Interferon and lamivudine combination therapy versus lamivudine monotherapy for hepatitis B e antigen-negative hepatitis B treatment:a meta-analysis of randomized controlled trials

BACKGROUND: It has been demonstrated that only a minority of patients with hepatitis B e antigen (HBeAg) negative chronic hepatitis B (CHB) obtain a sustained response after either interferon (IFN) or nucleos (t)ide analogue monotherapy. Therefore, combination therapy of drugs with synergistic antiviral effects was proposed to have a sustained response in these patients. We compared the effect and safety of lamivudine monotherapy and its combination with IFN including conventional interferon (CON-IFN) and pegylated interferon (PEG-IFN) for HBeAg-negative CHB patients. DATA SOURCES: A group of three independent reviewers identified 9 eligible randomized controlled trials through electronic searches (MEDLINE, OVID, EMBASE, the Cochrane Library Clinical Trials Registry, and the Chinese Medical Database), manual searches, and contact with experts. Sustained virological and biochemical responses were defined as primary efficacy measures. We performed quantitative meta-analyses to assess differences between CON-IFN plus lamivudine combination and lamivudine monotherapy groups. RESULTS: No greater sustained virological and biochemical rates were found in patients receiving CON-IFN/lamivudine combination therapy [29.1% vs. 26.7%, odds ratio (OR)=0.98, 95% confidence interval (CI) 0.65-1.50, P=0.94, and 41.8% vs. 40.3%, OR=1.13, 95% CI 0.78-1.65, P=0.51, respectively],though a reduced YMDD mutation rate was achieved in the combination group [8.39% vs. 30.0%, OR=0.16, 95% CI 0.076-0.33, P<0.001]. However, data from one PEG-IFN trial showed greater sustained virological and biochemical rates in patients receiving combination therapy [response rate 19.5% vs. 6.6%, OR=3.42, 95% CI 1.71-6.84, P<0.001 and 60.0% vs. 44.2%, OR=1.88, 95% CI 1.23-2.85, P=0.003, respectively]. CONCLUSIONS: Addition of CON-IFN to lamivudine did not improve treatment efficacy but suppressed YMDD mutation by lamivudine. Combination of PEG-IFN and lamivudine might increase the sustained response, and further clinical trials are needed for confirmation.

Long-term alpha interferon and lamivudine combination therapy in non-responder patients with anti-HBe-positive chronic hepatitis B:Results of an open,controlled trial

AIM: To investigate the safety and efficacy of long-term combination therapy with alpha interferon and lamivudine in non-responsive patients with anti-HBe-positive chronic hepatitis B.METHODS: 34 patients received combination treatment (1 month lamivudine, 12 month lamivudine+interferon, 6month lamivudine), 24 received lamivudine (12 months),24 received interferon (12 months). Interferon was administered at 6 MU tiw and lamivudine at 100 mg orally once daily. Patients were followed up for 6 months after treatment.RESULTS: At the end of treatment, HBV DNA negativity rates were 88 % with lamivudine+interferon, 99 % with lamivudine and 55 % with interferon, (P=0.004, combination therapy vs. interferon, and P=0.001 lamivudine vs.interferon), and serum transaminase normalization rates were 84 %, 91% and 53 % (P=0.01 combination therapy vs. interferon, and P=0.012 lamivudine vs. interferon). Six months later, HBV DNA negativity rates were 44 % with lamivudine+interferon, 33 % with lamivudine and 25 % with interferon, and serum transaminase normalization rates were 61%, 42 % and 45 %, respectively, without statistical significance. No YMDD variants were observed with lamivudine+interferon (vs. 12 % with lamivudine). The combination therapy appeared to be safe. CONCLUSION: Although viral clearance and transaminase normalization are slower with long-term lamivudine+interferon than that with lamivudine alone, the combination regimen seems to provide more lasting benefits and to protect against the appearance of YMDD variants. Studies with other regimens regarding sequence and duration are needed.

