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.

Objective To investigate the predictive value of age combined with albumin-bilirubin (ALBI) score for the occurrence of overt hepatic encephalopathy (OHE) in patients with cirrhosis complicated by esophageal and gastric variceal bleeding (EGVB) after transjugular intrahepatic portosystemic shunt (TIPS). Methods A retrospective analysis was performed on the clinical data of 87 patients with cirrhosis complicated by EGVB who underwent TIPS. The patients were followed up for 6 months, and were divided into OHE group (27 cases) and non-OHE group (60 cases) based on whether OHE occurred. The indicators with significant differences between the two groups were screened out through univariate analysis, and binary Logistic regression analysis was performed to identify the independent risk factors for OHE occurrence. The receiver operating characteristic (ROC) curve was plotted to evaluate the predictive performance of the individual and combined independent risk factors for OHE. The differences in area under the curve (AUC) were compared using MedCalc software. Results Among 87 patients, 27 developed OHE within 6 months after surgery, with a prevalence rate of 31.03%. Univariate analysis showed that there were significant differences in age, albumin, serum sodium, and ALBI score between the OHE group and the non-OHE group (P < 0.05). Binary Logistic regression analysis showed that age (OR=1.08; 95%CI, 1.02 to 1.14; P=0.01) and ALBI score (OR=13.68; 95%CI, 3.00 to 62.44; P < 0.01) were independent risk factors for OHE in patients with cirrhosis complicated by EGVB after TIPS. ROC curve analysis showed that the AUC for age and ALBI score in predicting OHE were 0.67 (95%CI, 0.55 to 0.79; P=0.01)and 0.72 (95%CI, 0.60 to 0.85; P < 0.01), respectively; the AUC for age combined with ALBI score in predicting OHE was 0.80 (95%CI, 0.70 to 0.91; P < 0.01), with a sensitivity of 77.8% and a specificity of 75.0%. There was no significant difference in the AUC by age and ALBI score alone in predicting OHE (P>0.05); however, the AUC for age combined with ALBI score in predicting OHE was greater than that of age or ALBI score alone in predicting OHE, and the difference was statistically significant (P < 0.05). Conclusion Age and ALBI score are independent risk factors for the occurrence of OHE in patients with cirrhosis complicated by EGVB after TIPS. The combination of age and ALBI score has a higher predictive efficacy in predicting OHE than age or ALBI score alone.

Objective To investigate the value of interleukin-6 (IL-6) combined with Model for End-stage Liver Disease (MELD) score in predicting the prognosis of patients with hepatitis B virus (HBV)-related acute-on-chronic liver failure (HBV-ACLF). Methods A total of 86 patients with HBV-ACLF who were hospitalized in The First Affiliated Hospital of Soochow University from January 2015 to December 2018 were enrolled, and according to their survival status after follow-up for 90 days, they were divided into death group with 50 patients and survival group with 36 patients. ELISA was used to measure the serum level of IL-6, and a statistical analysis was performed for general information. 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 distributed continuous data between two groups; the chi-square test was used for comparison of categorical data between two groups. A Pearson correlation analysis was performed for IL-6 and other variables; a binary logistic regression analysis was used to investigate the independent risk factors for the prognosis of patients with HBV-ACLF; the receiver operating characteristic (ROC) curve was used to assess the value of IL-6 combined with MELD score in predicting the prognosis of HBV-ACLF. Results There were significant differences between the death group and the survival group in hematocrit ( t =2.413), platelet count ( t =6.584), total bilirubin (TBil) ( t =-8.070), prothrombin time (PT) ( U =77.500), international standardized ratio ( U =102.000), HBV DNA ( t =-2.767), IL-6 ( t =-16.543), and MELD score ( t =-8.192), and the death group had a significantly higher level of IL-6 than the survival group (27.13±12.18 pg/mL vs 9.72±5.56 pg/mL, P < 0.001). The Pearson correlation analysis showed that IL-6 was positively correlated with TBil and PT ( r =0.579 and 0.681, both P < 0.001). The binary logistic regression analysis showed that IL-6 (odds ratio[ OR ]=1.480, 95% confidence interval [ CI ]: 1.196~1.833, P =0.007) and MELD score ( OR =1.128, 95% CI : 1.033~1.231, P < 0.001) were independent risk factors for the death of HBV-ACLF patients within 90 days. IL-6 combined with MELD score had an area under the ROC curve (AUC) of 0.891 (95% CI : 0.778~0.999), with a higher AUC than IL-6 (AUC=0.838, 95% CI : 0.687~0.989) or MELD score (AUC=0.783, 95% CI : 0.634~0.933). IL-6 combined with MELD score had a significantly higher value than IL-6 alone in predicting the prognosis of patients with HBV-ACLF ( Z =-2.257, P =0.024). Conclusion IL-6 combined with MELD score can be used as a good model for predicting the short-term prognosis of patients with HBV-ACLF.

