Oral anti-viral agents nucleos (t)ide analogues (NAs) are widely used in treatment of chronic hepatitis B (CHB) since they are well-tolerated in most patients.But clinical relapse occurs in a considerable part of patients after the cessation of NAs therapy.This paper reviews factors related to clinical relapse, including time for drug withdrawal, cccDNA level, age, baseline alanine aminotransferase (ALT) and HBV DNA levels, type of NAs, serum level of HBsAg and the immune status of patients.

OBJECTIVE: To evaluate the cost-effectiveness of 3 therapeutic schemes in the treatment of chronic Hepatitis B with YMDD mutation.METHODS: 90 patients were randomly assigned into three groups: the patients in Group A were assigned to receive Adefovir Dipivoxil in combination with Lamivudine for 12 weeks followed by administration of Adefovir alone for 36 weeks;Group B received Adefovir in combination with Lamivudine for 48 weeks,while Group C received Entecavir alone for 48 weeks.The cost-effectiveness of the 3 groups were analyzed.RESULTS: In the three groups(A,B,and C),the cost-effectiveness ratios for HBV DNA negative-conversion ratewere 12 685.6,15 481.3,and 31 462.2,respectively and the incremental cost-effectiveness ratios of Group B and Group C were 29 501.5 and 106 907.8 respectively as against Group A.The cost-effectiveness ratios of the three Groups(A,B,and C) for serum alanine aminotransferase normalization rate were 12 685.6,14 284.9,31 462.2 respectively,and the incremental cost-effectiveness ratios of Group B and Group C were 19 618.5 and 106 907.8 respectively as against Group A.The cost-effectiveness ratios of the three Groups(A,B,and C) for HBeAg/HBeAb seroconversion rate were 76 227.9,93 120.3,and 209 664.0 respectively,and the incremental cost-effectiveness ratios of Group B and Group C were 178 350.0 and 1 267 621.4 respectively as against Group A.In Group A,1 case showed rtA181V mutation and another one showed rtN236T mutation after 48-week treatment.CONCLUSION: Group B(ADV in combination with LAM) is more cost-effective in the treatment of chronic hepatitis B with YMDD mutation.

0.05).At week 52,there was significant difference in the undetectable HBV DNA rate between group C and group B(P0.05),and the rate of drug resistant genotype was 21.9%(7/32)、0、0(P

ObjectiveTo evaluate the efficacy and safety profiles of enteeavir (ETV) in patients with advanced schistosomiasis and hepatitis B virus (HBV) co-infection.Methods Totally sixty patients with advanced schistosomiasis and HBV co-infection were enrolled in this study.The patients were divided into ETV treatment group (n=30) and rhubarb treatment group who refused to receive antiviral treatment (n=30).The patients were treated with ETV or rhubarb thelepus ball on the basis of routine supportive therapy for 52 weeks.The hepatic fibrosis markers (e.g.hyaluronic acid,type Ⅲ procollagen,type Ⅳ collagen,laminin and fibronectin),alanine transaminase (ALT),HBV DNA,Child-Pugh score between two groups were compared.Intention to treat (ITT) population was used for analysis.The measurement data and the enumeration data were analyzed by t test and x2 test,respectively.ResultsAfter 52-week treatment,the hepatic fibrosis markers (hyaluronic acid,type Ⅲ procollagen,type Ⅳ collagen,laminin and fibronectin) were significantly improved in ETV treatment group compared to the rhubarb treatment group (t =3.952,3.765,3.857,3.122 and 3.735,respectively; all P＜0.05),and the fibrosis of liver tissue in ETV treatment group was significantly improved compared with rhubarb treatment group (x2 =11.207,P＜0.05).The ALT level,HBV DNA,Child-Pugh score after 52-weeks treatment in ETV treatment group were statistically reduced compared with rhubarb treatment group (t =3.287,4.382 and 3.872,respectively; all P＜0.05),meanwhile,the ALT normalization rate and HBV DNA undetectable rate were significantly increased in ETV treatment group (x2 =17.376 and 39.095,respectively; both P＜0.05).In addition,no obvious adverse reaction was observed during ETV treatment.Conclusion Entecavir is safe and effective in patients with advanced schistosomiasis and HBV co-infection.

Objective To retrospectively study the incidence and risk factors of thyroid disease induced by peginterferon plus ribavirin (Peg IFN/RBV) antiviral treatment in patients with chronic hepatitis C (CHC).Methods From January 2012 to December 2014,a total of 362 CHC patients were treated with Peg IFN/RBV antiviral therapy at Wuxi Fifth People's Hospital,among whom 315 patients were included in this study.Thyroid function,autoantibodies and thyroid ultrasound were measured at baseline,weeks 12,24 and 48.Comparisons between groups were performed using chi-square test for qualitative data and the unpaired t test for continuous variables.Results After treatment,thyroid dysfunction developed in 12.1％ of patients.Positive anti-thyroid peroxidase and anti-thyrobolulin antibodies were detected in 21％ of patients.The thyroid ultrasound changes developed in 14.9％ of the patients,among whom normal thyroid function and thyroid autoantibodies negative were detected in 8.7 ％ of patients.The titer of thyroid autoantibodies increased steadily from baseline to the end of treatment.Logistic regression analysis showed that positive thyroid autoantibody (OR =5.423,95％ CI:3.441 8.716),sustained virological response (OR=7.201,95％CI:6.231-10.206),female(OR=1.22,95％ CI:0.951-2.212) were the risk factors of thyroid dysfunction.Conclusions Peg IFN/RBV antiviral treatment increases the incidence of thyroid disease in CHC patients.Positive thyroid autoantibody,sustained virological response and the female gender are the risk factors of thyroid dysfunction.