Predictors for Efficacy of Combination Therapy with a Nucleos(t)ide Analogue and Interferon for Chronic Hepatitis B

This study aims to explore the efficacy of interferon-α（IFN-α） combined with either entecavir（ETV） or adefovir（ADV） therapy versus IFN-α mono-therapy for chronic hepatitis B（CHB） patients, and to identify the factors associated with treatment outcomes. Totally, 159 CHB patients receiving interferon-based treatment for 48 weeks were enrolled in this retrospective study, including IFN-α mono-therapy group（group A, n=44）, IFN-α plus ADV group（group B, n=53） and IFN-α plus ETV group（group C, n=62）. The primary measures of efficacy assessments were the changes in HBs Ag. Cox regression analysis was used to identify the predictors of treatment outcomes. The predictive values of the factors were assessed by ROC analysis. For patients with baseline hepatitis B surface antigen（HBs Ag） level 〈1000 IU/m L, the reductions in mean HBs Ag levels at week 48 were greater in group C than that in group A（P〈0.05）. Higher rate of HBeAg seroconversion was achieved in the combined therapy group than in IFN-α mono-therapy group at week 48（P〈0.05）. Two factors were independently associated with HBeAg seroconversion： baseline HBeAg level 〈2.215 log10 index/m L and △HBeAg（decline in HBeAg from baseline） 〉0.175 log10 at week 12. In conclusion, interferon-α plus ETV therapy can accelerate HBs Ag decline as compared with interferon-α mono-therapy in CHB patients with lower baseline HBs Ag levels, and the combination therapy was superior to IFN-α mono-therapy in increasing the rate of HBeAg seroconversion. Baseline HBeAg and △HBeAg at week 12 can independently predict HBeAg seroconversion in patients subject to interferon-based therapy for 48 weeks.

Interferon-伪 plus lamivudine vslamivudine reduces breakthroughs, but does not affect sustained response in HBeAg negative chronic hepatitis B

AIM： To investigate the efficacy of combination treatment of IFN-α and lamivudine compared to lamivudine monotherapy, after 24 mo of administration in HBeAgnegative hepatitis B patients. METHODS： Fifty consecutive patients were randomly assigned to receive IFN-α-2b （5 MU thrice per week, n = 24） plus lamivudine （100 mg daily） or lamivudine only （n = 26） for 24 mo. Patients were followed up for further 6 mo. The primary outcome was the proportion with sustained virological response （undetectable serum HBV DNA concentrations） and or sustained biochemical response （transaminase levels within normal range） at 30 mo （6 mo after the end of therapy）. Secondary end-points were timed from initial virological （biochemical） response to VBR （BBR, respectively） and the emergence of YMDD mutants across the two arms. RESULTS： Five of twenty-four （21%） patients in the combination arm vs 3/26 （12%） in the lamivudine arm had sustained response （i.e., normal serum transaminase levels and undetectable HBV DNA by PCR assay） 6 mo after treatment discontinuation. A reduction in the emergence of YMDD mutants and in the development of virological breakthroughs was observed in patients receMng combination treatment （10% vs46% , P= 0.01 and 14% vs46% , P= 0.03, respectively）. Time from initial virologic response to virologic breakthrough （VBR） was greater among initial responders receiving combination treatment compared to those receiving lamivudine （22.9 mo vs 15.9 mo, respectively; P = 0.005）.CONCLUSION： Our results demonstrate that IFN-α plus lamivudine combination therapy does not increase the sustained response, compared to lamivudine. However, combination therapy reduces the likelihood of VBR due to YMDD mutants and prolongs the time period until the breakthrough development.

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.

Risk for hepatocellular carcinoma in the course of chronic hepatitis B virus infection and the protective effect of therapy with nucleos(t)ide analogues

