胸腺肽α1联合拉米夫定治疗慢性乙型肝炎

目的　探讨胸腺肽α1(Tα1)和拉米夫定 (LAM )联合治疗慢性乙型肝炎的长期疗效和安全性。方法　按随机对照原则选择 80例HBVDNA、HBeAg阳性的慢性乙型肝炎患者 ,按 1∶1随机分配进入单一接受拉米夫定治疗组 (LAM组 )和拉米夫定联合治疗组 (LAM +Tα1组 )。结果　治疗5 2周时 ,LAM +Tα1组HBeAg血清转换率 (5 1.4 % ,18/35 )明显高于LAM组 (5 .4 % ,2 /37) ,P <0 .0 1。停药 1年后 ,持续的HBeAg血清转换率分别为 4 2 .9% (15 /35 )和 8.1% (3/37) ,P <0 .0 1。治疗过程中 ,两组HBVDNA定量明显下降 ,联合治疗组下降更显著 ,治疗后 ,两组的丙氨酸转氨酶(ALT)复常率基本一致 ,达 77.1% (2 7/35 )和 6 7.6 % (2 5 /37) ,但停药后LAM组仅有 18.9%持续正常 ,明显低于联合治疗组。治疗 5 2周 ,联合治疗组完全应答率 (42 .9% )明显高于LAM组 (8.1% ) ,停药后 1年 ,持续应答率分别为 6 0 .0 % (2 1/35 )和 18.9% (7/37) ,P <0 .0 1。治疗过程中LAM +Tα1组未发现HBV前C区变异株。LAM组有 10例 (2 7.0 % )发生YMDD变异株 ,联合组仅有 1例。治疗后肝组织炎症坏死程度明显地改善 ,肝纤维化程度降低 ,HBsAg、HBcAg的表达明显减少 ,治疗过程无明显的不良反应。结论　Tα1与LAM联合治疗慢性乙型肝炎 ,不良反应少 ,疗效优     

拉米夫定与胸腺肽α1联合治疗慢性乙型肝炎的临床研究

我们选取未曾接受抗病毒治疗的慢性乙型肝炎患者，比较拉米夫定与胸腺肽α1联合治疗与单用拉米夫定的疗效。     

胸腺肽α1联合干扰素治疗慢性乙型肝炎临床分析

目的研究胸腺肽α1联合干扰素对慢性乙型肝炎（CHB）的治疗作用。方法经临床诊断为CHB（轻、中度）并乙肝病毒复制指标阳性患者68例，随机分为2组，胸腺肽α1加干扰素组和单用干扰素组，疗程6个月。结果联合治疗组肝功能复常与对照组差异无显著性。病毒复制指标阴转率差异有显著性（P〈0．05）。结论胸腺肽α1、干扰素为治疗乙型肝炎较为有效的药物，两者合用有相加或协同作用，为治疗CHB较为理想的方案。     

拉米夫定联合胸腺肽α1治疗慢性乙型肝炎

目的观察拉米夫定(LAM)联合胸腺肽α1(Tα1)治疗慢性乙型肝炎的疗效和安全性。方法选择156例HBV-DNA、HBeAg阳性的慢性乙型肝炎患者分为单一使用拉米夫定组(LAM组)和拉米夫定联合胸腺肽α1组(LAM+Tα1组)。结果治疗52周时LAM+Tα1组HBeAg血清转换率38.5%明显高于LAM组11.5%(P0.05)。HBV-DNA阴转率LAM+Tα1组82.1%明显高于LAM组51.3%(P0.05)。ALT复常率LAM+Tα1组91.0%明显高于LAM组67.9%(P0.05)。综合疗效评价LAM+Tα1组完全应答率38.5%明显高于LAM组11.5%(P0.05)。治疗过程中无明显不良反应,LAM+Tα1组未发生HBV前C区变异株,LAM组发生YMDD变异19例,LAM+Tα1组仅2例。结论 LAM+Tα1治疗慢性乙型肝炎,不良反应少、安全、疗效确切,优于单一LAM治疗。     

