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Objective To investigate the effects and safety of short-term telbivudine intervention on blocking mother-to-child transmission (MTCT) of hepatitis B virus (HBV) in pregnant women with hepatitis B e antigens (HBeAg) positive during mid-gestation. Methods Fifty-four chronic HBV infection pregnant women with HBeAg positive from November 2016 to November 2017 in Dalian Sixth People′s Hospital Affiliated to Dalian Medical University were selected, and the serum HBV DNA (logarithmic transformation) of pregnant women was ≥1010 U/L. The pregnant women began oral telbivudine 600 mg at the 24th week of pregnancy, 1 time/d, and stopped at the day of delivery. The neonates were injected 10 μg hepatitis B vaccine and 100 U HBV immunoglobin 12 h after parturition, and they were injected 10 μg hepatitis B vaccine at 1 and 6 months of birth. The HBV DNA, creatine kinase (CK), alanine aminotransferase (ALT) and total bilirubin (TBIL) at 12th, 24th, 28th, 32th week of pregnancy and 1, 7 months after parturition were detected. The hepatitis B surface antibody (HBsAb) and hepatitis B surface antigen (HBsAg) of infants during 28 to 32 weeks of birth were detected. Results There were no statistical differences in CK, ALT and TBIL of 54 pregnant women (P＞0.05). The HBV DNA at 28th, 32th week of pregnancy and 1 month after parturition was significantly lower than that at 12th week of pregnancy (5.7 ± 2.2, 5.1 ± 2.3 and 8.3 ± 1.7 vs. 9.5 ± 1.0), and there was statistical difference (P＜0.05); there was no statistical difference between 7 months and 12th week of pregnancy after parturition (P＞0.05). During 28 to 30 weeks of birth, all the neonates showed serum HBsAb>109 U/L and HBsAg < 30 U/L. Conclusions Short-term intervention with telbivudine in mid-gestation for pregnant women infected with HBV could significantly reduce the level of serum HBV-DNA to the safety level or below. The adverse effects are not found during the telbivudine intervention period. Of note, after drug withdrawal, the HBV DNA level will rebound variously. The virus related detection conducted on the neonates indicates that short-term telbivudine intervention can realize complete MTCT blocking.
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Objective To explore the effects of telbivudine (LdT) and entecavir (ETV) on renal function in chronic hepatitis B (CHB) patients with renal damage after adefovir dipivoxil (ADV) treatment. Methods The clinical data of 40 CHB patients with renal damage after ADV treatment from January 2015 to February 2016 were retrospectively analyzed. The patients were divided into 2 groups according to the substitution drugs. Twenty patients in ETV group received ETV replacement therapy, and 20 patients in LdT group received LdT replacement therapy. The serum alanine aminotransferase (ALT), serum creatinine, serum creatine kinase (SCK), urinary β2-microglobulin (Uβ2-MG), estimated glomerular filtration rate (eGFR), classification of renal function, improvement of renal function and positive rate of HBV-DNA were compared between 2 groups. Results There was no statistical difference in serum ALT between 2 group (P＞0.05). The serum creatinine, SCK, Uβ2-MG and eGFR levels after treatment in LdT group were significantly better than those in ETV group: (92.08 ± 9.35) μmol/L vs. (101.21 ± 10.31) μmol/L, (133.69 ± 31.29) U/L vs. (106.14 ± 26.19) U/L, (5 126.17 ± 415.79) μg/L vs. (6 381.92 ± 574.12) μg/L and (81.61 ± 20.52) ml/(min·1.73 m2) vs. (75.34 ± 19.67) ml/(min·1.73 m2), and there were statistical differences (P＜0.05). There was no statistical difference in the positive rate of HBV-DNA after treatment between 2 groups (P＞0.05). The abnormal rate of renal function classification after treatment in LdT group was significantly lower than that in ETV group: 0 vs. 20.0% (4/20), the improvement rate of renal function in ETV group was significantly higher than that in ETV group: 100.0% (20/20) vs. 80.0% (16/20), and there were statistical differences (P＜0.05). Conclusions The effect of LdT on renal function improvement in CHB patients with renal damage after ADV treatment is more obvious than that of ETV, which can significantly improve serum creatinine, SCK, Uβ2-MG and eGFR, and reduce the abnormal renal function.
