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.

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.

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.

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.

The influence of diagnostic criteria of different guidelines on short-term prognosis of artificial liver therapy for acute-on-chronic liver failure / 临床肝胆病杂志

ObjectiveTo investigate the influence of different diagnostic criteria on the short-term prognosis of patients with acute-on-chronic liver failure （ACLF）. MethodsA total of 115 ACLF patients who were hospitalized in Department of Gastroenterology， The Second Affiliated Hospital of Kunming Medical University， from January 2018 to January 2022 were enrolled， and all patients received internal medical treatment combined with artificial liver therapy. According to the guidelines， the patients were divided into CMA guideline group （Diagnostic and treatment guidelines for liver failure by Chinese Medical Association）（n=100）， APASL guideline group （Consensus statements of Asian Pacific Association for the Study of the Liver）（n=94）， and EASL guideline group （Criteria proposed by European Association for the Study of the Liver）（n=36）. The above three guidelines were compared in terms of 90-day mortality rate. A one-way analysis of variance was used for comprision of continuous date between groups； the chi-square test was used for comprision of categorical date between groups. The receiver operating characteristic （ROC） curve of related variables. ResultsThe 90-day mortality rate was 50.0% in the CMA guideline group， 51.1% in the APASL guideline group， and 77.8% in the EASL guideline group， and the EASL guideline group had a significantly higher 90-day mortality rate than the CMA guideline group （χ2=8.351， P=0.004） and the APASL guideline group （χ2=7.650， P=0.006）. EASL guideline had a sensitivity of 22.2% and a specificity of 92.3% in predicting the risk of short-term mortality， with an area under the ROC curve was 0.576. ConclusionACLF patients who meet EASL guideline tend to have a worse short-term prognosis， and this guideline may help to identify patients at a relatively high risk of short-term death.

Value of albumin-related ratios in predicting the risk of death in patients with hepatitis B virus-related acute-on-chronic liver failure / 临床肝胆病杂志

‍ ObjectiveTo investigate and compare the value of albumin-related ratios ［total bilirubin-to-albumin ratio （TAR）， creatinine-to-albumin ratio （CAR）， prothrombin time-international normalized ratio-to-albumin ratio （IAR）， neutrophil count-to-albumin ratio （NAR）， and red blood cell distribution width-to-albumin ratio （RAR）］ in predicting the short-term prognosis of patients with hepatitis B virus-related acute-on-chronic liver failure （HBV-ACLF）. MethodsA retrospective analysis was performed for 354 patients with HBV-ACLF who were admitted to Department of Infectious Diseases， The Affiliated Hospital of Southwest Medical University， from June 2017 to February 2022， and according to their prognosis at 3 months of follow-up， they were divided into survival group （n=272） and death group （n=82）. Related indices were recorded for all patients， including age， sex， complications， and the results of routine blood test， liver function， and coagulation for the first time after admission， and albumin-related ratios and Model for End-Stage Liver Disease （MELD） score were calculated. The t-test was used for comparison of normally distributed continuous data between groups， and the Mann-Whitney U test was used for comparison of non-normally distribution continuous data between groups； the chi-square test was used for comparison of categorical data between groups. The Spearman correlation test was used to investigate the correlation between albumin-related ratios and MELD score. The Logistic regression analysis was used to explore the association of MELD score， TAR， CAR， IAR， NAR， and RAR with poor prognosis. The area under the ROC curve （AUC） was used to as sess the accuracy of albumin-related ratios and MELD score in predicting the short-term prognosis of HBV-ACLF patients， and the De-Long test was used for the comparison of AUC. ResultsCompared with the death group， the survival group had significantly lower MELD score （Z=-8.071， P<0.001）， TAR （Z=-6.695， P<0.001）， CAR （Z=-4.463， P<0.001）， IAR （Z=-7.912， P<0.001）， NAR （Z=-4.061， P<0.001）， and RAR （Z=-4.788， P<0.001）. MELD score was positively correlated with CAR （r=0.616， P<0.001）， IAR （r=0.733， P<0.001）， TAR （r=0.657， P<0.001）， NAR （r=0.392， P<0.001）， and RAR （r=0.380， P<0.001）. The multivariate regression analysis of MELD score and albumin-related ratios showed that high TAR （odds ratio ［OR］=1.014， 95% confidence interval ［CI］： 1.008 — 1.020， P<0.001） and high IAR （OR=22.052， 95%CI： 6.937 — 70.103， P<0.001） were independent risk factors for death. The ROC curves were plotted for albumin-related ratios and MELD score to evaluate their discriminatory ability for mortality， and the results showed that MELD score， TAR， CAR， IAR， NAR， and RAR had an AUC of 0.794， 0.744， 0.663， 0.788， 0.648， and 0.674， respectively， among which MELD score had the highest sensitivity of 86.59% and CAR had the highest specificity of 77.57%. TAR combined with IAR had an AUC of 0.809， with a sensitivity of 76.8% and a specificity of 71.3%. Subgroup analysis of HBV-ACLF showed that TAR combined with IAR had the highest AUC values of 0.884 and 0.733， respectively， in patients with type A or type C HBV-ACLF. ConclusionTAR and IAR can be used as simple and effective prognostic tools to predict the 90-day mortality of HBV-ACLF patients.

