Characterization of acute-on-chronic liver diseases: A multicenter prospective cohort study.

BACKGROUND: Acute-on-chronic liver disease (AoCLD) accounts for the majority of patients hospitalized in the Department of Hepatology or Infectious Diseases. AIM: To explore the characterization of AoCLD to provide theoretical guidance for the accurate diagnosis and prognosis of AoCLD. METHODS: Patients with AoCLD from the Chinese Acute-on-Chronic Liver Failure (ACLF) study cohort were included in this study. The clinical characteristics and outcomes, and the 90-d survival rate associated with each clinical type of AoCLD were analyzed, using the Kaplan-Meier method and the log-rank test. RESULTS: A total of 3375 patients with AoCLD were enrolled, including 1679 (49.7%) patients with liver cirrhosis acute decompensation (LC-AD), 850 (25.2%) patients with ACLF, 577 (17.1%) patients with chronic hepatitis acute exacerbation (CHAE), and 269 (8.0%) patients with liver cirrhosis active phase (LC-A). The most common cause of chronic liver disease (CLD) was HBV infection (71.4%). The most common precipitants of AoCLD was bacterial infection (22.8%). The 90-d mortality rates of each clinical subtype of AoCLD were 43.4% (232/535) for type-C ACLF, 36.0% (36/100) for type-B ACLF, 27.0% (58/215) for type-A ACLF, 9.0% (151/1679) for LC-AD, 3.0% (8/269) for LC-A, and 1.2% (7/577) for CHAE. CONCLUSION: HBV infection is the main cause of CLD, and bacterial infection is the main precipitant of AoCLD. The most common clinical type of AoCLD is LC-AD. Early diagnosis and timely intervention are needed to reduce the mortality of patients with LC-AD or ACLF.

sTREM-1 as promising prognostic biomarker for acute-on-chronic liver failure and mortality in patients with acute decompensation of cirrhosis.

BACKGROUND: Acute decompensation (AD) of cirrhosis is associated with high short-term mortality, mainly due to the development of acute-on-chronic liver failure (ACLF). Thus, there is a need for biomarkers for early and accurate identification of AD patients with high risk of development of ACLF and mortality. Soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) is released from activated innate immune cells and correlated with various inflammatory processes. AIM: To explore the prognostic value of sTREM-1 in patients with AD of cirrhosis. METHODS: A multicenter prospective cohort of 442 patients with cirrhosis hospitalized for AD was divided into a study cohort (n = 309) and validation cohort (n = 133). Demographic and clinical data were collected, and serum sTREM-1 was measured at admission. All enrolled patients were followed-up for at least 1 year. RESULTS: In patients with AD and cirrhosis, serum sTREM-1 was an independent prognosis predictor for 1-year survival and correlated with liver, coagulation, cerebral and kidney failure. A new prognostic model of AD (P-AD) incorporating sTREM-1, blood urea nitrogen (BUN), total bilirubin (TBil), international normalized ratio (INR) and hepatic encephalopathy grades was established and performed better than the model for end-stage liver disease (MELD), MELD-sodium (MELD-Na), chronic liver failure-consortium (CLIF-C) ACLF and CLIF-C AD scores. Additionally, sTREM-1 was increased in ACLF and predicted the development of ACLF during first 28-d follow-up. The ACLF risk score incorporating serum sTREM-1, BUN, INR, TBil and aspartate aminotransferase levels was established and significantly superior to MELD, MELD-Na, CLIF-C ACLF, CLIF-C AD and P-AD in predicting risk of ACLF development. CONCLUSION: Serum sTREM-1 is a promising prognostic biomarker for ACLF development and mortality in patients with AD of cirrhosis.

Increased expression of autophagy-related gene 5 indicates poor prognosis in patients with hepatocellular carcinoma.

