Albúmina en cirrosis: perspectiva inflamatoria / Albumin in cirrhosis: inflammatory perspective

La albúmina sérica humana es la proteína más abundante en el plasma, su estructura molecular le confiere estabilidad, pero también flexibilidad para ligar y transportar un amplio rango de moléculas. Su función oncótica es la propiedad más reconocida que la lleva a introducirse en la terapéutica médica como un expansor de volumen. Sin embargo, en los últimos años se le han adicionado funciones con carácter antioxidante, inmunomodulador y de estabilización endotelial, que hacen presumir que su impacto terapéutico está más allá de sus funciones volumétricas. En los últimos años, específicamente en la cirrosis y la falla hepática aguda sobre crónica, se ha tenido un cambio en el paradigma fisiológico, desde una perspectiva netamente hemodinámica hacia una perspectiva inflamatoria, en donde las funciones oncóticas y no oncóticas de la albúmina están alteradas y tienen un carácter pronóstico en estas entidades. Este conocimiento creciente, desde una perspectiva inflamatoria, hace que se fortalezca el uso terapéutico de la albúmina sérica humana desde las indicaciones tradicionales como prevención de la disfunción circulatoria posparacentesis, prevención y tratamiento de lesión renal aguda, hasta las discusiones para administración a largo plazo en pacientes cirróticos con ascitis.

Human serum albumin is the most abundant protein in plasma, with a molecular structure that provides stability while also allowing flexibility to bind and transport a wide range of molecules. Its oncotic function is the most recognized property, leading to its introduction in medical therapy as a volume expander. However, in recent years, additional functions with antioxidant, immunomodulatory, and endothelial stabilization properties have been identified, suggesting that its therapeutic impact extends beyond its volumetric functions. Specifically, in cirrhosis and acute-on-chronic liver failure, there has been a shift in the pathophysiological paradigm from a purely hemodynamic perspective to an inflammatory perspective, where both oncotic and non-oncotic functions of albumin are altered and have prognostic significance in these conditions. This growing understanding from an inflammatory perspective strengthens the therapeutic use of human serum albumin, not only for traditional indications such as the prevention of post-paracentesis circulatory disfunction, prevention and treatment of acute kidney injury, but also for discussions regarding long-term administration in cirrhotic patients with ascites.

Value of serum creatinine-to-cystatin C ratio in assessing the prognosis of hepatitis B virus-related acute-on-chronic liver failure / 临床肝胆病杂志

ObjectiveTo investigate the clinical value of serum creatinine-to-cystatin C ratio （CCR） in evaluating the prognosis of hepatitis B virus-related acute-on-chronic liver failure （HBV-ACLF）. MethodsA retrospective analysis was performed for the clinical data of 130 patients with HBV-ACLF （treatment group） who were hospitalized in Department of Infectious Diseases， The First Affiliated Hospital of Soochow University， from January 2021 to November 2022. According to the treatment outcome， they were divided into survival group with 87 patients and death group with 43 patients； according to the presence or absence of infection， they were divided into infection group with 37 patients and non-infection group with 93 patients. A total of 30 individuals who underwent physical examination during the same period of time were enrolled as control group. Routine blood test results were collected on the day of admission， including white blood cell count， platelet count， neutrophil count， and lymphocyte count； serum creatinine， cystatin C， serum albumin （Alb）， and prothrombin time （PT） were observed on the day of admission and on days 5， 10， and 15 of hospitalization， and related indicators were calculated， including CCR， neutrophil-to-lymphocyte ratio （NLR）， platelet-to-lymphocyte ratio （PLR）， prognostic nutritional index （PNI）， CCR5 （CCR on day 5 after admission）， ΔCCR5 （CCR on day 5 after admission minus CCR on the day of admission）， CCR10 （CCR on day 10 after admission）， ΔCCR10 （CCR on day 10 after admission minus CCR on day 5 after admission）， CCR15 （CCR on day 15 after admission）， and ΔCCR15 （CCR on day 15 after admission minus CCR on day 10 after admission）. The above indicators were compared between the survival group and the death group and between the infection group and the non-infection group. The Mann-Whitney U test was used for comparison of continuous data between two groups， and the Kruskal-Wallis H test was used for comparison between multiple groups. The univariate and multivariate logistic regression analyses were used to investigate the influencing factors for disease prognosis； the receiver operating characteristic （ROC） curve was used to assess the value of CCR in predicting HBV-ACLF death events， and the DeLong test was used for comparison of the area under the ROC curve （AUC）. ResultsThere were significant differences in CCR， NLR， PNI， PT， and Alb at baseline between the treatment group and the healthy control group （all P<0.001）， and there were significant differences in CCR， NLR， and PT between the survival group and the death group on the day of admission （all P<0.05）. Among the 130 patients with HBV-ACLF， there were 25 in the precancerous stage， 48 in the early stage， 32 in the intermediate stage， and 25 in the advanced stage， and there were significant differences in baseline CCR， PLR， and PT between the patients in different stages of HBV-ACLF （all P<0.05）. There were significant differences in ΔCCR5 and NLR between the infection group and the non-infection group （P<0.05）， and there were significant differences in ΔCCR5， CCR10， and CCR15 between the survival group and the death group （all P<0.05）. The multivariate logistic regression analysis showed that ΔCCR5 （odds ratio ［OR］=1.175， 95% confidence interval ［CI］： 1.098‍ — ‍1.256， P<0.001）， NLR （OR=0.921， 95%CI： 0.880‍ — ‍0.964， P<0.001）， and PT （OR=0.921， 95%CI： 0.873‍ — ‍0.973， P=0.003） were independent influencing factors for the prognosis of HBV-ACLF patients. ΔCCR5 had an AUC of 0.774， a sensitivity of 0.687， and a specificity of 0.757， and the AUC of ΔCCR5+PT+NLR was 0.824， which was significantly higher than the AUC of ΔCCR5， NLR， or PT alone （all P<0.05）. ConclusionΔCCR5， NLR， and PT can reflect the condition and prognosis of patients with HBV-ACLF and are independent predictive indicators for death events in patients with HBV-ACLF. The combination ofΔCCR5， PT， and NLR has the best predictive efficiency.