Hepatocellular carcinoma(HCC) is a major health problem worldwide, representing one of the leading causes of death. Chronic hepatitis B virus(HBV) infection(CHB) is the most important etiologic factor of this tumor, accounting for the development of more than50% of the cases in the world. Primary prevention ofHCC is possible by hepatitis B vaccination conferring protection from HBV infection. However, according to the World Health Organization Hepatitis B Fact sheet N° 204(update of July 2014) globally there exists a large pool of > 240 million people chronically infected with HBV who are at risk for development of HCC. These individuals represent a target population for secondary prevention both of cirrhosis and of HCC. Since ongoing HBV replication in CHB is linked with the progression of the underlying liver disease to cirrhosis as well as with the development of HCC, effective antiviral treatment in CHB has also been evaluated in terms of secondary prevention of HCC. Currently, most patients with active CHB are subjected to long term treatment with the first line nucleos(t)ide analogues entecavir and tenofovir. These compounds are of high antiviral potency and have a high barrier to HBV resistance compared to lamivudine, adefovir dipivoxil and even telbivudine. Many studies have shown that patients under antiviral treatment, especially those in virological remission, develop less frequently HCC compared to the untreated ones. However, the risk for development of HCC cannot be eliminated. Therefore, surveillance for the development of HCC of patients with chronic hepatitis B must be lifelong or until a time in the future when new treatments will be able to completely eradicate HBV from the liver particularly in the early stages of CHB infection. In this context, the aim of this review is to outline the magnitude of the risk for development of HCC among patients with CHB, in the various phases of the infection and in relation to virus, host and environmental factors as evaluated in the world literature. Moreover, the benefits of antiviral treatment of CHB with nucleos/tide analogs, which have changed the natural history of the disease and have reduced but not eliminated the risk of HCC are also reviewed.

Management of chronic hepatitis B infection: Current treatment guidelines, challenges, and new developments

Chronic hepatitis B(CHB)virus infection is a global public health problem,affecting more than 400 million people worldwide.The clinical spectrum is wide,ranging from a subclinical inactive carrier state,to progressive chronic hepatitis,cirrhosis,decompensation,and hepatocellular carcinoma.However,complications of hepatitis B virus(HBV)-related chronic liver disease may be reduced by viral suppression.Current international guidelines recommend first-line treatment of CHB infection with pegylated interferon,entecavir,or tenofovir,but the optimal treatment for an individualpatient is controversial.The indications for treatment are contentious,and increasing evidence suggests that HBV genotyping,as well as serial on-treatment measurements of hepatitis B surface antigen and HBV DNA kinetics should be used to predict antiviral treatment response.The likelihood of achieving a sustained virological response is also increased by extending treatment duration,and using combination therapy.Hence the paradigm for treatment of CHB is constantly evolving.This article summarizes the different indications for treatment,and systematically reviews the evidence for the efficacy of various antiviral agents.It further discusses the shortcomings of current guidelines,use of rescue therapy in drug-resistant strains of HBV,and highlights the promising clinical trials for emerging therapies in the pipeline.This concise overview presents an updated practical approach to guide the clinical management of CHB.

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.

The “return” of hepatitis B

There has been a significant advance in the treatment of chronic Hepatitis B virus （HBV） infection and the following drugs were approved for therapy： Conventional interferon （IFN）, pegylated interferon alfa-2a （PEG IFN α2a）, lamivudine, adefovir and entecavir. Compared to nucleoside analogues IFN induces higher rates of sustained remission and HBsAg loss. Conventional TFN in lower doses （1, 5-3 MIU） tiw for 4-6 mo has similar efficacy in comparison to ＂standard IFN therapy＂. Longer IFN treatment is a significant factor for longterm remission in HBeAg-negative CHB, but the higher actual IFN dose is not such a factor. PEG IFN is superior to conventional IFN. There is no significant difference between PEG IFN α2a at doses 90 mcg/wk and 180 mcg/wk in HBeAg-positive patients. These results provide a rational for further clinical trials with lower doses PEG IFN α2a given in prolonged course as maintenance or intermittent treatment. Serious new problems arose after the introduction of nucleoside/nucleotide analogues in clinical practice. The most important ones are drugresistance and the high rates of relapse after treatment discontinuation. Therapy should only be recommended if the expected benefit exceeds significantly the abstain from treatment. The choice of therapy should take into account the patient＇s age, co-morbidity, severity of liver disease and the risk of drug-resistance. New antivirals significantly suppress HBV-replication, but have no effect on cccDNA in hepatocytes, and after the treatment discontinuation viral relapses occurs. At the present level of knowledge it is impossible ＂to eradicate the virus＂ The realistic treatment goal is to achieve durable response by clearance of HBeAg, sustained decrease of serum HBV DNA levels, normalization of ALT, improvement of liver histology and stopping of liver fibrogenesis. The competition between IFN based therapy and nucleoside or nucleotide analogues still remains. IFN can cure the liver disease while nucleotide analogues only suppress the viral replication during therapy and can reduce the liver fibrosis. Treatment should be prolonged for 24-mo or longer by using maintenance or intermittent treatment course with the lowest effective IFN and PEG IFN doses. Nucleoside/nucleotide analogues are a promising treatment option, but additional data for treatment duration and long-term post-treatment outcome are necessary.

