泛昔洛韦治疗HBV慢性感染的临床研究

目的：观察泛昔洛韦对HBV慢性感染抗病毒的治疗效果。方法：慢性乙型肝炎患者89例，采用随机对照分组，和单用泛昔洛韦治疗组32例，和单用α－干扰素29例和单用拉米夫定28例两个对照组，对比观察三组抗病毒治疗效果。结果：治疗组泛昔洛韦血清HBV DNA阴转率40．62％（13／32），HBeAg阴转率21．88％（7／32）；对照组α－干扰素血清HBV DNA阴转率37．93％（11／29），HBeAg阴转率41．38％（12／29）；拉米夫定血清HBV DNA阴转率67．90％（19／28），HBeAg阴转率21．43％（6／28）。治疗组HBV DNA阴转时间最短1个月，最长3个月，平均1．3个月，无1例出现严重不良反应。结论：泛昔洛韦治疗HBV慢性感染安全有效。     

阿德福韦酯单药及其联合拉米夫定治疗拉米夫定耐药型HBeAg阳性慢性乙型肝炎的疗效比较

目的比较阿德福韦酯（ADV）单药及其联合拉米夫定治疗拉米夫定耐药型HBeAg阳性慢性乙型肝炎（chronic hepatitis B,CHB）的临床疗效。方法对24例ADV单药及28例ADV联合拉米夫定治疗拉米夫定耐药型HBeAg阳性慢性乙型肝炎患者的疗效进行回顾性分析,比较两组患者HBVDNA、ALT水平及HBV DNA检测不到率、ALT复常率的差异。结果两组患者的性别、年龄、治疗前的HBV DNA及ALT水平差异均无统计学意义。两组的HBV DNA、ALT水平在治疗48周、72周时分别与同组治疗前比较均有明显降低（P〈0．05）。治疗48周时,联合组的HBV DNA检测不到率虽高于单药组,但差异无统计学意义（50％vs25％,P〉0．05）;ALT复常率两组间无明显差别（67．9％vs75％,P〉0．05）。治疗72周时,联合组的HBV DNA检测不到率为68％,要显著高于单药组的33．3％（P〈0．05）;联合组的ALT复常率为93％,显著高于单药组的70．8％（P〈0．05）。结论ADV单药或联合拉米夫定均是治疗拉米夫定耐药HBeAg阳性CHB的有效方法,联合治疗的疗效要优于单药治疗。     

拉米夫定治疗慢性乙型肝炎的疗效研究

目的：研究抗－HBV药拉米夫定治疗慢性乙型肝炎的抗乙型肝炎病毒DNA的疗效。方法：分治疗组和对照组，治疗组每日1次口服拉米夫定100mg，疗程一年；对照组用一般护肝药治疗。定期检测血常规、肝功能及病毒学指标等。结果：拉米夫定治疗慢性乙型肝炎疗程一年，ALT复常率为90．7％，HBV DNA阴转率为73．1％，与对照组相比差异有显著性（P＜0．05），HBeAg阴转率为50．0％，HBeAg／抗－HBe的血清转换率为38．2％，与对照组相比差异无显著性（P＞0．05），病情反复，ALT再次升高者治疗组为3．1％，与对照组相比较差异有显著性（P＜0．05），治疗2例重症肝炎患者，无1例死亡。结论：拉米夫定能有效地抑制HBV DNA的复制，使ALT恢复正常，降低慢性乙型肝炎的复发率，提高患者存活率。     

拉米夫定联合胸腺五肽治疗慢性乙型肝炎疗效观察

目的：探索抗病毒药物联合免疫调节药物治疗慢性乙型肝炎的疗效。方法：采用拉米夫定联合胸腺五肽治疗慢性乙型肝炎，同期单用拉米夫定或胸腺五肽作对照，动态观察血清HBV复制指标及肝功能。结果：治疗结束时联合组血清HBeAg阴转及抗HBe阳转率明显优于拉米夫定组（P＜0．05），与胸腺五肽组比较差异无显著性（P＞0．05）；联合组的HBV DNA阴转率优于胸腺五肽组（P＜0．05），与拉米夫定组比较差异无显著性（P＞0．05）。治疗结束后6个月、12个月的病毒复制指标变化与治疗结束时无明显变化。联合组的显效率及总有效率均高于其他两组，且ALT复常率保持在85％以上。结论：拉米夫定联合胸腺五肽治疗慢性乙型肝炎，可达到有效而持续的抗病毒作用。亦有利于ALT持久复常。     