Current research status of animal models for acute-on-chronic liver failure / 临床肝胆病杂志

Acute-on-chronic liver failure has complex conditions， rapid progression， and a high mortality rate， and further studies are still needed to clarify its pathogenesis and etiology. The establishment of animal models for acute-on-chronic liver failure can not only provide a good basis for exploring the pathogenesis of acute-on-chronic liver failure， but also provide an experimental basis for clinical treatment. Through a literature review， this article summarizes the methods commonly used to establish the animal models of acute-on-chronic liver failure， including carbon tetrachloride combined with LPS/GaIN， thioacetamide combined with LPS， serum albumin， and bile duct ligation. This article analyzes the characteristics of various animal models， so as to provide documentary and experimental bases for further exploration of more ideal animal models.

Clinical features and early warning indicators of patients with acute-on-chronic liver failure and bacterial infection / 临床肝胆病杂志

ObjectiveTo investigate the clinical features of patients with acute-on-chronic liver failure （ACLF） and bacterial infection and early warning indicators associated with multidrug-resistant infections. MethodsA retrospective analysis was performed for 130 patients with ACLF and bacterial infection who attended The Second Affiliated Hospital of Air Force Medical University from January 1， 2010 to December 31， 2021， and according to the drug susceptibility results， the patients were divided into multidrug-resistant （MDR） bacterial infection group with 80 patients and non-MDR bacterial infection group with 50 patients. General information and laboratory examination results were compared between the two groups to screen for the early warning indicators associated with MDR bacterial infection. The Student’s t-test was used for comparison of normally distributed continuous data with homogeneity of variance between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data or continuous data with heterogeneity of variance between two groups； the chi-square test or the Fisher’s exact test was used for comparison of categorical data between two groups. The binary logistic regression analysis and the receiver operating characteristic （ROC） curve were used to assess the predictive value of early warning indicators. ResultsAmong the 130 patients with ACLF and bacterial infection， sputum （27.7%） was the most common specimen for detection， followed by blood （24.6%）， urine （18.5%）， and ascites （17.7%）. Bacterial infections were dominated by Gram-negative bacteria （58.5%）. Of all bacteria， Escherichia coli （18.5%）， Klebsiella pneumoniae （14.6%）， and Enterococcus faecium （13.8%） were the most common pathogens. Gram-positive bacteria had a high resistance rate to the antibacterial drugs such as erythromycin （72.2%）， penicillin （57.4%）， ampicillin （55.6%）， and ciprofloxacin （53.7%）， while Gram-negative bacteria had a high resistance rate to the antibacterial drugs such as ampicillin （73.3%）， cefazolin （50.0%）， and cefepime （47.4%）. The patients with ACLF and bacterial infection had a relatively high rate of MDR bacterial infection （61.5%）. Comparison of clinical data between the two groups showed that compared with the patients with non-MDR bacterial infection， the patients with MDR bacterial infection had significantly higher levels of alanine aminotransferase （Z=2.089， P=0.037）， aspartate aminotransferase （Z=2.063， P=0.039）， white blood cell count （Z=2.207， P=0.027）， and monocyte count （Z=4.413， P<0.001）. The binary logistic regression analysis showed that monocyte count was an independent risk factor for MDR bacterial infection （odds ratio=7.120， 95% confidence interval ［CI］： 2.478‍ ‍—‍ ‍20.456，P<0.001） and had an area under the ROC curve of 0.686 （95%CI： 0.597‍ ‍—‍ ‍0.776） in predicting ACLF with MDR bacterial infection（P<0.001）， with the optimal cut-off value of 0.50×109/L， a sensitivity of 0.725， and a specificity of 0.400. ConclusionACLF combined with bacterial infections is mainly caused by Gram-negative bacteria， with the common pathogens of Escherichia coli and Klebsiella pneumoniae and a relatively high MDR rate in clinical practice. An increase in monocyte count can be used as an early warning indicator to distinguish MDR bacterial infection from non-MDR bacterial infection.

