirrhosis ; Liver Diseases ; Liver Failure ; Population Characteristics ; Sepsis ; Uncertainty

Carbamazepine-induced liver injury is less common, but the consequences of the side effects can be very serious leading to death or a need for liver transplantation. We report a case of a 60-year-old female transverse myelitis patient with fulminant hepatic failure and Stevens-Johnson syndrome induced by carbamazepine who successfully underwent deceased donor liver transplantation. The patient, a 60-year-old female, was admitted to our service due to acute liver insufficiency and a drowsy mental state attributable to carbamazepine. She had been treated with carbamazepine to control transverse myelitis. Fifty days after the use of carbamazepine, she developed jaundice, erythematous papules and bullae, and decreased consciousness. The diagnosis of Stevens-Johnson syndrome was considered. She underwent deceased donor liver transplantation. She was discharged with normal graft functions 5 months after transplantation. Thus, liver transplantation can be a feasible therapy for patients with carbamazepine-induced hepatic failure associated with Stevens-Johnson syndrome.
Blister ; Carbamazepine ; Consciousness ; Female ; Hepatic Insufficiency ; Humans ; Jaundice ; Liver ; Liver Failure ; Liver Failure, Acute ; Liver Transplantation ; Middle Aged ; Myelitis, Transverse ; Stevens-Johnson Syndrome ; Tissue Donors ; Transplants

Liver transplant is an unreplaceable method for benign end-stage liver disease. The risk evaluation for the waiting list recipients and for post-transplant survival could provide practical indication for organ allocation. In recent years, there are two major kinds of evaluation scores. The first kind of evaluation scores is based on model for end-stage liver disease(MELD) score,including SOFT/P-SOFT score,UCLA-FRS score and BAR score. The other evaluation system is based on the concept of acute-on-chronic liver failure,including CLIF-C-ACLF score,TAM score,AARC-ACLF score and COSSH-ACLF score. The scores based on ACLF have been shown superior power in predicting waiting list survival and post-transplant prognosis than MELD. This article reviews the two kinds of evaluation scores,aiming for the better allocation policy and the better prognosis of benign end-stage liver disease.
Acute-On-Chronic Liver Failure ; End Stage Liver Disease/surgery* ; Humans ; Liver Transplantation ; Prognosis ; Retrospective Studies ; Severity of Illness Index

Emphysematous gastritis secondary to vaso-occlusive disease is a surgical emergency. It is a rare yet severe form of widespread phlegmonous gastritis. It is caused by corrosive ingestion, alcohol abuse, and on rare occasions, infections. The clinical presentation is diagnostic with supportive information from contrast-enhanced computed tomography (CECT) of the abdomen and gastroduodenoscopy. Here, we describe a case of emphysematous gastritis with spontaneous vaso-occlusive disease that was successfully managed without surgery.
Hepatic Insufficiency

OBJECTIVETo observe the clinical characteristics and short-term survival of patients with splenomegaly and acute-on-chronic liver failure related to chronic HBV infection.

METHODSElectronic medical records of patients with acute-on-chronic liver failure were collected to analyze the clinical parameters and 4-week survival of patients with or without splenomegaly.

RESULTSOf the 149 patients enrolled, the overall 28-day mortality rate was 48.3%, which was lower in patients with enlarged spleen than those without (34.2% vs 54.1%, P=0.034). Compared with patients without splenomegaly, patients with splenomegaly had lower platelet counts (P=0.001), lower ALT levels (P=0.005) and lower PT-INR (P=0.010). Although the occurrence of hepatic encephalopathy was comparable between patients with or without splenomegaly, severe conditions were more frequent in those without splenomegaly. Hepatic encephalopathy grades, serum creatinine levels, neutrophil percentages over 70%, PT-INR and splenomegaly were independent factors associated with the 28-day survival, and this novel model was superior to model of end-stage of liver disease in predicting the 4-week survival (P=0.017).

CONCLUSIONPatients with splenomegaly that evolves into acute-on-chronic liver failure have unique clinical characteristics and further clinical observations are warranted.

Acute-On-Chronic Liver Failure ; mortality ; physiopathology ; Chronic Disease ; Hepatic Encephalopathy ; physiopathology ; Humans ; Splenomegaly ; mortality ; physiopathology