拉米夫定联合安络化纤丸治疗慢性乙型肝炎患者肝纤维化的临床观察

目的研究联合使用抗病毒药物和安络化纤丸治疗慢性乙型肝炎抗肝纤维化疗效。方法分析单纯降酶治疗、拉米夫定、安络化纤丸、联合拉米夫定和安络化纤丸治疗的100例慢性乙型肝炎患者临床资料,比较治疗前后肝纤维化血清标志物、B超、HBVDNA、HBeAg阴转率。结果联合用药治疗有一定抗肝纤维化作用。联合用药、拉米夫定治疗后血清HBVDNA、HBeAg阴转率均高于降酶组、安络化纤丸组。降酶组、拉米夫定组、安络化纤丸组及联合组治疗后B超影像学改变均无明显差异。结论使用拉米夫定、安络化纤丸治疗慢性乙型肝炎均有抗肝纤维化作用,血清HBVDNA、HBeAg阴转率高于降酶组、安络化纤丸组,联合治疗组抗肝纤维化作用进一步加强。     

拉米夫定联合胸腺肽和甘利欣治疗慢性乙型肝炎疗效观察

目的观察拉米夫定联合胸腺肽、甘利欣治疗慢性乙型肝炎（CHB）的疗效。方法将316例CHB患者随机分为4组,A组84例采用拉米夫定联合胸腺肽与甘利欣治疗;B组81例用拉米夫定联合胸腺肽治疗;C组76例拉米夫定联用甘利欣治疗;D组75例用乙肝胶囊治疗。4组疗程均为6个月。结果疗程结束后4组病例ALT复常率分别为92.8%、77.8%、76.3%、52.0%,血清胆红素（SB）复常率分别为88.1%、70.4%、69.7%、45.3%,HBeAg转阴率分别为39.3%、30.8%、30.3%、30.3%,HBV-DNA转阴率分别为41.7%、28.4%、27.6%、27.6%。停药后随访一年,ALT复常率分别为85.7%、65.4%、64.5%、40.0%,SB复常率分别为84.5%、64.2%、63.2%、36.0%,HBeAg转阴率分别为38.1%、25.9%、25.0%、25.0%,HBV-DNA转阴率分别为38.1%、23.5%、22.4%、22.4%。疗程结束及随访1年时,各组患者ALT复常率、SB复常率及HbeAg、HBV-DNA转阴率间差异均有统计学意义（P〈0.01）;组间两两比较,A组与其余各组比较,差异均有统计学意义（P〈0.05）。结论3种药物联合治疗CHB可取得较好的远期疗效。     

血浆置换与拉米夫定联合治疗慢性重型乙型肝炎的疗效分析

目的观察血浆置换与拉米夫定联合治疗慢性重型乙型肝炎患者的临床疗效。方法两组采用类似的内科基础治疗,两组病例均给予拉米夫定100mg/d,每天一次抗病毒治疗。治疗组加血浆置换。结果治疗组肝功能明显改善,ALT、SB明显下降,CHE、PTA明显上升（P〈0.05）;两组HBV DNA差异有统计学意义（χ2=6.95,P〈0.01）;治疗组总的有效率明显高于对照组,两组比较差异有统计学意义（χ2=4.13,P〈0.05）;两组病死率比较差异有统计学意义（χ2=4.57,P〈0.05）。结论血浆置换与拉米夫定早期联合治疗慢性重型乙型肝炎可迅速抑制病毒复制,快速去除各种毒素,明显改善病情,降低病死率。     

拉米夫定治疗慢性重型乙型肝炎疗效观察

观察拉米夫定治疗慢性重型乙型肝炎的疗效和安全性。98例慢性重型乙型肝炎患者随机分为2组。对照组36例,给予常规的综合治疗;治疗组62例,在常规综合治疗的基础上,加拉米夫定100mg,每日1次口服。分别观察2组治疗前后肝功能和凝血酶原活动度(PTA)、血清HBV DNA水平变化及疗效情况。结果表明,治疗组的总有效率为79．0%,对照组为52．8%,(P＜0．01)。治疗后4周,与对照组比较,治疗组存活患者的总胆红素(TBil)降低(P＜0．001)、凝血酶原活动度(PTA)升高(P＜0．001)、血清HBV DNA水平降低得更明显(P＜0．001)。拉米夫定治疗期间未发现明显的毒副作用,治疗安全性良好。拉米夫定治疗慢性重型乙型肝炎有较好的疗效和安全性。     

拉米夫定联合阿德福韦酯治疗拉米夫定耐药慢性乙型肝炎患者48周的疗效

拉米夫定是第一个批准用于治疗慢性乙型肝炎(CHB)的核苷类似物,虽具有口服吸收完全、半衰期长、不良反应小和抑制HBV复制迅速等优点,但长期应用后部分病例产生病毒变异耐药.本研究采用拉米夫定联合阿德福韦酯对74例拉米夫定耐药的CHB患者进行抗病毒治疗.     

