拉米夫定和阿德福韦酯初始联合与恩替卡韦单药治疗慢性乙型肝炎的疗效和安全性比较

目的 观察拉米夫定(LAM)和阿德福韦酯(ADV)初始联合与恩替卡韦(ETV)单药治疗慢性乙型肝炎的疗效,并比较两者的安全性.方法 选择我院2007年6月-2008年1月符合抗病毒治疗的未曾使用核苷(酸)类似物的初治慢性乙型肝炎患者120例,分为联合组60例和单药组60例,联合组应用LAM 100 mg,ADV 10 mg,每日1次;单药组应用ETV 0.5 mg,每日1次.分别在基线、12、24、48、96周时留取血清,采用全自动分析生物化学仪检测肝功能、肾功能、血生物化学指标;采用化学发光法定量检测HBsAg和HBeAg;采用实时荧光定量PCR检测HBV DNA水平;采用PCR产物直接测序法检测病毒耐药基因.组间比较采用配对t检验,率的比较采用χ2检验.结果 (1)联合组54例,单药组50例完成了48周随访,联合组51例,单药组48例完成了96周随访.两组治疗前性别、年龄、血清ALT、血肌酐、HBV DNA、HBsAg水平及HBeAg阳性率,差异无统计学意义,具有可比性.(2)两组在治疗12周和24周时,HBV DNA＜300拷贝/ml和HBV DNA＜1000拷贝/ml的比率,差异无统计学意义.治疗12周时,单药组和联合组HBV DNA下降＜1 log10拷贝/ml的分别为3.7%(2/54)和18.0%(9/50),两组比较,χ2=5.556,P＜0.05,差异有统计学意义.(3)治疗48周时,单药组和联合组的ALT复常率、HBVDNA＜1000拷贝/ml的比率、HBeAg血清转换率以及与基线比较HBV DNA下降绝对值,差异均无统计学意义.联合组与单药组HBV DNA＜300拷贝/ml的患者分别为90.7%(49/54)和76.0%(38/50),两组比较,χ2=4.125,P＜0.05,差异有统计学意义.(4)治疗96周时,HBV DNA＜300拷贝/ml、HBV DNA＜1000拷贝/ml患者比率和HBeAg血清转换率,联合组分别为96.1%(49/51)、98.0%(50/51)、41.7%(15/36),单药组分别为79.2%(38/48)、87.5%(42/48)、16.7%(6/36),两组比较,χ2值分别为6.639、4.180、5.445,P值均＜0.05,差异有统计学意义;但两组患者与基线比较HBV DNA和HBsAg下降绝对值以及ALT复常率差异无统计学意义.(5)治疗96周时,联合组未见病毒学突破和耐药发生,而单药组累计发生病毒学突破4例,其中3例(6.3%,3/48)检测到ETV相关耐药基因变异位点,2例患者在基线时存在LAM相关耐药基因变异位点(rtL180M+M204V).(6)治疗48、96周时,联合组与单药组患者血肌酐水平及治疗前后血肌酐升高水平差异无统计学意义.在治疗期间,两组均无血清肌酐水平超过正常上限或由于肌酐升高0.5 mg/dl而调整剂量的患者.结论 LAM和ADV初始联合治疗,在减少病毒学突破和耐药发生,以及提高HBeAg血清转换率方面优于ETV单药治疗.

