拉米夫定联合母牛分枝杆菌菌苗治疗慢性乙型肝炎临床观察

目的　观察拉米夫定联合母牛分枝杆菌菌苗治疗慢性乙型肝炎 (CHB)的疗效。方法　 64例CHB患者随机分成治疗组 3 1例 (拉米夫定联合母牛分枝杆菌菌苗组 )和对照组 3 3例 (拉米夫定组 ) ,观察两组患者肝功能、HBeAg及HBVDNA的变化情况。结果　治疗组ALT复常率明显高于对照组 ( 3个月时P >0 .0 5 ,6个月、9个月、12个月时P <0 .0 5 ) ,HBVDNA阴转率也高于对照组 ,但差异无显著性 (P >0 .0 5 )。结论　拉米夫定联合母牛分枝杆菌菌苗治疗CHB较单用拉米夫定效果好 ,可以提高抗病毒疗效     

干扰素联合胸腺肽和苦参素治疗慢性乙型肝炎疗效观察

目的评价α干扰素(IFN-α)联合胸腺肽和苦参素治疗慢性乙型肝炎(CHB)的近、远期疗效和安全性,探讨三者联合治疗的协同作用。方法146例HBVDNA及HBeAg阳性的CHB患者随机分为2组。治疗组采用IFN-α和胸腺肽及苦参素联合治疗,对照组单用IFN-α,疗程均为6个月。结果2组比较,近、远期疗效均有显著性差异。结论IFN-α与胸腺肽及苦参素联合治疗CHB具有明显协同作用,可明显改善肝功能,抗病毒效果好,是CHB患者安全有效的治疗方法。     

干扰素α-2b联合苦参素治疗慢性乙型肝炎的临床研究

目的　探讨干扰素α 2b(IFNα 2b)联合苦参素治疗慢性乙型肝炎 (CHB)患者的临床疗效。方法　将 14 6例CHB ,随机分为A、B、C、D 4组。在常规保肝治疗 (D组 )基础上 ,A组加用IFNα 2b联合苦参素治疗 ;B组单用IFNα 2b ;C组单用苦参素 ,疗程 6个月 ,随访 6个月。采用免疫组织化学、放射免疫法及酶联免疫吸附法 ,对治疗前后肝组织学、肝组织转化生长因子 β(TGF β)的表达及血清TGF β、HBeAg、HBVDNA等指标的变化进行了观察。 结果　治疗后A组组织学肝纤维化程度计分、肝组织TGF β的表达及血清TGF β、HBeAg、HBVDNA等指标均显著下降 ,与B、C组比较差异有显著性 (P <0 .0 5或P <0 .0 1) ,肝组织TGF β的表达与肝脏纤维化的动态变化相一致 ;B组与C组相比差异无显著性 (P >0 .0 5 )。结论　IFNα 2b联合苦参素治疗慢性乙型肝炎的疗效优于单一用药。     

拉米夫定联合苦参素治疗慢性乙型肝炎临床观察

目的 观察啦米夫定联合苦参素治疗慢性乙型肝炎病人的近期疗效。方法 选择36例慢性乙型肝炎患者用拉米夫啶100mg，1次／d，服1年，苦参素胶囊200mg，3次／d，服3个月作为观察组。选择36例慢性乙型肝炎患者用拉米夫定100mg，1次／d，服1年治疗作为对照组。结果 疗程结束时，两组肝功能复常率比较无显著性差异(97．2％对91．67％，P＞0．05)；HBVDNA阴转率无显著性差异(97．2％对80．6％，P＞0．1)；HgeAg阴转率有显著性差异(69．23％对28％，P＜0．005)。治疗6个月时，HBVDNA阴转率比较有显著性差异(91．67％对52．78％，P＜0．005)。结论 拉米夫定联合苦参素胶囊治疗慢性乙型肝炎可显著提高HBeAg阳转率，巩固疗效。     

拉米夫定联合中药治疗慢性乙型肝炎11O例

[目的]探讨拉米夫定(LAM)联合中药治疗慢性乙型肝炎(CHB)的临床疗效.[方法]将212例CHB患者随机分为治疗组(110例)与对照组(102例).治疗组给予LAM联合中药治疗;对照组单用LAM治疗.LAM100 mg/d,疗程12个月;中医辨证治疗,根据不同证型,辨证施治,每日服中药1剂,疗程＞8个月.随访1 a.[结果]治疗6、12个月及随访1 a时,治疗组的丙氨酸氨基转移酶(ALT)复常率、HBeAg转阴率、HBeAg血清转换率均明显高于对照组(P＜0.01).HBV-DNA转阴率2组在治疗3、6个月时段差异无统计学意义,而在12个月及随访1 a时段,差异有统计学意义(P＜0.01).[结论]LAM联合中药治疗,可提高CHB患者抗病毒治疗的持续应答率,减少停药后的病情复发,提高临床疗效.     