An excerpt of American Association for the Study of Liver Diseases practice guidance on acute-on-chronic liver failure and the management of critically ill patients with cirrhosis in 2023 / 临床肝胆病杂志

The expert panel of American Association for the Study of Liver Diseases published Practice guidance on acute-on-chronic liver failure and the management of critically ill patients with cirrhosis on November 9， 2023 in Hepatology. This practice guidance elaborates on the definition of acute-on-chronic liver failure， prediction models， and the management of liver cirrhosis comorbid with acute-on-chronic liver failure and organ failure in critically ill patients， and this article gives an excerpt of the key points in the practice guidance.

The molecular mechanism of spleen-strengthening and moisture-nourishing liver prescription in treatment of acute-on-chronic liver failure based on network pharmacology and experimental verification / 中国药理学通报

To explore the mechanism of spleen- were obtained for the treatment of acute-on-chronic livstrengthening and moisture-nourishing liver prescription er failure, and 244 intersecting target genes and 7 core (JPLSYGF) in the treatment of acute-on-chronic liver target genes were screened. Molecular docking showed failure using network pharmacology and the molecular that the core target genes AKT1, SRC, VEGFA, docking. Methods Relying on TCMSP and Gene- STAT3 , EGFR, MAPK3 , HRAS had good affinity with Cards and other databases, the relevant targets of JPL- quercetin, the main active component in the JPLSYGF in the treatment of acute-on-chronic liver failure SYGF, and had strong binding activity. In addition, in were obtained. String and Cytoscape were used to con- vivo tests verified that the JPLSYGF could reduce the struct PPI networks of targets, core targets were expression of HRAS, EGFR, STAT3 , SRC, and VEGscreened out, and DAVID was used for GO function FA, to delay the progression of acute-on-chronic liver annotation and KEGG pathway enrichment analysis. failure. Conclusions JPLSYGF may act on core tar- The main active ingredients of the traditional Chinese gets such as HRAS, EGFR, STAT3, SRC, VEGFA medicine compound formula for JPLSYGF were select- and so on, to achieve the effect of treating acute-oned with a bioavailability OB value of =Э 30% and a chronic liver failure. drug-like DL

Clinical efficacy of double plasma molecular absorption system and sequential plasma exchange combined with continuous renal replacement therapy in treatment of acute-on-chronic liver failure with acute kidney injury / 临床肝胆病杂志

ObjectiveTo investigate the clinical efficacy of double plasma molecular adsorption system （DPMAS） and sequential plasma exchange （PE） combined with continuous renal replacement therapy （CRRT） in the treatment of patients with acute-on-chronic liver failure （ACLF） and acute kidney injury （AKI）. MethodsA retrospective analysis was performed for the clinical data of 90 patients with ACLF and AKI who were hospitalized in The Affiliated Hospital of Guizhou Medical University from January 2019 to December 2022， and according to the method for blood purification， they were divided into DPMAS sequential PE+CRRT group （observation group with 31 patients） and DPMAS sequential PE group （control group with 59 patients）. General data on admission and laboratory markers before and after blood purification were collected from all patients， including hepatic and renal function， coagulation function， and inflammation markers， and estimated glomerular filtration rate （eGFR） and MELD combined with serum sodium concentration （MELD-Na） score were calculated. The independent-samples t test was used for comparison of normally distributed continuous data between two groups； the Wilcoxon rank sum test was used for comparison of non-normally distributed continuous data within each group before and after treatment， and the Mann-Whitney U test was used for comparison between two groups； the chi-square test or the Fisher’s exact test was used for comparison of categorical data between two groups. ResultsThe observation group had a significantly higher response rate than the control group ［48.4% （15/31） vs 27.1% （16/59）， χ2=4.071， P=0.044］. The methods for blood purification in both groups could effectively improve total bilirubin， alanine aminotransferase， aspartate aminotransferase （AST）， prothrombin time activity， serum creatinine （Scr）， procalcitonin （PCT）， C-reactive protein， eGFR， and MELD-Na score （all P<0.05）， and both groups had significant reductions in platelet count （PLT） and hemoglobin （Hb） after treatment （all P<0.05）， while there were no significant changes in blood urea nitrogen， albumin， and international normalized ratio after treatment （all P>0.05）. There were significant differences between the two groups in the changes in AST， Scr， PCT， eGFR， MELD-Na score， Hb， and PLT after treatment （all P<0.05）. ConclusionDPMAS sequential PE combined with CRRT can effectively remove inflammatory mediators， improve renal function， stabilize the internal environment of human body， and achieve a relatively good clinical efficacy.