Abstract：

Objective To compare the efficacy and safety of Lamivudine (LAM) plus Adefovir dipivoxil (ADV) combination therapy and Entecavir(ETV) monotherapy for chronic hepatitis B patients.Methods 120 patients with chronic hepatitis B managed in a single-centre clinical practice (median 96 weeks)were split into 2 cohorts,one was treated with de-novo combination Lamivudine (100 mg/day) plus Adefovir (10 mg/day) (LAM+ADV),thc other with Entecavir (0.5 mg/day) monotherapy.Serum levels of ALT,creatinine,HBsAg,HBeAg and HBV viral load,together with genotypic resistence were analyzed at 0,12,24,48,96 weeks,respectively.HBV DNA was determined by real-time PCR.HBsAg and HBeAg were assessed by chemiluminescence.Serum levels of ALT and creatinine were detected by automatic biochemical analyzer.HBV genotypic resistence was tested by direct sequencing.Results (1) At the time point of 96 weeks,a total of 99 patients(51 cases in combination therapy cohort and 48 case in monotherapy cohort) were compared.The baseline characteristics as for HBV viral load,median age,serum levels of ALT and creatinine were compatible between combination therapy cohort and monotherapy cohort.(2) The rates of HBV DNA ＜300 copies/ml and HBV DNA ＜ 1000 copies/ml had no significant difference between LAM + ADV and ETV cohorts by the 12 and 24 weeks (P ＞ 0.05).(3) At the time point of 48 weeks,the rates of HBV DNA＜1000copies/ml,HBeAg seroconversion,and ALT normalization were similar in both cohorts,though the rate of HBV DNA ＜ 300 copies/ml was obviously higher in combination therapy cohort than that of monotherapy cohort (90.7% vs 76%,P ＜ 0.05).(4) At the time point of 96 weeks,the rates of HBV DNA ＜ 300 copies/ml (96.1% vs 79.2%),HBV DNA ＜ 1000 copies/ml (98% vs 87.5%) and the HBeAg seroconversion (41.7% vs 16.7%) were markedly higher in combination therapy cohort than those of monotherapy cohort statistically (P ＜ 0.05 for all).The mean values of decreases for HBV viral loads and HBsAg levels were smilar in both cohorts at 48 and 96 weeks.(5) Elevated serum creatinine not be found in both cohorts at the end of treatment.(6) No virological breakthrough occurred in combination therapy cohort at the end of treatment.Four patients in monotherapy cohort were found with virological breakthrough at 96 weeks and three cases among were confirmed to be of variants associated with ETV resistance (rtLl80M + T184L + M204V).Conclusions Present study suggests that Lamivudine plus Adefovir dipivoxil de-novo combination therapy was more efficacious than Entecavir monotherapy for CHB patients and the tolerance is compatible.     

Prevention of lamivudine‐resistant hepatitis B recurrence after liver transplantation with entecavir plus tenofovir combination therapy and perioperative hepatitis B immunoglobulin only

T. Karlas, J. Hartmann, A. Weimann, M. Maier, M. Bartels, S. Jonas, J. Mössner, T. Berg, H.L. Tillmann, J. Wiegand. Prevention of lamivudine‐resistant hepatitis B recurrence after liver transplantation with entecavir plus tenofovir combination therapy and perioperative hepatitis B immunoglobulin only.
Transpl Infect Dis 2011: 13: 299–302. All rights reserved Abstract: Combination therapy with antivirals plus hepatitis B immunoglobulin (HBIg) has become the standard treatment for prevention of post‐liver transplant hepatitis B virus (HBV) recurrence. However, HBIg therapy is inconvenient and expensive. Alternative therapeutic approaches with modern nucleos(t)ide analogues are limited so far. The present case report describes prevention of HBV recurrence with entecavir and tenofovir. A 48‐year‐old male patient with hepatitis B‐induced decompensated liver cirrhosis initially improved on lamivudine (LAM) until LAM resistance (rtL180M and rtM204V) emerged followed by renewed decompensation. Therefore, tenofovir was added to LAM leading to undetectable HBV DNA (<200 copies/mL). Six months later, low‐level viremia (479 copies/mL) was detected. Treatment was escalated to tenofovir plus entecavir. HBV DNA became negative again, and the patient underwent orthotopic liver transplantation. HBIg was administered during transplantation (10,000 IU) and on the second and third postoperative days (total dose 26,000 IU). Subsequently, the anti‐hepatitis B surface (HBs) titer rose to 1477 IU/L at day 4 post transplantation. Although HBIg should have been continued, the patient remained on combination therapy with tenofovir plus entecavir only. The anti‐HBs titer decreased and became negative 4 months later. However, under continued combination therapy with oral antivirals, HBV DNA and hepatitis B surface antigen remained negative during the entire follow‐up of 21 months after liver transplantation. Combination therapy with entecavir plus tenofovir may prevent post‐liver transplant hepatitis B recurrence even without HBIg maintenance therapy. This case illustrates that combination oral antiviral therapy might substitute for HBIg as indefinite prophylactic regimen due to profound antiviral efficacy and low risk of viral resistance. Efficacy and safety must be further investigated in randomized controlled trials.     