α干扰素联合苦参素治疗慢性乙型肝炎疗效观察

目的评价α干扰素联合苦参素治疗慢性乙型肝炎的疗效及安全性。方法将86例慢性乙型肝炎患者随机分成两组，43例患者接受α干扰素联合苦参素治疗，另43例单用α干扰素，疗程6个月。结果治疗组2个月时ALT复常率为93．02％，对照组为74．42％，6个月HBeAg及HBVDNA转阴率分别为65．12％和74．42％，对照组分别为51．16％和58．14％，两组白细胞减少率分别为23．26％和60．47％（P〈0．05）。结论α干扰素联合苦参素治疗慢性乙型肝炎有协同作用，同时，苦参素能对干扰素的降白细胞副作用有一定的拮抗作用。     

中药制剂联合母牛分枝杆菌菌苗治疗慢性乙型肝炎疗效观察

目的　观察中药制剂与母牛分枝杆菌菌苗、乙肝疫苗联合应用治疗慢性乙型肝炎 (CHB)的疗效。方法　选择HBsAg、HBeAg、HBVDNA均阳性半年以上的患者 65例 ,分为治疗组 40例 ,对照组 2 5例。治疗组给予中药胶囊 ,3粒 ,口服 3次 /日 ,饭后服用 ;母牛分枝杆菌菌苗 2 2 .5 μg ,深部肌肉注射 ,乙肝疫苗 40 μg ,皮下注射 ,每半月一次。对照组给予香菇多糖片 4片 ,口服 3次 /日 ,饭后服用。上述药物均连用 6个月。结果　治疗组 40例中 ,HBeAg阴转 2 4例 ,HBVDNA阴转 3 0例。对照组 2 5例中 ,HBeAg阴转 4例 (16% ) ,HBVDNA阴转 9例 (3 6% )。两组相比 ,HBeAg阴转率差异较显著 (P <0 .0 5 ) ,HBVDNA阴转率差异非常显著 (P <0 .0 1)。结论　中药制剂与母牛分枝杆菌菌苗联合应用治疗CHB总有效率优于对照组。     

拉米夫定联合苦参素治疗HBeAg阳性慢性乙型肝炎70例

[目的]观察拉米夫定联合苦参素治疗HBeAg阳性慢性乙型肝炎(CHB)的临床疗效。[方法]将140例CHB患者随机分为2组,治疗组70例给予拉米夫定联合苦参素治疗;对照组70例单服拉米夫定疗程均1 a。比较2组治疗后血清丙氨酸氨基转移酶(ALT)、天冬氨酸转氨酶(AST)复常率,HBeAg/抗-HBe转换率,HBeAg、HBV DNA转阴率,YMDD突变率。[结果]治疗组治疗后12个月血清HBeAg/抗-HBe转换率、HBeAg转阴率、YMDD突变率分别为35.7%、47.1%、12.9%;对照组分别为17.1%、27.1%2、8.6%,2组差异有统计学意义(P0.05),2组ALT、AST的复常率比较均P0.05,HBV DNA转阴率P0.05。[结论]拉米夫定联合苦参素治疗HBeAg阳性CHB疗效优于单用拉米夫定治疗。     