拉米夫定联合α1胸腺肽治疗慢性乙型肝炎的疗效观察

目的观察拉米夫定联合α1胸腺肽治疗慢性乙型肝炎的疗效和安全性。方法A组35例患者给予拉米夫定100mg口服,1次/d,治疗12个月,前6个月同时给予α1胸腺肽1.6mg,皮下注射,一周2次;B组仅给予拉米夫定100mg口服,1次/d,疗程12个月。两组均随访6个月,期间继续服拉米夫定。结果联合组与单用拉米夫定组在HBVDNA转阴方面疗效相近,但拉米夫定联合α1胸腺肽治疗可降低或减少YMDD变异。结论拉米夫定联合α1胸腺肽治疗无明显毒副作用,治疗安全性良好。     

乙肝疫苗、胸腺肽αl、拉米夫定联合治疗慢性乙型肝炎的临床研究

本文采用乙肝疫苗、胸腺肽α1、拉米夫定联合治疗慢性乙型肝炎(CHB)治疗12个月及疗程结束后6个月血清HBeAg阴转率达45%及42%,HBeAg/HBeAh血清转换率40.5%及37.6%.HBVDNA阴转率91.3%及72.4%,取得了较好的效果.治疗过程中无明显的临床副反应.     

拉米夫定联合胸腺肽α1治疗慢性乙型肝炎的疗效观察

在慢性乙型肝炎(chronic hepatitisB,CHB)患者的抗病毒治疗中,我们对胸腺肽α1联合拉米夫定的疗效进行了观察,现报道如下。     

拉米夫定分别与干扰素α-1b和胸腺肽联合治疗慢性乙肝疗效观察

我们自2002年1月-2003年12月间将拉米夫定分别与干扰素α-1b(IFN—α1b)和胸腺肽联合，用于治疗慢性乙肝取得了较好的疗效，现将有关资料报道如下：     

α干扰素、泛昔洛韦和胸腺肽联合治疗慢性乙型肝炎疗效观察

我们在泛昔洛韦和α干扰素联合治疗的基础上加用胸腺肽联合治疗慢性乙型肝炎,并与二联治疗进行对比,以观察疗效。     

拉米夫定联合胸腺肽治疗慢性乙型肝炎68例

目的：评价拉米夫定（Lamivudine)联合胸腺肽治疗慢性乙型肝炎的疗效,方法：将138例慢性乙型肝炎患者随机分成两组,治疗组68例给予Lamivudine每天100mg联合胸腺肽40mg隔日肌注1次,对照组70例单用干扰素αα-2b,5MU隔日肌注1次,两组疗程均为6个月,主要观察患者治疗前后的症状体征,肝功能,病毒复制指标的变化,结果：疗程结束时治疗组临床症状体征的缓解率为88．23％,生化应答率为88．23％,HBeAg阴转率为55．88％,HBVDNA阴转率为88．23％,对照组以上指标分别为48．58％,34．29％,48．58％,两组比较有显著性差异（P＜0．05）,结论：Lamivudine联合胸腺肽治疗慢性乙型肝炎,能迅速改善慢性乙型肝炎患者的症状体征,有效抑制HBV DNA的复制,促进HB Ag抗HBe的转换。     

拉米夫定、α-2b干扰素治疗HBeAg(+)慢性乙型肝炎疗效与基因型相关性研究

目的 探索乙型肝炎病毒(HBV)基因型与拉米夫定、α-2b干扰素序贯治疗及单独予拉米夫定、α-2b干扰素治疗HBeAg阳性慢性乙型肝炎患者的疗效的相关性.方法 HBeAg阳性慢乙肝患者,来自北京等四城市.分别拉米夫定、干扰素序贯治疗48周、拉米夫定48周或干扰素24周.停药后随访24周.评价HBV基因型与抗病毒治疗应答的关系.PCR-RFLP方法检测HBV基因型、基因亚型.结果 225例患者中C基因型184例,其中C2亚型165例;B基因型41例,均为Ba亚型.治疗结束、随访结束时,各治疗组B型与C型间病毒学应答、血清学应答及完全应答率差异均无显著性.结论 该四城市HBeAg阳性慢乙肝患者HBV基因型以B型和C型为主,亚型以Ba和C2亚型为主.治疗结束、随访结束时,各治疗组B型与C型间疗效无差异.     