OBJECTIVES: As a critical component of the autophagic machinery, autophagy-related gene 5 (ATG5) is essential for autophagosome formation. Autophagy participates in the transformation and progression of various malignant tumors, but the role of ATG5 in hepatocellular carcinoma (HCC) remains to be illustrated. In this study we aimed to investigate the prognostic significance of ATG5 in HCC. METHODS: ATG5 expression was evaluated in 89 pairs of HCC tissues and adjacent non-tumor tissues. The relationship between ATG5 expression and patients' clinicopathological characteristics and prognosis were evaluated. Moreover, subgroup analyses were performed regarding patients' age and number of tumors. Nomograms estimating overall survival (OS) and disease-free survival (DFS) were conducted. RESULTS: ATG5 expression was increased in HCC specimens rather than adjacent non-tumor tissues. The upregulated ATG5 expression was positively associated with serum α-fetoprotein (AFP) level. Moreover, cases with a strong ATG5 expression had a poorer disease-free survival (DFS) and overall survival (OS) than those with a weak ATG5 expression. Multivariate analysis showed that a strong expression of ATG5 was related to a poor OS and DFS in patients with HCC. Further analysis indicated that cases with a higher ATG5 expression had a poorer OS and DFS in the young patients (≤55 years) and those with solitary tumor. The nomogram suggested that there was a coherence between nomogram prediction and the actual situation of patient survival related to ATG5. CONCLUSION: ATG5 promotes tumor progression in HCC, making it a potential biomarker in the diagnosis and a therapeutic target of HCC.

The neutrophil-to-lymphocyte ratio represents a systemic inflammation marker and reflects the relationship with 90-day mortality in non-cirrhotic chronic severe hepatitis.

OBJECTIVES: To investigate the relationship between systemic inflammatory response and short-term mortality in patients with non-cirrhotic chronic severe hepatitis (CSH) by using several indicators of inflammation including neutrophil-to-lymphocyte ratio (NLR), neutrophil (NEU), white blood cell (WBC), platelet-to lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR). METHODS: Data were collected from two prospectively enrolled CATCH-LIFE noncirrhotic cohorts. Cox regression analysis was used to investigate the association between systemic inflammatory biomarkers and 90-day liver transplant (LT)-free mortality. A generalized additive model (GAM) was used to illustrate the quantitative curve relationship between NLR and 90-day LT-free mortality. Kaplan-Meier method was used to estimate the 90-year LT-free survival. RESULTS: The prevalence of CSH was 20.5% (226/1103). The 28-day and 90-day LT-free mortality rates were 17.7% and 26.1%, respectively, for patients with non-cirrhotic CSH. Patients with no infection accounted for 75.0% of all CSH patients, and NLR was independently associated with 90-day LT-free mortality. NLR of 2.9 might be related to disease deterioration in CSH patients without infection. CONCLUSIONS: NLR may be an independent risk factor for 90-day LT-free mortality in patients with non-cirrhotic chronic liver disease. A NLR of 2.9 as the cut-off value can be used to predict disease aggravation in CSH patients without infection.

Prevalence and clinical characteristics of autoimmune liver disease in hospitalized patients with cirrhosis and acute decompensation in China.

