Combination Therapy with Pegylated Interferon alpha-2b and Adefovir Dipivoxil in HBeAg-positive Chronic Hepatitis B versus Interferon Alone: A Prospective, Randomized Study

Currently available monotherapies of oral nucleoside/nucleotide analogs or interferon are unable to achieve a sustained and effective response in most of patients with chronic hepatitis B（CHB）. The objective of the present study was to compare the efficacy and safety of pegylated interferon（Peg-IFN） alpha-2b plus adefovir dipivoxil combination therapy versus Peg-IFN alpha-2b alone. Sixty-one HBeAg-positive chronic hepatitis B patients were randomized to receive Peg-IFN alpha-2b alone（1.5 μg/kg once weekly） or Peg-IFN alpha-2b plus adefovir（10 mg daily） for up to 52 weeks. Efficacy and safety analyses were performed on all participants who received at least one dose of study medication. The rate of HBeAg seroconversion and undetectable HBV-DNA were evaluated after 52 weeks of therapy. At the end of treatment, 11 of 30（36.7%） patients receiving combination therapy achieved HBeAg seroconversion versus 8 of 31（25.8%） in the monotherapy group（P=0.36）. In contrast, the percentage of patients with undetectable serum HBV DNA was significantly higher in the combination group than in the monotherapy group（76.7% vs. 29.0%, P〈0.001）. Thyroid dysfunction was more frequent in the combination group than in the monotherapy group（P〈0.05）. In HBeAg-positive CHB, combination of Peg-IFN alpha-2b and adefovir for 52 weeks resulted, at the end of treatment, in a higher virological response but without significant impact on the rate of HBeAg seroconversion and possibly an adverse effect on thyroid function.

Efficacy compared between entecavir and adefovir dipivoxil on HBeAg-positive nucleos(t)ide-naive patients with chronic hepatitis B at week 12 and week 48

Objective:To evaluate the efficacy of entecavir and adefovir dipivoxil on HBeAg-positive nucleos(t)ide-naive patients with chronic hepatitis B with the method of Meta analysis.Methods:We searched PUBMED,EMBASE,CNKI (China National Knowledge Infrastructure),the Cochrane Central Register of Controlled Trials and the Cochrane Database of Systematic Reviews with reference to all data documented before May 2010.The dosage of entecavir and adefovir dipivoxil was 0.5 mg/d and 10 mg/d,respectively.Heterogeneity was examined by Chi-square test,the relative risk calculated and forest plot drawn.Rates of undetected serum HBV DNA,serum alanine aminotransferase (ALT) normalization,HBeAg clearance,HBeAg seroconversion and adverse effect occurrence were analyzed.Results:Six articles were included,which fit well in with this study.Meta analysis showed that the rate of undetected serum HBV DNA(P=0.000 2 at week 12,P=0.002 at week 48)and that of serum ALT normalization(P=0.04 at week 12,P=0.008 at week 48)in the entecavir group were higher than those in the adefovir dipivoxil group.However,no statistic significance existed between the two groups in the rate of HBeAg clearance (P=0.17),the rate of HBeAg seroconversion(P=0.53)or the rate of adverse effect occurrence(P=0.92)at week 48.Conclusion:Entecavir was superior to adefovir dipivoxil in decreasing serum HBV DNA and normalizing serum ALT in the HBeAg-positive nucleos(t)ide-naive patients with chronic hepatitis B.

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.

Surgical treatment of HCC in a patient with lamivudine-resistant hepatitis B cirrhosis with adefovir dipivoxil

We describe a 77-year-old woman with chronic hepatitis B who became resistant to lamivudine.She was started on adefovir(10 mg daily)while still continuing lamivudine therapy.Four mo later her liver function improved and serum Hepatitis B virus(HBV)-DNA level became undetectable.Three years after the start of additional adefovir treatment,hepatocellular carcinoma (HCC)was detected and the patient underwent a successful hepa-tectomy.Our findings suggest tha-t the addition of adefovir to ongoing lamivudine therapy cannot completely suppress hepatocarcinogenesis,but is useful for improving liver function in patients with lamivudine-resistant HBV-related cirrhosis,allowing HCC surgery.

