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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.
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Objective@#To explore the characteristics underlying Th1/Th2/Th17 expression level after entecavir (ETV) discontinuation of chronic hepatitis B (CHB) patients who were HBeAg-positive and define the role of Th1/Th2/Th17 in maintaining virological response after ETV discontinuation.@*Methods@#We selected 112 HBeAg positive CHB patients who met the withdrawal criteria according to the guideline of prevention and treatment of chronic hepatitis B (2010 version), and we also separated them into virology sustained response (SVR) group and virological relapse (VR) group according to the recurrence in 52 weeks. We detected serum level of Th1/Th2/h17 related cytokines during 0, 12, 24 and 52 weeks follow-up to further analyze their dynamic changes and expression differences.@*Results@#The results of the study reveals that serum levels of IFN-γ in the group of SVR were at a higher level compared with VR group during follow-up (all P<0.05). While, the serum level of IL-10 decreased in SVR group and was lower than the paired IL-10 level in VR group with significance during follow-up. In VR group, the serum level of IFN-γ decreased during the first 24 weeks after ETV withdrawal, and after then, the level rose. The serum levels of IFN-γ (Th1) in SVR patients were significantly higher than those in VR patients in the different follow-up time points after ETV discontinuation (all P<0.05). And the serum levels of IL-10 (Th2) in SVR patients were significantly lower than that in VR patients (all P<0.05). The comparison of serum levels of IL-17A (Th17) between the two groups had no significant difference (all P>0.005).@*Conclusions@#The serum level of IFN-γ in SVR group maintained a high level is conducive to maintaining virological response after ETV withdrawal and high level of IL-10 may be related to virologic relapse.
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Objective To explore the relationship between viral load and expression of CD 226 on the surface of peripheral blood T follicular helper cells (Tfh) in patients with chronic hepatitis C (CHC) . Methods One hundred and thirty-five CHC patients hospitalized at Wuxi Fifth People′s Hospital from March 2015 to April 2017 were collected ,and another 30 healthy blood donors were set as healthy control group .CHC patients were divided into two groups based on hepatitis C virus (HCV) RNA level ,with 49 cases (36 .3％ ) in low viral load group and 86 cases (63 .7％ ) in high viral load group .Expression of CD226 on the surface of peripheral blood Tfh cells , Tfh cells ,interleukin (IL )-21 and HCV specific cytotoxic lymphocyte (CTL) levels of two patient groups were compared .Categorical data were compared with chi-square test and normally distribute continuous data were compared with t test .Correlations between different factors were analyzed by Pearson correlation analysis .Results Expression of CD226 on the surface of peripheral blood Tfh cells in 135 cases of CHC patients was (77 .69 ± 5 .42)％ ,which was lower than that of healthy control ([90 .06 ± 5 .83]％ ) ,and the difference between the two groups was significant (t= 7 .541 , P < 0 .01) .The CD226 expression on the peripheral blood Tfh cells in low viral load group was (88 .75 ± 6 .68)％ ,which was higher than that of high viral load group ([69 .23 ± 5 .86]％ ) ,and the difference between the two groups was significant (t = 19 .232 , P< 0 .01) .The viral load was negatively correlated with Tfh cell surface CD 226 expression (r = - 0 .705 , P < 0 .01) .The peripheral blood Tfh cell level in 135 CHC patients was higher than that of healthy control ,and the difference between the two groups was significant (t= 13 .878 , P< 0 .01) .The peripheral blood Tfh cell level in low viral load group was higher than that in high viral load group ,and the difference between the two groups was significant (t= 26 .993 , P< 0 .01) .The IL-21 level of 135 CHC patients was lower than that of healthy control ([70 .35 ± 1 .6]％ ) ,and the difference between the two groups was significant (t=18 .322 , P< 0 .01) .The IL-21 level in peripheral blood of low viral load group was higher than that of high viral load group ,and the difference between the two groups was significant (t= 84 .54 , P< 0 .01) . HCV specific CTL level in peripheral blood of low viral load group was higher than that of high viral load group ,and the difference between the two groups was significant (t = 29 .869 , P< 0 .01) .The viral load was negatively correlated with levels of HCV specific CTL (r= -0 .734 ,P< 0 .01) .Conclusions In patients with chronic hepatitis C ,different levels of viral load can result in different levels of CD 226 expression on the peripheral blood Tfh cells .Patients with low viral load has high CD226 expression on Tfh cell surface , resulting in rise of Tfh cell level ,IL-21 level and HCV specific CTL level .