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Objective@#To compare the effect of combined therapy using lamivudine (LAM) plus adefovir (ADV) versus telbivudine (LdT) plus adefovir corresponding to the renal function of CHB patients.@*Methods@#A total of 120 patients with chronic hepatitis B were enrolled. According to single daily dosing, they were divided into 4 groups: LdT + ADV group (n = 32), ADV+LdT group (n = 28), LAM + ADV group (n = 38) and ADV + LAM group (n = 22). Hepatorenal function, HBV serological markers, HBV DNA quantification, creatine kinase (CK) and other parameters were examined every 3 months. Serum alanine aminotransferase (ALT) normalization rate, undetectable HBV DNA rate, hepatitis B e antigen (HBeAg) seroconversion rate, level of serum creatinine (CR) and estimated glomerular filtration rate (eGFR) were analyzed at baseline time, and at weeks 24 and 52.Stastical data were analyzed by t- test and analysis of variance, count data using χ 2 test.@*Results@#There was no statistically significant difference between the four groups in terms of ALT normalization rate, HBeAg seroconversion rate, undetectable HBV DNA rate at 24 and 52 weeks. Compared with baseline, at 24 weeks of treatment, there was no significant change in serum creatinine and eGFR in the 4 groups, but after 52 weeks of treatment, serum creatinine decreased in LdT + ADV and ADV + LdT groups and eGFR increased (P < 0.05); Serum creatinine in ADV and ADV + LAM increased, and eGFR was decreased than before (P < 0.05). After treatment, there was no significant difference in renal function between the four groups at 24 weeks, but at week 52, eGFR increased and serum creatinine decreased in LdT + ADV group compared with LAM + ADV group (P < 0.05); ADV + LdT Compared with ADV + LAM group, eGFR increased and serum creatinine decreased (P < 0.05). At 52 weeks of treatment, 5 patients with mildly impaired renal function in the ADV + LdT group [n = 10, eGFR 60-90 ml·min-1 ·(1.73 m2)-1] returned to normal, and none of the ADV + LAM group (n = 9) returned to normal.@*Conclusion@#For patients with mild impaired renal function, adding LdT combined with ADV can improve renal function compared to that of LAM plus ADV.
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Objective@#To investigate the efficacy of sequential therapy with telbivudine in the treatment of HBeAg-positive chronic hepatitis B (CHB) patients with partial response after a standard course of interferon therapy.@*Methods@#A retrospective cohort study was performed for 58 HBeAg-positive CHB patients with partial response at the end of interferon therapy (48-60 weeks) from January 2009 to December 2013. According to whether telbivudine was used sequentially or withdrawn at the end of the course of treatment, the patients were divided into telbivudine sequential therapy group and withdrawal group, and the two groups were compared with in terms of biochemical, virological, and serological response rates. The chi-square test, the t-test, and the non-parametric test were used based on data type.@*Results@#A total of 58 patients were enrolled in this study, with 31 in the telbivudine sequential therapy group and 27 in the withdrawal group. At 12 and 24 weeks after interferon therapy ended, the telbivudine sequential therapy group had a significantly higher HBeAg clearance rate than the withdrawal group (22.6%/29.0% vs 0%/3.7%, P < 0.05). At week 48 of follow-up, the telbivudine sequential therapy group had a significantly higher combined response rate than the withdrawal group (22.6% vs 0%, P = 0.015). Among the 31 patients in the telbivudine sequential therapy group, 11 had an increase in creatine kinase during the administration of telbivudine. No patient in either group experienced serious adverse reactions during follow-up, such as muscular soreness, myositis, peripheral neuropathy, renal dysfunction, and liver function decompensation.@*Conclusion@#In HBeAg-positive CHB patients with partial response to interferon therapy, sequential therapy with telbivudine can increase serological HBeAg clearance rate and combined response rate at week 48, and it is safe in HBeAg-positive CHB patients achieving partial response at the end of interferon therapy.
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PURPOSE: To estimate long-term outcomes after treatment modification in patients with chronic hepatitis B (CHB) treated with entecavir (ETV) and telbivudine (LdT). MATERIALS AND METHODS: The study enrolled 131 nucleos(t)ide analogue (NA)-naïve CHB patients treated with ETV or LdT. During the 3-year study, NA treatment history including the incidence, the type of treatment modification, reasons for the modification, and overall complete virologic response (CVR) rate were retrospectively evaluated using the patients' medical records. RESULTS: Among the 131 patients, 84 and 47 were initially treated with ETV and LdT, respectively. During the course of 3-year study, 82 patients in the ETV group (97.6%) maintained initial treatment whereas only 19 in the LdT group (40.4%). In the LdT group, 26 patients (92.9%) switched to another NA and another NA was added in 2 (7.1%) patients. An assessment of the CVR rate at 3 years, including treatment modification, showed that 89.3% and 95.7% of patients in the ETV and LdT groups, respectively, had undetectable serum hepatitis B virus DNA levels (p=0.329). Among LdT patients with treatment modification, the cumulative incidence rate of a CVR for rescue therapy was significantly higher in the tenofovir than in the ETV group (p=0.009). CONCLUSION: During the 3-year study, there were no significant differences in the CVR between the ETV and LdT groups if appropriate rescue therapy was considered.