Value of peripheral blood lymphocyte count in evaluating the short－term prognosis of patients with acute－on－chronic liver failure / 临床肝胆病杂志

ObjectiveTo investigate the influencing factors for the prognosis of patients with acute－on－chronic liver failure （ACLF）， and to establish a short－term prognostic model. MethodsA retrospective analysis was performed for the baseline clinical data of 247 patients with ACLF who were hospitalized in Department of Infectious Diseases， The First Affiliated Hospital of Xi’an Jiaotong University， from January 2011 to December 2016， and the patients were divided into survival group and death group. The two groups were compared to identify the influencing factors for prognosis； a prognostic model was established， and the receiver operating characteristic （ROC） curve was used to assess its predictive efficacy and determine the optimal cut－off value. The independent－samples t test was used for comparison of normally distributed continuous data between groups， and the Mann－Whitney U rank sum test was used for comparison of non－normally distributed continuous data between groups； the Fisher’s exact test or the Pearson’s chi－square test was used for comparison of categorical data between groups. The univariate and multivariate logistic regression analyses were used to investigate the independent risk factors for 28－ and 90－day prognosis， and the Kaplan－Meier method was used to plot the 28－day survival curves. ResultsA total of 220 patients with ACLF were included based on the inclusion and exclusion criteria； there were 148 patients in the 28－day survival group and 72 patients in the 28－day death group， with a 28－day transplantation－free survival rate of 67.27%； there were 115 patients in the 90－day survival group and 105 patients in the 90－day death group， with a 90－day transplantation－free survival rate of 52.27%. The logistic regression analysis showed that female sex （odds ratio ［OR］=2.149， P=0.030）， high Model for End－Stage Liver Disease （MELD） score （OR=1.120， P<0.001）， and low lymphocyte count （OR=0.411， P=0.002） were independent risk factors for 28－day prognosis， and an LS－MELD model for 28－day prognosis was established as Logit （28－day prognosis）=－3.432+0.765×sex－0.890×lymphocyte count×10－9+0.113×MELD（1 for male sex and 2 for female sex）. The ROC curve analysis showed that this model had an optimal cut－off value of 0.35， and then the patients were divided into low LS－MELD group （≤0.35） and high LS－MELD group （>0.35）； the low LS－MELD group had a significantly higher 28－day survival rate than the high LS－MELD group （P<0.001）. ConclusionPeripheral blood lymphocyte count combined with sex and MELD score has a certain value in predicting the short－term prognosis of ALCF patients.

Acute－on－chronic liver failure： Features and prognosis of a new clinical classification system based on onset manifestations / 临床肝胆病杂志