Sequential combination therapy of HBe antigen-negative/virus-DNA-positive chronic hepatitis B with famciclovir or lamivudine and interferon-alpha-2a.

BACKGROUND/AIMS: Hepatitis B e antigen-negative/hepatitis B virus (HBV) DNA-positive chronic hepatitis B (CHBe-) exhibits a high relapse rate on monotherapy with lamivudine or interferon-alpha (IFN-alpha). We investigated, whether sequential therapy with famciclovir or lamivudine followed by combination with IFN-alpha-2a improves durable virologic response in CHBe- characterized by mutation analysis of the HBV precore genome region. METHODS: Fourteen patients were treated with famciclovir (n=3) or lamivudine for 4 weeks to reduce the viral load, and subsequently with the combination of the nucleoside analogue and IFN-alpha-2a until 16 weeks beyond the loss of serum HBV-DNA. RESULTS: Median duration of therapy was 29.0 weeks (range 20.6-48.3 weeks). Serum HBV-DNA was undetectable and alanine aminotransferase had normalized in all patients at the end of treatment. Seven (50%) patients maintained a sustained response 12 months after end of treatment. Only two of them had been infected by HBV with the G1896A mutation. Most patients (5/7) with the G1896A mutation relapsed within 4 months after therapy. CONCLUSION: Sequential combination therapy can induce sustained virologic response in a subgroup of CHBe-, but most with the G1896A precore mutant HBV relapse. Trials of CHBe- should be based on characterization of HBV mutants.     

Efficacy of granulocyte-macrophage colony-stimulating factor or lamivudine combination with recombinant interferon in non-responders to interferon in hepatitis B virus-related chronic liver disease patients

BACKGROUND AND AIMS: Non-response to interferon (IFN) monotherapy is a major therapeutic problem in the management of chronic hepatitis B infection. The efficacy of combination therapy to enhance the immunomodulatory effect of IFN by combining granulocyte-macrophage colony-stimulating factor (GMCSF) or decreasing viral load by adding an antiviral agent such as lamivudine was evaluated prospectively. METHODS: Twenty-four patients with chronic hepatitis B who were non-responders to previous IFN therapy were randomized to receive an IFN and GMCSF (group A, n = 10) or IFN and lamivudine (group B, n = 14) combination for 6 months. The end-of-treatment response was assessed by hepatitis B virus (HBV)-DNA and hepatitis B e antigen (HBeAg) determination. RESULTS: All patients successfully completed both the treatment schedules. The mean age, alanine aminotransferase (ALT) levels, liver histology, HBV-DNA levels and distribution of HBV genotypes were comparable between the two groups. At the end of treatment there was a significant decrease in mean ALT levels. The HBV-DNA and HBeAg loss was seen in six of 10 (60%) patients in group A and in seven of 14 (50%) patients in group B. During a mean follow-up of 15 +/- 3 months, two of six (33%) patients in group A and three of seven (43%) patients in group B relapsed with HBV-DNA and HBeAg positivity, which meant an overall sustained response of 40% and 28%, respectively. None of the factors such as HBV viral load, ALT levels or liver histology could predict the non-response to combination therapy or occurrence of relapse. There was a trend in patients with genotype A compared with genotype D towards non-response to therapy, although the difference was not significant. CONCLUSIONS: The combination of IFN plus GMCSF or lamivudine was effective in non-responders to IFN monotherapy. Larger studies using such combination therapies would be helpful in improving treatment strategies for chronic hepatitis B.     