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.

Objective:To analyze the relationship between antithrombin Ⅲ(AT-Ⅲ) activity and survival, bleeding and thrombosis complications in patients with acute-on-chronic liver failure (ACLF), and to explore the prediction value of AT-Ⅲ activity in the prognosis of ACLF patients.Methods:The clinical data of 130 hospitalized patients with ACLF were retrospectively collected in Wuxi No.5 People′s Hospital from January 1, 2013 to April 1, 2019. The liver function, international normalized ratio (INR), and 90-day survival rate were detected. The AT-Ⅲ activity values at admission, week two, week four, and week eight of hospitalization were recorded, and the occurrences of fecal occult blood and femoral vein thrombosis were also recorded. The measurement data were compared by t test, analysis of variance, or rank sum test, and the categorical data were compared by chi-square test. The risk factors affecting the survival of ACLF patients were analyzed by Cox regression. The survival analysis was performed using the Kaplan-Meier method. Results:At the end of 90-day follow-up of 130 patients, 56 patients died, 20 patients (15.38%) were fecal occult blood positive and 15 (11.54%) had femoral vein thrombosis. The baseline AT-Ⅲ activity in the death group was lower than that in the survival group ((17.89±13.68)% vs (36.03±11.96)%), and the difference was statistically significant ( t=-8.045, P<0.01). The baseline AT-Ⅲ activities in fecal occult blood positive and negative patients were (18.26±11.52)% and (25.06±10.97)%, respectively, and in femoral vein thrombosis and non-thrombotic patients were (17.55±10.33)% and (32.48±11.88)%, respectively. The differences were both statistically significant ( t=8.746 and 8.090, respectively, both P<0.01). Through dynamic monitoring of AT-Ⅲ, the AT-Ⅲ activity showed a downward trend in the death group, while that showed an upward trend in the survival group, but the differences were not statistically significant ( F=0.282 and 0.401, respectively, both P>0.05). The Cox regression analysis suggested INR (odds ratio ( OR)=1.364, 95% confidence interval ( CI) 1.078-1.726, P=0.010) and AT-Ⅲ activity ( OR=0.930, 95% CI 0.906-0.954, P<0.01) were the independent factors affecting the survival of patients with ACLF. The area under the receiver operator characteristic curve of the AT-Ⅲ activity for predicting 90-day survival outcome of the patient was 0.706 (95% CI 0.773-0.952, P<0.01), and the cut-off value was 25%. Patients with AT-Ⅲ activity ≥ 25% had a higher survival rate than those with AT-Ⅲ activity <25% ( χ2=58.20, P<0.01). Conclusions:AT-Ⅲ activity is associated with fecal occult blood positive and femoral vein thrombosis in ACLF patients. The AT-Ⅲ activity is an independent influencing factor for predicting the prognosis of ACLF patients. Patients with AT-Ⅲ activity less than 25% have the higher mortality rate.

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.

Objective:To explore the therapeutic effect of multi-mode sequential combination of artificial liver in the treatment of hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF).Methods:The clinical data of HBV-ACLF patients treated with artificial liver in Wuxi Fifth People′s Hospital from January 2018 to June 2021 were retrospectively analyzed. Eighty-six patients were divided into artificial liver multi-mode sequential combination therapy group (sequential combination group) and conventional treatment group. The cytokine level changes and model for end-stage liver disease (MELD) score were analyzed at 14 days of disease duration. The survival outcome and complications of artificial liver were analyzed after 30 days of follow-up. Two independent samples t test and chi-square test were used for statistical analysis. Cox regression analysis was used to analyze the risk factors of death, and Kaplan-Meier method was used to analyze the survival rate of patients. Results:A total of 86 patients were enrolled, including 48 patients in sequential combination group with the average number of artificial liver of 4.68 times/person, and 38 patients in conventional treatment group with the average number of artificial liver of 3.17 times/person. At 14 days of disease duration, interleukin (IL)-6, IL-8, interferon γ-inducible protein (IP)-10 level and MELD score in sequential combination group decreased significantly than those in the conventional treatment group ( t=3.80, 3.62, 4.95 and 1.11, respectively, all P<0.050). After 30 days of follow-up, 63 patients survived and 23 patients died. Cox regression analysis showed that baseline international normalized ratio (hazard ratio ( HR)=0.558, 95% confidence interval ( CI) 0.193 to 0.856, P=0.027), baseline antithrombin Ⅲ activity ( HR=0.876, 95% CI 0.824 to 0.932, P<0.001), artificial liver mode ( HR=0.819, 95% CI 0.236 to 0.992, P=0.005), spontaneous peritonitis ( HR=0.170, 95% CI 0.045 to 0.647, P=0.009) and hepatic encephalopathy ( HR=0.004, 95% CI 0.001 to 0.030, P<0.001) were independent influencing factors for 30-day survival outcome. The cumulative survival rate of sequential combination group was higher than that of conventional treatment group, and the difference was statistically significant ( χ2=5.45, P=0.020). There were no significant differences in the proportions of bleeding, deep vein thrombosis, heart rate and blood pressure instability between the two groups ( χ2=0.63, 1.20 and 0.54, respectively, all P>0.050). The platelet decline of patients in sequential combination group was slighter than that in conventional treatment group, and the difference was statistically significant ( t=-4.17, P=0.002). Conclusions:Multi-mode sequential combination therapy of artificial liver could eliminate cytokines and reduce MELD score more effectively in patients with HBV-ACLF, and prolong the survival time of patients and have little effect on platelet count.

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.