ObjectiveTo investigate the characteristics of intrahepatic and extrahepatic organ failure at the onset of acute－on－chronic liver failure（ACLF）， to explore the features of a new clinical classification system of ACLF， and to provide a basis for the diagnosis， treatment， prognostic analysis of the disease. MethodsA retrospective analysis was performed for the clinical data of the patients who were hospitalized Beijing YouAn Hospital， Capital Medical University， from January 2015 to October 2022 and were diagnosed with ACLF for the first time. According to the conditions of intrahepatic and extrahepatic organ failure at disease onset， they were classified into type Ⅰ ACLF and type Ⅱ ACLF. Type Ⅰ ACLF referred to liver failure on the basis of chronic liver diseases， and type Ⅱ ACLF referred to acute decompensation of chronic liver diseases combined with multiple organ failure. The clinical features of patients with type Ⅰ or type Ⅱ ACLF were analyzed， and the receiver operating characteristic （ROC） curve was used to assess the value of MELD， MELD－Na， and CLIF－C ACLF scoring system in predicting the 90－day prognosis of ACLF patients with type Ⅰ or type Ⅱ ACLF. The independent－samples t test was used for comparison of normally distributed continuous data between two groups， and the Wilcoxon rank－sum test was used for comparison of non－normally distributed continuous data between two groups； the chi－square test or the Fisher’s exact test was used for comparison of categorical data between two groups. ResultsA total of 582 patients with ACLF were enrolled， among whom there were 535 patients with type Ⅰ ACLF and 47 patients with type Ⅱ ACLF. Hepatitis B and alcoholic liver disease were the main causes in both groups， with no significant difference between the two groups （P>0.05）. Chronic non－cirrhotic liver disease （28.2%） and compensated liver cirrhosis （56.8%） were the main underlying liver diseases in type Ⅰ ACLF， while compensated liver cirrhosis （34.0%） and decompensated liver cirrhosis （61.7%） were the main underlying liver diseases in type Ⅱ ACLF， and there was no significant difference in underlying liver diseases between the patients with type Ⅰ ACLF and those with type Ⅱ ACLF （P<0.001）. The patients with type Ⅱ ACLF had significantly higher median MELD score， MELD－Na score， and CLIF－C ACLF score than those with type Ⅰ ACLF （all P<0.001）. The patients with type Ⅱ ACLF had significantly higher 28－ and 90－day mortality rates than those with type Ⅰ ACLF （38.3%/53.2% vs 15.5%/27.5%， P<0.001）. For the patients with type Ⅰ ACLF who did not progress to multiple organ failure， the patients with an increase in MELD score accounted for 63.7% in the death group and 10.1% in the survival group （P<0.001）， while for the patients with type Ⅰ ACLF who progressed to multiple organ failure， there was no significant difference in the change in MELD score between the survival group and the death group （P>0.05）. In the patients with type Ⅰ ACLF， MELD score， MELD－Na score， and CLIF－C ACLF score had an area under the ROC curve （AUC） of 0.735， 0.737， and 0.740， respectively， with no significant difference between any two scores （all P>0.05）. In the patients with type Ⅱ ACLF， CLIF－C ACLF score had a significantly higher AUC than MELD score （0.880 vs 0.560， P<0.01） and MELD－Na score （0.880 vs 0.513， P<0.01）. ConclusionThere are differences in underlying liver diseases， clinical features， and prognosis between type Ⅰ and type Ⅱ ACLF， and different prognosis scoring systems have different emphases， which provide a basis for the new clinical classification system of ACLF from the perspective of evidence－based medicine.

An excerpt of EASL clinical practice guidelines on acute－on－chronic liver failure （2023） / 临床肝胆病杂志

Acute－on－chronic liver failure （ACLF） is a serious form of acute decompensation of liver cirrhosis， which is characterized by multiple organ failure， systemic inflammatory response， and a high short－term mortality rate. In 2023， the European Association for the Study of the Liver gave recommendations to clinicians， aiming to help them with the diagnosis of ACLF， the decision of triage （whether it is necessary to transfer a patient to the ICU for treatment）， the identification and management of acute predisposing factors， the identification of organs that need support or replacement therapy， the definition of potential criteria for ineffective ICU treatment， and the determination of potential indications for liver transplantation. This article gives an excerpt of the above main contents in the guidelines.

Prognostic evaluation of acute－on－chronic liver failure / 临床肝胆病杂志

Acute－on－chronic liver failure （ACLF） is a common clinical syndrome of severe liver disease characterized by a high short－term mortality rate in clinical practice. Therefore， early and accurate evaluation of the prognosis of ACLF patients is of great significance for making clinical decisions and improving prognosis. This article reviews the recent research advances in markers for the prognostic evaluation of ACLF， in order to improve the existing prognostic evaluation system， assist clinicians in providing timely and appropriate clinical intervention， and further reduce the mortality rate of patients.

Development of acute－on－chronic liver failure in progressive chronic liver diseases： Risk prediction and stratified management / 临床肝胆病杂志

Patients with advanced chronic liver disease （ACLD） are hospitalized due to hepatitis， acute decompensation or liver failure and its complications， and they often require stratified management due to different severities. The patients with acute－on－chronic liver failure （ACLF） have the highest short－term mortality rate among ACLD patients and should be treated in tertiary hospitals. Although non－ACLF patients tend to have a relatively low mortality rate， they still have the risk of progression to ACLF， and there is a significant increase in mortality rate after progression to ACLF， which requires stratified management. The patients with extremely low progression rates often have favorable clinical outcomes and can be administrated in primary hospitals， while the high－risk population should be closely monitored and timely transferred in case of disease progression. However， currently there is still a lack of accurate predictive models for evaluating the risk of progression to ACLF， and further studies are needed to find new biomarkers or algorithms.

Evolution of the clinical scoring and classification system for acute－on－chronic liver failure / 临床肝胆病杂志

Acute－on－chronic liver failure （ACLF） has complex pathogeneses， difficulties in clinical treatment， and poor prognosis. Due to the differences in the distribution of chronic liver diseases in different countries and regions， more than ten scoring and classification systems for ACLF have been proposed in the past few decades， indicating that there are great differences in the definition， scoring， and classification of ACLF. By analyzing the characteristics of several widely used scoring and classification systems， this article discusses their evolution process and the classification criteria applicable to China， so as to provide a reference for optimizing treatment regimens.