恩替卡韦联合苦参素治疗慢性乙型肝炎患者疗效及其对外周血辅助性T淋巴细胞的影响*

目的 探讨恩替卡韦联合苦参素治疗慢性乙型肝炎(CHB)患者疗效及其对外周血淋巴细胞百分比的影响。方法 随机将180例CHB 患者分为对照组90例和观察组90例。两组患者均接受恩替卡韦治疗,观察组患者在此基础上加用苦参素口服,观察6个月。采用ELISA 法检测血清基质金属蛋白酶-9(MMP-9)和转化生长因子-β1(TGF-β1),采用RIA 法测定血清血管紧张素II(Ang-II)水平,使用流式细胞仪检测外周血辅助性T细胞及CD80 和CD86 阳性细胞百分比。结果 在治疗6个月末,观察组血清ALT 复常、HBeAg 和HBV DNA 阴转率分别为34.4%、91.1% 和86.7%,显著高于对照组的18.9%、78.9%和63.3%(P<0.05);血清MMP-9、TGF-β1 和Ang-II 水平分别为(30.5±3.6)ng/ml 、(19.5±2.2) ng/ml 和(33.7±4.1)ng/dL,与对照组【(22.4±2.7)ng/ml 、(22.6±2.8) ng/ml 和(46.3±4.9)ng/dL,P<0.05】比,差异显著;Th2和Th1细胞及CD80和CD86阳性细胞百分比分别为(6.6±1.5)%、(9.8±2.3)%、(2.5±0.7)%和(1.6±0.5)%,与对照组【(9.0±2.7)%、(7.9±1.4)%、(1.9±0.3)%和(1.1±0.2)%,P<0.05】比,差异显著。结论 应用恩替卡韦联合苦参素治疗CHB患者可能通过改善机体的免疫功能而提高近期疗效。     

Lamivudine/pegylated interferon alfa-2b sequential combination therapy compared with lamivudine monotherapy in HBeAg-negative chronic hepatitis B

BACKGROUND AND AIM: Monotherapy has been proven insufficient in achieving sustained control of chronic hepatitis B. We aimed to assess the efficacy of combined sequential administration of lamivudine and pegylated interferon alfa-2b in patients with hepatitis Be antigen (HBeAg)-negative chronic hepatitis B. METHODS: Eighteen patients were given sequential combination treatment starting with 3 months of lamivudine monotherapy followed by 9 months of pegylated interferon alfa-2b (after a 3-month period of concomitant administration of the two drugs) and 24 patients received lamivudine monotherapy. RESULTS: At the end of treatment, 88.9% of the patients who received sequential combination treatment and 70.8% of those who received lamivudine monotherapy had hepatitis B virus (HBV) DNA levels below 400 copies/mL (P = not significant). At the end of treatment, 72.2% of the patients who received sequential combination treatment and 70.8% of those who received lamivudine monotherapy achieved alanine aminotransferase normalization (P = not significant). After 12 months of follow up, 33.3% of the patients who received sequential combination treatment and 16.7% of those who received lamivudine monotherapy had HBV-DNA levels below 400 copies/mL (P = 0.4). After 12 months of follow up, 72.2% of the patients who received sequential combination treatment and 25.0% of those who received lamivudine monotherapy had normal alanine aminotransferase levels (P < 0.01). Twenty-five percent of the patients in the lamivudine monotherapy group had virological breakthrough compared to none in the sequential combination treatment group (P = 0.06). CONCLUSIONS: Sequential combination treatment is able to improve sustained biochemical response rates and prevent the emergence of lamivudine-resistant mutants in patients with HBeAg-negative chronic hepatitis B.     