Resistant mutants induced by adefovir dipivoxil in hepatitis B virus isolates

AIM: To investigate the loci of adefovir dipivoxil (ADV)-induced resistance in hepatitis B virus (HBV) isolates and optimize the management of ADV-treated patients.

Relationship Between Serum DNA Replication, Clinicopathological Characteristics and Prognosis of Hepatitis B Virus-associated Glomerulonephritis with Severe Proteinuria by Lamivudine Plus Adefovir Dipivoxil Combination Therapy

Objective To explore the relationship between HBV DNA and the clinical manifestations, pathological types, injury severity, and prognosis with HBV-GN. Methods 102 patients with HBV-GN were divided into 3 groups, according to the serum titer of the HBV DNA. 24-h urine protein excretion, and other parameters were measured. Renal biopsy were performed. The association between HBV DNA and the pathological stage of membranous nephropathy was analyzed in 78 patients with HBV-MN. 24-h urine protein excretion was used for the evaluation of the prognosis, and the relationship between HBV DNA and prognosis were analyzed. Results Several findings were demonstrated with the increase of serum HBV DNA： 24-h urine protein excretion, plasma cholesterol, and triglycerides increased significantly（P〈0.05）, while the plasma level of albumin decreased significantly（P〈0.05）; The changes of serum creatinine, C3 and C4 were found but no statistical significance. Glomerular deposition of HBVAg increased, and the pathological injury was more severe. The clinical remission rate was lower in the high replication group after treatment as compared with the low replication group（P〈0.01）. Conclusion With the increase of serum HBV DNA, the urine protein excretion and the kidney injury were more severe, and the clinical remission rate was decreased.

Short-term overlap lamivudine treatment with adefovir dipivoxil in patients with lamivudine-resistant chronic hepatitis B

AIM： To evaluate the efficacy of short-term overlap lamivudine therapy with adefovir in patients with lamivudine-resistant and naive chronic hepatitis B, we compared patients receiving overlap therapy with those receiving adefovir alone. METHODS： Eighty patients who had received lamivudine treatment for various periods and had a lamivudineo resistant liver function abnormality were enrolled. Forty of these patients received adefovir treatment combined with lamivudine treatment for ≥ 2 mo, while the other 40 received adefovir alone. We assessed the levels of hepatitis B virus （HBV） DNA at 0, 12 and 48 wk and serum alanine aminotransferase （ALT） levels after 0, 12, 24 and 48 wk of adefovir treatment in each group. RESULTS： We found serum ALT became normalized in 72 （87.5%） of the 80 patients, and HBV DNA decreased by ≥ 2 Ioglo copies/mL in 60 （75%） of the 80 patients at the end of a 48-wk treatment. HBV DNA levels were not significantly different between the groups. The improvements in serum ALT were also not significantly different between the two groups. CONCLUSION： These findings suggest short-term overlap lamivudine treatment results in no better virological and biological outcomes than non-overlap adefovir monotherapy.

De novo combination therapy with lamivudine and adefovir dipivoxil in chronic hepatitis B patients