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Humanos , DNA , Vírus da Hepatite B , Hepatite B Crônica , Hepatite Crônica , Incidência , Prontuários Médicos , Estudos Retrospectivos , TenofovirRESUMO
Objective To investigate the baseline independent prognostic factors for 24 months survival of hepatitis B virus (HBV)-associated acute-on-chronic liver failure (ACLF) patients treated with telbivudine.Methods The prospective cohort study was conducted in HBV-associated ACLF patients who were hospitalized in Mengchao Hepatobiliary Hospital of Fujian Medical University and volunteered to be treated with telbivudine for more than 24 months.The patients were observed for survival at month 1,3,6,12,and 24 after treatment.The baseline biochemical index,coagulant function,model for end-stage liver disease (MELD) score,HBV DNA level as well as comorbidities were analyzed in this study.The count data were compared with kappa test or Fisher's exact test.For the normal distributed measurement data,the homogeneity test of variances (Levene test) was firstly used for comparison between groups.Further,the group t test was applied for variance homogeneity,while the approximate t test was applied for variance non-homogeneity and the Mann-Whitney U test was applied for the non-distributed measurement data.Results A total of 41 patients were enrolled,including 3 drop-outs and 38 accomplishments.Among these 38 patients,there were 3 females (7.9 ％) and 35 males (92.1％),with ages (38.5 ± 11.1) years.There were 32 patients alive and 6 dead during 1 month's follow-up,while baseline MELD score was the independent prognostic factor (RR=1.864,95％CI:1.151-3.019) for survival.There were 31 patients alive and 7 dead during 3 months' follow-up,while baseline MELD score and upper gastrointestinal hemorrhage (UGH) were the independent prognostic factors (RR =2.053,95％CI:1.163-3.625;RR=394.939,95％CI:1.880-82 948.817).There were both 26 patients alive and 12 dead during 6 and 12 months' follow-up,while baseline MELD score was the independent prognostic factor (RR=1.761,95％ CI:1.230-2.523).At the end of 24 months' follow-up,there were 15 patients alive and 23 dead.Viral rebounds were observed in 6 patients and 3 of them were dead.Baseline HBV DNA level,MELD score and electrolyte imbalance were the independent prognostic factors (RR-9.722,95％ CI:1.607-58.821;RR=l.518,95％ CI:1.066-2.162;RR=87.505,95％ CI:2.263-3 384.232) for 24 months'survival.Conclusions Although telbivudine is not recommended as the first-line treatment,ACLF patients with low MELD score and low HBV DNA level at baseline,individualized treatment may improve patient's survival rate.UGH and electrolyte imbalance may affect the efficacy of telbivudine and reduce the survival rate of ACLF patient.
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Objective@#To investigate the association between single nucleotide polymorphisms (SNPs) of rs3130542 and rs4821116 in the HLA-C and UBE2L3 genes and the effect of telbivudine antiviral therapy during pregnancy in HBeAg-positive mothers through a large-sample control study, and to provide a basis for the development of individualized blocking strategies for pregnant women with a high viral load.@*Methods@#The genotypes of rs3130542 and rs4821116 were determined for 312 pregnant women with a high viral load who received telbivudine antiviral therapy during the second or third trimester of pregnancy, and the dominant model, recessive model, and additive model were used to analyze the association between the genotypes of these two loci and the reduction in HBV DNA load. The Shapiro-Wilk test and the Levene test were used to evaluate data normality and homogeneity of variances, and the t-test or the non-parametric Mann-Whitney U test was selected based on data type and was used for the comparison of means between groups. The Hardy-Weinberg equilibrium was used to determine the genotype of SNPs, and the dominant model, recessive model, and additive model were used for analysis.@*Results@#Mothers with an AA/AG genotype of rs3130542 in the HLA-C gene had a significantly higher probability of HBV DNA load ≥103 IU/ml at the time of delivery (P < 0.05) and a significantly higher risk of failure in the prevention of mother-to-child transmission, no matter whether they started to take telbivudine at week 24 or 28 of pregnancy. The association between the genotype of rs4821116 in the UBE2L3 gene and the reduction in viral load in pregnant women needed to be confirmed by studies with a larger sample size.@*Conclusion@#Pregnant women with a high viral load and an AA/AG genotype of rs3130542 in the HLA-C gene tend to have poor response to antiviral therapy during pregnancy, and early antiviral intervention is recommended for such patients.