BACKGROUND: Autoimmune liver disease (AILD) has been considered a relatively uncommon disease in China, epidemiological data for AILD in patients with cirrhosis and acute decompensation (AD) is sparse. AIM: To investigate the prevalence, outcome and risk factors for AILD in cirrhotic patients complicated with AD in China. METHODS: We collected data from patients with cirrhosis and AD from two prospective, multicenter cohorts in hepatitis B virus endemic areas. Patients were regularly followed up at the end of 28-d, 90-d and 365-d, or until death or liver transplantation (LT). The primary outcome in this study was 90-d LT-free mortality. Acute-on-chronic liver failure (ACLF) was assessed on admission and during 28-d hospitalization, according to the diagnostic criteria of the European Association for the Study of the Liver (EASL). Risk factors for death were analyzed with logistic regression model. RESULTS: In patients with cirrhosis and AD, the overall prevalence of AILD was 9.3% (242/2597). Prevalence of ACLF was significantly lower in AILD cases (14%) than those with all etiology groups with cirrhosis and AD (22.8%) (P < 0.001). Among 242 enrolled AILD patients, the prevalence rates of primary biliary cirrhosis (PBC), autoimmune hepatitis (AIH) and PBC-AIH overlap syndrome (PBC/AIH) were 50.8%, 28.5% and 12.0%, respectively. In ACLF patients, the proportions of PBC, AIH and PBC/AIH were 41.2%, 29.4% and 20.6%. 28-d and 90-d mortality were 43.8% and 80.0% in AILD-related ACLF. The etiology of AILD had no significant impact on 28-d, 90-d or 365-d LT-free mortality in patients with cirrhosis and AD in both univariate and multivariate analysis. Total bilirubin (TB), hepatic encephalopathy (HE) and blood urea nitrogen (BUN) were independent risk factors for 90-d LT-free mortality in multivariate analysis. The development of ACLF during hospitalization only independently correlated to TB and international normalized ratio. CONCLUSION: AILD was not rare in hospitalized patients with cirrhosis and AD in China, among which PBC was the most common etiology. 90-d LT-free mortality were independently associated with TB, HE and BUN.

Plasma Exchange-Based Non-bioartificial Liver Support System Improves the Short-Term Outcomes of Patients With Hepatitis B Virus-Associated Acute-on-Chronic Liver Failure: A Multicenter Prospective Cohort Study.

Background and aims: Hepatitis B virus-associated acute-on-chronic liver failure (HBV-ACLF) is a complicated syndrome with extremely high short-term mortality. Whether plasma exchange (PE) improves HBV-ACLF outcomes remains controversial. Here, PE-based non-bioartificial liver support system (NB-ALSS) effects on short-term HBV-ACLF patient outcomes were investigated. Materials and methods: HBV-ACLF patients from Chinese Acute-on-chronic Liver Failure (CATCH-LIFE) cohort receiving standard medical therapy (SMT) alone or PE-based NB-ALSS in addition to SMT were allocated to SMT and SMT+PE groups, respectively; propensity score matching (PSM) was used to eliminate confounding bias. Short-term (28/90-day and 1-year) survival rates were calculated (Kaplan-Meier). Results: In total, 524 patients with HBV-ACLF were enrolled in this study; 358 received SMT alone (SMT group), and the remaining 166 received PE-based NB-ALSS in addition to SMT (SMT+PE group). PSM generated 166 pairs of cases. In the SMT+PE group, 28-day, 90-day, and 1-year survival rates were 11.90, 8.00, and 10.90%, respectively, higher than those in the SMT group. Subgroup analysis revealed that PE-based NB-ALSS had the best efficacy in patients with ACLF grade 2 or MELD scores of 30-40 (MELD grade 3). In MELD grade 3 patients who received SMT+PE, 28-day, 90-day, and 1-year survival rates were improved by 18.60, 14.20, and 20.10%, respectively. According to multivariate Cox regression analysis, PE-based NB-ALSS was the only independent protective factor for HBV-ACLF patient prognosis at 28 days, 90 days, and 1 year (28 days, HR = 0.516, p = 0.001; 90 days, HR = 0.663, p = 0.010; 1 year, HR = 0.610, p = 0.051). For those who received SMT+PE therapy, PE-based NB-ALSS therapy frequency was the only independent protective factor for short-term prognosis (28-day, HR = 0.597, p = 0.001; 90-day, HR = 0.772, p = 0.018). Conclusions: This multicenter prospective study showed that the addition of PE-based NB-ALSS to SMT improves short-term (28/90 days and 1-year) outcomes in patients with HBV-ACLF, especially in MELD grade 3 patients. Optimization of PE-based NB-ALSS may improve prognosis or even save lives among HBV-ACLF patients.

Analysis of the Effect of Proton-Pump Inhibitors on the Course of COVID-19.

