Objective To analyze the serum keratin 18 (K18) level of patients with hepatitis B virus (HBV)-related acute-on-chronic liver failure (HBV-ACLF) and its correlation with prognosis.Methods From December 2012 to October 2014,120 patients who visited Fuzhou Infectious Diseases Hospital and diagnosed with HBV-ACLF were enrolled,and 20 chronic hepatitis B (CHB) patients and 20 healthy controls were enrolled with matched gender and age.Enzyme linked-immunosorbent assay was used for the detection of K18 (M30,M65) and the differences of M30,M65,M30/M65 and other laboratory results were analyzed among the first enrolled 40 patients with HBV-ACLF,20 CHB patients and 20 healthy controls.All HBV-ACLF patients were followed up for 3 months and divided into two groups (death group and survival group).And M30 and M65 in both groups were detected and their clinical data were collected.Continuous variables between groups were compared using t test and one-way analysis of varicmce.Categorical variables were compared using X2 test.Receiver operating characteristic (ROC) curve was used for prognostic analysis.Results The serum M30 in HBV-ACLF group,CHB group and healthy controls group were (2.99 ±0.29),(3.12±0.26) and (2.16 ±0.12) lg U/L,respectively (F=95.36,P＜ 0.01).The serum M65 in the three groups were (3.41 ± 0.29),(3.38+0.29) and (2.01±0.11) lg U/L,respectively (F=217.60,P＜0.01).And M30/M65 the three groups were 0.39 ± 0.11,0.55 ± 0.09 and 1.45 ± 0.34,respectively (F=202.63,P＜0.01).The white blood cell,total bilirubin,alanine aminotransferase and aspartate aminotransferase in HBV-ACLF patients were the highest,and platelet,albumin,serum sodium and prothrombin time activity were the lowest.After following up for 3 months of 120 patients with HBV-ACLF,40 of them died with fatality rate of 33.3％.The area under ROC curve (AUC) of the M30/M65 was 0.871,and that of score of model for endstage liver disease (MELD) was 0.668 (Z=3.011,P＜0.01).The M30/M65 ratio was significantly negatively correlated with the MELD score (r=-0.389,P＜0.01).Conclusions K18 (M65 and M30)are strongly associated with liver disease severity.The M30/M65 ratio may be a potential diagnostic and prognostic marker for the patients with HBV-ACLF.

Objective To investigate the relationship between hepatitis B surface antigen (HBsAg) levels and liver pathology at different phases of natural history in chronic hepatitis B (CHB) patients, and to establish a non-invasive liver fibrosis diagnostic model based on HBsAg quantification.Methods A total of 145 CHB patients were enrolled and underwent liver biopsy from January 2013 to January 2015, among which 73 patients were hepatitis B e antigen (HBeAg) positive.HBsAg levels and HBV DNA levels were compared between patients at different phases of natural history and between patients with different HBeAg statuses.Logistic analysis was used to analyze the risk factors associated with fibrosis in HBeAg-positive patients, and to evaluate the predictive value of non-invasive liver fibrosis diagnostic model based on HBsAg quantification.Analysis of variance was used for statistical analysis, and t test analysis was used for the comparison between two independent samples.Results The serum HBsAg levels at the immunologic tolerance phase, immunologic clearance phase, low copy phase and reactivation phase of CHB patients were (4.29±0.69), (3.56±0.61), (3.22±0.64), and (3.54±0.50) lg IU/mL, respectively (F=16.72, P<0.01), and the HBV DNA levels were (8.48±0.58), (6.69±1.44), (3.80±0.59), and (6.21±1.06) lg IU/mL, respectively (F=76.73, P<0.01).In HBeAg-positive CHB patients with liver inflammation stage (G)≤G1, G2, G3 and G4, the serum HBsAg levels were (4.44±0.65), (4.00±0.72), (3.74±0.62), and (3.28±0.50) lg IU/mL, respectively (F=9.198, P<0.01).In HBeAg-positive CHB patients with liver fibrosis stage (S)≤S1, S2, S3, and S4, the serum HBsAg levels were (4.55±0.54), (4.04±0.89), (3.59±0.63), and (3.34±0.50) lg IU/mL, respectively (F=10.66, P<0.01).Logistic analysis showed that age (OR=1.091, 95%CI: 1.013-1.175) and HBsAg level (OR=0.190, 95%CI: 0.066-0.542) were independent factors for predicting fibrosis stage.The area under receiver operating characteristic curve of the non-invasive fibrosis model based on age and HBsAg level was 0.849, which was higher than aspartate aminotransferase to platelet ratio index (0.749) and fibrosis index based on the 4 factors (0.763).Conclusions The serum HBsAg levels are significantly different among the different phases of natural history in CHB patients.The serum HBsAg levels decline with the progression of liver fibrosis in HBeAg-positive CHB patients.The non-invasive diagnostic model that based on HBsAg quantification could be used to evaluate the stage of liver fibrosis.