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Objective@#To investigate the clinical effect of 156-week telbivudine sequential therapy in HBeAg-positive chronic hepatitis B patients with suboptimal response to pegylated interferon-α-2a (Peg-IFN-α-2a) therapy.@*Methods@#A total of 35 HBeAg-positive CHB patients with HBV DNA < 500 IU/ml who were treated with Peg-IFN-α-2a for 48 weeks and did not experience seroconversion of HBeAg were given telbivudine sequential therapy for 156 weeks. HBeAg clearance rate, HBeAg seroconversion rate, HBV DNA clearance rate, safety, and drug resistance rate were analyzed. The t-test was used for the analysis of continuous data and the chi-square test was used for the analysis of categorical data. A multivariate Cox regression analysis was used to identify the influencing factors for HBeAg seroconversion.@*Results@#Telbivudine sequential therapy achieved an ideal HBeAg seroconversion rate of 87.88% with good tolerability and low drug resistance. The HBeAg clearance rate and HBeAg seroconversion rate increased over the time of treatment and were 45.45% and 45.45%, respectively, at 24 weeks and 93.94% and 87.88%, respectively, at 156 weeks. No patient had virologic breakthrough or HBsAg clearance during treatment. The multivariate Cox regression analysis showed that baseline HBsAg level (hazard ratio [HR] = 0.404, P = 0.003) and > 0.5 lg IU/ml reduction in HBeAg at 24 weeks (HR = 2.196, P = 0.048) were predictive factors for HBeAg seroconversion at 156 weeks.@*Conclusions@#In HBeAg-positive CHB patients with suboptimal response to Peg-IFN-α-2a therapy, 156-week telbivudine sequential therapy has a good clinical effect and can be used as an optimal regimen for such patients.
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Objective To investigate the risk factors of creatine kinase (CK) elevation in chronic hepatitis B (CHB) patients and treatment outcomes for better management of such patients. Methods The CHB patients complicated with CK elevation who were treated during the period from June 2013 to June 2015 were reviewed retrospectively with their clinical data. CK elevation was examined in terms of antiretroviral regimens, and glycyrrhizin therapies. The clinical outcome was evaluated in terms of grade 3/4 CK elevation. Results A total of 364 CHB patients with CK elevation were included in this analysis. CK elevation was primarily associated with telbivudine monotherapy and combination therapy, followed by entecavir treatment. Grade 3/4 CK elevation was identified in 30 patients, which was mainly associated with telbivudine monotherapy and combination therapy. Good outcome was observed in most of these?patients?(76.7?%,?23/30).?Myopathy?was?confirmed?in?one?patient?by?muscle?biopsy.?Glycyrrhizin?was?not?associated?significantly?with CK elevation in CHB patients. Conclusions Creatine kinase elevation usually occurs in the CHB patients receiving telbivudine-containing therapies. CHB patients should be monitored for CK level during antiviral therapy. Concomitant glycyrrhizin treatment is not associated with CK elevation.
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Objective To observe the clinical effects of anti-hepatitis B virus with telbivudine combined with adefovir dipivoxil.Methods 82 cases of patients diagnosed with chronic hepatitis B from January 2014 to February 2016, were randomly divided into two groups, the control group were treated with adefovir ester treatment, the observation group were treated with telbivudine combined with adefovir dipivoxil treatment, patients were followed up and recorded Child-Pugh score, aspartate aminotransferase ALT, total bilirubin TBIL, aspartate aminotransferase AST, albumin ALB, HBV-DNA negative rate, HbeAg seroconversion rate case, the use of statistical methods for data analysis.Results After treatment, the observation group Child-Pugh score, ALT values were(4.01±0.79)points,(37.19±4.82)U/L, were better than the control group(5.46±1.16)points,(61.49±9.78)U/L, and the differences were statistically significant (P<0.05).Observation group after treatment TBIL, AST, ALB, respectively(34.91±5.49)μmol/L,(56.49±5.28)U/L,(45.51±4.24)g/L, were better than the control group(61.62±10.06)μmol/L,(78.64±8.16)U/L,(38.76±3.21)g/L, and the differences were statistically significant (P<0.05).The observation group after treatment for HBV-DNA negative rate and HbeAg seroconversion rate(82.93%, 58.54%)respectively were higher(58.54%, 29.27%), and the difference was significant (P<0.05).Conclusion Telbivudine combined with adefovir dipivoxil anti-HBV effect is good, better than medication alone is worthy of further research and application.