OBJECTIVE: This study is to evaluate the effect of proton-pump inhibitors on the course of COVID-19. METHODS: Clinical data of moderate COVID-19 patients admitted to the Shanghai Public Health Clinical Center for treatment from January 20, 2020, to March 16, 2020, were collected. A retrospective study was conducted and the patients were divided into two groups according to whether they used proton-pump inhibitors or not. The differences in SARS-CoV-2 clearance and hospital stay between the two groups were compared by Cox proportional hazards (PH) regression models and the propensity score matching method. RESULTS: A total of 154 patients with moderate COVID-19 were included in this study, including 80 males (51.9%), 35 patients (22.7%) in the proton-pump inhibitor group, and 119 patients (77.3%) in the control group. In the proton-pump inhibitor group and the control group, the duration of the SARS-CoV-2 clearance was 7 days (95% CI, 6-9) and 7 days (95% CI, 6-11), and the duration of the hospital stay was 21 days (95% CI, 16-25) and 20 days (95% CI, 15-26), respectively. There was no significant difference between the both groups in the cumulative incidence of the SARS-CoV-2 clearance and the discharge, and the same results were obtained after the propensity score matching, all P > 0.05. There was no significant association between the use of proton-pump inhibitors and the duration of SARS-CoV-2 clearance, according to univariate analysis (HR, 1.309; 95% CI, 0.893-1.918) and multivariate analysis (HR, 1.575; 95% CI, 0.993-2.499). There was no significant association between the use of proton-pump inhibitors and the duration of hospital stay for COVID-19, according to univariate analysis (HR, 1.044; 95% CI, 0.714-1.528) and multivariate analysis (HR, 1.064; 95% CI, 0.651-1.740). CONCLUSION: The use of proton-pump inhibitors has no effect on prolonging or shortening the course of adults hospitalized with COVID-19.

Early Diagnostic Biomarkers of Sepsis for Patients with Acute-on-Chronic Liver Failure: A Multicenter Study.

INTRODUCTION: Sepsis is a complication in acute-on-chronic liver failure (ACLF) patients associated with high rates of mortality and morbidity. Early diagnosis of sepsis in ACLF patients can improve prognosis. This study aimed to explore potential effective biomarkers for the early diagnosis of sepsis in ACLF patients. METHODS: Ninety-four ACLF patients with sepsis were enrolled from 10 hospitals across China from January 2015 to June 2016 as well as 49 ACLF patients without infection from Xiangya Hospital. The first-day admission data and SOFA score and CLIF-SOFA score were collected. The differences of indicators between groups were compared with Kruskal-Wallis test. The receiver-operating characteristic (ROC) curve was analyzed to evaluate the diagnostic efficiency of the selected factors. RESULTS: Soluble triggering receptor expressed on myeloid cell-1 (sTREM-1) and presepsin were significantly higher in ACLF-sepsis patients compared with ACLF patients with no infection (P < 0.001). sTREM-1 and presepsin presented higher diagnostic value in sepsis for ACLF patients compared with other biomarkers [white blood cells (WBC), procalcitonin (PCT) and C-reactive protein (CRP)]. Combining sTREM-1 or presepsin with the CLIF-SOFA score increased the diagnostic efficiency (AUC = 0.876 or AUC = 0.913, respectively). CONCLUSIONS: sTREM-1 and presepsin are potential biomarkers for the early diagnosis of sepsis in ACLF patients. The combination of presepsin and the CLIF-SOFA score is a promising method for diagnosing sepsis in ACLF patients. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT02457637.

Risks and predicting factors of bleeding complications in hepatitis B virus-related acute-on-chronic liver failure.