拉米夫定联合苦参素治疗拉米夫定撤药性慢性乙型肝炎疗效观察

目的 比较苦参素联合拉米夫定与单用拉米夫定治疗拉米夫定撤药性慢性乙型肝炎治疗效果。方法 52例HBeAg阳性拉米夫定撤药性慢性乙型肝炎患者，随机分为治疗组30例和对照组22例，治疗组应用苦参素联合拉米夫定，对照组单用拉米夫定，疗程6个月。结果 治疗结束时，治疗组ALT复常率(100％)，明显高于对照组(86．7％)；停药半年后ALT复常率(86．7％)，明显高于对照组(63．6％)。治疗组血清HBeAg阴转率(63．3％)明显高于对照组(22．7％)；治疗组停药半年后HBeAg阴转率(53．3％)明显高于对照组(9．0％)。治疗组血清HBeAg血清转换率(46．7％)明显高于对照组(9．0％)；停药半年后血清HBeAg血清转换率治疗组(36．7％)明显高于对照组(4．5％)。治疗组血清HBVDNA阴转率(96．7％)明显高于对照组(77．3％)；治疗组停药半年后血清HBVDNA持续阴转率(76．7％)明显高于对照组(40．9％)。结论 苦参素联合拉米夫定治疗慢性乙型肝炎优于单用拉米夫定治疗，对拉米夫定撤药性肝炎有一定的疗效。     

中西药联用治疗慢性乙型肝炎的疗效分析

目的 探讨国产抗病毒药物单磷酸阿糖腺苷(Ara—AMP)、苦参素、胸腺肽联合治疗慢性乙型肝炎(CHB)的疗效。方法 将136例CHB患者分为4组：A组30例，单独使用Ara-AMP,400mg加入10％葡萄糖200ml静滴，1／d，30d为1个疗程；B组30例，单独使用苦参素注射液6ml肌注，1／d，3个月为1个疗程；C组46例，苦参素、胸腺肽、Ara-AMP联合应用，胸腺肽100mg，静滴，1／d，30d为1个疗程；D组30例，为对照组，仅应用保肝药。结果 A、B、C组均有不同程度抗病毒作用，治疗后1年HBeAg、HBV DNA转阴率分别为33．33％、33．33％、52．34％和33．33％、30％、50％，均明显高于对照组(10％和10％)，P＜0．05；C组ALT复常率高于A、B2组，P＜0．05。HBeAg、HBV DNA转阴率与A、B组比较无明显差异，P＞0．05。结论 Ara—AMP、苦参素、胸腺肽联合治疗CHB疗效可靠，无毒副作用。     

拉米夫定与α干扰素联合治疗慢性乙型肝炎

目的 观察拉米夫定(LAM)联合干扰素α1b(IFNα1b)治疗慢性乙型肝炎的近期疗效和安全性。方法 HBV DNA和HBeAg均阳性的90例慢性乙型肝炎患者，按1：1：1的比例进入三个不同的治疗组。联合治疗组：用IFNα1b 5MU，隔日肌肉注射，及口服LAM 100mg／d，共6个月，随后单用口服LAM 100mg／d6个月；LAM组：口服LAM 100mg／d共12月：IFN组：IFN α1b 5MU，隔日肌肉注射，共6个月。结果 治疗结束时，HBV DNA转阴率，联合治疗组为90．0％，LAM组为80％，IFN组为46．7％。丙氨酸氨基转移酶(ALT)复常率，联合治疗组为90．0％，LAM组为80．0％，IFN组为53．3％。HBeAg／抗HBe血清转换率，联合治疗组为46．7％，LAM组为13．3％，IFN组为33．3％。联合治疗组患者治疗结束时无一例检测到YMDD变异。结论 联合治疗组对HBV DNA抑制作用及ALT复常率高于单用干扰素组，与单用拉米夫定组接近。HBeAg／抗HBe血清转换率高于拉米夫定组，与单用干扰素组相近。初步显示联合治疗组发生YMDD变异较少。     