Higher efficacy of sequential therapy with interferon-alpha and lamivudine combination compared to lamivudine monotherapy in HBeAg positive chronic hepatitis B patients

BACKGROUND: Monotherapy with interferon (IFN) or lamivudine is effective in a limited proportion of chronic hepatitis B (CHB) patients. A sequential combination may have better therapeutic effects by sustained viral suppression combined with immunomodulation. AIM: To compare the efficacy of sequential lamivudine and IFN therapy versus lamivudine monotherapy in HBeAg positive CHB patients. PATIENTS AND METHODS: Seventy-five treatment na?ve HBeAg positive patients with histologically proven CHB and alanine aminotransferase (ALT) >1.5 x ULN received lamivudine 100 mg per day for 52 wks with IFN 5 MIU per day added for 16 wks after the first 8 wks (group A, n = 38; age 30 +/- 12 yr; M:F = 35:3) or lamivudine 100 mg per day for 52 wks (group B, n = 37; age 30 +/- 16 yr; M:F = 31:6). Biochemical and virologic responses were assessed at weeks 52 and 76 and analysis was done on intention-to-treat. Serial samples were studied for the emergence of lamivudine-resistant YM552I/VDD mutations by direct sequencing. RESULTS: At week 52, HBeAg loss occurred in 15 (39.5%) in group A and 14 (37.8%) in group B (p= 1.00). HBeAg loss, anti-HBe appearance, and undetectable DNA levels were seen in 26.3% and 13.5% (p= 0.249), respectively. Nine of 10 (90%) patients in group A and 1 of 5 (20%) in group B maintained the response through week 76 (p= 0.017). At week 76, 5 additional patients in group A and 3 in group B further achieved the primary end point and the overall HBeAg loss was observed in 44.7% and 18.9% (p= 0.025) and HBeAg loss, anti-HBe appearance, and undetectable hepatitis B virus (HBV) DNA levels in 36.8% and 10.8% in group A and group B, respectively (p= 0.026). At week 76, undetectable HBV DNA was seen in 39.5% and 16.2% in groups A and B, respectively (p= 0.039). Normal ALT was seen in 47.7% and 40.5% at week 52 (p= 0.489) and ALT was normal in 39.5% and 13.5% at week 76 (p= 0.018) in groups A and B, respectively. YM552I/VDD-resistant mutants emerged in 6 of 38 (15.5%) patients in group A, and 3 of 37 (8.1%) in group B (p= ns). The rate of histological improvement was comparable in the two groups. CONCLUSIONS: Our results demonstrate that sequential therapy is superior to lamivudine monotherapy in achieving sustained seroconversion, ALT normalization, and HBV DNA loss. Compared to 80% with sequential therapy, only 20% Indian patients with CHB did not relapse after stopping lamivudine monotherapy.     

序贯聚乙二醇干扰素α-2a治疗恩替卡韦经治未达满意终点乙型肝炎的疗效

目的 评估序贯聚乙二醇干扰素(Peg-IFN)α-2a治疗恩替卡韦经治HBeAg阳性慢性乙型肝炎的疗效与安全性.方法 57例恩替卡韦治疗96周达到HBV DNA＜500拷贝/ml且0.227PEIU/ml＜HBeAg≤50.000 PEIU/ml的HBeAg阳性慢性乙型肝炎患者,27例接受ETV与PegIFN α-2a联合治疗12周后改为Peg-IFN α-2a单药治疗至48周(试验组),30例继续接受恩替卡韦治疗48周(对照组),分别在治疗的24、48周进行生物化学、病毒学、血清学评估.统计学处理用t检验或x2检验.结果 试验组与对照组基线ALT、HBsAg、HBeAg水平有可比性.治疗48周,试验组HBeAg阴转率与HBeAg血清学转换率分别为40.7％和37.0％,与对照组的16.7％和13.3％相比,差异有统计学意义(x2值分别为4.079和5.11,P值均＜0.05).试验组HBsAg清除率和HBV DNA反弹率分别7.4％与11.1％,对照组无HBsAg清除和HBV DNA反弹(x2值分别为2.307 和3.519,P值均＞0.05).治疗48周,试验组HBsAg水平明显低于对照组[(2866.0±2580.4)IU/ml对比(4335.8±2650.0) IU/ml,t=5.11,P＜0.05]. 结论 恩替卡韦经治的HBeAg阳性慢性乙型肝炎患者,序贯Peg-IFNα-2a治疗有助于实现HBeAg血清转换和HBsAg定量下降.     