Response of TT virus to IFN plus ribavirin treatment in patients with chronic hepatitis C

AIM:TT virus (TTV) is a newly described DNA virus related to postransfusion hepatitis that produces persistent viremia in the absence of clinical manifestations.PEG-IFN plus ribavirin have been useful in the treatment of chronic hepatitis C infection.This study investigated the responses of TT virus (TTV) and hepatitis C virus (HCV) to PEG-IFN plus ribavirin therapy. METHODS:Fifteen patients infected with HCV were treated with PEG-IFN(0.5 μg/body weight/week) and ribavirin (1000 mg-1 200 mg/daily) for 48 weeks,Blood samples were drawn at the beginning and the end of the therapy.Serum TTV DNA and HCV RNA were quantified by real time PCR. RESULTS:At the beginning of treatment,TTV infection was detected in 10/15 (66.6%) of HCV-infected patients.Loss of serum TTV DNA at the end of therapy occurred in 6/10 (60%) patients.Out of these 6 patients,4 (67%) became positive for TTV DNA after 6 months of therapy.Regarding HCV viremia,11/15 (73%) patients were negative for serum HCV RNA after 48 weeks of therapy,7/11 (64%) of these cases also became negative for TTV DNA following the combined treatment.In the 3/4 (75%) patients who were positive for HCV RNA at the end of therapy,TTV DNA was detected as well.Sustained HCV response at 6 months after treatment was 53% (8/15). CONCLUSION:No TTV sustained response can be achieved in any patient after PEG-IFN plus ribavirin administration.

HBeAg阳性慢性乙型肝炎患者干扰素治疗24周应答不佳时的治疗方案

目的对干扰素单药治疗24周应答不佳的HBe Ag阳性慢性乙型肝炎（CHB）患者采用不同的治疗方案进行后续治疗,分析比较其疗效和安全性。方法回顾性分析2010年9月~2013年1月南方医科大学南方医院193例干扰素治疗24周时应答不佳的HBe Ag阳性的CHB患者,根据不同后续治疗方案分成：联用恩替卡韦（ETV）或阿德福韦（ADV）治疗（A组）,继续干扰素单药治疗（B组）,换为NAs治疗（C组）,直接停止治疗（D组）。观察比较第24、48、72周时各组患者的临床疗效与安全性。结果继续治疗至疗程48周时,A组和C组HBV DNA转阴率、ALT复常率均高于B组（A组：χ^2=26.808,P〈0.001和χ^2=5.485,P=0.017;C组：χ^2=21.257,P〈0.001和χ^2=5.369,P=0.018）;同时发现,加ETV组HBV DNA转阴率高于加ADV组（χ^2=8.255,P=0.004）。疗程72周时,A组患者有27例（39.7%）发生HBe Ag血清学转换,明显高于B、C两组（χ^2=4.238,P=0.04和χ^2=7.681,P=0.006）;58例（85.3%）获得HBV DNA转阴,59例（86.8%）ALT恢复正常,均高于B组（χ^2=23.018,P〈0.001和χ^2=5.987,P=0.014）,但与C组比较差异无统计学意义（P〉0.05）;同时发现,联合ETV组HBV DNA转阴率和HBe Ag血清学转换率均高于加ADV组（χ^2=9.823,P=0.002和χ^2=5.450,P=0.020）。D组,28例患者的HBV DNA均持续较高水平复制,HBe Ag水平升高,ALT反复波动。结论对于干扰素单药治疗24周时应答不佳的CHB患者,联用NAs并延长疗程可明显提高HBe Ag血清学转换率、HBV DNA转阴率及ALT复常率,特别是联用ETV并延长疗程时。