ObjectiveTo investigate the protective effect of fecal microbiota transplantation (FMT) on mice with acute-on-chronic liver failure (ACLF) and its effect on intestinal flora. MethodsA total of 40 mice were randomly divided into control group (CON group), model group (MOD group), FMT group (feces of the mice in the CON group were used as fecal microbiota donor), and FMT model group (ANFMT group, with feces of the mice in the MOD group as fecal microbiota donor), with 10 mice in each group. All mice were observed in terms of body weight, death, liver histopathology, and changes in aspartate aminotransferase (AST), alanine aminotransferase (ALT), and intestinal flora. A one-way analysis of variance was used for comparison of normally distributed continuous data between multiple groups, and the SNK-q test was used for further comparison between two groups. ResultsCompared with the CON group, the MOD group had a significant reduction in body weight and significant increases in AST and ALT (all P＜0.05), as well as large patchy necrosis of hepatocytes, significant increases in Verrucomicrobia, Akkermansia, and Erysipelatoclostridium, and significant reductions in Dubosiella and Duncaniella (all P＜0.05). Compared with the CON group, the ANFMT group had a significant increase in AST (P＜0.05), hepatocyte swelling and mild ballooning degeneration, significant increases in Unclassified and Faecalibaculum, and significant reductions in Patescibacteria, Deferribacteres, Muribaculum, Candidatus_Saccharimonas, Rikenella, Odoribacter, Mucispirillum, and Lachnospiraceae_unclassified (all P＜0.05). Compared with the MOD group, the FMT group had significant reductions in AST and ALT (both P＜0.05), mild hepatocellular necrosis and marked ballooning degeneration, significant increases in Paramuribaculum and Bilophila, and significant reductions in Firmicutes, Rikenella, and Absiella (all P＜0.05). ConclusionIntestinal flora disturbance is observed in ACLF mice, and dysbacteriosis may lead to liver injury. FMT can alleviate liver inflammation in ACLF mice and thus exert a protective effect.

ObjectiveTo investigate the value of interleukin-32 (IL-32) combined with Model for End-Stage Liver Disease (MELD) in predicting the prognosis of patients with hepatitis B virus (HBV)-related acute-on-chronic liver failure (HBV-ACLF). MethodsA total of 92 patients with HBV-ACLF who were hospitalized in The First Affiliated Hospital of Soochow University from January 2015 to December 2018 were enrolled, and according to the follow-up results at 3 months after diagnosis, the patients were divided into survival group with 40 patients and death group with 52 patients. ELISA was used to measure the serum level of IL-32. Clinical data of the patients were collected, including age, sex, underlying diseases, major complications, white blood cell count (WBC), platelet count (PLT), hematocrit (HCT), total bilirubin (TBil), alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin (Alb), serum creatinine (SCr), prothrombin time (PT), international normalized ratio (INR), and HBV DNA. The t-test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups; the chi-square test was used for comparison of categorical data between two groups; a Pearson correlation analysis was performed for IL-32 and other variables; a binary logistic regression analysis was performed to investigate the independent risk factors for the prognosis of patients with HBV-ACLF. The receiver operating characteristic(ROC) curve(AUC) was used to evaluate the value of IL-32 combined with MELD score in predicting the prognosis of patients with HBV-ACLF. The normal Z test was used for comparison of AUC. ResultsThere were significant differences between the two groups in HCT, PLT, TBil, SCr, PT, INR, HBV DNA, IL-32, and MELD score (all P＜0.05). IL-32 was positively correlated with TBil (r=0.952, P＜0.001) and MELD score (r=0850, P＜0.001). IL-32 (odds ratio ［OR］=1.137, 95% confidence interval ［CI］: 1040-1243, P=0.005) and MELD score (OR=1.055, 95% CI: 1.001-1.109, P=0.025) were independent risk factors for the death of HBV-ACLF patients. IL-32 combined with MELD score had the highest value in predicting the prognosis of patients with HBV-ACLF (AUC=0.992, 95% CI: 0.981-1000), with a significantly higher AUC than IL-32 (0.992 vs 0.984, Z=2.265, P＜0.05) and MELD score (0.992 vs 0877, Z=3182, P＜0.05). ConclusionBoth IL-32 and MELD score can predict the prognosis of patients with HBV-ACLF, and the combination of these two indicators has a better predictive value.

