ABSTRACT
Objective:To analyze the value of serum ceruloplasmin (CP) levels in predicting the outcome of patients with hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF).Methods:The clinical data of 1 751 patients with HBV-ACLF treated in the Third Affiliated Hospital of Sun Yat-sen University from January 2010 to March 2018 were retrospectively analyzed. According to 30-day outcomes, 1 220 survival patients were classified into group A; 465 fatal patients and 46 patients receiving liver transplantation were classified into group B (total 531 cases). Risk factors associated with 30-day survival were estimated using Cox proportional hazards regression. ROC curve analysis was performed to evaluate the predictive value of CP on the 30-day outcome of patients with HBV-ACLF.Results:Multivariate analysis indicated that CP, albumin and alpha fetoprotein were independent protective factors for 30-day survival of HBV-ACLF patients ( P<0.05 or <0.01), while age, white blood cell count, AST, total bilirubin, INR, serum creatinine, HBV DNA, hepatorenal syndrome and hepatic encephalopathy were independent risk factors ( P<0.01). The area under the ROC curve (AUC) of CP was 0.570 (95% CI 0.540-0.599, P<0.01); while AUC of MELD score was 0.783 (95% CI 0.759-0.807, P<0.01) and MELD-Na score was 0.774 (95% CI 0.750-0.798, P<0.01). Compared with MELD score and MELD-Na score, the value of CP in predicting the 30-day prognosis of HBV-ACLF patients was lower ( P<0.01). The cut-off value of CP for predicting 30-day outcome of HBV-ACLF patients was 0.173 g/L, with the sensitivity of 69.4%, and the specificity of 41.6%. According to the cut-off value, the patients were divided into low CP level group (level of CP<0.173 g/L) and high CP level group (level of CP≥0.173 g/L); the 30-day cumulative survival rate of low CP level group was lower than that of high CP level group ( χ2=17.75, P<0.01). Conclusions:Serum CP level can predict the 30-day outcome of HBV-ACLF patients to a certain extent.
ABSTRACT
Objective To evaluate the efficacy and long-term safety of autologous bone marrow stem cells(ABMSC)transplantation in patients with hepatitis B virus(HBV)-associated decompensated liver cirrhosis.Methods This was an open-label,prospective matched case-control study.Thirty patients with HBV-associated decompensated liver cirrhosis hospitalized at the Third Affiliated Hospital of Sun Yat-Sen University from January 2005 to June 2010 were collected and infused with stem cells(stem cell group). Another thirty patients in control group were matched according to baseline characteristics and treated with standard medicine therapy.The patients in stem cell group were treated with stem cells infusion by hepatic artery or portal vein based on standard medicine therapy.All the patients were followed up for 5 to 10 years after surgery. Biochemical indicators were evaluated within the first 48 weeks after transplantation.The complications of cirrhosis and the cumulative incidence rate of hepatocellular carcinoma(HCC)were observed.Measurement data with normal distribution were analyzed by t test. Measurement data with non-normal distribution were compared by Mann-Whitney test.Count data were compared by χ2 test.The cumulative incidence rate of HCC development was compared by Kaplan-Meier analysis.Results The bone marrow aspiration and transplantation surgery were well tolerated in all patients in stem cell group.No complication related to stem cell transplantation therapy was observed. The levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST),total bilirubin(TBil) and prothrombin time(PT)decreased,albumin level increased,while model for end-stage liver disease (MELD)scores decreased in both groups after treatment.Serum albumin level in stem cell group increased and ALT level decreased markedly at week 4,compared with that in control group at week 4(Z=2.188,P=0.029,Z=3.296,P=0.001,respectively).In stem cell group,21 patients received stem cells transplantation by hepatic artery and 9 patients by portal vein.Biochemical indicators were improved in all patients compared to baseline.However,there was no statistically significant differences between hepatic artery group and portal vein group.The median follow-up time was 6 years.Two patients in stem cell group and 1 patient in control group died(χ2=0.351,P=0.554).Six patients in stem cell group (20.0%)and 11 patients(36.7%)in control group developed HCC.There was no significant differences in the cumulative incidence rate of HCC between two groups(χ2= 0.148,P= 0.701).Hepatorenal syndrome did not development in either group.There were no statistically significant differences in the rates of complications including spontaneous peritonitis,hepatic encephalopathy and gastrointestinal hemorrhage between two groups after 5 to 10 years of follow-up(χ2=0.162,P=0.688,χ2=1.071,P=0.301,χ2=1.071,P=0.301,respectively).Conclusion ABMSC transplantation in patients with HBV-associated decompensated liver cirrhosis improves liver function transiently and has long-term safety.