恩替卡韦联合长效干扰素治疗HBeAg阳性慢性乙型肝炎临床研究

目的探讨恩替卡韦(ETV)联合长效干扰素α(IFN-α)治疗乙型肝炎(简称乙肝) e抗原(HBeAg)阳性慢性乙肝的效果。方法共纳入100例首次接受抗病毒治疗的HBeAg阳性慢性乙肝患者,随机分为研究组和对照组,各50例,两组患者均口服恩替卡韦片(0. 5 mg/d),研究组患者加用聚乙二醇干扰素α-2a注射液(180μg,皮下注射,1次/周),持续治疗48周。结果治疗48周时,研究组HBeAg转阴率及血清学转换率分别为36. 00%和32. 00%,明显高于对照组的18. 00%和16. 00%(P <0. 05);研究组乙肝表面抗原(HBsAg)转阴率及血清学转换率分别为6. 00%和4. 00%,与对照组的2. 00%和2. 00%相当(P> 0. 05);研究组乙肝病毒脱氧核糖核酸(HBV DNA)转阴率为86. 00%,与对照组的82. 00%相当(P> 0. 05);两组ALT、天门冬氨酸氨基转移酶(AST)、总胆红素(TBil)均明显下降,且研究组ALT和TBil降幅明显大于对照组(P <0. 05);高、低ALT水平组HBeAg血清学转换率、HBV-DNA转阴率均相当(P> 0. 05)。结论恩替卡韦联合长效干扰素治疗HBeAg阳性慢性乙肝48周时,可有效提高HBeAg转阴率和血清学转换率。

干扰素α2b与苦参素、胸腺肽α1联合序贯治疗慢性乙型肝炎的实验研究

了解干扰素α2b与苦参素、胸腺肽α1联合治疗慢性乙型肝炎的实验研究。98例HBeAg阳性的慢性乙型肝炎患者随机分成治疗组和对照组。治疗组49例,同时使用干扰素α2b与苦参素、胸腺肽a1 13周,随后使用干扰素α2b及胸腺肽α1 13周,最后单用干扰素α2b 26周;对照组49例单用同样剂量干扰素α2b 52周。疗程中定期检测血常规、丙氨酸转氨酶(ALT)、HBeAg、抗-HBe、HBVDNA、透明质酸酶(HA)。全部患者完成1年治疗。治疗组 ALT、HA复常率、HBeAg／抗-HBe血清转换率、HBVDNA阴转率明显高于对照组(分别为81．6％和53．1％,P< 0．005;44．9％和22．4％,P<0．025;42．9％和20．4％,P<0．025:79．6％和51．0％,P<0．005)。干扰素α2b与苦参素、胸腺肽α1联合治疗慢性乙型肝炎疗效优于单用干扰素α2b。

聚乙二醇化干扰素α-2a对拉米夫定治疗失败的HBeAg阳性慢性乙型肝炎患者的疗效

目的探讨拉米夫定治疗失败的HBeAg阳性慢性乙型肝炎患者,接受聚乙二醇化干扰素α-2a(PEGIFNα-2a)序贯治疗的临床疗效。方法对22例经拉米夫定治疗失败的HBeAg阳性慢性乙型肝炎患者,在继续使用拉米夫定的情况下,加用PEGIFNα-2a180μg,每周1次,联用12周,然后停用拉米夫定,单用PEGIFNα-2a至48周,每月检查1次肝功能、血常规;每3个月检查乙型肝炎病毒(HBV)血清标志物及HBV DNA定量;治疗结束后随访48周。结果 HBV DNA基线平均表达水平为(6.54±0.90)copies/mL(log10)。在治疗结束后,有40.91%(9/22)的患者实现HBeAg血清转换和HBV DNA血清表达水平减少,13.64%(3/22)的患者实现HBsAg血清转换。随访48周,36.36%(8/22)的患者维持HBeAg血清转换和HBV DNA水平的降低,在维持HBeAg血清学转换的8例患者中,有2例患者持续维持HBsAg血清转换。结论 PEGIFNα-2a能部分明显降低拉米夫定治疗失败患者的HBV DNA水平,促进HBe Ag和HBs Ag的血清学转换。