阿德福韦酯联合拉米夫定对拉米夫定耐药的慢性乙型肝炎疗效观察

目的 比较阿德福韦酯联合拉米夫定治疗拉米夫定不同耐药位点变异的慢性乙型肝炎患者的疗效.方法 40例对拉米夫定耐药的慢性乙型肝炎门诊,住院患者根据耐药位点分为两组:联合用药A组和联合用药B组.A组患者为180位点变异组,B组患者为204位点变异.所有患者均治疗1年.治疗前和治疗后4局、12周、24周、48周分别检测血清HBV DNA和ALT.结果 两组患者治疗后平均ALT水平均显著降低,HBV DNA转阴率和ALT复常率显著增加,B组明显优于A组.结论 对于拉米夫定204位点变异的慢性乙型肝炎患者,阿德福韦酯联合拉米夫定疗效较180位点变异好.     

鳖甲煎丸联合恩替卡韦治疗慢性乙型肝炎疗效观察

目的观察鳖甲煎丸联合恩替卡韦对慢性乙型肝炎患者肝功能、血清肝纤维化指标、细胞免疫功能的影响。方法 115例慢性乙型肝炎患者随机分为两组,治疗组59例给予鳖甲煎丸3 g/次,3次/d,口服,ETV0.5 mg/次,1次/d,口服,疗程48周;对照组56例给予ETV0.5 mg/次,1次/d,口服,疗程48周。治疗前后检测肝功能、肝纤维化指标及细胞免疫功能。结果治疗组治疗后血清透明质酸(HA)、层黏连蛋白(LN)、Ⅲ型前胶原(PCⅢ)、Ⅳ型胶原(Ⅳ-C)较治疗前明显下降(P均0.001),且下降幅度明显优于对照组(P均0.05);治疗组治疗后丙氨酸氨基转移酶(ALT)、球蛋白明显降低(P均0.05),外周血CD4~+、CD4~+/CD8~+明显升高(P均0.05),CD8~+明显下降(P0.05)。结论鳖甲煎丸联合ETV能够促进肝功能恢复,提高机体细胞免疫功能,改善血清肝纤维化指标,安全性与耐受性良好,疗效上显著优于对照组。     

拉米夫定治疗HBeAg阳性慢性乙型肝炎的早期疗效预测

拉米夫定治疗慢性乙型肝炎(CHB)已积累了大量的临床数据,近期疗效良好,但是长期治疗易发生HBV变异和耐药[1].若能够在治疗的早期预测患者的远期疗效,将有利于对患者进行优化治疗.我们通过对拉米夫定治疗成人HBeAg阳性CHB患者的临床资料进行了分析,以期探索实际有用的疗效预测指标.     

拉米夫定联合阿德福韦酯治疗YMDD变异HBeAg阳性慢性乙型肝炎效果观察

目的观察阿德福韦酯（ADV）联合拉米夫定（LAM）治疗酪氨酸-蛋氨酸-天门冬氨酸-天门冬氨酸（YMDD）变异HBeAg阳性慢性乙型肝炎（慢乙肝）的疗效及安全性。方法将YMDD变异HBeAg阳性的慢乙肝患者42例随机分为观察组及对照组各21例,观察组予LAM联合ADV口服,连续治疗1a;对照组方法同上,但于4～8周后停服ALM。两组均于治疗后3、6、12个月检测ALT复常率、HBV DNA转阴率、HBeAg转阴率,观察有无ADV耐药及不良反应。结果治疗后3、6个月时观察组HBV DNA转阴率、ALT复常率高于对照组（P〈0．05）;对照组2例治疗过程中出现病毒学反弹及生化学突破,观察组未出现ADV耐药;两组均未发现与药物相关的不良反应。结论初期ADV与LAM联合治疗YMDD变异HBeAg阳性慢乙肝效果优于ADV单药治疗,安全性高。     

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.     