BACKGROUND/AIMS: This study aimed to provide supporting evidence for prevention and prognostic evaluation of bleeding complications in the early stage by exploring the risk and predicting factors in patients with acute-on-chronic liver failure (ACLF). MATERIALS AND METHODS: A total of 101 hospitalized patients with ACLF were retrospectively included from January 1, 2014 to December 31, 2015. The patients were divided into bleeding (n=38) and nonbleeding groups (n=63). Demographic data and laboratory tests were recorded and compared between the two groups. The incidence, risk factors, and prognosis of bleeding complications among patients with ACLF were investigated. RESULTS: A total of 38 cases (37.62%) had bleeding complications: 26 (25.74%) were spontaneous and 12 (11.88%) were postprocedural. Patients with bleeding complications had lower platelet (p=0.008), fibrinogen (p<0.001), factor V (p=0.001), and factor VII (p=0.026) levels; higher serum creatinine levels (p=0.004); and a higher proportion of cirrhosis (p=0.013). Logistic regression analysis showed that cirrhosis (odds ratio=3.251, p=0.046), fibrinogen level (odds ratio=0.352, p=0.007), and factor VII level (odds ratio=0.951, p=0.011) contributed to the development of bleeding complications. A subgroup analysis of invasive manipulation-induced bleeding complications showed lower levels of factors V (p=0.018) and VII (p=0.021) in the postprocedural bleeding group. Follow-up studies showed that the nonbleeding group had a higher survival rate than the bleeding group at day 90 (73.33% versus 51.85%, p=0.040). CONCLUSION: Liver cirrhosis, lower levels of fibrinogen, and major coagulation factor activity in patients with ACLF were associated with an elevated risk of bleeding events during hospitalization, which further impaired the 90-day survival rate.

High Expression of Interleukin-33/ST2 Predicts the Progression and Poor Prognosis in Chronic Hepatitis B Patients with Hepatic Flare.

BACKGROUND: Interleukin-33 (IL-33), along with its receptor suppression of tumorigenicity 2 (ST2), is capable of regulating immune responses. Immunologically mediated events play a critical role in the acute phase of chronic hepatitis B (CHB) infection. The present study primarily aimed to determine whether the IL-33/ST2 axis could be used as a reliable biomarker to predict disease progression and prognosis. METHODS: The study included 130 cases of CHB, with 48 cases in stable condition, 50 cases of progression to hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF), and 32 cases of progression to HBV related pre-ACLF. The demographic data and laboratory test results were recorded and compared among the groups. The blood samples for the measurement of serum IL-33 and soluble ST2 (sST2) levels were collected at admission and evaluated twice using the ELISA method. RESULTS: The patients in which the disease progressed to HBV-ACLF had the highest serum IL-33 and sST2 levels among the three groups (p<0.001). The correlation analysis showed that the serum IL-33 levels were associated with the levels of ALT (r = 0.367, p<0.001), AST (r = 0.456, p<0.001) and the MELD score (r = 0.377, p = 0.001). The area under the curve (AUC) of IL-33 and sST2 levels for differentiation of disease progression were 0.861 (95% CI: 0.787-0.934, p<0.001) and 0.788 (95% CI: 0.692-0.884, p<0.001), respectively. The serum IL-33 levels combined with the MELD score had the highest 90-day mortality prediction efficiency, with an AUC of 0.918 (95% CI: 0.859-0.977, p<0.001), a sensitivity of 92.3%, and a specificity of 88.7%. CONCLUSIONS: The IL-33/sST2 axis could be used to evaluate the progression and mortality in CHB patients with hepatic flare. The combinatorial use of multiple indicators could achieve the highest diagnostic and predictive accuracy.

Prevalence and Clinical Significance of Portal Vein Thrombosis in Patients With Cirrhosis and Acute Decompensation.