Falla hepática aguda sobre crónica / Acute on chronic liver failure

La falla hepática aguda sobre crónica (ACLF) es un síndrome que se presenta en pacientes con cirrosis descompensada, y se caracteriza por una mortalidad elevada a 28 días, que se diagnostica con la combinación de falla hepática y extrahepática. Se han publicado numerosas definiciones, de las cuales se resalta la realizada por la Asociación Europea para el Estudio del Hígado (EASL), la cual tiene en cuenta 6 sistemas orgánicos (hígado, riñón, pulmón, cerebro, coagulación y circulación), y gradúa su gravedad basada en el número de sistemas comprometidos en el momento de la presentación. Entre los pilares en el abordaje del paciente con ACLF es imperiosa la búsqueda de los factores precipitantes, siendo los más frecuentes las infecciones bacterianas, el consumo excesivo de alcohol, la hemorragia de vías digestivas, la injuria hepática inducida por medicamentos y la cirugía hepática o cirugía mayor, teniendo en cuenta que aproximadamente en el 50 % de los casos no se logrará establecer la causa. Los pilares angulares del tratamiento constarán de la reversión o interrupción del factor precipitante, el soporte orgánico y, en aquellos pacientes que cumplan los criterios para trasplante, su realización oportuna.

Acute-on-chronic liver failure is a syndrome that occurs in patients with acute decompensated cirrhosis and is characterized by high 28-day mortality that is diagnosed with a combination of hepatic and extrahepatic organ failure. Numerous definitions have been published with great concern related to the etiology and cause of the decompensation, of which the one made by the European Association for the Study of the Liver (EASL) stands out, taking into account 6 organic systems (liver, kidney, lung, brain, coagulation, and circulation), and grades its severity based on the number of systems involved at the time of presentation. Among the pillars in the approach to the patient with ACLF, the search for precipitating factors is imperative, the most frequent being bacte-rial infections, excessive alcohol consumption, digestive tract bleeding, drug-induced liver injury, liver surgery or major surgery, keeping in mind that in approximately 50% of cases the cause will not be established. The cornerstones of treatment will consist of the reversal or interruption of the precipitating factor, organ support and, in those patients who meet the criteria for transplantation, its timely performance.

Application of different prognostic scores in liver transplantation decision-making for acute-on-chronic liver failure / 中华肝脏病杂志

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.

Assessment of liver transplant benefit and a novel strategy for liver donor allocation in acute-on-chronic liver failure / 中华肝脏病杂志

Acute-on-chronic liver failure (ACLF) is a type of complex clinical syndrome that is mainly characterized by acute deterioration of liver function based on chronic liver disease, hepatic and extrahepatic organ failures, and a high short-term mortality rate. The comprehensive medical treatment efficacy of ACLF is currently limited; thus, liver transplantation is the only viable potential treatment method. However, considering the severe liver donor shortage, economic and social costs, as well as the differences in disease severity and prognosis of different disease courses, it is particularly important to accurately assess the benefits of liver transplantation in patients with ACLF. Early identification and prediction, timing, prognosis, and survival benefits are discussed here by combining the latest research findings so as to optimize the liver transplantation treatment strategy for ACLF.

Management of liver transplantation perioperative period in acute-on-chronic liver failure / 中华肝脏病杂志

Acute-on-chronic liver failure (ACLF) is a potentially reversible entity that occurs in patients with chronic liver disease accompanied with or without cirrhosis and is characterized by extrahepatic organ failure and high short-term mortality. Currently, the most effective treatment method for patients with ACLF is liver transplantation; therefore, admission timing and contraindications must be emphasized. The function of vital organs such as the heart, brain, lungs, and kidneys should be actively supported and protected during the liver transplantation perioperative period in patients with ACLF. Focusing on the anesthesia management level during anesthesia selection, intraoperative monitoring, three-stage management, prevention and treatment of post-perfusion syndrome, monitoring and management of coagulation function, volume monitoring and management, and body temperature monitoring management for liver transplantation should strengthen anesthesia management. Additionally, standard postoperative intensive care treatment should be recommended, and grafts and other vital organ functions should be monitored throughout the perioperative period to promote early postoperative recovery in patients with ACLF.

Focusing on timing selection and whole-course management of liver transplantation treatment for patients with acute-on-chronic liver failure / 中华肝脏病杂志

Acute-on-chronic liver failure (ACLF) is a clinical syndrome of acute decompensation accompanied by organ failure that occurs on the basis of chronic liver disease and has a high short-term mortality rate. Currently, there are still differences in relation to the definition of ACLF; thus, baseline characteristics and dynamic changes are important bases for clinical decision-making in patients with liver transplantation and others. The basic strategies for treating ACLF currently include internal medicine treatment, artificial liver support systems, and liver transplantation. Multidisciplinary active collaborative management throughout the whole course is of great significance for further improving the survival rate in patients with ACLF.