Objective To investigate the clinical features of pulmonary infection in patients with hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF).Methods A total of 666 hospitalized patients with HBV-ACLF in Department of Liver Disease of Fuzhou Infectious Diseases Hospital were retrospectively analyzed.Data of demographic and clinical parameters (sex,age,presence of liver cirrhosis and diabetes),complications (spontaneous bacterial peritonitis,hepatorenal syndrome,hepatic encephalopathy,and upper gastrointestinal hemorrhage),and baseline biochemical parameters were collected from the medical records database.Univariate and multivariate regression analyses were performed to determine the independent risk factors of pulmonary infection in patients with ACLF.Distributions of the pathogenic bacteria were further analyzed.Student t test was used for the means consistent with normal distribution,while non-parametric statistics were used for the data consistent with abnormal distribution.Mann-Whitney U test was used for the data between two groups.Chi square test and Fisher exact probability method were used for comparing the count data.Results A total of 125 out of 666 patients with ACLF developed pulmonary infection.The incidence of pulmonary infection was 18.76 ％ (125/666)..Most patients were infected with fungi (54.84％).The incidence rate of pulmonary infection in patients with liver failure over 60 years (41.18％) was significantly higher than that in patients under 60 years (16.91％;x2 =19.136,P＜0.01).The incidence of cirrhosis or diabetes in the 125 patients with pulmonary infection was higher than patients with no pulmonary infection.The difference between the two groups was statistically significant (P＜0.01).Levels of albumin,cholesterol,alphafetoprotein,white blood cell count,hemoglobin,plasma thromboplastin antecedent,international normalized ratio (INR),and serum sodium were all significantly different between the two groups (all P＜ 0.05).The incidence of spontaneous bacterial peritonitis,hepatorenal syndrome,and hepatic encephalopathy in patients with pulmonary infection were significantly higher than those without pulmonary infection (P＜0.01).Spontaneous bacterial peritonitis,age,albumin,hemoglobin and serum sodium were important factors in the development of the pulmonary infection.And albumin,hemoglobin and serum sodium were protective factors.Conclusions Pulmonary infection,as one of the common and serious complications,significantly affects the prognosis of liver failure patients.Prediction of pulmonary infection in the early stage is essential.Patients with elder age,spontaneous bacterial peritonitis,low albumin level,low serum sodium level and low hemoglobin level should be timely monitored to prevent the development of pulmonary infection.

ObjectiveTo investigate the risk factors for antibiotic prophylaxis failure in patients with liver cirrhosis and upper gastrointestinal bleeding. MethodsEighty-two patients with liver cirrhosis and upper gastrointestinal bleeding who were admitted to our hospital from January 2011 to June 2014 were analyzed retrospectively. All patients received third-generation cephalosporins as the antibiotic prophylaxis for 7 days. The therapeutic effect of prophylaxis within two weeks was analyzed, and the clinical features were compared between prophylaxis response group and non-response group. The t-test or Mann-Whitney U test was applied for comparison of continuous data between groups, the chi-square test was applied for comparison of categorical data between groups, and the logistic regression analysis was applied to determine the risk factors for antibiotic prophylaxis failure. ResultsA total of 38 patients (46.4%) developed secondary infection. There were significant differences in prothrombin time, proportion of patients admitted to the intensive care unit (ICU), duration of ICU stay, proportion of patients who received deep venipuncture, Child-Pugh classification, and Child-Pugh score between the prophylaxis response group and non-response group (P＜0.05). Child-Pugh classification (OR=2.455, 95%CI: 1.01-5.97, P=0.048) and admission to the ICU (OR=4.12, 95%CI: 1.32-12.83, P=0.015) were the independent risk factors for antibiotic prophylaxis failure. ConclusionAntibiotic prophylaxis with third-generation cephalosporins has a high failure rate, and admission to the ICU and a high Child-Pugh classification are the independent risk factors for antibiotic prophylaxis failure.

Objective To investigate the optimal therapy for patients with acute-on-chronic liver failure induced by hepatitis B.Methods A total of 302 patients with acute-on-chronic liver failure induced by hepatitis B in the Affiliated Infectious Diseases Hospital of Fujian Medical University were enrolled during January 2008 to January 2010.Patients were divided into group A ( medical treatment,n =57 ),group B (medical + antiviral treatment,n =80),group C ( medical + antiviral + artificial liver support system (ALSS),n =124) and group D (medical + antiviral + ALSS + traditional Chinese medicine treatment,n =41 ).Liver and renal function,prothrombin activity (PTA) and HBV DNA load were observed at the baseline,week 1,4,8,12 and the end of the treatment.All groups were followed up for 48 weeks to observe the survival rates.Kruskal-Willis H test was used to compare the efficacies in four groups,and Cox proportional hazards regression model was used for survival analysis. Results There was no difference among four groups in curative effects at week 4 ( H =3.213,P =0.360 ),but there was significant difference at week 12 (H =8.722,P =0.033).The one-year mortality rates for groups A,B,C,D were 36.84％ (21/57),32.50％ (26/80),26.61％ (33/124) and 24.39％ ( 10/41 ),respectively.The death risks of group C and D were 0.566 and 0.396 times of that in group B ( P =0.036 and 0.016).Conclusion Nucleoside analogue and ALSS plus medical treatment can effectively increase the survival rates of the patients with acute-on-chronic liver failure induced by hepatitis B.