BACKGROUND & AIMS: Portal vein thrombosis (PVT) is a common and serious complication in patients with cirrhosis. However, little is known about PVT in patients with cirrhosis and acute decompensation (AD). We investigated the prevalence and clinical significance of PVT in nonmalignant patients with cirrhosis and AD. METHODS: We performed a retrospective study of 2 cohorts of patients with acute exacerbation of chronic liver disease who participated in the Chinese AcuTe on CHronic LIver FailurE study, established by the Chinese Chronic Liver Failure Consortium, from January 2015 through December 2016 (n = 2600 patients) and July 2018 through January 2019 (n = 1370 patients). We analyzed data on the prevalence, clinical manifestations, and risk factors of PVT from 2826 patients with cirrhosis, with and without AD. RESULTS: The prevalence of PVT in patients with cirrhosis and AD was 9.36%, which was significantly higher than in patients with cirrhosis without AD (5.24%) (P = .04). Among patients with cirrhosis and AD, 63.37% developed PVT recently (the first detected PVT with no indication of chronic PVT). Compared with patients without PVT, a significantly higher proportion of patients with PVT had variceal bleeding (47.33% vs 19.63%; P < .001) and patients with PVT had a significantly higher median serum level of D-dimer (2.07 vs 1.25; P < .001). Splenectomy and endoscopic sclerotherapy were independent risk factors for PVT in patients with cirrhosis and AD. The 1-year mortality rate did not differ significantly between patients with vs without PVT. CONCLUSIONS: In an analysis of data from 2826 patients with cirrhosis, a significantly higher proportion of those with AD had PVT than those without AD. PVT was associated with increased variceal bleeding, which would increase the risk for AD. Strategies are needed to prevent PVT in patients with cirrhosis, through regular screening, to reduce portal hypertension. ClinicalTrials.gov no: NCT02457637 and NCT03641872.

Cardiac health in patients with hepatitis B virus-related cirrhosis.

Not only alcoholic cirrhosis related to cardiac dysfunction, cirrhosis caused by nonalcoholic etiology including hepatitis B virus (HBV) infection also related to impaired cardiac health. The aims of present study were to perform a noninvasive evaluation of cardiac function and to evaluate exercise performance in HBV related cirrhotic patients without typical symptoms of cardiac disease.Seventy-nine HBV related cirrhotic patients and 103 matched subjects without a previous history of cardiac involvement were recruited. Clinical examination and cardiac health evaluation were performed. The incidence, risk factors of cardiac dysfunction and exercise tolerance were investigated.A correlation between QTc interval and model for end-stage liver disease score (R = 0.239, P = .018) was detected, however, the connection between QTc prolongation and the severity of liver disease was uncertain. Patients with HBV related cirrhosis had a tendency toward left ventricular wall thickening (P = .007). Forty-one patients (51.90%) were in accordance with the definition of cirrhotic cardiomyopathy, and a significant increase in the incidence of cardiac diastolic dysfunction (CDD) could be found with increasing Child-Pugh grade (P = .004). HBV related cirrhotic patients with CDD had a higher level of pro-brain natriuretic peptide (P = .025), international normalized ratio (P = .010) Child-Pugh score (P = .020), and a higher proportion of ascites (P < .001). The higher Child-Pugh score (odds ratio = 1.662, P = .010) was an independent diagnostic predictor of CDD. The cardiac depression and exercise tolerance also got worse with increasing Child-Pugh score (P < .001).Impaired cardiac health was common in HBV related cirrhotic patients. Cardiogenic factors must be carefully considered in the integral therapy of cirrhosis. Hepatology physicians should lay emphasis on exercise training in daily life.

Acute-on-Chronic Liver Failure in China: Rationale for Developing a Patient Registry and Baseline Characteristics.

Definitions and descriptions of acute-on-chronic liver failure (ACLF) vary between Western and Eastern types, and alcoholism and hepatitis B virus (HBV) are, respectively, the main etiologies. To determine whether there are unified diagnostic criteria and common treatment programs for different etiologies of ACLF, a multicenter prospective cohort with the same inclusion criteria and disease indicators as those used in the European Consortium Acute-on-Chronic Liver Failure in Cirrhosis Study is urgently needed in Asia, where the prevalence of HBV is high. A multicenter prospective cohort of 2,600 patients was designed, drawing from 14 nationwide liver centers from tertiary university hospitals in China, and 2,600 hospitalized patients with chronic liver disease (both cirrhotic and noncirrhotic) of various etiologies with acute decompensation or acute hepatic injury were continuously recruited from January 2015 to December 2016. Data were collected during hospitalization, and follow-ups were performed once a month, with plans to follow all patients until 36 months after hospital discharge. Of these patients, 1,859 (71.5%) had HBV-related disease, 1,833 had cirrhotic disease, and 767 had noncirrhotic disease. The numbers and proportions of enrolled patients from each participating center and the baseline characteristics of the patients with or without cirrhosis are presented.