Evaluation of peripheral blood T-lymphocyte subpopulations features in patients with hepatitis B virus-related acute-on-chronic liver failure based on single-cell sequencing technology / 中华肝脏病杂志

Objective: T lymphocyte exhaustion is an important component of immune dysfunction. Therefore, exploring peripheral blood-exhausted T lymphocyte features in patients with hepatitis B virus-related acute-on-chronic liver failure may provide potential therapeutic target molecules for ACLF immune dysfunction. Methods: Six cases with HBV-ACLF and three healthy controls were selected for T-cell heterogeneity detection using the single-cell RNA sequencing method. In addition, exhausted T lymphocyte subpopulations were screened to analyze their gene expression features, and their developmental trajectories quasi-timing. An independent sample t-test was used to compare the samples between the two groups. Results: Peripheral blood T lymphocytes in HBV-ACLF patients had different differentiation trajectories with different features distinct into eight subpopulations. Among them, the CD4(+)TIGIT(+) subsets (P = 0.007) and CD8(+)LAG3(+) (P = 0.010) subsets with highly exhausted genes were significantly higher than those in healthy controls. Quasi-time analysis showed that CD4(+)TIGIT(+) and CD8(+)LAG3(+) subsets appeared in the late stage of T lymphocyte differentiation, suggesting the transition of T lymphocyte from naïve-effector-exhausted during ACLF pathogenesis. Conclusion: There is heterogeneity in peripheral blood T lymphocyte differentiation in patients with HBV-ACLF, and the number of exhausted T cells featured by CD4(+)TIGIT(+)T cell and CD8(+)LAG3(+) T cell subsets increases significantly, suggesting that T lymphocyte immune exhaustion is involved in the immune dysfunction of HBV-ACLF, thereby identifying potential effective target molecules for improving ACLF patients' immune function.

Clinical study of serum human-βeta-defensin-1 level for evaluating short-term prognosis in patients with acute-on-chronic liver failure / 中华肝脏病杂志

Objective: To evaluate the diagnostic value of serum human-βeta-defensin-1 level (HBD-1) for short-term (28-day) prognosis in patients with acute-on-chronic liver failure (ACLF). Methods: Fifty cases diagnosed with ACLF were selected. 20 cases with decompensated cirrhosis and 20 cases with compensated cirrhosis who were admitted at the same time were included. Age, gender, serum HBD-1 level, C-reactive protein (CRP), procalcitonin (PCT), neutrophil count/lymphocyte ratio (NLR), blood routine, coagulation function, liver function, kidney function, and other indicators from the three groups of patients were collected. Patients with ACLF were screened for indicators related to the short-term (28-day) prognosis. Patients were divided into an improvement group and a worsening group according to the 28-day disease outcome. The serum HBD-1 level and other above-mentioned indicators were compared between the two patient groups. The receiver operating characteristic (ROC) curve was used to analyze the diagnostic efficacy of serum HBD-1 levels for short-term prognosis in patients with ACLF. PCT, NLR, and prothrombin activity (PTA) application as a mono indicator and HBD-1 in combination with NLR, PCT, and PTA were compared to evaluate diagnostic efficacy for short-term prognosis in patients with ACLF. The intergroup mean of measurement data was determined using a t-test or analysis of variance. χ (2) test was used for comparison of count data. Spearman's rank correlation analysis was used for correlation analysis. Results: There was no statistically significant difference in age and gender among the three groups: ACLF, decompensated cirrhosis, and compensated cirrhosis (P > 0.05). The expression levels of serum HBD-1 in the ACLF group, decompensated cirrhosis group, and compensated cirrhosis group were (319.1 ± 44.4) ng/ml, (264.5 ± 46.5) ng/ml and (240.1 ± 35.4) ng/ml, respectively, while the ACLF group expression levels were significantly increased, with statistical significance (P < 0.01).The serum HBD-1 level was significantly higher in the ACLF worsening group (346.2 ± 43.6) ng/ml than that in the improvement group (308.5 ± 40.6) ng/ml, and the difference was statistically significant (P < 0.05). Correlation analysis showed that HBD-1, NLR, PCT, prothrombin time (PT), and international standardized ratio (INR) were negatively correlated with the 28-day disease outcome (improvement) of patients (P < 0.05). PTA was positively correlated with 28-day disease outcome (improvement) (P < 0.05). The area under the receiver operating characteristic curve (AUC) for evaluating HBD-1's diagnostic efficacy for short-term prognosis in patients with ACLF was 0.774, with a sensitivity of 0.750, a specificity of 0.786, and a cut-off point of 337.96 ng/ml. PCT, NLR, and PTA had greater diagnostic efficacy. HBD-1 combined with PTA had the highest diagnostic efficacy, with an AUC of 0.802, a sensitivity of 0.778, and a specificity of 0.786. The diagnostic efficacy of HBD-1+PCT, HBD-1+NLR and HBD-1, PCT, and NCR was superior to PTA mono. Conclusion: The serum HBD-1 level gradually increases with the aggravation of liver function injury and is negatively correlated with the short-term prognosis in patients with ACLF. Serum HBD-1 level has high sensitivity and specificity in predicting short-term prognosis in patients with ACLF, and its diagnostic efficacy is superior to that of PCT, NLR, and PTA. The combined application of HBD-1 and PTA has higher diagnostic efficacy; however, when the serum HBD-1 level is greater than 337.96ng/ml, it indicates poor prognosis in patients.