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Objective To compare the impact of Telbivudine (LDT) and Entecavir (ETV) administration on estimates of glomerular filtration rate for anti-viral therapy in patients with hepatitis B virus (HBV)-related compensated cirrhosis by an open, prospective randomized controlled study.Methods Patients with HBV-related compensated cirrhosis at clinic or hospitalized in Shaoxing Municipal Hospital from January 2012 to June 2013 were included.A total of 170 patients were randomly divided into LDT (600 mg/d) or ETV (0.5 mg/d) groups at a ratio of 1∶1 according to the random number table method.All patients were treated for more than 36 months.The LDT group was optimized according to the roadmap.Patients with poor response or resistance in both treatment group were added with Adefovir dipivoxil (ADV) 10 mg/d for optimal treatment.The clinical outcome, creatinine (CR), estimated glomerular filtration rate (eGFR) of patients before and after 36 months of treatment were compared between two groups.All categorical data were analyzed using chi-square test and data accorded with normal distribution were compared by t test.Results After 36 months of treatment, the virological and biochemical responses in LDT group and ETV group were similar.The mean CR levels at month 24 and 36 in LDT group were (74.25±22.98) μmol/L and (70.72±24.75) μmol/L, respectively, which were both lower than baseline level ([83.09±17.68] μmol/L, t=2.811 and 3.145, respectively, both P<0.01).The mean CR levels at month 36 between two groups were statistically different (t=3.431, P=0.001).The mean eGFR levels at month 12, 24 and 36 in LDT group were all significantly lower than that at baseline (t=3.976,8.297 and 10.629, respectively, all P<0.01).The mean eGFR levels at month 24 and 36 between two groups were statistically different (t=9.684 and 15.019, respectively, both P<0.01).A total of 64 patients including 34 in LDT group and 30 in ETV group had mild nephritic injury at baseline.The mean eGFR in patients with mild nephritic injury at baseline in LDT group at month 12, 24 and 36 were significantly different compared to baseline (t=6.098,10.191 and 14.378, respectively, all P<0.01).The mean eGFR level at month 36 in ETV group had statistical difference compared to baseline (t=2.058, P<0.05).The mean eGFR levels at months 12, 24 and 36 were all statistical different between two groups (all P<0.01).The mean eGFR levels at month 24 and 36 in the optimized group were superior to ETV group (P<0.01).Conclusions In patients with HBV-related compensated cirrhosis, LDT and ETV treatment have similar clinical efficacy.LDT is more effective in protecting nephritic function than ETV.
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Objective To evaluate the efficacy of telbivudine in HBeAg-positive chronic hepatitis B (CHB) patients by comparing the efficacy of initial telbivudine therapy in treatment-naive patients with sequential telbivudine therapy in patients with poor response to adefovir.Methods A total of 90 HBeAg-positive CHB patients were assigned to receive sequential telbivudine therapy following poor response to adefovir dipivoxil (n=45),or initial telbivudine therapy in antiviral treatment-naive patients (n=45).All patients were treated with telbivudine 600 mg daily for 104 weeks.The efficacy was evaluated in terms of liver function tests,serum HBV markers,HBV DNA and antiviral drug resistance.Results Telbivudine showed good overall efficacy after treatment for 104 weeks in terms of alanine aminotransferase normalization rate (91.1％),HBV DNA negative conversion rate (80.0％),HBeAg loss rate (57.8％),and HBeAg/HBeAb seroconversion rate (30.0％).The HBV DNA negative conversion rate in initial treatment group was significantly higher than that in sequential treatment group (P＜0.05).However,among the patients with early response,the efficacy did not show significant difference between groups (P＞0.05).The patients with early response showed significantly better efficacy than those without early response,in terms of higher HBV DNA negative conversion rate,higher HBeAg loss rate and HBeAg/ HBeAb seroconversion rate (P＜0.000 1 or P＜0.05),but lower virological breakthrough rate (P＜0.05).Conclusions Telbivudine has shown reliable efficacy in CHB patients.Initial telbivudine therapy is better than sequential therapy in CHB patients with poor response to adefovir.However,for patients with early response to telbivudine,no statistical difference is found between initial and sequential therapy in long-term treatment efficacy (104 weeks).The patients receiving sequential telbivudine therapy should be monitored closely for early antiviral response to optimize treatment.