拉米夫定耐药的慢性乙肝患者联合干扰素或苦参素治疗疗效观察

目的 观察拉米夫定耐药的慢性乙型肝炎患者联合干扰素或苦参素治疗的效果。方法 40例患者在继续应用拉米夫定的前提下，A组14例联合应用干扰素a-2b3MU IM每日1次，30d，然后隔日1次，共计6个月。B组15例联合苦参素，苦参素60mg，IM每日1次，3个月，然后改为口服0．2g每日3次3个月。C组11例继续单用拉米夫定100mg每日1次口服。疗程结束后，观察乙肝病毒血清学指标HBVDNA、HBeAg阴转及HBeAg／anti-HBe转换，肝功能(ALT)恢复情况。结果 联合干扰素治疗组，HBVDNA阴转率为35．71％(5／14)；联合苦参素治疗组HBVDNA阴转率为13．33％(2，15)，ALT复常率分别为85．71％(12／14)、86．67％(13／15)。C组无HBVDNA及HBeAg阴转，ALT复常率为36．36％(4／11)。结论 对拉米夫定耐药的慢性乙型肝炎患者，联合干扰素或苦参素治疗后，可以提高拉米夫定疗效，抑制病毒复制，促进肝功能恢复。     

山东地区HBV基因型分布及拉米夫定抗病毒治疗对基因分型的影响

目的 确定乙型肝炎病毒（HBV）基因型在山东地区的分布及拉米夫定抗病毒疗效的影响。方法 采用PCR微板核酸分子杂交酶联显色技术，对临床服用拉米夫定一年的131例乙型肝炎患者血清中的HBV．DNA进行基因分型，与未服用拉米夫定组对照。结果 治疗组C型为87．4％（90／103），D型为12．6％（13／103）。对照组C型为89．3％（25／28），D型为10．7％（3／28），两组间差异无统计学意义。均未发现A、B、E和F基因型。结论 首次从临床慢性乙肝患者中得出山东地区HBV优势基因型为C基因型，同时存在D基因型。服用拉米夫定治疗一年对HBV基因型没有影响。     

阿德福韦酯联合胸腺五肽治疗慢性乙型肝炎初探

目的 探索核苷类似物(阿德福韦酯)与胸腺五肽联合治疗慢性乙型肝炎抗乙肝病毒的效果.方法 选取慢性乙性病毒性肝炎27例,阿德福韦酯联合胸腺五肽组15例,单用阿德福韦酯组12例,用药前、用药1月、3月后复查HBV DNA. 结果 用药前2组HBV DNA水平比较无显著性差异(2.2E 7±5.3E 7 copies/ml vs2.0E 7±4.5E 7 copies/ml,P＞0.05),用药1月后2组HBV DNA水平皆有明显下降,2组HBV DNA水平比较无显著性差异(3.3E 4±6.9E 4 copies/ml vs2.1E 4±2.8E 4 copies/ml,P＞0.05),用药3月后2组HBV DNA水平有显著性差异,阿德福韦酯 胸腺五肽组 HBV DNA水平低于单用阿德福韦酯组(8.0E 2±2.1E 3 copies/ml vs2.9E 3±2.9E 3 copies/ml,P＜0.05),用药1月后阿德福韦酯 胸腺五肽组HBV-DNA转阴率40% ,单用阿德福韦酯组HBV-DNA转阴率为0,用药3月后阿德福韦酯 胸腺五肽组HBV-DNA转阴率明显高于单用阿德福韦酯组(87%vs33%,P＜0.05).结论 阿德福韦酯是一较好的抗HBV药物,无论单用或与胸腺五肽合用在用药1～3月后皆使HBV DNA水平明显下降, 但在与胸腺五肽联用后使HBV DNA水平下降更加显著,特别是提高了HBV DNA转阴率,显示核苷类似物阿德福韦酯与胸腺五肽联用能增强抗乙肝病毒的效力,有助于病毒的清除.     