诺和锐30联合茵陈蒿汤加减方治疗慢性乙型肝炎合并糖尿病的疗效分析

目的探讨慢性乙型肝炎合并糖尿病的治疗方法。方法选取本院传染区2008年1月-2012年12月住院的慢性乙型肝炎合并糖尿病患者68例,按治疗方法分为治疗组41例、对照组27例。在常规护肝基础上,对照组以诺和锐30控制血糖,治疗组则以诺和锐联合茵陈蒿汤加减方控制血糖。治疗期间定时检测肝功能、血糖水平、糖化血红蛋白,统计肝功能复常时间,记录并统计每例患者低血糖事件次数及胰岛素日用量。治疗前后及组间均数比较使用t检验。结果治疗后2组肝功能均较前显著改善(P0.01),血糖水平、糖化血红蛋白较前显著下降(P0.01)。其中治疗后,治疗组糖化血红蛋白(6.3%±0.6%)较对照组(7.3%±0.5%)更接近正常且差异有统计学意义(t=7.46,P0.01)。治疗组肝功能复常时间[(28.7±5.61)d]短于对照组[(35.5±6.33)d]且差异有统计学意义(t=4.53,P0.01)。低血糖事件治疗组为(0.8±0.3)次/例,显著低于对照组(2.2±0.8)次/例(t=8.78,P0.01)。胰岛素日用量治疗组为(37.4±5.2)U,低于对照组(44.6±6.5)U,2组比较差异有统计学意义(t=4.86,P0.01)。结论诺和锐联合茵陈蒿汤加减方是治疗慢性乙型肝炎合并糖尿病的经济、有效、安全的方法。     

Clinical outcomes of chronic hepatitis B patients with persistently detectable serum hepatitis B virus DNA during lamivudine therapy

BACKGROUND AND AIM: A small proportion of chronic hepatitis B patients have persistently detectable serum hepatitis B virus (HBV) DNA despite lamivudine therapy. The incidence and clinical outcomes of patients who persistently have detectable serum HBV-DNA during lamivudine therapy was investigated. METHOD: We enrolled 221 chronic hepatitis B patients who underwent lamivudine therapy for more than 6 months. Among them, 180 were HBeAg positive. Serum HBV-DNA, HBeAg, anti-HBe and alanine aminotransferase (ALT) levels were serially monitored. The study groups were defined, using a hybridization assay, as patients with reductions in serum HBV-DNA below the detectable level (group I) or patients with persistently detectable serum HBV-DNA (group II) during the initial 6 months of lamivudine therapy. RESULTS: The incidence of patients who had persistently detectable HBV-DNA was 7.7%. After the first year, the rates of viral breakthrough, HBeAg loss and serum ALT normalization of group I versus group II were 21% versus 63%, 38% versus 0%, and 71% versus 28%, respectively (P < 0.001). The log(10) reduction of serum HBV-DNA at 6 months was -4.58 log(10) for group I and -1.97 log(10) for group II (P < 0.001, bDNA assay). There were no pretreatment lamivudine-resistant mutants in group II. CONCLUSION: Lamivudine had little effect on serum HBV-DNA suppression, viral breakthrough suppression and rate of HBeAg loss and ALT normalization in chronic hepatitis B patients with persistently detectable serum HBV-DNA during the initial 6 months of therapy. Early termination of lamivudine therapy is advocated for these patients.     

Two years of lamivudine therapy in anti-HBe-positive patients with chronic hepatitis B

There is no standard therapy for patients with anti-HBe-positive chronic hepatitis B. The aims of this study were to analyse the efficacy of lamivudine therapy for two years in these patients and to study the sequence variations in the precore and polymerase hepatitis B virus (HBV) regions in relation to therapy. Sixteen patients with chronic anti-HBe-positive hepatitis were treated with lamivudine (100 mg) once daily for 2 years. Levels of alanine aminotransferase (ALT), HBV-DNA and HBsAg were monitored during therapy. The polymerase and precore genes were amplified by polymerase chain reaction and their products were sequenced directly. Thirteen of 16 patients (81%) had a virological and biochemical response after 1 year of therapy and 11 (69%) maintained the complete response after 2 years of lamivudine therapy. Among the three patients without initial virological or biochemical response at year 1, prolonging therapy to 2 years was not associated with an increase in the response. YMDD variants were detected in 19% of cases in the first year and in 44% in the second year: YVDD being the most frequent mutations detected during year 1 and YIDD during year 2 of therapy. YMDD variants were found in 7–27% of cases with complete response depending on the duration of therapy. Our results show that prolonging lamivudine therapy is safe, well tolerated and maintains viral inhibition in anti-HBe-positive patients. However, its efficacy tends to decrease overtime and it is associated with an increase in YMDD variants, even in some cases, of complete response.     

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.     