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Objective To study the correlation between interleukin(IL)-21 and the recurrence of chronic hepatitis B(CHB)in hepatitis B e antigen(HBeAg)-positive patients after discontinuation of entecavir(ETV).Methods A total of 112 HBeAg-positive CHB patients treated with ETV were enrolled.Serum levels of IL-21 at week 0,12,24 and 52 after ETV discontinuation were detected.The Cox regression model was used to analyze the correlation between IL-21 and the recurrence after ETV discontinuation.The receiver operating characteristic(ROC)curve was applied to determine the predictive value of IL-21 for CHB recurrence after ETV discontinuation.The expression differences of IL-21 were compared between sustained viral response(SVR)group and viral relapse(VR)group.The t test and Chi-square test were used for statistical analysis.Results The serum levels of IL-21 in SVR group at week 0,12,24 and 52 after ETV withdrawal were(60.0 ± 10.8),(60.2 ± 14.7),(60.6 ± 19.5)and (61.2 ± 15.4)ng/L,respectively,which were all significantly higher than those in VR group(47.5 ± 10.7),(47.3 ± 12.9),(46.9 ± 12.2)and(46.4 ± 12.8)ng/L,respectively(t=6.153,4.926,4.382 and 5.515,respectively,all P< 0.01).The area under curve(AUC)was 0.811(95% CI:0.728 ~0.893,P<0.01)and the best cut-off value of serum IL-21 level was 49.8 ng/L.The recurrence rates of patients with serum IL-21 level ≥49.8 ng/L and <49.8 ng/L at time of ETV withdrawal was 25.4%(16/63)and 77.6%(38/49),respectively.The difference was statistically significant(χ2=30.027,P<0.01).The serum IL-21 level at the time of drug withdrawal(P= 0.005),serum hepatitis B surface antigen(HBsAg)level at the time of HBeAg seroconversion(P= 0.008)and age(P= 0.016)were factors associated with CHB recurrence after ETV withdrawal by multivariate Cox model analysis.The serum levels of ALT,HBV DNA,HBeAg and HBsAg in SVR group were significantly lower than those of VR group at week 12,24 and 52 after ETV withdrawal(t= -5.968,-7.691,-8.093; -3.047,-9.477,-28.900;-2.872,-10.424,-18.330;-4.633,-4.030 and -5.032,respectively;all P<0.01).Serum level of IL-21 was negatively correlated with HBsAg in SVR group after ETV withdrawal (r= -0.241,P<0.01),while positively correlated with HBsAg in VR group(r=0.286,P<0.01). Conclusions The serum IL-21 level at the time of drug withdrawal is associated with the recurrence after ETV discontinuation.IL-2l may play an important role as an immunomodulatory factor in maintaining virological responses in HBeAg-positive CHB patients after ETV withdrawal.
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Objective To explore the relationship between serum HBV DNA level , expression of PD-1 on CTL and liver functions in patients with hepatitis B virus cirrhosis. Methods 109 HBV hepatic cirrhosis patients with , HBV DNA positive , HBeAg positive and HLA-A2 positive were divided into two groups according to their HBV DNA levels,52 cases in group A, HBV DNA 2-4 log10 copies/mL, 57cases in group B, HBV DNA 5-7 log10 copies/mL , differences of HBV specific CTL surface PD-1 expressions , HBV specific CTL levels and liver functions were compared between two groups. Results HBV specific CTL surface PD-1 expressions of group A were lower than that of group B (t = 11.101, P < 0.01), HBV specific CTL levels of group A were higher than that of group B (t = 24.424, P < 0.01), ALT of group A were lower than that of group B (t = 2.652, P < 0.01), ALB of group A were higher than that of group B (t = 2.347, P < 0.05). Child-pugh rating, grade C of group A was lower than that of group B (χ2= 4.262,P < 0.05). Conclusions HBV specific CTL surface PD-1 expression levels were higher in those hepatic cirrhosis patients with , high level of serum HBV DNA, and HBV specific CTL levels were lower, liver functions damage were much serious. So, lower HBV DNA levels , lower HBV specific CTL surface PD-1 expression levels and higher HBV specific CTL levels can product relatively good effect of anti-viral treatment.
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Objective To investigate the effects ofZhenqi-Fuzheng capsule combined with highly active antiretroviral therapy (HAART) the Thl/Th2, Tcl/Tc2, and CD4+ T lymphocytes in patients with advanced AIDS.Methods A total of 70 patients with advanced AIDS were randomly divided into a treatment group and a control group, with 35 patients in each group. The treatment group was treated withZhenqi-Fuzheng capsule combined with HAART, while the control group was treated with HAART only. The patients in both groups were treated for 24 weeks. The Thl, Th2, Tcl, Tc2 and CD4+ T lymphocytes in peripheral blood were detected by flow cytometer.Results After treatment, the ratios of Th1/Th2 (6.27 ± 0.70vs. 5.39 ± 0.64;P<0.05) and Tcl/Tc2 (10.70 ± 0.68vs. 10.16 ± 0.85;P<0.05) in the treatment group showed significantly higher than those in the control group. The CD4+T lymphocytes after the treatment in both groups showed significantly increased than that before the treatment (treatment group: 289.2 ± 101.5/mlvs. 121.1 ± 77.5/ml,P<0.01; control group: 231.6 ± 97.6/mlvs. 118.9 ± 76.2/ml,P<0.01). The CD4+T lymphocytes in the treatment group showed significantly increased than that in the control group after the treatment (P<0.05).ConclusionsZhenqi-Fuzhengcapsule combined with HAART may regulate the Thl/Th2 and Tcl/Tc2, and increase the CD4+ T lymphocytes in patients with advanced AIDS.