Impact of baseline hepatitis B core antibody on prognosis of patients with hepatitis B virus related acute-on-chronic liver failure / 中华检验医学杂志

Objective:To analyze the impact of baseline quantification of hepatitis B core antibody (qHBcAb) on prognosis of patients with hepatitis B virus (HBV) related acute-on-chronic liver failure (HBV-ACLF).Methods:A total of 91 HBV-ACLF patients (HBV-ACLF group), who admitted to Wuxi No.5 People′s Hospital from July 1, 2019 to December 30, 2021, were included in this study. Fifty chronic hepatitis B (CHB) patients (CHB group) and 50 chronic HBV carriers (HBV carrier group) were enrolled as controls. Baseline clinical data such as qHBcAb, blood routine examination biochemical, and coagulation indices, HBsAg, hepatitis B e antigen (HBeAg), HBV DNA levels were recorded and analyzed retrospectively. The HBV-ACLF, HBsAg and HBV-DNA data were converted logarithmically. Patients were followed-up for 90 days. Cox regression was used to analyze the correlation between HBV-ACLF and survival outcome; survival rate was estimated by the Kaplan-Meier method; receiver operating characteristic (ROC) curve was used to evaluate the predictive value of baseline qHBcAb for the prognosis in patients with HBV-ACLF.Results:The baseline qHBcAb level in HBV-ACLF patients was (4.83±0.42) IU/ml, which was significantly higher than that in the CHB group [(4.59±0.54) IU/ml] and chronic HBV carrier group [(3.86±0.74) IU/ml] (all P<0.05). At the end of 90 days follow-up, 46 patients (50.55%) survived, and 45 patients (49.45%) died in the HBV-ACLF group. The baseline qHBcAb level was significantly higher in the survival group [(4.93±0.22) IU/ml] than in the death group [(4.70±0.52) IU/ml, P<0.01]. Significant differences were also found in the alpha fetoprotein, international normalized ratio, prothrombin activity, antithrombin Ⅲ activity, platelet, end-stage liver disease model score and hepatic encephalopathy complication between the two groups ( P<0.05). Cox regression analysis showed that the baseline qHBcAb was an independent risk factor affecting the 90-day survival of HBV-ACLF patients [hazard ratio=0.027,95% confidence interval ( CI) 0.001-0.696, P<0.05]. The area under the ROC curve of baseline qHBcAb level for predicting the 90-day survival outcome of HBV-ACLF patients was 0.639 (95% CI 0.525-0.752, P<0.05), with a cut-off value of 4.89 IU/ml. The cumulative survival rate of patients with baseline qHBcAb≥4.89 IU/ml was higher than that of patients with baseline qHBcAb<4.89 IU/ml ( P<0.05). Conclusions:Higher baseline qHBcAb level is associated with favorable outcome of HBV-ACLF patients and baseline qHBcAb may be used as a new biomarker to predict the clinical outcome of HBV-ACLF patients. HBV-ACLF patients with serum qHBcAb lower than 4.89 IU/ml face increased risk of short-term death.

Evaluation of neutrophil/lymphocyte ratio and the end-stage liver disease-sodium model in predicting short-term prognosis of patients with HBV-related acute-on-chronic liver failure / 中华全科医师杂志

Objective:To evaluate neutrophil/lymphocyte ratio(NLR) and the model for end-stage liver disease-sodium(MELD-Na)score in predicting short-term prognosis of patients with HBV-related acute-on-chronic liver failure(HBV-ACLF).Methods:A total of 234 consecutive HBV-ACLF patients(194 males and 40 females, aged 23-85 years)admitted to Hangzhou Xixi Hospital from January 2019 to December 2021 were enrolled. According to the 12-week clinical outcomes, patients were divided into good prognosis group( n=141)and poor prognosis group( n=93). Univariate and multivariate Logistic regression were performed to identify independent risk factors for poor prognosis of HBV-ACLF patients. Receiver operating characteristics(ROC)curve was applied to evaluate the accuracy of risk factors in predicting short-term prognosis of HBV-ACLF patients. Results:The age [(48.7±11.9) vs. (52.5±9.9) years old, t=-2.59, P=0.011], proportion of males [78.0%(110/141) vs. 90.3%(84/93), χ2=5.99, P=0.014], total bilirubin[202.9(141.2, 287.6) vs. 320.0(224.4, 400.0) μmol/L, Z=-5.14, P<0.001], creatinine [71.0(59.0, 78.0) vs. 81.0(64.0, 111.0)μmol/L, Z=-3.98, P<0.001], international normalized ratio[1.66(1.52, 1.86) vs. 1.91(1.66, 2.27), Z=-5.46, P<0.001], leukocyte count[5.16(3.99, 6.95)×10 9/L vs. 6.57(4.83, 8.30)×10 9/L, Z=-4.14, P=0.001], NLR[2.77(2.02, 3.55) vs. 5.48(3.44, 8.53), Z=-8.48, P<0.001], MELD score[22.0(20.0, 24.0) vs. 26.0(24.0, 29.0), Z=-9.22, P<0.001], MELD-Na score[22.8(20.0, 25.6) vs. 29.0(25.0, 36.0), Z=-9.16, P<0.001], liver cirrhosis[77.3%(109/141) vs. 88.2%(82/93), χ2=4.41, P=0.036], hepatorenal syndrome[4/141(2.8%) vs. 12/93(12.9%), χ2=8.91, P=0.003] and the proportion of artificial liver treatment[21/141(14.9%) vs. 24/93(25.8%), χ2=4.30, P=0.038] were significantly elevated in poor prognosis group compared with survival group. Logistic regression analysis showed that NLR( OR=3.76, 95 %CI: 2.10-6.74, P<0.001)and MELD-Na score( OR=2.24, 95 %CI: 1.17-4.29, P=0.015) were independent risk factors for poor short-term prognosis of HBV-ACLF patients. The area under the ROC curve(AUC)of NLR, and MELD-Na for the short-term prognosis of HBV-ACLF patients was 0.792 and 0.822, respectively. The AUC of the combination of NLR with MELD-Na was 0.858, which was significantly higher than that of NLR( Z=-3.04, P=0.001) or MELD-Na score( Z=-2.16, P=0.031)alone. Based on the cut-off value of the combined model, patients were classified into high combined model score (≥0.04) group and low combined model score (<0.04) group, the survival rate of the high group was significantly higher than that of the low group( χ2=67.47, P<0.001). Conclusions:NLR and MELD-Na score are independent risk factors of the short-term prognosis of HBV-ACLF patients. The combination of NLR and MELD-Na score will be beneficial to predict the short-term prognosis of HBV-ACLF patients.