AIM:To investigate the appropriate time for combination therapy in HBeAg positive chronic hepatitis B(CHB) patients with decompensated cirrhosis.METHODS:Thirty HBeAg positive CHB patients with decompensated cirrhosis were enrolled in the study.All of the patients were given 48 wk combination therapy with lamivudine(LAM) and adefovir dipivoxil(ADV) .Briefly,10 patients were given the de novo combination therapy with LAM and ADV,whereas the other 20 patients received ADV in addition to LAM after hepatitis B virus(HBV) genetic mutation.RESULTS:Serum alanine aminotransferase and total bilirubin were both improved in the two groups at 4,12,24 and 48 wk after treatment.Serum albumin was also improved at 24 and 48 wk after combination therapy in both groups.The serum HBV DNA level wasstill detectable in every patient in the two groups at 4 and 12 wk after combination treatment.However,in the de novo combination group,serum HBV DNA levels in 4(40%) and 9(90%) patients was decreased to below 1×10 3 copies/mL at 24 and 48 wk after the combination treatment,respectively.In parallel,serum HBV DNA levels in 2(20%) and 8(40%) patients in the add-on combination group became undetectable at 24 and 48 wk after combination treatment,respectively.Furthermore,6(60%) patients in the de novo combination group achieved HBeAg seroconversion after 48 wk treatment,whereas only 4(20%) patients in the add-on combination group achieved seroconversion.Child-Pugh score of patients in the de novo combination group was better than that of patients in the add-on combination group after 48 wk treatment.Moreover,patients in the de novo combination group had a significantly decreased serum creatinine level and elevated red blood cell counts.CONCLUSION:De novo combination therapy with LAM and ADV was better than add-on combination therapy in terms of Child-Pugh score,virus inhibition and renal function.

Adefovir dipivoxil for the treatment of lamivudine-resistant hepatitis B mutants

BACKGROUND: The recurrence of chronic hepatitis B after liver transplantation results in increased risk for graft failure and death of patients. Lamivudine has been shown to be effective in the treatment of chronic hepatitis B, but resistance to this agent is common after prolonged administration. METHODS: One patient with chronic hepatitis B virus (HBV) infection developed resistance to lamivudine after 15 months of treatment. The resistance was confirmed by mutation in the HBV DNA polymerase gene. The patient was treated subsequently with adefovir dipivoxil for 7 months. RESULT: HBV DNA and HBsAg were tested negative, but HBeAb and HBsAb were positive. CONCLUSION: This study provides an evidence that adefovir dipivoxil can be effective in the treatment of lamivudine-resistant HBV mutants.

Observation on the effect of adefovir dipivoxil in combined with lamivudine in the treatment of hepatitis B cirrhosis

Objective:To explore the effect of adefovir dipivoxil in combined with lamivudine on the liver function in patients with hepatitis B cirrhosis and the antiviral efficacy.Methods:A total of 156 patients with hepatitis B cirrhosis who were admitted in our hospital were included in the study and randomized into the treatment group and the control group with 78 cases in each group. The patients in the treatment group were given adefovir dipivoxil in combined with lamivudine, while the patients in the control group were given entecavir. After 12-month treatment, the efficacy was evaluated. The liver function, serum virology indicators, and AFP before and after treatment in the two groups were compared. The adverse reactions during the treatment process were recorded.Results: The serum GTP, ALT, AST, and TBIL levels after treatment in the two groups were significantly reduced when compared with before treatment (P<0.05);moreover, ALT and TBIL levels in the treatment group were significantly lower than those in the control group (P<0.05). HBeAg, HBV-DNA, and AFP levels after treatment in the two groups were significantly reduced when compared with before treatment (P<0.05), HBeAg and AFP levels in the treatment group were significantly lower than those in the control group (P<0.05), and the comparison of HBV-DNA between the two groups was not statistically significant (P>0.05). ALT normalization rate and HBeAg negative conversion rate after treatment in the treatment group were significantly higher than those in the control group (P<0.05). The comparison of HBV-DNA negative conversion rate and HBeAg conversion rate between the two groups was not statistically significant (P>0.05). No obvious drug adverse reactions and liver function damage occurred during the treatment process in the two groups. Conclusions:Adefovir dipivoxil in combined with lamivudine can significantly improve the liver function and serum virology indicators in patients with hepatitis B cirrhosis, with antiviral efficacy significantly superior to that by entecavir.