Lamivudine-high dose interferon combination therapy for chronic hepatitis B patients co-infected with the hepatitis D virus

Currently, the best option for patients with hepatitis delta is interferon alpha therapy for at least one year. To evaluate the effect of the combination lamivudine-high-dose interferon alpha therapy, we first treated eight patients with chronic hepatitis delta infection with lamivudine for at least 24 weeks; then lamivudine was combined with a high dose of interferon alpha followed by a regular dose (9 MU tiw). Follow-up was 12 weeks. Virological, biochemical and histological features were evaluated for response to therapy. At baseline, all patients were HBsAg positive in serum and HDV RNA-(PCR)positive in plasma; HBV DNA was undetectable with the Digene Hybrid Capture assay (limit of detection 1.5 x 10(6) geq ml-(1)) in all cases. Transaminases were elevated in all patients; median ALT 68 (range 48-143) IU l(1). Seven of eight patients completed the course; one patient with a pre-existing sickle cell trait was withdrawn from the trial due to the development of a nephrotic syndrome. The HBsAg-concentration in serum decreased in two out of seven patients (29%). However, there was no significant decrease in the HBsAg-concentration in serum during treatment (median 3654 PEU l(-1) (range 548-7,684) to 5300 PEU l(-1) (range 168-19,639)). The drop of HDV RNA in plasma from baseline during treatment was not significant. Decrease of HDV RNA was observed in three out of seven patients (43%) (median 10(5) geq ml(-1); range 10(3)-10(6) to median 10(3) geq ml(-1); range 10(2)-10(7)). Serum ALT did not change as reflected by a median of 68 IU l(-1) (range 48-143) at start of therapy to 63 IU l(-1) (range 20-171) at the end of therapy. At the end of treatment transaminases had normalised in one patient and decreased in three other patients (improvement in 57%). However, three of these four patients showed a rebound after withdrawal of therapy. The Histology Activity Index (HAI) indicated a drop from a median score of 7 (range 5-9) at baseline to 5 (range 3-8) at the end of treatment, but an increase in fibrosis from a median grade of 2 (range 1-3) at baseline to 3 (range 1-4) at the end of treatment was observed. In conclusion, this study does not yield support for the combination of an HBV suppressor and 16 weeks of high-dose interferon for therapy aimed at eradicating the hepatitis delta virus.     

Interferon/long-term lamivudine combination therapy in anti-HBe positive chronic hepatitis B patients

BACKGROUND: Monotherapy with a single antiviral agent is insufficient in controlling hepatitis B virus infection in the majority of patients with anti-HBe positive chronic hepatitis B. Interferon/long-term lamivudine combination therapy was evaluated to determine if this strategy would improve treatment efficacy and reduce the emergence of lamivudine resistance. METHODS: In total, 36 consecutive anti-HBe positive patients were treated with interferon (3 MU subcutaneously three times weekly) and lamivudine (100 mg orally once a day) for 12 months. After completion of the combined treatment, all patients continued to receive lamivudine monotherapy indefinitely. RESULTS: Overall, 35 patients (97%) showed virological response at 12 months. Four patients (11%) cleared HBsAg and developed anti-HBs. During the follow-up time, after the discontinuation of interferon, of 30 +/- 12 months (range: 7-57 months), 13 patients (36%) exhibited breakthrough infection. The cumulative rates of breakthrough infection at the end of 1, 2, 3 and 4 years of treatment were 0%, 14%, 32%, and 59%, respectively. CONCLUSIONS: Combination therapy appears to be effective and may also delay the selection of lamivudine-resistant variants. However, controlled trials are definitely warranted to clarify the potential benefits of combination antiviral treatment over monotherapy.     