拉米夫定耐药慢性乙型肝炎患者改用或加用阿德福韦酯治疗48周疗效比较

目的观察拉米夫定(LAM)与阿德福韦酯(ADV)联合应用和单用ADV治疗LAM耐药HBeAg阳性慢性乙型肝炎患者的疗效及安全性。方法收集2006年1月至2011年12月在本院就诊的LAM耐药HBeAg阳性慢性乙型肝炎患者40例,单药组与联合组各20例,分别以ADV与LAM联合或单用ADV进行治疗。观察治疗24周、48周时的血清HBV DNA水平及转阴率、HBeAg转阴率、ALT复常率以及治疗过程中药物的不良反应和耐药性。组间比较计量资料采用t检验,计数资料采用卡方检验。结果两组患者在性别、年龄、治疗前的HBV DNA及ALT水平上差异均无统计学意义(P0.05);治疗结束时联合组的血清HBV DNA转阴率和ALT复常率分别为90%及95%,而单药组的血清HBV DNA转阴率和ALT复常率分别为60%及65%,两组比较差异有统计学意义(P0.05);治疗结束时联合组血清HBeAg转阴率为45%,单药组为35%,两组比较差异无统计学意义(χ2=0.417,P=0.519)。结论 ADV联合LAM或ADV单药治疗LAM耐药HBeAg阳性慢性乙型肝炎患者均有较好的临床疗效,但ADV与LAM联合治疗可提高HBV DNA转阴率及ALT复常率,其安全性良好,值得借鉴。     

拉米夫定联合胸腺肽治疗慢性乙型肝炎的疗效观察

目的 评价拉米夫定联合胸腺肽治疗慢性乙型肝炎(CHB)的近、远期疗效和安全性，探讨两者联合治疗的协同作用。方法 将207例HBV DNA及HBeAg阳性的CHB患者随机分为甲乙两组，甲组采用拉米夫定和胸腺肽联合治疗，乙组单用拉米夫定治疗。胸腺肽15mg口服，每日1次，疗程6个月。两组拉米夫定治疗均为100mg，每日1次，口服，其中甲组92例(92／124)、乙组70例(70／83)用药超过12个月。两组在治疗6个月、12个月时分别进行疗效评价，治疗结束后继续随访12个月。结果 治疗6个月时，甲乙两组ALT复常率分别为87．1％和74．7％，甲组显著高于乙组(P＜0．05)，但两组HBV DNA阴转率、HBeAg阴转率及HBeAg／抗—HBe血清转换率均无显著性差异(P＞0．05)。治疗12个月时，甲乙两组ALT复常率和HBV DNA阴转率无显著性差异(P＞0．05)，甲组HBeAg阴转率及HBeAg／抗-HBe血清转换率均显著高于乙组(P＜0．05)。随访结束时，甲组从量复常率、HBV DNA阴转率、HBeAg阴转率及HBeAg／抗—HBe血清转换率均显著高于乙组(P＜0．05)。结论 拉米夫定与胸腺肽联合治疗CHB，疗效明显优于单用拉米夫定，是CHB患者安全有效的治疗方法。     

Lamivudine monotherapy and lamivudine plus interferon alpha combination therapy in HBeAg negative chronic hepatitis B not responding to previous interferon alpha monotherapy

BACKGROUND AND STUDY AIMS: To investigate the efficacy of the combined therapy of lamivudine (LAM) plus alpha interferon (IFN) and LAM monotherapy in HBeAg negative chronic hepatitis B (CHB) patients who were unresponsive to previous IFN monotherapy, and the incidence of YMDD mutations. PATIENTS-METHODS: Forty-five HBeAg negative patients were enrolled in this study. 24 of these were treated with LAM (100 mg/day, PO, for 24 months) alone (group 1) and 21 with combined therapy (IFN-alpha-2b, 10 MU, tiw, SC, for 6 months plus LAM 100 mg/day, PO, for 24 months) (group 2). Normal alanine aminotransferase values and negativity of HBV DNA (molecular hybridization; Digene, USA) were accepted as treatment response. YMDD variants were analyzed at the end of treatment or when clinical breakthrough was observed (Inno-Lipa Innogenetic kit, Belgium). RESULTS: End of follow-up response rate was 29.2%, by ITT in group 1, 19% in group 2 (p > 0.05). Histological activity index was statistically decreased by LAM monotherapy as compared to combination therapy. YMDD mutation rates were 59% in group 1, 62.5% in group 2 (p > 0.05). CONCLUSIONS: Additional IFN-alpha therapy to LAM in HBeAg negative CHB not responding to previous IFN-alpha monotherapy does not increase the response rate compared to LAM monotherapy and does not also decrease the incidence of YMDD mutations.     