Acute-on-chronic liver failure treated by split liver transplantation:a single-center experience on 9 cases / 中华普通外科杂志

Objective:To evaluate the short-term efficacy of split liver transplantation (SLT) in patients with acute-on-chronic liver failure (ACLF).Methods:The clinical data of 9 ACLF patients receiving SLT in our center from Mar 2021 to May 2022 were retrospectively analyzed to evaluate its safety and efficacy.Results:The preoperative APASL ACLF Research consortium (AARC) score of the 9 ACLF patients was 8 points in 1 case, 9 points in 3 cases, 10 points in 3 cases, 11 points in 1 case and 12 points in 1 case, 7 cases were in AARC-ACLF grade 2, and 2 cases in grade 3.In-situ liver splitting was performed in 9 deceased donors, including 4 classical split cases, 5 full size split cases. Among these 9 ACLF patients, 2 received left half liver transplantation, 3 received right half liver transplantation, and 4 received extended right lobe liver transplantation. After transplantation, all 9 recipients were discharged fully recovered, 1 case developed Clavien grade Ⅳa complication and 2 cases developed Clavien grade Ⅲb complication.After SLT treatment the median postoperative hospital stay was 27 days, the 1-year survival rate was 100%, and the organ survival rate was 88.9%.Conclusion:Split liver transplantation is a safe and feasible treatment method for ACLF patients.

Prognostic value of systemic immune-inflammation index in patients with hepatitis B virus-related acute-on-chronic liver failure / 中华传染病杂志

Objective:To investigate the prognostic value of systemic immune-inflammation index (SII) in patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF).Methods:The clinical data, including age, gender, complications, laboratory examination results post-admission, SII, model for end-stage liver disease (MELD) score, MELD-Na score, Child-Turcotte Pugh (CTP) score of HBV-ACLF patients treated in Huashan Hospital, Fudan University from January 2016 to August 2021 were retrospectively analyzed. The patients were divided into survival group and death group according to the outcome at 90 days of follow-up.Paired sample t test, Mann-Whitney U test and chi-square test were used for statistical analysis.Pearson correlation was used to analyze the correlation between SII and the prognosis prediction model of HBV-ACLF. The area under the curve (AUC) was used to analyze the clinical efficacies of SII, MELD score, MELD-Na score and CTP score in predicting the prognosis of HBV-ACLF patients, and the optimal cut-off value of SII for predicting the prognosis of HBV-ACLF was calculated. Kaplan-Meier method was used for survival analysis. Results:A total of 140 patients with HBV-ACLF were included. There were 88 patients in the survival group, including 65 males and 23 females, with the age of (47.69±11.96) years. There were 52 cases in the death group, including 40 males and 12 females, with the age of (52.73±12.22) years. The age, aspartate aminotransferase, total bilirubin, serum creatinine, international normalized ratio, neutrophil-to-lymphocyte ratio, monocyte-to-lymphocyte ratio, SII, MELD score, MELD-Na score, CTP score and the incidence of infection in the death group were all significantly higher than those in the survival group, and albumin, lymphocyte count, platelet count, prognostic nutritional index in the death group were all significantly lower than those in the survival group, and the differences were all statistically significant ( t=-2.39, Z=-2.84, t=-4.81, Z=-2.15, Z=-4.91, Z=-3.47, Z=-3.36, Z=-3.83, Z=-4.69, Z=-4.56, Z=-6.31, χ2=24.96, t=3.06, t=3.03, Z=-7.57 and t=4.12, respectively, all P<0.05). Pearson correlation analysis showed that SII was positively correlated with CTP score ( r=0.272 7, P=0.001), MELD score ( r=0.365 8, P<0.001) and MELD-Na score ( r=0.381 1, P<0.001). The AUC of SII was the largest of 0.80, and 0.76 for MELD score, 0.74 for MELD-Na score and 0.73 for CTP score. The optimal cut-off value of SII was 447.49. Kaplan-Meier analysis showed that the 90 days survival rate of patients with SII≥447.49(38.60%(22/57)) was lower than that of SII<447.49 group (79.52%(66/83)), and the difference between the two groups was significant ( χ2=23.80, P<0.001). Conclusions:SII can be used to assess the severity and prognosis of HBV-ACLF patients. SII ≥447.49 indicates poor prognosis.