Interferon and lamivudine monotherapy on chronic hepatitis B in Japan

Aim:  We show data of interferon (IFN) and lamivudine monotherapy on chronic hepatitis B in Japan.
Methods:  Data collected from sixty-six chronic hepatitis B (CHB) Japanese patients who were treated with IFN for 6 months were analyzed. The efficacy of long-term IFN therapy in 52 patients with e-antigen positive CHB, and data from 290 chronically HBV-infected patients who were treated with lamivudine for more than 3 years, were analyzed.
Results:  Six-month IFN therapy: among 45 patients with HBeAg at commencement of IFN therapy, nine (20%) were responders. Young patients especially those with high serum alanine aminotransferase (ALT) levels were much more likely to respond to IFN therapy. Twelve-month IFN therapy: theresponse rate was 31% among 52 patients with HBeAg. Long-term lamivudine therapy: YMDD motif mutation was detected in 167 of 290 patients (58%) during lamivudine treatment. Breakthrough hepatitis from lamivudine resistant virus was detected in 93 of 290 patients (32%). Finally, 813 patients were treated by lamivudine between September 1995 and February 2006. Fifteen patients lost HBsAg during and after lamivudine therapy.
Conclusion:  Long-term interferon therapy has a better response than short-term interferon therapy. Some patients lost HBsAg during and after lamivudine therapy.     

Pharmacology,clinical efficacy and safety of lamivudine in hepatitis B virus infection

Lamivudine was the first nucleoside analog for the treatment of chronic hepatitis B (CHB). It is well-tolerated and induces a decrease in serum HBV DNA levels associated with normalization of serum alanine aminotransferase levels. However, a sustained response with hepatitis B ‘e’ antigen to anti-hepatitis B e seroconversion is obtained in a smaller proportion of patients and hepatitis B surface antigen loss is exceptional. The response is maintained during therapy, and needs to be continued indefinitely in the majority of patients since withdrawal of treatment is generally followed by a rapid reappearance of the virus. However, mutations can be induced in long-term treatment.     

Treatment of chronic hepatitis B with the combination of pegylated interferon with lamivudine

Several agents are currently approved for the treatment of chronic hepatitis B: interferon alpha (IFN), pegylated interferon-α (PEG IFN), lamivudine, adefovir, and entecavir. Each agent has inherent limitations. IFN is effective in a minority of patients and has frequent side effects that limit its tolerability. Large randomized controlled trials have demonstrated the efficacy of PEG IFN in the treatment of chronic hepatitis B. The efficacy of lamivudine is limited by the emergence of drug-resistant hepatitis B virus (HBV) mutants, restricting its utility as a long-term therapy. Adefovir is well tolerated and is associated with low incidence of resistance, but its antiviral effect is not optimal. Entecavir has a high antiviral effect and is well tolerated. However, its long term efficacy and resistance profile are not yet determined. Lamivudine, adefovir and entecavir have the advantages of oral administration and excellent safety profiles. However, theyinduce a sustained response after withdrawal of therapy in only a minority of patients, and therefore, the treatment needs to be indefinitely administered in most patients. IFNs have two mechanisms of action: (i) direct antiviral effect by inhibiting synthesis of viral DNA and by activating antiviral enzymes; and (ii) exaggeration of the cellular immune response against hepatocytes infected with HBV. PEG IFN, administered for 48 weeks, gives an overall sustained response rate of approximately 30%. Two large randomized controlled trials have conducted to registration of PEG IFN-α-2a in the treatment of chronic hepatitis B.     

川芎嗪联合拉米夫定治疗慢性乙型肝炎效果观察

探讨川芎嗪联合拉米夫定治疗慢性乙肝的临床疗效。治疗组 5 1例慢性乙肝患者每日静脉输入 (80 - 2 0 0 )mg川芎嗪 ,对照组 34例每日静脉输入甘草酸二铵 15 0mg ,输液治疗 10天 ,然后 ,两组均口服降酶保肝药和拉米夫定10 0mg/d,疗程 30天。 30天后 ,川芎嗪治疗组ALT复常率达 90 1% ,对照组只有 5 5 9% ,两者有显著差别 (P <0 0 1) ,HBVDNA及HBeAg阴转率略高于对照组 ,但无统计学差异。川芎嗪药物来源方便、价格低廉、值得临床推广使用。     

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.