拉米夫定联合干扰素α-2b治疗慢性乙型肝炎疗效观察

目的观察拉米夫定联合干扰素α-2b(安福隆)治疗慢性乙型肝炎(CHB)治疗效果,总结经验。方法选择2009年6月～2010年6月许昌市人民医院CHB患者81例,其中男性45例,女性36例;年龄18～35岁,平均年龄28岁。随机分为联合治疗组、拉米夫定治疗组,分别41、40例。使用拉米夫定联合干扰素α-2b 500万单位隔日肌内皮下注射1次,疗程12个月;对照组单用拉米夫定治疗12个月。检查所有患者的肝功能、乙型肝炎病毒DNA(HBV-DNA)、乙型肝炎e抗原(HBeAg)转阴率和血清转换率,进行对比。结果联合治疗组能够提高CHB患者对拉米夫定的生物化学和血清学应答率,降低其耐药发生率。结论拉米夫定联合α-2b干扰素是一种较好的抗HBV的治疗方法。     

比较α-干扰素不同联合治疗方案对儿童HBeAg阳性慢性乙型肝炎的疗效

目的评估两种不同的α-干扰素联合治疗对儿童HBeAg阳性慢性乙型肝炎的临床疗效。方法选择HBeAg阳性慢性乙型肝炎儿童120例,随机分为3组,每组各40例:第1组(A组)为α-干扰素(IFN-α)组;第2组(B组)为IFN-α 拉米夫定(LAM)组。第3组(C组)为α-干扰素(IFN-α) 乙肝疫苗组。其中干扰素疗程6个月,拉米夫定疗程6个月,所有病例均观察至12个月。结果治疗结束时丙氨酸转氨酶(ALT)复常率3组无差异。治疗6个月和12个月时B组HBeAg阴转率和HBV DNA的阴转率明显高于A组和B组,差异有统计学意义(P<0.05)。结论α-干扰素与拉米夫定联合治疗对HBeAg阳性慢性乙型肝炎儿童的病毒学应答(VR)疗效明显优于单用α-干扰素组和α-干扰素 乙肝疫苗组。     

双环醇与拉米夫定治疗慢性乙型肝炎的抗病毒和复常肝功能效应的成本-效益分析

目的评价双环醇与拉米夫定在治疗慢性乙型肝炎中的抗病毒和复常肝功能的疗效、不良反应、成本-效益．方法将100例慢性乙型肝炎患者随机分成治疗组和对照组，分别予双环醇或拉米夫定．运用药物经济学成本-效益分析方法，对2组方案的复常肝功能和抗病毒效应的疗效及成本进行比较．结果在临床治疗终点的48周末，双环醇组与拉米夫定组的ALT复常率、HBV—DNA阴转率分别为92．0％、82．0％和44．0％、60．0％，2组的差异无显著性意义（P〉0．05）．双环醇与拉米夫定ALT复常率成本-效益比分别为55．3和70．0；HBV—DNA阴转率的成本-效益比分别为115．7和95．7．结论在疗程结束时，2组的复常肝功能和抗HBV效应基本相似．双环醇治疗慢乙肝的成本-效益比优于拉米夫定．     

Comparison of the efficacy of lamivudine and famciclovir in Asian patients with chronic hepatitis B: results of 24 weeks of therapy

Lamivudine therapy improves hepatic necro-inflammatory activity, decreases progression of fibrosis, and suppresses hepatitis B virus (HBV) replication. Famciclovir has also been shown to have some effect in the suppression of HBV replication. The aim of the study was to compare the effect of treatment with lamivudine and famciclovir on serum HBV DNA levels in patients with chronic hepatitis B and to assess safety. A prospective randomised clinical study was carried out on 100 patients with chronic hepatitis B infection (50 patients received lamivudine 100 mg daily and 50 patients received famciclovir 500 mg three times a day for 12 weeks. From the twelfth week onwards, patients were offered lamivudine 100 mg daily up to 48 weeks). Significantly more patients treated by lamivudine than by famciclovir had undetectable HBV DNA levels after 12 weeks of therapy (P < 0.001). The median HBV DNA levels were significantly lower in the lamivudine-treated patients from the second week of treatment onwards (P < 0.001 for all time points up to 12 weeks). At week 16, 4 weeks after the famciclovir treated patients were put on lamivudine, there was no longer any difference in HBV DNA levels between the two groups of patients. Both treatments were well tolerated and no serious adverse events were reported. It was concluded that in Chinese patients with chronic hepatitis B infection, lamivudine achieved effective suppression of HBV DNA levels within 4 weeks of therapy whereas famciclovir had a significantly weaker action.     