Experience of Professor WANG Xianbo in Treating Hepatitis B Virus Associated Acute-on-Chronic Liver Failure by Differentiating Syndromes from Dampness， Heat， Toxicity， Stasis and Deficiency / 中医杂志

By summarising Professor WANG Xianbo's clinical experience in treating hepatitis B virus associated acute-on-chronic liver failure （HBV-ACLF）， it is believed that HBV-ACLF is a syndrome of root-cause deficiency and manifestation excess， with spleen deficiency as the root cause and dampness-heat-toxicity-blood stasis as the manifestation， and the therapeutic methods proposed as “detoxification and cooling of the blood to promote circulation of the internal organs， and strengthening spleen and resolving dampness to take care of the middle energizer”. In the treatment of HBV-ACLF， for syndrome of stasis-heat-toxicity mass， it was common to use the Jiedu Liangxue Formula （解毒凉血方） by detoxifying and cooling blood； For syndrome of dampness-heat-toxicity mass， it was common to use in the Jiedu Liangxue Lishi Formula （解毒凉血利湿方） by detoxifying and cooling the blood， strengthening the spleen and resolving dampness； For syndrome of spleen-deficiency and dampness-heat， it was common to use in the Jiedu Liangxue Jianpi Formula （解毒凉血健脾方， also known as Zhonggan No.2 Formula） by strengthening the spleen and reple-nishing qi， clearing heat and resolving dampness.

Value of MELD 3.0， MELD， and MELD-Na scores in assessing the short-term prognosis of patients with acute-on-chronic liver failure： A comparative study / 临床肝胆病杂志

ObjectiveTo investigate the value of MELD 3.0， MELD， and MELD-Na scores in assessing the 90-day prognosis of patients with acute-on-chronic liver failure （ACLF） through a comparative study. MethodsA retrospective analysis was performed for the clinical data of 605 patients with ACLF who were treated in Tianjin Third Central Hospital， The Fifth Medical Center of Chinese PLA General Hospital， and Beijing YouAn Hospital from November 2012 to June 2019， and according to the 90-day follow-up results after admission， they were divided into survival group with 392 patients and death group with 213 patients. The receiver operating characteristic （ROC） curve， the area under the ROC curve （AUC）， net reclassification improvement （NRI）， integrated discrimination improvement （IDI）， and decision curve analysis （DCA） curve were used to investigate the value of MELD 3.0， MELD， and MELD-Na scores at baseline， day 3， week 1， and week 2 in predicting the prognosis of the disease. ResultsAt day 3 and week 1， MELD 3.0 score had an AUC of 0.775 and 0.808， respectively， with a better AUC than MELD score （P<0.05）. At day 3， week 1， and week 2， MELD 3.0 score showed an NRI of 0.125， 0.100， and 0.081， respectively， compared with MELD in predicting the prognosis of ACLF patients， as well as an NRI of 0.093， 0.140， and 0.204， respectively， compared with MELD-Na score in predicting prognosis. At baseline， day 3， week 1， and week 2， MELD 3.0 showed an IDI of 0.011， 0.025， 0.017， and 0.013， respectively， compared with MELD in predicting the prognosis of ACLF patients. At day 3 and week 2， MELD 3.0 showed an IDI of 0.027 and 0.038， respectively， compared with MELD-Na in predicting the prognosis of ACLF patients. All the above NRIs and IDIs were >0， indicating a positive improvement （all P<0.05）. DCA curves showed that MELD 3.0 was superior to MELD at day 3 and was significantly superior to MELD-Na at week 2. There was no significant difference in the ability of the three scores in predicting the prognosis of ACLF patients with different types， and there was also no significant difference in the ability of the three scores in predicting the prognosis of ACLF patients with the etiology of HBV infection， alcohol， or HBV infection combined with alcohol， while MELD 3.0 was superior to MELD for ACLF patients with other etiologies （P<0.05）. ConclusionMELD 3.0 score is better than MELD and MELD-Na scores in predicting the 90-day survival of patients with ACLF， but with limited superiority.