Risk Factors and Outcomes of Acute Kidney Injury in Patients With Hepatitis B Virus-Related Acute-on-Chronic Liver Failure.

BACKGROUND: Acute kidney injury (AKI) is common in patients with hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF); however, few studies concerning the risk factors and recovery patterns of renal function have been published. MATERIALS AND METHODS: A retrospective analysis of 150 patients with HBV-ACLF was performed. The occurrence, risk factors and functional recovery of AKI among patients with HBV-ACLF were investigated. RESULTS: A total of 90 patients (60%) with HBV-ACLF developed AKI. Patients with AKI had higher creatine kinase (P = 0.004), total bilirubin (P = 0.039), HBV viral load (P = 0.044), serum creatine (P < 0.001) and model for end-stage liver disease (MELD) score (P < 0.001) values and a higher proportion of hepatic encephalopathy (P = 0.032) and spontaneous bacterial peritonitis (SBP) (P = 0.042) than patients without AKI. Logistic regression analysis illustrated that SBP (odds ratio = 6.214, P = 0.012) and MELD score (odds ratio = 1.097, P = 0.006) were risk factors for the development of AKI. A subgroup analysis of recovery patterns in renal function showed that patients with a severe AKI stage had worse outcomes (P = 0.007). The proportion of patients who experienced a complete recovery was higher in survivors than in the overall AKI populations (P = 0.004). Follow-up studies showed that the no-AKI group had a higher transplant-free survival rate than the AKI group at day 90 (80.0% versus 26.7%, respectively, P < 0.001). The survival rate among patients with AKI Stage 1 was higher than that of patients with AKI Stage 2 and patients with AKI Stage 3 (P < 0.001). CONCLUSIONS: AKI is common in patients with HBV-ACLF. The SBP and MELD score have some prognosis value for patients with AKI. AKI and its stages affect the 90-day transplant-free mortality rate. It is important to focus on exploring the early recognition of AKI and early intervention of those risk factors in individuals with HBV-ACLF.

[Study on type I interferon and phospho-IRF3 in murine liver dendritic cells after intervened by HBV].

OBJECTIVE: To detect the secretions of type I interferon and the expressions of phospho-IRF3 in murine liver dendritic cells intervened by HBV. METHODS: The murine liver dendritic cells were isolated via anti-CD11c microbeads and were incubated in the presence of GM-CSF and IL-4 to induce the DC generation and proliferation in 24-well cell culture plates. HBV virions were isolated via ultracentrifugation and were detected by quantitative Realtime-PCR. The DCs were divided into two groups: one group was cultured with HBV virions for 24 hours, the other group was cultured without HBV as control group. The cells were harvested at Oh, 1h, 2h, 6h and 24h after being stimulated with poly I:C and the expressions of p-IRF3 and the concentration of IFN beta in supernatants were detected with western blot and ELISA respectively. RESULTS: The IFN beta concentrations at 0 h, 6 h and 24 h in the supernatants of the HBV group and the control group were (12.38 +/- 3.71) pg/ml, (88.67 +/- 9.01) pg/ml and (69.89 +/- 5.80) pg/ml vs (10.83 +/- 4.11) pg/ml, (137.68 +/- 12.28) pg/ml and (72.25 +/- 8.61) pg/ml, respectively. No statistical differences found at 0 h (t = 0.8398, P > 0.05) and 24 h (t = 0.6820, P > 0.05) between the two groups except that at 6 h (t = 9.653, P < 0.01). The expressions of phospho-IRF3 in HBV group were lower than that in control group. CONCLUSIONS: The type I interferon secretion and the phospho-IRF3 expression were decreased in murine liver dendritic cells when intervened by HBV.

Correlation of the expression of toll-like receptors in monocyte-derived dendritic cells with prognosis of chronic severe hepatitis B.