ABSTRACT
Objective To assess the application of a new scoring system for severity evaluation of acute-on-chronic liver failure induced by hepatitis B.Methods A total of 399 patients (203 survivals and 196 deaths) with acute-on-chronic liver failure induced by hepatitis B were collected from the Third Affiliated Hospital of Sun Yat-sen University during January 2003 and June 2008.All patients were graded with the new scoring system and model for end-stage liver disease (MELD) at critical stage (survivals) or terminal stage (deaths).The survival rates and fatality rates of patients who were graded by two scoring systems were analyzed and compared.Results With MELD system,the fatality rate was 11.89％ (17/143) in patients with scores of 15-26,64.68％ (141/218) with scores of 27-48,and 100％ (38/38) with scores of 49-69.No score range with fatality rate of 0 was found.While with the new scoring system,the survival rate was 99.2％ (126/127) when the severity scores were between 2 to 8,and patients with scores 2,3,4,5,6 and 8 were all survived; the fatality rates were gradually raised from 4.2％ (1/24) with scores of 9-17 to 100％ (82/82) with scores of 18 and above.Conclusion The new scoring system is more objective,simple and sensitive than MELD system,which can be used for severity evaluation of acute-onchronic liver failure induced by hepatitis B.
ABSTRACT
Objective To evaluate the therapeutic efficacy and its related factors of entecavir treatment for patients with acute on chronic hepatitis B liver failure (ACHBLF).Methods One hundred and eight patients with ACHBLF were enrolled and divided into entecavir group (n=53) and control group (n=55).HBV DNA level, liver function and 48-week survival rate were observed, and C ox regression model was established to identify the factors which may affect the efficacy of entecavir treatment.Results Totally 70 patients died in the study and 66 died within 12 weeks.The statistical difference on cumulative survival rate between two groups was observed from the third week on (χ2=5.357, P ＜ 0.05).The 48-weekcumulative survival rate in entecavir group was 47.2% (25/53), while that in the control group was 23.6%(13/55) (χ2=7.432, P ＜ 0.01).In entecavir group, for patients aged ＜ 40 with serum bilirubin level ＜513 μnol/L and international normalized ratio (INR) ＜ 2.5, the fatality rates decreased 74.9%, 75.3%and 76.0%, respectively.Conclusions Entecavir may improve the survival rate of patients with ACHBLF.Age, serum bilirubin level and INR are major factors related to the therapeutic efficacy.
ABSTRACT
Objective To investigate the relationship between serum levels of alanine aminotransferase (ALT)or aspartate aminotransferase (AST)apportioned by the same hepatic parenchyma cell volume and liver histological necroinflammation grades in HBeAg-negative chronic hepatitis B (CHB)patients.Methods A total of 145 CHB patients were divided into four groups:Gl,G2,G3 and G4 based on the liver histological necroinflammation grade.The serum ALT and AST levels were determined by automatic biochemical instrument in these four groups.Furthermore,serum ALT and AST levels were then apportioned by the same hepatic parenchyma cell volume.The data were analyzed by ANOVA.Results Mean serum ALT levels in G1,G2,G3 and G4 groups were (35.3±29.1),(91.6±120.4),(111.6± 116.1)and (118.0±122.1)U/L,respectively,and the serum ALT levels apportioned by same hepatic parenchyma cell volume were ( 54.0 ± 45.1 ),( 144.2 ± 184.9 ),(191.3± 204.8)and (215.1 ± 226.5)U/L,respectively.The pairwise comparison between G1 and other three groups all showed statistically significant difference (P＜0.05).Meanwhile,AST levels in G1 to G4 groups were (35.5± 29.0),(64.9±71.7),(96.0±81.9)and (102.8±77.0)U/L,respectively and the serum AST levels apportioned by the same hepatic parenchyma cell volume were (54.3±44.6),(102.3± 107.9),(165.2±148.7)and (189.4±145.4)U/L,respectively.The pairwise comparison between G1 and G3,G1 and G4,G2 and G3,G2 and G4 all showed statistically significant difference (P＜0.05).Conclusion Both AST and ALT levels are sensitive indicators for liver inflammation grading in HBeAg-negative CHB patients during the natural history of the disease.