聚乙二醇干扰素α-2b联合替诺福韦二吡呋酯治疗HBeAg阳性慢性乙肝的临床效果

目的观察聚乙二醇干扰素α-2b联合替诺福韦二吡呋酯治疗乙肝e抗原(HBeAg)阳性慢性乙肝的临床效果。方法选取2019年1月—2023年1月厦门市第三医院收治的HBeAg阳性慢性乙肝患者80例,按随机数字表法分为联合组(n=40)和单药组(n=40)。单药组予替诺福韦二吡呋酯治疗,联合组在单药组基础上予聚乙二醇干扰素α-2b治疗,2组均持续治疗6个月。比较2组HBeAg及乙肝病毒脱氧核糖核酸(HBV-DNA)转阴率,治疗前后肝功能指标[天冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)、总胆红素(TBil)]、血清炎性因子[肿瘤坏死因子-α(TNF-α)、白介素(IL)-6、IL-10]、肝纤维化指标[透明质酸(HA)、Ⅲ型前胶原(PCⅢ)、层粘连蛋白(LN)]及不良反应。结果与单药组比较,联合组HBeAg及HBV-DNA转阴率均更高(χ^(2)=10.208,P=0.001;χ^(2)=4.507,P=0.034);与治疗前比较,治疗6个月后,2组AST、ALT、TBil、TNF-α、IL-6、IL-10、HA、PCⅢ、LN水平均降低,且联合组低于单药组(P<0.01)。联合组与单药组不良反应总发生率比较差异不明显(12.50%vs.7.50%,χ^(2)=0.139,P=0.709)。结论HBeAg阳性慢性乙肝患者应用聚乙二醇干扰素α-2b联合替诺福韦二吡呋酯治疗效果确切,有助于提高HBeAg、HBV-DNA转阴率,改善肝功能,减轻炎性反应及肝纤维化程度,且安全性较高。

HBeAg/HBeAb双阳性慢性乙型肝炎患者血清HBV RNA的变化及临床转归分析

目的探讨HBeAg/HBeAb双阳性慢性乙型肝炎(CHB)患者血清HBV RNA的变化及临床转归分析。方法选取2020年6月至2022年8月诊治的102例HBeAg/HBeAb双阳性CHB患者作为研究对象,设立为双阳组,同期选取51例HBeAg阳性、HBeAb阴性的CHB患者和52例HBeAg阴性、HBeAb阳性的CHB患者设立为对照1组和对照2组,对比血清HBV RNA变化。根据治疗方法不同将双阳组分为干扰素组(予以干扰素治疗,n=52)和恩替卡韦组(予以恩替卡韦治疗,n=50),对比HBeAg、HBeAb浓度及HBeAg转阴,HBeAb仍阳性、HBeAg和HBeAb同时转阴、HBeAg未转阴,HBeAb仍阳性占比。结果双阳组的HBV RNA水平均高于对照1、2组(P<0.05)。治疗前,干扰素组和恩替卡韦组的HBeAg、HBeAb、HBV RNA比较,差异无统计学意义(P>0.05),治疗后,干扰素组的HBeAg、HBeAb、HBV RNA低于恩替卡韦组(P<0.05)。干扰素组的HBeAg转阴,HBeAb仍阳性占比高于恩替卡韦组,而HBeAg未转阴,HBeAb仍阳性占比低于恩替卡韦组(P<0.05)。2组HBeAg和HBeAb同时转阴占比比较,差异无统计学意义(P>0.05)。ROC曲线分析显示,HBV RNA预测CHB患者HBeAg/HBeAb双阳性和临床转归不良的AUC值分别为(0.936、0.954,P<0.05);敏感度分别为100.00%、93.10%;特异度分别为88.70%、76.70%。结论HBV RNA在HBeAg/HBeAb双阳性CHB患者中呈高表达趋势,观察其水平变化有助于为预测临床转归提供指导。

Clinical significance of hepatitis B e antigen level measurement during long-term lamivudine therapy in chronic hepatitis B patients with e antigen positive