Adefovir dipivoxil alone or in combination with ongoing lamivudine in patients with decompensated liver disease and lamivudine-resistant hepatitis B virus

The purpose of this prospective study was to evaluate the efficacy and safety of adefovir dipivoxil with or without ongoing lamivudine in decompensated lamivudine-resistant chronic hepatitis B patients. Forty-six hepatitis B e antigen (HBeAg)-positive patients with decompensated liver function and lamivudine-resistant hepatitis B virus (HBV) were assigned to adefovir dipivoxil monotherapy (n=18) or combination therapy with ongoing lamivudine (n=28) according to their own preference. After 24 weeks of treatment, 83% of monotherapy and 86% of combination therapy showed serum HBV DNA below detection limit (<0.5 pg/mL). Alanine aminotransferase (ALT) normalized in 78% and 82% respectively. Median Child-Pugh-Turcotte (CPT) score or Model for End-Stage Liver Disease (MELD) score reduced significantly by 3 or 5 point in monotherapy and 2 or 2 point in combination therapy respectively. There were no significant differences in rate of undetectable serum HBV DNA, median change of ALT and median reduction of CPT or MELD scores between the two groups. In conclusion, both adefovir dipivoxil monotherapy and combination therapy with ongoing lamivudine result in comparable virologic, biochemical, and clinical improvements in HBeAg-positive patients with decompensated liver function and lamivudine-resistant HBV. Combination with lamivudine showed no additional benefit over monotherapy during 24 weeks of treatment in these patients.     

Management of hepatitis B in China

A randomised, multicentre, double-blind, placebo controlled trial was conducted in Chinese patients with chronic hepatitis B to compare the efficacy of once-daily lamivudine and placebo on serum HBV DNA, and to assess the long-term efficacy and safety of lamivudine. Patients received lamivudine 100 mg (n = 322) or placebo (n = 107) once daily for 12 weeks, and were then offered open-label lamivudine treatment for 2 years. Lamivudine therapy resulted in increased hepatitis B e antigen (HBeAg) loss and seroconversion (loss of HBeAg plus the development of antibodies to HBeAg) in patients with high baseline serum alanine aminotransferase (ALT) concentrations. At 2 years, loss of HBeAg was achieved by 27% (38/140), 38% (25/66) and 60% (9/15), and seroconversion was achieved by 17% (24/140), 24% (16/66) and 33% (5/15) of patients with baseline serum alanine aminotransferase (ALT) concentrations of >1 x upper limit of normal (ULN), >2 x ULN and >5 x ULN, respectively. With lamivudine treatment, serum HBV DNA decreased rapidly to very low concentrations and remained low throughout the 2 years of the study. At 1 year, 15% (43/295) of patients in the lamivudine group had developed YMDD (tyrosine-methionine-aspartate-aspartate amino acid motif of HBV polymerase) variant HBV. These patients derived clinical benefit with continued lamivudine therapy, demonstrated by serum HBV DNA and ALT concentrations below baseline, or normal serum ALT concentrations. Lamivudine was well tolerated and an effective once-daily oral therapy for Chinese patients with chronic hepatitis B with viral replication and liver disease.     

In vivo immunization by vaccine therapy following virus suppression by lamivudine: a novel approach for treating patients with chronic hepatitis B.