Analysis of efficacy and factors influencing sequential combination therapy with tenofovir alafenamide fumarate after treatment with entecavir in chronic hepatitis B patients with low-level viremia

<正>Objective To observe the efficacy and factors influencing sequential or combined tenofovir alafenamide fumarate(TAF) after treatment with entecavir(ETV) in patients with chronic hepatitis B(CHB) with low-level viremia(LLV).Methods 126 CHB cases treated with ETV antiviral therapy in the Department of Infectious Diseases of the First Affiliated Hospital of Nanchang University from January 2020 to September 2022 were retrospectively collected.Patients were divided into a complete virologic...     

5-year efficacy of entecavir in Indian patients with chronic hepatitis B

Background

Entecavir, a drug with high potency and genetic barrier against hepatitis B virus, was believed to become very effective in reducing the hepatitis B burden in India. Long-term studies on its treatment outcome are scarce.

Methods

One hundred and six chronic hepatitis B (CHB) patients (17 cirrhotics of Child class A/B) who received entecavir therapy (0.5/1 mg/day) in a prospective open-label study from January 2010 to September 2015 were included in the analysis. Strict drug compliance was ensured. At least 1-year follow up was mandatory. Patients were followed up for HBV DNA negativity, e antigen seroconversion and hepatic events. Subgroup analysis for HBV DNA negativity was done for age (below and above 60 years), sex, HBV DNA level, e antigen status, cirrhosis and prior other modes of therapy.

Results

One (0.94 %) patient had primary drug resistance. Mean follow up was 2.5 (1 to 5) years. Overall HBV DNA negativity was 89 % to 98 % at 1 to 5 years and e antigen seroconversion rate 18.2 % at 5 years. ALT normalization paralleled HBV DNA negativity. No flare, decompensation, hepatocellular cancer or adverse reaction to drug was observed. Most achieved HBV DNA negativity after 6 months of therapy with lower response in those with high HBV DNA level, cirrhosis and prior therapy at baseline but only up to 1 year. Relapse was universal after stoppage of therapy. None lost HBsAg.

Conclusion

Entecavir will need to be continued indefinitely in Indian patients with CHB.

     

恩替卡韦联合乙肝免疫球蛋白预防肝移植术后乙肝再感染

目的:评价恩替卡韦联合乙肝免疫球蛋白(HBIG)预防原位肝移植(OLT)术后HBV再感染的效果,并探讨术前存在YMDD患者的预防策略.方法:回顾性分析2003-05/2008-01行同种异体原位肝移植术患者,比较长期使用与拉米夫定+肌注型HBIG预防HBV再感染的效果;并观察术前出现YMDD患者应用恩替卡韦+肌注型HBIG的疗效;两组患者观察截止2008-10,对HBV DNA定量水平、乙肝两对半、HBV再感染率进行统计学分析.结果:恩替卡韦组40例患者,随访时间19.5±9.4 mo,未发现HBV再感染;拉米夫定组共84例患者,随访时间18.1±6.4 mo,其中10例出现了HBV再感染,再感染率为11.9%,两组差异有统计学意义.6例术前出现YMDD患者应用恩替卡韦+肌注型HBIG预防,无术后乙肝再感染.结论:恩替卡韦联合HBIG与拉米夫定联合HBIG相比,有效地降低了肝移植术后HBV再感染率,对术前存在YMDD变异的的患者有效.     

Short-term entecavir therapy of chronic severe hepatitis B

BACKGROUND:Chronic severe hepatitis B patients often have limited survival.This investigation aimed to evaluate the short-term effects of nucleoside analog therapy on chronic severe hepatitis B. METHODS:We retrospectively,randomly collected the data of 129 chronic severe hepatitis B patients:55 were treated with entecavir,and the remaining 74 were not treated with nucleoside analogues. RESULTS:No significant difference in short-term survival rate was found between the group treated with entecavir and that t...     