OBJECTIVE: This study aims to measure the expression of toll-like receptors (TLR) in monocyte-derived dendritic cells (MoDC) from chronic severe hepatitis B (CSHB), to assess the contribution of TLRs in CSHB. METHODS: Peripheral blood was collected from 40 CSHB patients, 30 chronic hepatitis B (CHB) patients, and 30 healthy individuals who served as healthy controls (HCs). Purified monocytes were isolated by a combination of Histopaque-1.077 and CD14 Microbeads. MoDCs were induced with granulocyte macrophage colony-stimulating factor and interleukin-4 for 6 days from CD14(+) monocytes. The expression of TLRs in MoDC was measured using real-time PCR and flow cytometry. RESULTS: The expressions of TLR-1, -2, -7 were significantly higher in MoDC of CSHB than that of HCs, of which the level of TLR-3 was decreased. Particularly in CSHB patients, the TLR-3 expression was further decreased compared to CHB patients. In non-survival CSHB patients, TLR-3 level was significantly decreased, while TLR-2 expression was dramatically increased. Linear correlation analysis demonstrated significant correlations between TLR-3 level and disease severity markers (total bilirubin, prothrombin activity, creatinine, white blood cell count, and maximum volume of ascitic fluid) in individual CSHB patients. CONCLUSIONS: TLR-2 and TLR-3 may be involved in the pathogenesis of CSHB, and TLR-3 may influence the prognosis of CSHB.

[Expression of nuclear factor-κB and its regulated cytokines in dendritic cells in patients with chronic severe hepatitis B and its clinical significance].

OBJECTIVE: To investigate the correlation of nuclear factor-κB (NF-κB) level and its regulated cytokines in monocyte-derived dendritic cells (MoDC) with illness severity and prognosis in patients with chronic severe hepatitis B (CSHB). METHODS: Peripheral blood mononuclear cells (PBMC) were isolated by Ficoll density gradient separation from 37 patients with CSHB, 20 chronically HBV-infected patients, and 20 normal controls. Monocytes were acquired using immunomagnetic anti-CD14-beads. Next, monocytes were induced into immature DC (iDC) in vitro. On day six, polyI:C was added to induce DC maturation. Then mature DCs (mDCs) were collected at 48 h after polyI:C treatment to test the expression of NF-κB p50 by real time PCR. The supernatants were also collected respectively. The expression of TNFα and IL-6 in the supernatants were measured by ELISA. RESULTS: The expression of NF-κB p50 in mDCs of patients with CSHB was the highest in three groups (F=19.01, P<0.01). The secretion of TNFα and IL-6 in mDCs from group CSHB was extremely high when compared with the other two groups, the secretions of TNFα in groups CSHB, CHB and NC were(15317.69+/-4124.90) pg/ml, (9670.29+/-3654.68) pg/ml and (6547.43+/-1027.20) pg/ml (F=45.77, P<0.01) respectively, and the productions of IL-6 in groups CSHB, CHB and NC were (1423.78+/-375.14) pg/ml, (862.68+/-93.68) pg/ml and (567.26+/-167.04) pg/ml (F = 67.60, P is less than 0.01), respectively. NF-κB p50 showed significant correlations with TNFα(r=0.52, P<0.01) and IL-6 (r=0.65, P<0.01) in mDCs. Furthermore, the secretions of TNFα and IL-6 in mDCs from group CSHB were negatively associated with PTA (r=-0.41, P=0.01; r=-0.40, P=0.01), but not with ALT, TBil and virus loads (r=-0.03, P=0.85, r=0.01, P=0.93, r=0.01, P=0.95; r=-0.09, P=0.58, r=0.16, P=0.34, r=0.09, P=0.59). No significant difference found in the expression of TNFα and IL-6 between the survival subgroup and the death subgroup in group CSHB (t=0.42, P=0.67; t=0.76, P=0.45). CONCLUSIONS: The expression levels of NF-κB and its regulated cytokines in monocyte-derived DCs in patients with chronic severe hepatitis B were up-regulated and perhaps associated positively with the illness severity.