苦参素胶囊对慢性乙型肝炎患者血清TNF-α、IL-6和HBV标志物的影响

目的　观察苦参素胶囊对慢性乙型肝炎患者血清肿瘤坏死因子 α、白细胞介素 6和乙型肝炎病毒标志物的影响。方法　将 47例慢性乙型肝炎患者 (轻度 2 8例、中度 17例、重度 5例 )分别于治疗前和治疗 3月、6月后采集静脉血作TNF α、IL 6、HBV标志物和肝功能的检测。结果　慢性乙型肝炎肝损害的程度与血清INF α、IL 6水平密切相关 ,肝损害越重其值升高越明显。经苦参素胶囊治疗 3个月后 ,其值下降明显 ,与治疗前相比有显著性差异 (P <0 .0 5 ) ,肝损害较轻者变化不明显 ,治疗前后无显著性差异 (P >0 .0 5 ) ;单用苦参素胶囊对慢性乙型肝炎患者HBeAg、HBVDNA转阴率较低 ,但肝功能复常率均在 80 %以上。结论　苦参素胶囊能显著降低慢性乙型肝炎患者血清炎性细胞因子INF α、IL 6水平 ,从而保护肝细胞膜的稳定性 ,有较好的降酶退黄作用 ,但单用苦参素胶囊对HBV标志物的影响则不甚理想     

Combined lamivudine and famciclovir therapy for patients with chronic hepatitis B

OBJECTIVE: No single antiviral drug is able to eradicate hepatitis B virus (HBV) infection. It has been shown in vitro that lamivudine and panciclovir (the active metabolite of famciclovir) act synergistically to inhibit HBV replication. To study the therapeutic efficacy of combined lamivudine and famciclovir therapy in patients with chronic hepatitis B. METHODS: Twenty‐one patients with chronic hepatitis B, who had been given lamivudine monotherapy for more than 6 months without improve­ment, had increased serum alanine aminotransferase (ALT) and HBV‐DNA levels, and were positive for hepatitis B surface antigen (HBsAg); 17 were positive for HBeAg. The diagnosis was verified by histology in 12 HBeAg‐positive cases. All patients were given combined therapy with lami­vudine (100 mg q.d.) and famciclovir (500 mg t.i.d.) orally for 4 months, and then with lamivudine alone for 5?10 months. RESULTS: Serum HBV‐DNA levels were initially 1 × 10^{8.19 ± 1.18} copies/mL, then decreased to 1 × 10^{5.25 ± 1.18} copies/mL at the end of the combined treatment and 1 × 10^{5.25 ± 1.82} copies/mL in the follow‐up period (P < 0.01). Serum ALT decreased from 225 ± 110 U/L before the trial to 79 ± 50 U/L at the end of the combined treatment and 81 ± 48 U/L in the follow‐up period (P < 0.01). In 17 HBeAg‐positive patients, eight (47.1%) had HBeAg/anti‐hepatitis B e antigen (HBeAg) seroconversion with a significant decrease of HBV‐DNA (<1 × 10⁴ copies/mL) and normal ALT (P < 0.01). Of four HBeAg‐negative patients, three had decreased levels of HBV‐DNA, to below 1 × 10⁴ copies/mL, which was associated with a significant decrease in ALT. Two patients had recurrent flare‐ups in the follow‐up period, but both HBV‐DNA and ALT were lower than the pretreatment levels. In 10 patients who underwent a second liver biopsy, improvements in inflammatory activity and fibrosis were seen in eight (80%) and four (40%) cases, respectively (P < 0.05). CONCLUSIONS: The combination treatment of lamivudine and famciclovir has synergistic or additive anti‐HBV effects, and may be an alternative therapy for patients with active chronic hepatitis B.     

拉米夫定联合抗乙肝转移因子和强肝胶囊治疗慢性乙型肝炎的疗效观察

目的观察拉米夫定联合抗乙肝转移因子和强肝胶囊治疗慢性乙型肝炎的疗效。方法将160例慢性乙型肝炎患者随机分为拉米夫定联合抗乙肝转移因子及强肝胶囊治疗组(80例)和单用拉米夫定组(80例)。拉米夫定100mg/d口服,疗程12个月,抗乙肝转移因子4mg/d皮下注射,前1个月每日1次,以后隔日1次,疗程6个月,强肝胶囊2.0,每日2次,每服6日停1日,疗程6个月。结果治疗6个月、12个月及随防6个月时联合治疗组ALT复常率、HBeAg转阴率,HBeAg/抗HBe血清转换率均显著高于拉米夫定组(P<0.01),两组HBVDNA转阴率则无显著性差异(P>0.05);两组治疗12个月及随防6个月联合组HA、LN及IV-C水平显著低于对照组(P<0.05),联合治疗组肝组织学纤维化好转率为86.6%(13/15),与拉米夫定组的60.0%(6/10)有显著性差异(P<0.01)。结论拉米夫定与抗乙肝转移因子及强肝胶囊联合治疗慢性乙型肝炎可提高抗病毒和抗肝纤维化疗效。     