基因B/C型HBeAg(+)慢性乙型肝炎患者初始拉米夫定、阿德福韦酯联合治疗疗效

目的:观察初始拉米夫定(LAM)和阿德福韦酯(ADV)联合与LAM、恩替卡韦(ETV)单药治疗基因B/C型HBe Ag(+)慢性乙型肝炎(慢乙肝)患者的疗效。方法:招募182例符合中国慢乙肝防治指南中治疗标准的基因B/C型HBe Ag(+)慢乙肝初始治疗患者,随机分为3组,分别以LAM和ADV联合、LAM或ETV单药治疗48周,观察疗效。结果:基线水平无差异的3组患者分别经过3种方案治疗后,联合治疗组生化学应答率(12周P<0.01,24周P<0.01,48周P<0.01)、HBe Ag血清学应答率(12周P<0.01,24周P<0.05,48周P<0.05)、完全病毒学应答率(12周P<0.05,24周P<0.05,48周P<0.05)均高于LAM组。联合治疗组在生化学应答方面较ETV组存在一定优势。结论:LAM和ADV初始联合治疗是我国以B/C型基因为主的慢乙肝患者抗病毒治疗的优良策略。

干扰素α-2b联合阿德福韦酯治疗慢性乙型肝炎疗效观察

目的探讨干扰素(IFN)α-2b联合阿德福韦酯(ADV)治疗慢性乙型肝炎(chronic hepatitis B,CHB)患者的疗效。方法 47例CHB患者随机分为2组,IFNα-2b联合ADV组(联合用药组)22例,单用ADV组(单药组)25例。监测2组患者治疗12、24、48、96周的HBV DNA水平、HBV血清标志物及ALT变化。结果治疗48周时,联合用药组患者血清中HBV DNA转阴率和ALT复常率明显高于单药组,联合用药组在停用IFNα-2b48周后上述指标仍高于单药组。治疗48周时,联合用药组完全应答率为59%,高于单药组的28%(P<0.05)。结论IFNα-2b联合ADV治疗CHB优于单用ADV,可提高HBeAg/抗HBe血清学转换率及完全应答率。

恩替卡韦联合聚乙二醇干扰素α-2a治疗HBeAg阳性慢性乙型肝炎的临床研究

目的观察恩替卡韦联合聚乙二醇干扰素α-2a(PEG-IFNα-2a)治疗对HBeAg阳性慢性乙型肝炎患相关转阴率及肝组织病理的影响。方法选取我院收治的76例慢性乙肝患者为研究对象,随机分为观察组与对照组,各38例。对照组采用恩替卡韦治疗,观察组采用恩替卡韦联合PEG-IFNα-2a治疗,比较两组治疗后血清丙氨酸氨基转移酶(ALT)复常率、HBV DNA转阴率及HBeAg阴转率,并比较两组肝组织病理变化情况。结果治疗6个月后,两组ALT复常率、HBV DNA转阴率、HBeAg转阴率比较均无统计学意义(P>0.05);治疗12个月后,两组ALT复常率、HBV DNA转阴率比较仍无统计学意义(P>0.05);但观察组较对照组HBeAg转阴率明显升高,差异有统计学意义(P<0.05)。治疗后,观察组肝组织炎症活动度、纤维化程度较治疗前明显降低,且显著低于对照组(P<0.05)。结论恩替卡韦联合PEG-IFNα-2a治疗HBeAg阳性慢性乙肝对提高HBeAg阴转率效果显著,并且能降低肝炎症活动度及纤维化程度,效果优于单纯恩替卡韦治疗,值得推广应用。