AIM： To determine the changes of quantitative hepatitis B e antigen （HBeAg） that predicts early detection of non-response or breakthrough to long-term lamivudine （LAM） therapy. METHODS： Among HBeAg positive chronic hepatitis B patients who failed to achieve HBeAg seroconversion within 12 too, we retrospectively analyzed 220 patients who had received LAM more than 24 too. RESULTS： The mean duration of LAM therapy was 36 （range, 24-72） mo. HBeAg seroconversion after the first 12 mo of LAM therapy was achieved in 53 （24.1%） patients. Viral breakthrough was observed in 105 （47.7%） patients. To find out whether the changing patterns of HBeAg levels can predict the outcome of LAM therapy, we analyzed the reduction rates of HBeAg levels during LAM therapy. Using the decrease more than 90% of pretreatment HBeAg levels, the sensitivity and specificity of response were 96.2% and 70.1%, respectively. Patients were divided into 3 groups according to the reduction patterns of the decrease of quantitative HBeAg： decrescendo, decrescendo-crescendo, no change or fluctuating groups. The optimal time to predict non-response or breakthrough was the first 9 mo of therapy. At 9 mo of therapy, 49 （92.5%） of 53 patients who had achieved HBeAg seroconversion were included in the decrescendo group. On the contrary, in the no change or fluctuating group, only four （7.5%） had achieved HBeAg seroconversion. Among patients who did not show the continuous decrease of HBeAg levels at 9 too, 95.2% （negative predictive value） failed to achieve HBeAg seroconversion. CONCLUSION： Almost all patients who failed to show a continuous decrease of HBeAg levels at 9 mo of LAM therapy were non-response or breakthrough. Therefore, monitoring changes of HBeAg levels during LAM therapy in HBeAg positive chronic hepatitis B may be valuable for identifying patients who are at high risk of non-response or breakthrough.

Impact of Lamivudine plus Adefovir therapy in chronic hepatitis B Iranian patients, resistant to Lamivudine treatment alone, on disease inhibition: A pilot study

AIM: To evaluate the impact of combination therapy with Lamivudine and Adefovir for treatment of chronic hepatitis B in Lamivudine-resistant patients. METHODS: Among the 110 adult chronic hepatitis B Iranian patients whom were treated with Lamivudine, for 36 months, nineteen patients (17%) with no any biochemical and viral responses to Lamivudine alone, were selected and enrolled in the study. Due to resistancy, Adefovir was added to Lamivudine, and continued for 30 months. We measured HBV_DNA viral load and serum AST, ALT in 0, 12, 24, 30 and 0, 6, 12, 18, 24, 30 months, respectively. RESULTS: Between biochemical and viral characteristics, Repeated Measure analysis identified just biochemical markers— Aspartate Aminotransferase level (AST) (P = 0.002) and Alanine Aminotransferase level (ALT) (P = 0.007) —as predictors of response to treatment, while, viral marker—HBV DNA load—was not statistically significant (P = 0.128). CONCLUSIONS: Treatment for a long time, such as 21.5 ± 8.8 months, with Lami- vudine and Adefovir, can cause liver enzymes including AST and ALT, decreasing and being normal. But, this finding is not indicative, for HBV-DNA viral load.