De novo combined lamivudine and adefovir dipivoxil therapy vs entecavir monotherapy for hepatitis B virus-related decompensated cirrhosis

AIM:To compare efficacy of combined lamivudine(LAM)and adefovir dipivoxil(ADV)therapy with that of entecavir(ETV)monotherapy for hepatitis B virus(HBV)-related decompensated liver cirrhosis.METHODS:A total of 120 na ve patients with HBVrelated decompensated cirrhosis participated in this study.Sixty patients were treated with combined LAM and ADV therapy(LAM+ADV group),while the other60 were treated with ETV monotherapy(ETV group)for two years.Tests for liver and kidney function,alpha-fetoprotein,HBV serum markers,HBV DNA load,prothrombin time(PT),and ultrasonography or computed tomography scan of the liver were performed every1 to 3 mo.Repeated measure ANOVA and theχ2test were performed to compare the efficacy,side effects,and the cumulative survival rates at 48 and 96 wk.RESULTS:Forty-five patients in each group were observed for 96 wk.No significant differences in HBV DNA negative rates and alanine aminotransferase(ALT)normalization rates at weeks 48(χ2=2.12 and 2.88)and96(χ2=3.21 and 3.24)between the two groups were observed.Hepatitis B e antigen seroconversion rate in the LAM+ADV group at week 96 was significantly higher in the ETV group(43.5%vs 36.4%,χ2=4.09,P<0.05).Viral breakthrough occurred in 2 cases(4.4%)by week 48 and in 3 cases(6.7%)by week 96 in the LAM+ADV group,and no viral mutation was detected.In the ETV group,viral breakthrough occurred in 1 case(2.2%)at the end of week 96.An increase in albumin(F=18.9 and 17.3),decrease in total bilirubin and in ALT(F=16.5,17.1 and 23.7,24.8),reduced PT(F=22.7 and 24.5),and improved Child-Turcotte-Pugh and the model for end-stage liver disease scores(F=18.5,17.8,and 24.2,23.8)were observed in both groups.The cumulative rates of mortality and liver transplantation were 16.7%(10/60)and 18.3%(11/60)in the LAM+ADV and ETV groups,respectively.CONCLUSION:Both LAM+ADV combination therapy and ETV monotherapy can effectively inhibit HBV replication,improve liver function,and decrease mortality.     

Rescue therapy for lamivudine‐resistant chronic hepatitis B: Comparison between entecavir 1.0 mg monotherapy,adefovir monotherapy and adefovir add‐on lamivudine combination therapy

Background and Aim: There have been no reports comparing the therapeutic results of adefovir (ADV) and entecavir (ETV) rescue therapy for patients with lamivudine (LAM)‐resistant chronic hepatitis B (CHB). We aimed to compare the cumulative efficacy and resistance of ETV 1.0 mg monotherapy, ADV monotherapy and ADV add‐on LAM combination therapy in LAM‐refractory patients. Methods: One hundred and four patients were included in the following three treatment groups; group 1 (n = 24), LAM was switched to ETV (1.0 mg once a day); group 2 (n = 44), LAM was switched to ADV (10 mg once a day); and group 3 (n = 36), ADV was added to LAM (10 mg once a day). Results: After 6 months of rescue treatment, alanine aminotransferase normalization was observed in 75.0%, 65.9% and 74.3% of patients receiving ETV monotherapy, ADV monotherapy and ADV add‐on therapy, respectively. A significantly higher log₁₀HBV‐DNA drop at 6 months occurred in the ADV add‐on group compared with the ETV group. The rate of HBV‐DNA polymerase chain reaction undetectability (<300 copies/mL) 6 months after initiation of ETV monotherapy, ADV monotherapy and ADV add‐on therapy was 33.3%, 27.3% and 68.6%, respectively (P = 0.003). The cumulative HBeAg seroconversion rate was significantly higher in ADV add‐on/ADV monotherapy groups compared with the ETV monotherapy group (P = 0.022). Viral breakthrough and genotypic resistance were detected in six (25.0%) and six (13.6%) patients in the ETV and ADV monotherapy groups, whereas no cases of genotypic resistance were detected in ADV add‐on group 24 months after initiation of antiviral treatment (P < 0.01). Conclusion: Adefovir add‐on treatment in patients with LAM‐resistant CHB suppresses HBV replication more effectively than ETV or ADV monotherapy. Additionally, no genotypic resistance was detected in the ADV add‐on group.     