Recognition of the clinical classification of acute－on－chronic liver failure： Redefinition from a new perspective of onset manifestations and dynamic outcomes / 临床肝胆病杂志

Acute－on－chronic liver failure （ACLF） refers to acute liver function decompensation on the basis of chronic liver diseases and is a complex clinical syndrome characterized by organ failure and high short－term mortality. ACLF is reversible and has diverse long－term outcomes and prognoses. The clinical classification of ACLF based on disease characteristics is of great significance for optimizing the management pathways for ACLF. With reference to the definition and clinical features of ACLF in the East and the West， this article redefines ACLF from the new perspective of onset manifestations and dynamic outcomes and proposes a new clinical classification of ACLF. The first classification of ACLF is based on the clinical features of intrahepatic and extrahepatic organ failure at disease onset， i.e.， type Ⅰ ACLF （liver failure on the basis of chronic liver diseases） and type Ⅱ ACLF （acute decompensation on the basis of chronic liver diseases comorbid with multiple organ failure）. The second classification is the dynamic clinical classification of ACLF based on clinical outcome， i.e.， type A （rapid progression）， type B （rapid recovery）， type C （slow progression）， type D （slow recovery）， and type E （slow persistence）. The proposed clinical classification of ACLF from the new perspective expects Eastern and Western scholars to have a more inclusive understanding of ACLF， narrow differences， optimize disease management paths， and rationally use medical resources， thereby providing a reference for clinicians.

Bioinformatic Exploration of Hub Genes in Acute-on-chronic Liver Failure and Verification of Traditional Chinese Medicine Candidates / 中国实验方剂学杂志

ObjectiveTo explore the hub genes of acute-on-chronic liver failure （ACLF） using bioinformatics methods， predict the potential traditional Chinese medicines （TCMs） against ACLF， and verify the treatment mechanism based on experiments. MethodPerl and R were used to analyze the GSE142255 dataset to obtain the differentially expressed genes （DEGs）， from which the hub genes in the protein-protein interaction of DEGs were identified by five algorithms of the CytoHubba plug-in. The receiver operating characteristic （ROC） curve and GSE168048 dataset were then used to verify the hub genes. Coremine Medical was employed to map the TCMs corresponding to the hub genes and then the natures， tastes， and meridian tropism of the TCMs were analyzed. The TCM systems pharmacology database and analysis platform （TCMSP） and DEGs were used to obtain the common targets shared by high-frequency TCMs and ACLF， and Cytoscape was used to establish the "hub gene-high-frequency TCM-active ingredient-common target" network. Furthermore， gene ontology （GO） annotation， Kyoto encyclopedia of genes and genomes （KEGG） enrichment analysis， and in vitro experiments were performed. ResultA total of 388 DEGs were obtained， in which the 7 hub genes encoded CD4 integrin subunit alpha M （ITGAM）， CD2， lymphocyte-specific protein tyrosine kinase （LCK） proto-oncogene， C-C motif chemokine ligand 5 （CCL5）， matrix metallopeptidase-9 （MMP-9）， and Fc epsilon receptor IG （FCER1G）. The TCM candidates for treating ACLF were mainly cold， bitter， and had tropism to the liver meridian， among which the high-frequency TCMs （Hedyotis Diffusae Herba， Ganoderma， and Astragali Radix） and the active ingredients （quercetin， kaempferol， and beta-sitosterol） had significant therapeutic potential. The enrichment analysis results showed that TCMs acted on multiple targets and pathways such as autophagy， oxidative stress， and inflammatory cytokines in addition to regulating hub genes. L02 cell experiments showed that the quercetin group had lower levels of tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， and malondialdehyde （MDA）， lower protein levels of ubiquitin-binding protein p62 and MMP-9， and higher levels of superoxide dismutase （SOD）， glutathione （GSH）， and microtubule-associated protein 1 light chain 3 Ⅱ/Ⅰ （LC3 Ⅱ/Ⅰ） than the D-galactosamine （D-GaLN） group （P<0.05， P<0.01）. In addition， the pretreatment with 3-methyladenine （3-MA） inhibited the activating effect of quercetin on the autophagy of L02 cells. ConclusionThe potential TCMs and active ingredients predicted based on the hub genes of ACLF have a great research value. Quercetin has the potential to treat ACLF by inhibiting the D-GaLN-induced oxidative stress and inflammatory response in L02 cells and regulating the expression of MMP-9， which may be associated with the activation of autophagy.

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.