白花香莲解毒方联合阿德福韦酯治疗HBeAg阳性慢性乙型肝炎的临床研究

目的通过观察壮药白花香莲解毒方联合阿德福韦酯对乙肝病毒e抗原(HBeAg)阳性的慢性乙型肝炎患者的影响,评估其临床疗效。方法采用多中心随机临床研究方法,240例HBeAg阳性的慢性乙型肝炎患者随机分为试验组和对照组,每组120例。对照组给予阿德福韦酯胶囊10mg,每日1次,试验组在对照组治疗基础上加用白花香莲解毒方,每日2次,疗程均为48周,观察治疗12、24、48周时两组患者的病毒学、血清学、生化学、慢性肝病量表(CLDQ)评分及不良事件。结果 (1)乙肝病毒脱氧核糖核酸(HBVD-NA)下降值、病毒应答率及阴转率:从治疗12周始,试验组HBVDNA下降的对数值与对照组比较,差异有统计学意义(P<0.05);试验组治疗12、24周病毒应答率分别为62.71%、77.97%,对照组为49.57%、67.52%,差异有统计学意义(P<0.05);而治疗48周,两组总的病毒应答率差异无统计学意义(P>0.05);试验组治疗12、24、48周的HBVDNA阴转率分别为22.03%、41.52%、55.08%,对照组为11.11%、21.37%、30.77%,差异有统计学意义(P<0.05)。(2)HBeAg/抗-HBe血清应答率:治疗24、48周试验组HBeAg血清应答率分别为26.27%、39.83%,对照组为13.68%、29.06%,差异有统计学意义(P<0.05);治疗48周,试验组HBeAg阴转率为22.03%,对照组为11.96%,差异有统计学意义(P<0.05)。(3)血清生化应答率:治疗24、48周,试验组血清生化应答率分别为74.58%、87.29%,对照组为60.68%、79.49%,差异有统计学意义(P<0.05)。(4)CLDQ评分:两组患者治疗后CLDQ评分均升高,与治疗前比较,差异有统计学意义(P<0.05);试验组治疗24、48周的CLDQ评分均优于对照组,差异有统计学意义(P<0.05)。(5)不良反应:两组患者主要不良反应为头痛、腹痛、恶心;并发生磷酸肌酸激酶升高9例,发生率为3.83%。结论白花香莲解毒方联合阿德福韦酯治疗HBeAg阳性慢性乙型肝炎患者,能显著提高对HBVDNA的抑制作用,增加HBeAg的血清学转换率,加快肝功能的恢复速度,改善生活质量,且安全性高。

回顾性分析拉米夫定联合阿德福韦酯治疗HBeAg阳性失代偿期乙肝肝硬化患者的临床疗效

目的探究拉米夫定联合阿德福韦酯治疗HBeAg阳性失代偿期乙肝肝硬化患者的临床疗效。方法回顾性分析2014年1月~2015年1月收治的HBeAg阳性失代偿期乙肝肝硬化患者,共100例,将给予拉米夫定初始治疗耐药后加用阿德福韦酯挽救治疗的50名患者作为对照组,同时选取给予拉米夫定加阿德福韦酯初始联合治疗的患者50例,作为观察组,比较分析2组治疗的临床疗效。结果观察组患者治疗后HBeAg血清学转阴率26.00%显著高于对照组4.00%（P〈0.05）;观察组患者治疗后12周（9.63±1.42）、24周（8.57±1.45）、48周（7.43±1.57）Child-Pugh分级评分分数显著低于对照组（9.74±1.21）、（9.45±1.33）、（8.57±1.04）（P〈0.05）;观察组患者治疗后血清中HBV-DNA载量（2.23±1.25）显著低于对照组（5.18±1.63）,且观察组治疗后（2.23±1.25）血清中HBV-DNA载量显著低于治疗前（6.47±1.55）（P〈0.05）。结论治疗HBeAg阳性失代偿期乙肝肝硬化患者采用初始联合拉米夫定和阿德福韦酯治疗,临床效果显著,HBeAg血清学转阴率高,且Child-Pugh分级评分分数降低,改善肝脏储备功能,血清中HBV-DNA载量降低。

阿德福韦对HBeAg阳性慢性乙型肝炎患者Th1和Th2相关细胞因子的影响

目的观察HBeAg阳性慢性乙型肝炎患者阿德福韦治疗前后不同时相点血清IFN-γ、IL-4的水平、Th1/Th2比值以探讨阿德福韦治疗对机体的免疫功能的影响。方法采集30例阿德福韦治疗前、治疗16周、52周和132周患者血清,其中完全应答组14例,非完全应答组16例及健康对照组10例,ELISA检测IFN-γ和IL-4的水平。结果完全应答组各时相点IFN-γ水平显著高于部分应答组(P均<0.05)及正常对照组(P<0.05),部分应答组与健康对照组相比无差异(P>0.05);完全应答组IL-4水平在治疗后逐渐下降,部分应答组变化不大;两组Th1/Th2比值均有所上升,但完全应答组升高显著。结论阿德福韦治疗后慢性乙型肝炎患者细胞免疫应答有一定程度的恢复。