BACKGROUND: Both the hepatitis B virus (HBV) and the immune response of the hosts to HBV play important roles in the pathogenesis of chronic hepatitis B (CHB). Lamivudine is a potent antiviral agent with minimal immune modulator capacity. Moreover, lamivudine causes severe side effects like breakthrough of HBV DNA and breakthrough hepatitis in patients with CHB. On the other hand, vaccine therapy, a recently-developed immune therapy, exhibits potent immune modulatory potentials and almost no side effects, but possesses little antiviral capacity in patients with CHB. OBJECTIVES: The aim of this clinical trial is to evaluate the efficacy of a combination therapy of lamivudine and vaccine in patients with CHB. STUDY DESIGN: Seventy-two patients with CHB (hepatitis B e antigen (HBeAg)-positive, 40; antibody to HBeAg (anti-HBe)-positive, 32). All patients received lamivudine at a dose of 100 mg daily for 12 months. Fifteen patients (HBeAg+, 9; anti-HBe+, 6) receiving oral lamivudine were also given a vaccine containing 20 microg of hepatitis B surface antigen, intradermally, once every 2 weeks for 12 times (combination therapy). RESULTS: Twelve months after the start of therapy, serum HBV DNA became negative in 9 of 9 (100%) HBeAg+ CHB patients receiving combination therapy and in 15 of 31 (48%) HBeAg+ CHB patients receiving lamivudine monotherapy (P < 0.05). The rate of seroconversion from HBeAg to anti-HBe was also significantly higher in patients receiving combination therapy (56% versus lamivudine monotherapy, 16%, P < 0.05). Of the 57 patients receiving lamivudine monotherapy, breakthrough of HBV DNA was found in 10 and breakthrough hepatitis was found in 4; however, these were not seen in any patient receiving combination therapy. CONCLUSIONS: Combination therapy represents a better therapeutic regimen with few complications in patients with CHB.     

Persistence of acute infection with hepatitis B virus genotype A and treatment in Japan

Among the 97 adult patients with acute hepatitis B who were admitted to the Toranomon Hospital in Metropolitan Tokyo during 28 years from 1976 to 2003, 31 (32%) were infected with hepatitis B virus (HBV) genotype A, nine (9%) with genotype B, 44 (45%) with genotype C, one (1%) each with genotypes E and F. HBV in the remaining 11 (11%) patients were untypeable. All the 31 patients with acute hepatitis B caused by HBV genotype A infection were male with a median age of 31 years, and 16 (52%) contracted infection through extramarital sexual contacts. The baseline HBV DNA level was higher in the seven (23%) patients in whom infection with HBV genotype A persisted than the remaining 24 (77%) with spontaneous resolution (median: >8.7 vs. 6.0 log genome equivalents/ml, P = 0.004). Persistent infection was more frequent in patients with maximum alanine aminotransferase <500 IU/L than > or =500 IU/L (83% [5/6] vs. 4% [1/25], P = 0.0001). Of the six patients with persistent HBV genotype A infection who received interferon and/or lamivuidine for treatment of chronic active hepatitis, three (50%) responded with the loss of hepatitis B e antigen (HBeAg); hepatitis B surface antigen (HBsAg) was cleared from serum in one patient who received interferon and lamivudine in sequence. HBV genotype A persisted along with HBeAg in the remaining three patients given antiviral therapy as well as another who was not treated. In conclusion, infection with HBV genotype A prevails in patients with acute hepatitis B in Japan where genotypes B and C are common, is often contracted sexually (16/31 [52%]) and tends to persist (7/31 [23%]). Infection was cleared in only one of the six (17%) patients who received antiviral therapy.     

Response of pre-core mutant chronic hepatitis B infection to lamivudine

The proportion of chronic liver disease associated with the pre-core mutant of hepatitis B virus (HBV) infection is increasing, particularly in Mediterranean Europe and in Asia. The pre-core mutant HBV is unable to produce hepatitis B e antigen (HBeAg), so that patients with this variant do not present with HBV characterised by HBeAg in the serum. Pre-core mutant chronic hepatitis B infection usually proceeds to serious liver disease. Wild-type HBV infection may be mild and respond relatively well to interferon (IFN) alpha therapy, but IFN alpha is not an effective therapeutic option in pre-core mutant hepatitis B infection and new therapeutic options are needed. Clinical data show that lamivudine is an effective treatment for patients with pre-core mutant hepatitis B. There is profound suppression of HBV replication and improvement in indicators of liver disease in most patients. In conclusion, lamivudine is suitable for treatment of a wide range of patients with chronic hepatitis B, including those with pre-core mutant HBV infection.