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PURPOSE: This study examined 2-year outcome of consecutive therapy using entecavir (ETV) followed by telbivudine (LdT) in subjects with undetectable hepatitis B virus (HBV) DNA level and normal alanine aminotransferase level after the initial 6 months of ETV treatment. MATERIALS AND METHODS: Sixty subjects were randomized to continue with ETV or switch to LdT. Significant difference in baseline characteristics was not found between the two groups. Persistent HBV DNA level of 20–60 IU/mL in three consecutive samples collected three months apart or singly measured HBV DNA level of >60 IU/mL was defined as virological rebound. RESULTS: During 96 weeks of follow-up, all subjects of the ETV-only group (n=30) resulted in undetectable HBV DNA level. On the other hand, 83.3% (n=25) of the LdT-switched group showed treatment success. Virological rebound time varied from week 24 to 84 after switching to LdT. HBV DNA level was 180 to 2940 IU/mL at rebound time. All subjects with virological rebound (n=5) showed drug-resistant mutation: three had mutation rtM204I, and two had mutation rtM204V. Consecutive treatment using ETV followed by LdT showed virological rebound in 16.7% of subjects during 96 weeks of follow-up. HBV DNA negativity during initial ETV therapy could not be achieved in patients who switched to LdT. CONCLUSION: Consecutive treatment using ETV followed by lamivudine was ineffective for treating chronic hepatitis B. LdT was found as a more potent antiviral agent than lamivudine. However, this conclusion requires larger-scale, long-term prospective reviews of the treatment effects of ETV-LdT switch therapy.
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Humanos , Alanina Transaminase , DNA , DNA Viral , Seguimentos , Mãos , Vírus da Hepatite B , Hepatite B , Hepatite B Crônica , Hepatite , Lamivudina , Estudos ProspectivosRESUMO
Objective@#To investigate the optimal treatment regimen for patients with HBeAg-positive chronic hepatitis B (CHB) after suboptimal response to 24 weeks of pegylated interferon (Peg-IFN) α-2a.@*Methods@#A total of 188 patients with HBeAg-positive CHB who had suboptimal response to 24 weeks of Peg-IFN α-2a were randomly divided into entecavir group (n = 93) and telbivudine group (n = 95). The two groups received entecavir 0.5 mg/d and telbivudine 0.6 g/d, respectively, for 208 weeks. After 208 weeks of treatment, the following indices were assessed: HBeAg clearance rate and seroconversion rate, hepatitis B virus (HBV) DNA clearance rate (HBV DNA < 500 IU/ml), safety, and drug resistance rate. The data were subjected to intention-to-treat (ITT) analysis and per protocol (PP) analysis. Univariate and multivariate logistic regression analyses were performed for the drugs used and baseline characteristics in patients with or without HBeAg seroconversion, and stratification analysis was performed based on the baseline HBeAg level.@*Results@#Six cases in the entecavir group and four cases in the telbivudine group did not complete the treatment. Sequential entecavir and telbivudine were well tolerated and safe for all patients. There was a significant difference in HBV DNA clearance rate at 52 weeks of treatment between the entecavir group and the telbivudine group (ITT analysis: 93.55% [87/93] vs 77.89% [74/95], χ 2 = 9.363, P = 0.002; PP analysis: 93.10% [81/87] vs 76.92% [70/91], χ 2 = 9.049, P = 0.003). The suppression rates of HBV DNA at 208 weeks of treatment were 95.70% (89/93) vs 92.63% (88/95) (ITT analysis) and 95.40% (83/87) vs 92.31% (84/91) (PP analysis). There was a significant difference in HBeAg seroconversion rate at 208 weeks of treatment between the entecavir group and the telbivudine group (ITT analysis: 38.71% [36/93] vs 62.11% [59/95], χ 2 = 10.290, P = 0.001; PP analysis: 41.38% [36/87] vs 64.84% [59/91], χ 2 = 9.833, P = 0.002). Univariate and multivariate logistic regression analyses suggested that sequential use of telbivudine, male sex, and the baseline level of HBeAg were significantly associated with HBeAg seroconversion at 208 weeks of treatment (P = 0.003, hazard ratio [HR] = 0.386; P = 0.009, HR = 0.303; P = 0.001, HR = 3.502).@*Conclusion@#For patients with HBeAg-positive CHB after suboptimal response to 24 weeks of Peg-IFNα-2a, sequential use of telbivudine is the optimal treatment regimen according to the baseline level of HBeAg (baseline guidance). The incidence of HBeAg seroconversion during 208 weeks of sequential treatment can be significantly increased according to the HBeAg decline curve in early treatment (24 weeks) and 104 weeks (response guidance).