ObjectiveTo investigate the role of coagulation function parameters and platelet indices in thrombotic events in patients with hepatitis B virus-associated acute-on-chronic liver failure (HBV-ACLF). MethodsA total of 56 patients with HBV-ACLF who were hospitalized in The First Affiliated Hospital of Soochow University from January 2015 to December 2019 were enrolled and divided into thrombotic complication (TC) group with 24 patients and non-thrombotic complication (NTC) group with 32 patients. A retrospective analysis was performed for their general clinical data on admission, and the patients were observed in terms of the changes in coagulation function, platelet count (PLT), and the platelet function-related index mean platelet volume (MPV) on days 1-7 after admission. The t-test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U rank sum test was used for comparison of non-normally distributed continuous data between two groups; the chi-square test was used for comparison of categorical data between two groups. A repeated measures analysis of variance was used to compare coagulation markers within and between groups at different time points. ResultsOn admission, the TC group had a significantly younger age than the NTC group ［31.5 (29.0-34.0) years vs 48.5 (36.0-50.7) years, Z=-2.637, P=0.008］. On the day of admission, there was no significant difference in MPV between the TC group and the NTC group (P ＞0.05), while on days 2-7 after admission, there was a significant difference in MPV between the two groups (t=-2.696、-2.742、-2.894、-4.174、-3.945、-4.716,all P ＜0.01). In the TC group, MPV reached the peak value on day 5 of admission, with a mean value of 13.90±1.12 fl, which was higher than the range of normal values. On admission, all patients had a mean prothrombin time (PT) of 28.8±7.2 s, a mean activated partial thromboplastin time (APTT) of 50.5±8.7 s, and a mean international normalized ratio (INR) of 2.6±0.7, which were higher than normal values; all patients had a mean fibrinogen (Fb) level of 1.16±0.3 g/L and a mean PLT of (107.7±26.5)×109/L, which were lower than normal values. There were no significant differences in PT, APTT, Fb, INR, and PLT between the TC group and the NTC group (all P ＞0.05). ConclusionCoagulation disorder in patients with liver failure is more of a low-equilibrium state, which is complex and heterogeneous and requires individualized treatment. For patients with HBV-ACLF, the development of thrombotic events may be more associated with platelet function than PLT or conventional coagulation markers.