Long-term outcomes of add-on adefovir dipivoxil therapy to ongoing lamivudine in patients with lamivudine-resistant chronic hepatitis B

Aim: Add-on adefovir dipivoxil (ADV) therapy has been a standard rescue treatment for patients with lamivudine (LAM)-resistant chronic hepatitis B, but the overall benefits of long-term add-on ADV therapy are still limited. The aim of this study was to evaluate the long-term efficiency of add-on ADV treatment and to explore predictive factors associated with it. Methods: A total of 158 patients with LAM-resistant chronic hepatitis B were included in this retrospective, multicenter, nationwide study in Japan. After confirming LAM resistance, ADV was added to LAM treatment. Three types of events were considered as outcomes: virological response, hepatitis B e antigen (HBeAg) clearance and alanine aminotransferase (ALT) normalization. Virological response was defined as serum hepatitis B virus (HBV) DNA levels of less than 3 log copies/mL. Baseline factors contributing to these outcomes were examined by univariate and multivariate analyses. Results: The median total duration of ADV treatment was 41 months (range, 6–84). The rate of virological response was 90.8% at 4 years of treatment; HBeAg clearance and ALT normalization were achieved by 34.0% and 82.7%, respectively, at the end of follow up. Each outcome had different predictive factors: baseline HBV DNA and albumin level were predictive factors for virological response, history of interferon therapy and ALT level for HBeAg clearance, and sex and baseline albumin level for ALT normalization. Conclusion: Long-term add-on ADV treatment was highly effective in LAM-resistant chronic hepatitis B patients in terms of virological and biochemical responses. Lower HBV replication and lower albumin level at baseline led to better outcomes.     

联合核苷类药物治疗干扰素应答不佳的慢性乙型肝炎时机选择及疗效研究

目的：探讨干扰素治疗HBeAg阳性慢性乙型肝炎时,联合核苷（酸）类药物的不同时机对治疗应答的影响。方法：观察干扰素治疗患者分别在治疗起始时联合阿德福韦酯、12周应答不佳者及24周应答不佳者联合拉米夫定最终各组疗效。结果：48周时及停药后24周时,起始时联合阿德福韦酯治疗组及12周应答不佳者联合拉米夫定组患者的病毒转阴率、 ALT复常率、 HBeAg转阴率均高于对照组（ P＜0.05）,而HBeAg转换率并未有明显提高（ P＞0.05）。结论：治疗起始干扰素联合阿德福韦酯或根据12周应答情况加用拉米夫定治疗均能一定程度提高治疗应答率。     

Lamivudine and high-dose interferon-alpha combination therapy for naive children with chronic hepatitis B infection

BACKGROUND: More than half of the children with chronic hepatitis B infection are nonresponders to interferon-alpha. The aim of this study was to investigate the efficacy of lamivudine and interferon-alpha combination therapy after a 3-month lamivudine induction in children with chronic hepatitis B. STUDY: Twenty naive children were given lamivudine (4 mg/kg per day; maximum, 100 mg) alone for 3 months; then interferon-alpha (10 MU/m, thrice weekly) was added to lamivudine for 6 months. After interferon-alpha was stopped, lamivudine alone was continued for 6 months. Therapy was stopped 6 months after HBeAg seroconversion. Every 3 months, HBV markers were studied and virologic response was defined as HBV DNA negativity, and HBeAg loss with AntiHBe seroconversion. RESULTS: At the end of 15 months, virologic response was achieved in 11 (55%) of patients and 12 patients (60%) cleared hepatitis B e antigen. Therapy was well tolerated. CONCLUSION: Preliminary results of our study seem to indicate that lamivudine and high-dose interferon-alpha combination therapy after a 3-month lamivudine induction may represent an effective treatment option for children with chronic hepatitis B.