拉米夫定联合阿德福韦酯治疗HBeAg阳性育龄期女性慢性乙型肝炎96周分析

目的探讨适合HBeAg阳性育龄期女性慢性乙型肝炎(CHB)抗病毒治疗的方法。方法对110例HBeAg阳性育龄期女性CHB,50例给予LAM 100 mg+ADV 10 mg联合口服治疗,1次/d;60例给予LAM 100 mg单药口服,1次/d。疗程均为96周。结果治疗至48、96周时,联合组有54%和82%%患者HBV DNA<1 000Copies/ml优于单药组(48.33%,68.33%),但差异无统计学意义(P>0.05);联合48周时有74%ALT复常优于单药组(61.67%),差异无统计学意(P>0.05);当至96周时,联合组90%患者ALT复常与单药组(75%),差异有统计学意义(P<0.05);48、96周时,联合组HBeAg血清阴转或转换率优于单药组(P<0.01)。联合组未出现病毒学突破和基因耐药发生患者,单药组有21.67%,16.67%和38.33%,30%的患者出现毒学突破和基因耐药(P<0.05)。结论 LAM与ADV初始联合治疗可明显改善HBeAg阳性育龄期CHB患者肝功能,降低单药引起的耐药问题,延长疗程可提高HBeAg阳性育龄期CHB患者HBeAg血清转换率。

拉米夫定联合α干扰素治疗HBeAg阳性慢性乙型肝炎

目的 :观察拉米夫定和干扰素联合治疗HBeAg阳性慢性乙型肝炎的疗效及其影响因素。方法 :64例HBeAg阳性的慢性乙型肝炎患者随机分成治疗组和对照组。治疗组32例 ,同时使用α干扰素及拉米夫定9个月 ,随后单用拉米夫定15个月,对照组32例 ,单用拉米夫定24个月 ,定期检测丙氨酸转氨酶 (ALT)、HBeAg、抗 -HBe、HBVDNA ,并作YMDD变异检测 ,两组在治疗结束时进行疗效评价。结果 :治疗组ALT复常率为90.6 % (29/32) ,对照组ALT复常率为87.5 % (28/32) ,两组差异无显著性 (P>0.05),治疗组HBeAg阴转率为68.8 % (22/32) ,对照组HBeAg阴转率为37.5 % (12/32) ,两组比较差异有显著性 (P<0.05) ,治疗组HBeAg/抗 -HBe血清转换率为53.1 % (17/32) ,对照组HBeAg/抗 -HBe血清转换率为25 % (8/32) ,两组比较差异有显著性 (P<0.05),治疗组HBVDNA阴转率为78.1 % (25/32) ,对照组HBVDNA阴转率为59.4 % (19/32) ,两组比较差异无显著性 (P>0.05) ,治疗组YMDD变异率为21.9 % (7/32) ,对照组YMDD变异率为40.6 % (13/32) ,两组比较差异无显著性 (P>0.05) ,同时治疗组ALT复常率、HBeAg转换率、HBVDNA阴转率与治疗前ALT及HBVDNA基线水平有关。结论 :α干扰素联合拉米夫定治疗HBeAg阳性的慢性乙型肝炎对于ALT中度升高、HBVDNA高水平复制?

干扰素α-2b联合拉米夫定治疗慢性乙型肝炎疗效观察

目的观察干扰素联合拉米夫定治疗慢性乙型肝炎患者的疗效。方法90例慢性乙型肝炎患者随机分为两组:42例干扰素α-2b联合拉米夫定治疗组,48例单用拉米夫定对照组:观察比较两组患者治疗后HBVDNA水平,乙型肝炎病毒血清标志物及肝功能变化。结果治疗结束时,联合治疗组患者血清中HBVDNA阴性率和肝功能复常率明显高于单用拉米夫定治疗组,联合治疗组完全应答率40.5%,优于单用拉米夫定治疗组22.9%(P<0.01);随访24周联合治疗组的上述指标仍高于拉米夫定对照组(P<0.05)。结论干扰素α-2b联合拉米夫定治疗慢性乙型肝炎,可提高HBeAg/抗HBe血清转换率及综合应答率,并可防止或减少YMDD变异的发生。