ObjectiveTo investigate the value of Model for End-Stage Liver Disease (MELD) score combined with platelet-to-white blood cell ratio (PWR) in predicting the short-term prognosis of patients with hepatitis B virus-associated acute-on-chronic liver failure (HBV-ACLF). MethodsA retrospective analysis was performed for the clinical data of 123 HBV-ACLF patients who were admitted to The First Affiliated Hospital of Suzhou University from June 2014 to June 2019, and according to the prognosis on day 90 after admission, these patients were divided into survival group with 53 patients and death group with 70 patients. Related clinical data were recorded, including age, sex, and total bilirubin (TBil), alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT), alkaline phosphatase (ALP), serum creatinine (SCr), Albumin (Alb), prealbumin (PAB), international normalized ratio (INR), white blood cell count (WBC), lymphocyte count (LY), monocyte count (MO), neutrophil count (NE), hemoglobin (Hb), and platelet count (PLT) within 24 hours after admission, and PWR and MELD score were calculated. The t-test and the Mann-Whitney U test were used for comparison of continuous data between two groups; univariate and multivariate binary logistic regression analyses were used to analyze the association between each factor and the prognosis of HBV-ACLF; a predictive model of MELD score combined with PWR was established. The receiver operating characteristic (ROC) curve was plotted, and Youden index, cut-off value, sensitivity, and specificity were calculated; the area under the ROC curve (AUC) was calculated for MELD score alone or combined with PWR to compare their value in predicting the prognosis of HBV-ACLF patients. ResultsThere were significant differences between the two groups in TBil, ALT, SCr, INR, WBC, MO, NE, Hb, PLT, PWR, and MELD score (all P＜0.05). TBil, SCr, INR, WBC, MO, NE, and MELD score were risk factors for prognosis of HBV-ACLF patients(all P＜0.05); PWR (odds ratio ［OR］=0.883, 95% confidence interval ［CI］: 0.798-0.977, P=0.016) and MELD score (OR=1.442, 95%CI: 1.225-1698, P＜0.001) were independent predictive factors for the prognosis of HBV-ACLF patients. MELD score combined with PWR had a stronger predictive efficiency than MELD score alone in predicting the prognosis of HBV-ACLF patients ［0.895 (95%CI: 0.827-0943) vs 0.842 (95%CI: 0.765-0.902), P＜0.05］. ConclusionMELD score combined with PWR can improve the efficiency of MELD score alone in predicting the prognosis of HBV-ACLF patients.

ObjectiveTo investigate the level of vascular endothelial growth factor (VEGF) in the peripheral blood of patients with liver cirrhosis and portal vein thrombosis (PVT) and its clinical significance in the diagnosis of liver cirrhosis with PVT. MethodsA total of 60 patients with liver cirrhosis and PVT who were followed up or hospitalized in the outpatient service of The First Affiliated Hospital of Soochow University from January 2017 to December 2019 were enrolled as PVT group, and 161 patients with liver cirrhosis and portal hypertension who had no thrombi were enrolled as LC group. Related clinical data were collected, including sex, age, white blood cell count, platelet count, total bilirubin, alanine aminotransferase, albumin, prothrombin time, international normalized ratio, and antithrombin Ⅲ. Double-antibody sandwich ELISA was used to measure the serum level of VEGF. The t-test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups; the chi-square test was used for comparison of categorical data between two groups. The Pearson correlation test was used for correlation analysis, and a binary logistic regression analysis was used to investigate the risk factors for PVT in patients with liver cirrhosis. ResultsThe comparison of baseline indices showed that there was a significant difference in serum VEGF between the PVT group and the LC group (P＜0.05). The comparison of the patients with Child-Pugh class A, B or C disease showed that there was a significant difference in serum VEGF between the two groups (Z=3.749， 5.469， all P＜0.05). The stepwise logistic regression analysis showed that only serum VEGF (odds ratio=1004, 95% confidence interval: 1.003-1.006, P＜0.001) was an independent risk factor for liver cirrhosis with PVT. ConclusionPatients with liver cirrhosis and PVT tend to have a high level of VEGF in peripheral blood, which provides guidance for clinical diagnosis.