Response to tenofovir monotherapy in chronic hepatitis B patients with prior suboptimal response to entecavir

Summary. Both entecavir (ETV) and tenofovir (TDF) are potent antiviral agents for hepatitis B virus (HBV). Suboptimal response (SOR) following antiviral therapy is associated with an increased risk of subsequent treatment failure and viral resistance. It remains unclear whether switching to TDF is a reasonable approach in patients with SOR to ETV treatment. This study was aimed to determine how HBV patients with SOR to ETV respond to TDF monotherapy. Data of patients with SOR to ETV (failure to achieve >1 log₁₀ HBV‐DNA reduction during the last 24 weeks of ETV treatment) who were switched to TDF monotherapy during 2005 and 2010 were reviewed. Treatment adherence was assessed by pill‐count. Fourteen patients (2.9%) were identified from a total cohort of 482 ETV‐treated patients. All 14 patients were Chinese and were infected with HBV genotype C (71%) or B (29%). Nine patients were men, and the median age was 41.5 years (19–64). Twelve were treatment naïve (one lamivudine‐ and one peginterferon‐experienced patient); 85.7% were HBeAg positive. The median baseline HBV‐DNA was 7.55 (5.30–9.40) log₁₀ copies/mL, and 57% had abnormal serum alanine aminotransferase (ALT) levels. Precore and/or basal core promoter mutations were detected in four patients, whereas no genotypic resistance was detected at baseline and before switching to TDF. The median duration of ETV treatment was 64.5 (26–126) weeks. The median HBV‐DNA at the time of switching to TDF was 3.69 (3.00–4.90) log₁₀ copies/mL. The median HBV‐DNA reduction from baseline and during the last 6‐month observation period prior to switching to TDF was 4.04 (0.51–6.06) log₁₀ and 0.43 (?0.09–1.13) log₁₀ copies/mL, respectively. After the switching to TDF, all 14 patients (100%) achieved undetectable HBV‐DNA and ALT normalization within a median duration of 30 weeks. In 12 patients who were HBeAg positive, HBeAg seroconversion was observed in two patients after TDF treatment of 75‐ and 84‐weeks duration. There was no virological breakthrough observed after switching to TDF with a median follow‐up period of 50 (24–160) weeks. TDF treatment was safe and well tolerated. In conclusion, suboptimal response to ETV is rare (approximately 3%). TDF monotherapy is safe and very effective in the management of HBV patients with SOR to ETV.     

Australian tertiary care outcomes of entecavir monotherapy in treatment naive patients with chronic hepatitis B

AIM:To evaluate the long-term treatment outcomes of entecavir monotherapy in treatment naive patients in an Australian tertiary care setting. METHODS:A retrospective analysis of treatment naive patients receiving entecavir monotherapy through Westmead Hospital was performed.Patients were excluded if they had received previous treatment with another nucleoside or nucleotide analogue,were pregnant or less than 18 years old. RESULTS:Out of 336 patients,163 patients fulfilled the selection criteria.Range of follow up was 3-46 mo (mean 26 mo).134 patients(82.2%)had pre-treatment biopsies,with 26 patients(16.0%)demonstrating F3-4 fibrosis.In total,153 patients(93.9%)achieved at least Partial Virological Suppression(PVS),with 134 patients (82.2%)achieving complete virological suppression. The cumulative CVS and PVS rates at 36 mo were 82.1%and 96.4%,respectively.3 patients(1.8%)failed to achieve PVS,while 5 patients(3.0%)developed virological rebound.128 patients(78.5%)maintained CVS throughout follow up.Predictors of CVS included lower baseline DNA level(P=0.001),hepatitis B virus e antigen negative status(P=0.001)and increasing age at treatment(log rank 0.001).No significant adverse effects were reported necessitating cessation of entecavir. CONCLUSION:Entecavir monotherapy is efficacious and safe in an Australian tertiary care setting.Resistance and rebound rates are very low.This is similar to data from controlled and uncontrolled trials around the world.     