ABSTRACT
Objective To establish a scoring system for evaluating the severity of hepatitis B patients with acute-on-chronic liver failure and to compare the validity of this system with model for end-stage liver disease (MELD). Methods MELD score was used in hepatitis B patients with acuteon-chronic liver failure who were divided into survival group (203 cases) and death group (196 cases).Seven clinical relative indices, including prothrombin activity, serum creatinine, hepatic encephalopathy, accompanying infections, serum total bilirubin, the dimension of liver, the amount of ascites, were selected for evaluating the severity. Each index was graded with 1 to 4 points based on the severity. Then the total score was counted by adding up scores of each index. T test and area under receiver operating characteristic (ROC) were used to evaluate the difference and similarity of the two systems. Results According to the new scoring system, the total score was 8. 07±3. 14 in the survival group and 16. 91 ±3. 54 in the death group. There was a statistically significant difference between these two groups (t = 26.125. P<0.01). In 81.32% of survival patients, their scores ranged from 3.91 to 12.23, while in 81.32% of dead patients, their scores ranged from 12.23 to 21.60. The two ranges overlapped at 12.23. According to the MELD system, the total score was 26. 43 ±5. 58 in the survival group and 40. 16 ±10. 22 in the death group. The difference between the two groups was statistically different (t = 16. 566, P<0. 01). In 61.02% of survival patients, the MELD scores ranged from 21. 49 to 31. 19, while in 61. 02% of the dead patients, the MELD scores ranged from 31. 19 to 48. 94. The two ranges overlapped at 31.19. The areas under ROC of the new scoring system and MELD system were 0.960 (95% CI: 0. 944-0. 977) and 0.886 (95% C/;0. 852 - 0. 920). No overlap was found in these two 95%CJ and there was a statistically significant difference. Conclusions The new scoring system is applicable for evaluating the severity and prognosis of acute-on-chronic liver failure in hepatitis B patients. The sensitivity of this new scoring system is approximate to the MELD system.
ABSTRACT
Objective To investigate the susceptibility of bone marrow mesenchymal stem cell (BMSC) to hepatitis B virus (HBV) infection during induction toward hepatocyte and the role of asialoglycoprotein receptor (ASGPR) in BMSC HBV infection. Methods BMSC obtained from hepatitis B patients were tested for HBV infection and then cultured with HBV infectious serum in vitro and induced to differentiate into hepatocyte through exposure to hepatocyte growth factor (HGF), fibroblast growth factor-4(FGF-4), and epidermal growth factor(EGF). Subsequently these cells were determined for the presence of hepatitis B virus e antigen( HBeAg), hepatitis B virus surface antigen(HBsAg) and ASGPR. All experiments were repeated for 3 times in 5 different samples. The results were analyzed by non-parametric test. Results After 6 days of exposure, BMSC-derived hepatocyte-like cells expressed hepatic special genes and proteins, including alpha fetoprotein(AFP),cytokeratin18 (CK18), albumin (Alb), and manifested hepatocyte functions, including glycogen synthesis, urea secretion and albumin synthesis. Expressions of CK18 and Alb were increased, and AFP was decreased with time of induction. The BMSC were resistant to HBV infection both in vitro and in vivo or after induction toward hepatocyte. ASGPR expression level was low in BMSC, which was increased in the induced BMSC but still lower than that of the control HepG2 cells. Conclusions BMSC are resistant to HBV infection both in vitro and in vivo. The low level expression of ASGPR may be a reason for this.
ABSTRACT
Objective To investigate the balance of Th1/Th2 cytokines and its relationship with prognosis of severe chronic hepatitis B ( CHB ). Methods Peripheral blood samples were collected from 112 severe CHB patients, 30 CHB patients and 30 healthy controls. IL-4, IFN-γ levels and HBV DNA loads were measured by ELISA and fluorescent PCR, respectively. The levels of cytokines in different stages, and their correlations with HBV DNA loads and short-term prognosis were analyzed. Results Higher levels of IL-4, IFN-γ and Th1/Th2 ratios in peripheral blood were detected in patients with severe CHB than those with CHB and the healthy controls (Z = 8.968, 10. 004 and 26. 067, P =0. 009, 0. 007 and 0. 000). IL4 levels in patients with end-stage server CHB were markedly higher than those in other stages ( Z = 3. 672 and 3. 158, P= 0.000 and 0.002), while their Thl/Th2 ratios were lower (Z=3. 161 and 2. 166, P=0.002 and 0. 030). No significant differences on levels of IL-4, IFN-γ and Th1/Th2 ratios were observed in severe CHB patients with different HBV DNA levels (Z =4.431, 2.626 and 0. 140, P =0.219, 0.403 and 0. 987). Elevated IL-4 was closely correlated with the high case-fatality rate within 12 weeks. Conclusions The balance between Th1 and Th2 cytokines is- disturbed in patients with severe CHB. Thl/Th2 ratio decreases with the aggravation of diseases, which may indicate unfavorable short-term prognosis.