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ObjectiveTo investigate the establishment of a predictive model for early virologic response in previously untreated chronic hepatitis B (CHB) patients treated with telbivudine, since early virologic response can predict the long-term efficacy of nucleotide analogues. MethodsA total of 135 CHB patients who visited Mengchao Hepatobiliary Hospital of Fujian Medical University from January 2007 to August 2014 were enrolled and treated with telbivudine (600 mg qd) for at least 24 weeks. Follow-up was performed once every 2 weeks, and the patients′ baseline data and data measured during treatment were recorded. The t-test was used for comparison of continuous data between groups, the chi-square test was used for comparison of categorical data between groups, and the Cox proportional hazards regression model was used to analyze the influencing factors for early virologic response and establish the predictive model. ResultsThe patients without a family history of hepatitis B virus (HBV) infection (P=0.000 3) and with high baseline levels of total bilirubin (TBil) (P=0.002 6) and aspartate aminotransferase (AST) (P=0.007 4) and a low HBV DNA load (P=0.002 3) tended to show early virologic response. The predictive model was established based on these variables, and the risk score (R) of CHB patients was calculated. The CHB patients with R＞0.85 were more likely to achieve early virologic response. ConclusionThe model established based on the four variables of family history, baseline TBil level, baseline AST level, and HBV DNA level can well predict early virologic response in previously untreated CHB patients treated with telbivudine.
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ObjectiveTo investigate the efficacy of telbivudine combined with adefovir dipivoxil and PEG-IFN-α-2a combined with entecavir as the antiviral therapy for HBeAg-positive patients with chronic hepatitis B (CHB) and a high viral load. MethodsA total of 80 previously untreated HBeAg-positive CHB patients with a high viral load who were treated in The Sixth People′s Hospital of Qingdao from November 2012 to November 2015 were enrolled and randomly divided into two groups. The patients in group A were treated with telbivudine combined with adefovir dipivoxil, and those in group B were treated with PEG-IFN-α-2a combined with entecavir. Biochemical and virologic response rates and seroconversion rate were observed at weeks 12, 24, and 48 of administration. The drug resistance rate and incidence rates of adverse events were observed in both groups. The Chi-square test was applied for comparision of categorical data between the two groups, and the t-test was applied for comparision of continuous data between the two groups. ResultsBiochemical and virologic response rates at weeks 12, 24, and 48 of administration showed no significant differences between the two groups. The seroconversion rates at weeks 12 and 24 of administration showed no significant differences between the two groups, while at week 48 of administration, group B had significantly higher HBeAg clearance rate and seroconversion rate than group A (450% vs 675%， 225% vs 450%，χ2=4.114 3 and 4.528 3, both P＜0.05). Group B had significantly higher incidence rates of adverse events than group A. ConclusionTelbivudine combined with adefovir dipivoxil and PEG-IFN-α-2a combined with entecavir can effectively inhibit the replication of high-load HBV DNA, delay disease progression, and realize HBeAg seroconversion. However, the two regimens have their own advantages and disadvantages and should be selected according to clinical situation.
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Objective To investigate the expression of PD-1 on CD4 +and CD8 + T cells in patients with HBeAg-positive chronic hepatitis B(CHB)treated with telbivudine.Methods Fifty-six HBeAg-positive CHB patients admitted in the First Affiliated Hospital of Zhengzhou University during January 201 3 and June 201 4 were enrolled in this study.The expression of PD-1 on CD4 +and CD8 + T cells was detected with flow cytometry at baseline,24,48 and 72 wks after telbivudine treatment.The relationship of PD-1 expression with alanine aminotransferase (ALT)level,HBeAg seroconversion and HBV DNA loads was analyzed.t test and completely random variance analysis were used to analyze the data.Results The PD-1 expression on CD4 + and CD8 + T cells at baseline was higher in patients with low ALT levels compared to those with high ALT levels(t =1 2.20 and 9.69,both P <0.01 ),while higher levels of PD-1 expression was also observed in patients with high HBV DNA load (≥5 lgIU /mL)compared to those with low HBV DNA load (t =4.39 and 4.85,both P <0.01 ).PD-1 levels on CD4 + and CD8 + T cells presented a declining trend after telbivudine treatment(F =6.98 and 8.97,both P <0.01 ),PD-1 expression in patients with HBeAg seroconversion showed lower levels compared with baseline values (t =1 8.45 and 1 8.01 ,both P <0.01 ). Conclusion In HBeAg-positive CHB patients,the expression of PD-1 on CD4 + and CD8 + T lymphocytes shows a decreasing trend during the treatment with telbivudine,indicating that antiviral therapy may alleviate the immunosuppression in these patients.