Efficacy of hepatitis B vaccination and interferon-alpha-2b combination therapy versus interferon-alpha-2b monotherapy in children with chronic hepatitis B

BACKGROUND: Although interferon (IFN) has been approved in the treatment of chronic hepatitis B in children, it is effective only in 30-40% of patients. In some studies it has been suggested that therapeutic use of anti-hepatitis B virus (HBV) vaccine may be beneficial in patients with chronic hepatitis B. The aim of the present study was to compare the efficacy of hepatitis B vaccination and IFN-alpha-2b in combination and IFN-alpha-2b monotherapy in children with chronic hepatitis B. METHODS: Fifty treatment-naive children with chronic hepatitis B infection were randomly assigned to receive either 5 million units/m(2) recombinant IFN-alpha-2b subcutaneously three times per week for 9 months, and pre-S2/S vaccine at the beginning and 4 and 24 weeks after initiation of IFN therapy (n = 25) or recombinant IFN-alpha-2b (5 million units/m(2) subcutaneously thrice weekly) alone for 9 months (n = 25). Children were followed for at least 6 months after the end of therapy. RESULTS: There was no statistically significant difference in the mean alanine aminotransferase levels, histologic activity index and fibrosis scores between combination and IFN monotherapy groups at the end of the therapy and end of the follow-up period. When combination and monotherapy groups were compared, the mean HBV-DNA values were significantly reduced in combination group at the end of the therapy (P = 0.004), but no statistically significant difference was found at the end of the follow up. Sustained HBeAg seroconversion with clearance of HBV-DNA was obtained in 13 of 25 children (52%) treated with combination therapy, and in eight of 25 patients (32%) treated with IFN monotherapy (P = 0.251). CONCLUSION: Although the difference was statistically insignificant, the sustained response rates were better in the combination therapy group than in the monotherapy group. The potential benefit of combining IFN and hepatitis B vaccine should be investigated in further studies with different regimens of combination therapy.     

恩替卡韦治疗慢性乙型肝炎病毒携带者近期疗效观察

目的 观察恩替卡韦治疗慢性HBV携带者的近期疗效与安全陛,探讨慢性HBV携带者抗病毒治疗的临床意义. 方法 慢性HBV携带者47例,慢性乙型肝炎患者46例,诊断均符合“慢性乙型肝炎防治指南(2010年版)”.两组患者均给予恩替卡韦分散片0.5 mg/d口服治疗,观察两组患者治疗第4、12、24、48周血清学应答率、生物化学应答率与突破率的差异,并观察药物相关不良事件发生率.数据均使用SPSS17.0统计分析软件进行,分别采用t检验和x2检验.结果 第4、12、24、48周完全病毒学应答率:慢性HBV携带者组分别为14.9％、51.1％、76.6％和97.9％;慢性乙型肝炎患者组分别为,17.4％、63.0％、89.1％和100.0％,两组间各时间点比较,差异均无统计学意义.第4、12、24、48周部分病毒学应答率:慢性HBV携带者组分别为42.6％、57.4％、85.0％和100.0％;慢性乙型肝炎患者组分别为47.8％、65.2％、89.1％和100.0％,两组间各时间点比较,差异均无统计学意义.第4、12、24、48周HBeAg阴转率:慢性HBV携带者组分别为0、2.1％、4.3％和8.5％;慢性乙型肝炎患者组分别为4.4％、8.7％、13.0％和21.7％,两组间各时间点比较,差异均无统计学意义.第4、12、24、48周HBeAg血清学转换率:慢陛HBV携带者组分别为0、0、2.1％和6.4％;慢性乙型肝炎患者组分别为0、4.4％、10.9％和17.4％,两组间各时间点比较,差异均无统计学意义.HBsAg阴转率与血清学转换率,两组各观察时段均为0.慢性乙型肝炎患者组第4、12、24、48周ALT复常率分别为26.1％、65.2％、91.3％和97.8％.两组患者均无病毒学突破和生物化学突破病例.两组患者均未观察到肾毒性、骨髓抑制、横纹肌溶解或其他药物相关不良事件.结论 采用恩替卡韦分散片治疗慢性HBV携带者近期疗效好、安全.