ObjectiveTo investigate the association between mean platelet volume (MPV) and prognosis of hepatitis B virus-associated acute-on-chronic liver failure (HBV-ACLF) and the value of MPV in prognostic evaluation. MethodsA retrospective analysis was performed for the clinical data of 37 patients with hepatitis B cirrhosis, 44 patients with HBV-ACLF, and 27 patients with chronic hepatitis B, who were admitted to Department of Infectious Diseases, The First Affiliated Hospital of Soochow University, from January 2015 to December 2019, as well as 24 individuals who underwent physical examination during the same period of time. Related clinical data included sex, age, total bilirubin (TBil), creatinine (Cr), blood urea nitrogen (BUN), albumin (Alb), blood ammonia (NH3), routine blood test results, Model for End-Stage Liver Disease (MELD) score, and blood coagulation parameters. According to prognosis, the patients with HBV-ACLF patients were divided into improvement group with 19 patients and non-improvement group with 25 patients, and the patients were followed up for 3 months. The Kruskal-Wallis H test was used for comparison between multiple groups, and the Wilcoxon rank sum test was used for comparison within each group， the Mann-Whitney U test was used for comparison between two groups； a binary logistic regression analysis was used to investigate the independent influencing factors for prognosis, and the receiver operating characteristic (ROC) curve was used to predict the accuracy of variables. ResultsThere were significant differences in MPV, platelet count, prothrombin time (PT), international normalized ratio (INR), Alb, BUN, TBil, and MELD score between the liver cirrhosis group, the HBV-ACLF group, the chronic hepatitis group, and the healthy group (χ2=39.031， 75.837, 59.894, 56.033, 22.760, 83.353 and 70.299, all P＜0.001). Further comparison of MPV between two groups showed that the HBV-ACLF group had a significantly higher MPV than the healthy group and the chronic hepatitis group (Z=9.076 and 4.435, both corrected P＜0.001), and the liver cirrhosis group had a significantly higher MPV than the healthy group (Z=2.646, corrected P=0.049). For the patients with HBV-ACLF, there were significant differences in MPV, age, PT, INR, and MELD score between the improvement group and the non-improvement group (Z=-3.710， -2.726， -2.678， -2.322 and -2.610, all P＜0.05), and further binary logistic regression analysis showed that MPV (odds ratio ［OR］=1.175, 95% confidence interval ［CI］: 1.067-2.756, P=0.026) and MELD score (OR=1.643, 95% CI: 1.021-2.644, P=0.041) were independent influencing factors for the prognosis of HBV-ACLF. MPV alone, MELD score alone, and MPV combined with MELD score had an area under the ROC curve of 0.742, 0.731, and 0.791, respectively, in predicting the prognosis of HBV-ACLF, and MPV combined with MELD score had relatively high sensitivity (0.72) and specificity (0.895). ConclusionMPV is an independent influencing factor for the prognosis of HBV-ACLF and has a good value in predicting prognosis. MPV combined with MELD score has advantages over MPV or MELD score alone in predicting the prognosis of HBV-ACLF.

Objective:To investigate the feasibility of cationic antimicrobial peptide cathelicidin-PY(PY) therapy through a mouse model of acute liver failure.Methods:The ability of different concentrations of antimicrobial peptide PY to neutralize endotoxin / lipopolysaccharide (LPS) in vitro was detected by Limulus Amebocyte Lysate (LAL) assay. Cell counting kit-8 (CCK-8) was used to detect the toxic effect of different concentrations of antimicrobial peptide PY on mouse monocyte macrophages (RAW264.7). An in vitro hemolysis experiment was used to evaluate the activity of antimicrobial peptide PY on healthy human erythrocytes. D-galactosamine combined with LPS- induced mouse model of acute liver failure was constructed. The antimicrobial peptide PY effect on survival rate of mouse model was observed. HE staining was used to observe the pathological changes of liver tissue. Immunohistochemistry and Western blotting were used to detect the expression of apoptosis-associated protein caspase-3. Intra-group comparisons were performed using t-test and analysis of variance. χ2 test was used for the comparison of rates. Results:An in vitro experiment showed that the endotoxin neutralization rate was higher at very low dose (0.01 μmol/L), and exceeded 70% at medium-dose (10-40 μmol/L), and the difference between groups with different concentration was statistically significant ( F = 569.22, P < 0.05). Medium-dose antimicrobial peptide PY had strong endotoxin neutralizing effect, low cytotoxicity and hemolytic activity. Moreover, in vivo experiments showed that the degree of liver injury and survival rate of mouse model was significantly improved with the medium-dose of antimicrobial peptide PY. Immunohistochemistry results showed that the expression of caspase-3 in the liver tissue was significantly depleted in the medium-dose group than that of the liver failure group, and the results were consistent with protein immunoblotting testing. Conclusion:Antimicrobial peptide PY possesses a strong ability to neutralize endotoxin and few toxic side effects. A specific dose of antimicrobial peptide PY can attenuate hepatocyte apoptosis and significantly improve the survival rate of animal model, and thus provides a new idea for the liver failure treatment.