替比夫定与恩替卡韦治疗HBeAg阳性慢性乙型肝炎的对比研究

目的:观察替比夫定与恩替卡韦治疗HBeAg阳性慢性乙型肝炎患者的临床疗效及安全性。方法:将140例慢性乙型肝炎患者随机分为替比夫定治疗组75例,恩替卡韦组治疗组65例,疗程均为72周。观察两组治疗8、12、24、52、72周时ALT复常率、HBVDNA低于检测下限值率、HBeAg血清学转换率及药物的安全性。结果:治疗8、12、24、52、72周时ALT复常率、HBVDNA低于检测下限值率两组比较差异均无统计学意义(均P>0.05);治疗8、12、24周时HBeAg血清学转换率两组比较差异均无统计学意义(均P>0.05);治疗52周及72周时两组HBeAg血清学转换率分别为30.7%和16.9%(P<0.05),36.0%和23.1%(P<0.05)。两组均未发现明显不良反应。结论:替比夫定与恩替卡韦治疗HBeAg阳性慢性乙型肝炎均具有快速强效抗病毒作用,近期ALT复常率、HBVDNA低于检测下限值率、HBeAg血清学转换率均无明显差异,但治疗52、72周时替比夫定组HBeAg血清学转换率高于恩替卡韦组。两药治疗的安全性和耐受性良好。

替比夫定与阿德福韦酯治疗HBeAg阳性慢性乙型肝炎的疗效观察

目的比较替比夫定与阿德福韦酯治疗HBeAg阳性慢性乙型肝炎的疗效和安全性。方法 175例HBeAg阳性慢性乙型肝炎患者被随机分为替比夫定组(85例)和阿德福韦酯组(90例),比较两组在治疗后48周时的疗效。结果治疗后12周、24周、36周和48周时,替比夫定治疗患者HBV DNA水平低于阿德福韦酯组(P<0.01),HBV DNA转阴率和ALT复常率均高于阿德福韦酯组(P<0.05或P<0.01);治疗后12周、24周和36周HBeAg转阴或血清学转换率和完全应答率也高于阿德福韦酯组(P<0.05或P<0.01);治疗48周,替比夫定组有2例,阿德福韦酯组有1例出现病毒学反弹;两组均有良好的安全性。结论替比夫定较阿德福韦酯有更强的抑制HBV作用,其治疗可提高HBeAg转阴或血清学转换率和完全应答率。

替比夫定治疗HBeAg阳性慢乙肝患者的HBeAg血清转换预测因素探讨

目的:观察替比夫定治疗HBeAg阳性慢性乙型肝炎52周的临床疗效并探讨HBeAg血清转换预测因素。方法:100例入组患者,口服替比夫定600 mg,每天1次,治疗52周进行疗效评估。以52周出现HBeAg血清转换有无为应变量,以年龄、性别、基线ALT、基线HBeAg、基线HBV DNA、治疗期间HBV DNA变化模式(12、24、36周HBV DNA低于检测下限)、治疗期间HBeAg变化模式(12、24、36周HBeAg下降>1 log及12、24、36周HBeAg下降>2 log)14个因素作为自变量进行多因素Lo-gistic回归分析。结果:替比夫定治疗52周完全病毒学应答率81%,HBeAg血清转换率31%,病毒学突破率4%。治疗52周时HBeAg血清转换与基线HBeAg值相关(P<0.01),而与基线ALT值和基线HBV DNA无相关性。其中基线HBeAg≤500 PEIU/ml与HBeAg>500 PEIU/ml的患者52周时HBeAg血清转换率有统计学差异(P<0.01)。多因素Logistic回归分析显示3个因素进入Logistic回归方程,按其作用强弱依次为:24周时HBeAg下降>2 log PEIU/ml;12周时HBeAg下降>1 log PEIU/ml;基线HBeAg值,HBV DNA未能进入。结论:替比夫定治疗HBeAg阳性慢性乙型肝炎,52周HBeAg血清转换的预测因素以24周HBeAg下降>2 log PEIU/ml的预测效果最强。