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Objective To explore the efficacy and safety of sequential telbivudine ( LDT) therapy following interferon-α( IFN-α) in hepatitis B e antigen (HBeAg) positive chronic hepatitis B patients.Methods 94 chronic hepatitis B patients in our hospital hepatitis clinic archives from August 2008 to September 2013 were divided into two groups, 45 patients treated with LDT following IFN-αdue to unsatisfactory response to peginterferon-α-2a (peg-IFN-α-2a)treatment in the sequential group and 49 patients treated with LDT initially in the controlled group.In the sequential group, 22 patients failed to respond to IFN-αtreatment, 4 patients obtained IFN-resistance, 6 patients developed severe side effects, 1 patients had pre-C mutation and 12 patients switched to LDT due to economic factors or fertility requirement.The biochemical response and virological response, virological breakthrough and serological response were observed.Chi-square test was adapted for data analysis.Results After 32.35 months of LDT therapy, 88.9%(40/45) patients had with HBV-DNA <100 IU/mL in the experiment group compared with 44.9%(22/49) patients in the control group (P<0.05).The rates of HBeAg loss and HBeAg seroconversion in the experiment group were 53.3%(24/45) and 51.1%(23/45) respectively, which were significantly higher than that of the control group, 24.5%(12/49) and 24.5% (12/49) (P<0.05).6.7% (3/45) patients developed virological breakthrough in the sequential group compared with 34.7%(17/49) in the control group (P<0.05).Above results suggested the synergistic antiviral activity between peg-IFN-α-2a and LDT.Conclusion Sequential LDT therapy following peg-IFN-α-2a is better efficacy and safety compared with treating patients with LDT alone initially.
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Objective To explore antiviral efficacy, safety and blocking of mother-to-infant transmission by administrating telbivudine in pregnant patients with chronic hepatitis B (CHB) throughout pregnancy. Methods Sixty-four cases of female patients were enrolled. The study participants were divided into the telbivudine treatment group (n = 31) and the control group (n = 33). Data were recorded from beginning of administration to ending pregnancy, as well as notation of any adverse reactions. The neonates and infants were evaluated in HBV infection, parameters of growth and development. Results The recovery rates of ALT, respectively, were 90.32% vs. 57.58% (P = 0.003), 93.55% vs. 62.50% (P = 0.003) at 24 weeks and ante partum and the HBVDNA-negative conversion rates, respectively, were 48.39% vs. 3.03% (P = 0.000), 83.87%vs. 6.06% (P = 0.000), 90.32% vs. 6.25% (P = 0.000) respectively, at 12, 24 weeks of pregnancy and at ante partum between the treatment and control groups. The HBsAg-positive and HBVDNA-positive rates of the infants, respectively, were 12.90% vs. 37.50% (P = 0.025) and 0 vs. 21.88% (P = 0.018) at birth, and respectively, were all 0 vs. 18.75% (P = 0.035) and 0 vs. 18.75% (P = 0.035) at 1, 6, 12 months old between the treatment and control groups. The treatment group showed lower incidence of intrauterine HBV infection (0 vs. 18.75%, P = 0.035). The gestational ages, fetal weights and Apgar scores were not significant different in the children born in the mothers from the two groups. Conclusions Telbivudine administration showed a good antiviral curative effect and effectively blocked mother-to-infant transmission in women with CHB. The treatment was safe and caused no obvious adverse reaction.
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Objective To study the effect of telbivudine (TBV) on the ratio of CD4+ CD25+CD127low/-regulatory T cell (Treg) of HBeAg-positive chronic hepatitis B (CHB). Methods The ratios of Treg before and after treatment for 12, 24, 36 and 48 weeks with TBV of thirty-five patients with HBeAg-positive CHB were detected. Results Ratios of Treg were (12.55 ± 1.78)%, (10.42 ± 1.04)%, (9.55 ± 0.74)%, (8.78 ± 0.67)%, (8.74 ± 0.71)%respectively before and after treatment of 12, 24, 36 and 48 weeks and all the values were lower than its former one (P < 0.05), except the 48 weeks′. Conclusions The ratio of Treg of HBeAg (+) CHB decreases after treatment with TBV.