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。     

拉米夫定联合阿德福韦酯治疗HBeAg阳性慢性乙型肝炎患者48周临床观察

我国现有慢性乙型肝炎（CHB）患者约2000万例,其中HBeAg阳性CHB患者近60%,常常表现为ALT持续或间歇升高,HBV复制活跃,肝组织重度炎症坏死,与HBeAg阴性患者相比,有较高的肝硬化比率[1]及较快速的病情进展[2]。而持续的高病毒载量又与肝细胞癌（HCC）直接相关[3],那么最大限度地长期抑制HBV,减轻肝细胞炎症坏死及纤维化,延缓和减少肝脏失代偿、肝硬化、HCC及其并发症的发生,从而改善生存质量和延长生存时间[4]成为CHB治疗的总体目标。核苷和核苷     

乙型肝炎核心相关抗原对慢性乙型肝炎患者拉米夫定耐药的预测作用

目的评价乙型肝炎核心相关抗原（HBcrAg）对慢性乙型肝炎患者拉米夫定（LAM）耐药的预测作用。方法收集2009年1月至2011年12月期间住院和门诊收治的43例慢性乙型肝炎初治患者,拉米夫定治疗≥6个月,随访≥6个月,根据随访期间HBV DNA测序结果分为耐药组2l例,非耐药组22例。分别检测各研究节点ALT、HBsAg、HBeAg、HBcrAg、HBV DNA水平。计量资料两组问比较采用独立样本t检验,方差不齐采用Mann—Whitney U检验;计数资料采用卡方检验。相关性分析采用Spearman分析。影响因素采用Logistic回归分析。结果LAM抗病毒前HBcrAg与HBV DNA水平有较好的一致性,Spearman相关系数为0．863（P〈0．001）。LAM抗病毒治疗后,外周血HBcrAg与HBV DNA水平均有所下降,但HBcrAg下降速度与幅度均低于HBV DNA。Logistic回归分析显示,随访结束时HBcrAg水平可能为LAM耐药的影响因素（P〈0．01）。HBcrAg对LAM耐药预测价值较高,ROC曲线下面积为0．872（P〈0．001）。结论LAM抗病毒前外周血HBcrAg与HBV DNA有较好的一致性,随访结束时HB—crAg水平可较好的预测LAM耐药。     

Factors related to post-treatment relapse in chronic hepatitis B patients who lost HBeAg after lamivudine therapy

BACKGROUND AND AIM: It is uncertain if a patient's lamivudine response after HBeAg loss is durable. In Korean chronic hepatitis B patients, the relapse rate is high after termination of lamivudine therapy for patients with HBeAg loss. We evaluated the factors related to relapse in chronic hepatitis B patients with HBeAg loss after lamivudine therapy. METHODS: A total of 132 chronic hepatitis B patients, who initially had HBeAg and did not have decompensated features, were analyzed in this study. These patients lost the HBeAg after lamivudine therapy and then their therapy was stopped. Post-treatment serum alanine aminotransferase (ALT), HBeAg, anti-HBe and hepatitis B virus (HBV) DNA were monitored until relapse. RESULTS: Seventy-five patients relapsed (cumulative relapse rate: 56% at 6 months). Upon univariate analysis, the factors of age, serum total bilirubin, presence of anti-HBe after HBeAg loss, and the duration of additional lamivudine therapy after HBeAg loss were associated with relapse. Upon multivariate analysis, older age, a higher serum total bilirubin and the shorter duration of additional lamivudine therapy were significant risk factors for relapse. Patterns of relapse were the re-elevation of ALT, re-emergence of HBV DNA (69 patients) and reappearance of HBeAg (55 patients). CONCLUSIONS: To prevent relapse in patients with chronic hepatitis B infection after lamivudine therapy, age and serum bilirubin level of patients as well as a prolonged duration of additional lamivudine therapy should be considered.     

慢性肝炎肝纤维化中西医结合治疗问题

慢性肝炎肝纤维化主要由乙、丙型肝炎所致,合理治疗应包括抗病毒、调节免疫及抗肝纤维化治疗,有效抗病毒是治疗本病的关键,以西药为主辅以中药可提高疗效。当前在所谓的保（护）肝及对肝纤维化治疗方面药物虽多,但迄今尚乏特（有）效药物。研究表明：以＂瘀血证＂立论,重用丹参配黄芪活血化瘀为主,益气、舒肝、健脾中医中药对肝细胞炎症、坏死及肝纤维化等病变治疗具有良好作用。但面对众多慢性肝炎、肝纤维化患者,可用于临床的抗肝纤维化有效治疗措施仍很有限,而且目前＂861＂、＂益肝康颗粒剂＂;强肝、扶正化瘀胶囊等有效中药投产者不多,尚需做进一步随机对照、盲法、大样本、多中心临床试验研究,并重视肝组织学治疗前后复查结果,进一步验证疗效。