拉米夫定治疗慢性乙型重型肝炎的疗效观察

目的观察拉米夫定治疗慢性乙型重型肝炎的临床疗效及安全性。方法选择我院2002年4月至2004年8月所收治的慢性乙型重型肝炎患者66例,分治疗组39例,对照组27例,分别在不同时期给予拉米夫定治疗72周,观察其疗效与不良反应。结果治疗组疗效明显优于对照组,有显著性差异(P<0.05)。结论拉米夫定治疗慢性乙型重型肝炎,能提高患者救治成功率,安全性好,及早使用疗效较好。     

拉米夫定治疗HBV DNA阳性慢性重型乙型肝炎疗效分析

目的为了阻断HBV诱导的免疫性肝损伤、提高慢性重型肝炎患者的存活率,我们采用拉米夫定治疗血清HBV DNA阳性的慢性重型乙型肝炎患者,观察治疗效果与不良反应发生情况。方法 106例慢性重型乙型肝炎患者,入院时血清HBVDNA阳性而其它肝炎病毒血清学指标阴性,并排除妊娠性和酒精性肝病。随机分为A、B两组,A组在护肝、促进肝细胞再生、降酶、利胆等一般综合疗法的基础上加服拉米夫定100mg,每晚1次,不再使用其它抗病毒药物;B组仅采用一般综合疗法。两组患者住院日均大于30d,观察疗程均为1年,治疗中肝功能恢复后又出现异常者为肝炎再活动。所有病例入院时、入院后每月定期采血用ELISA法检测HBVM,荧光定量PCR法检测HBV DNA;同时观察血清总胆红素、血常规及甲胎蛋白等指标。结果 A组患者存活率为67.9％(36/53),与B组(49.1％,26/53)比较具有显著性差异(P<0.05)。存活患者中,A组HBeAg、HBV DNA阳性率分别为25.0％(9/36)、5.6％(2/36),B组分别为61.5％(16/26)、84.6％(22/26),两组差异有高度显著性(P均<0.01);A组血清HBV DNA阳性者的HBVDNA平均含量(103.8±126.0 copy/μl)也显著低于B组(5 196.4±2 353.8 copy/μl)(P<0.01),两者与入院时(3 944.7±859.6 copy/μl)比较,差异均有高度显著性(P<0.01)。A组TBiL复常时间(98.5±21.3d)比B组(124.7±32.0d)明显缩短(P<0.01),1年后肝炎再活动率(13.9％,5/36)明显低于B组(65.4％,17/26)(P<0.01)。A组中仅个别患者出现轻度腹泻,未见血常规和甲胎蛋白检测异常。结论拉米夫定能够抑制HBV DNA合成,减少新表达的靶抗原量,使炎症反应逐渐缓解。本研究发现,应用拉米夫定治疗血清HBV DNA阳性的慢性重型乙型肝炎,可促使HBeAg和HBV DNA转阴,且血清HBV DNA未转阴者的HBV DNA平均含量也显著低于对照病例与自身治疗前水平,说明患者体内HBV DNA的复制受到抑制。相反,对照病例经一般综合治疗后血清HBV DNA阳性者的HBV DNA平均含量不仅明显高于拉米夫定治疗患者,还明显高于自身治疗前水平,表明未采用拉米夫定治疗患者体内仍存在HBV DNA大量复制。我们还观察到经拉米夫定治疗后,患者TBiL复常时间明显缩短,肝炎再活动率也明显降低,说明拉米夫定能够促进肝功能的恢复、减少肝炎的复发。此外,拉米夫定副作用少见,对造血系统和肝细胞增生无明显抑制作用。上述机制可能与本研究中采用拉米夫定治疗时患者生存率较高有关。本研究证明:拉米夫定是治疗慢性重型乙型肝炎、抗HBV的安全有效药物。     

拉米夫定治疗慢性重型乙型肝炎疗效观察

慢性重型乙型肝炎病情严重 ,预后凶险 ,其治疗长期以来无明显突破 ,是临床上急待解决的难题。我们试用拉米夫定治疗慢性重型乙型肝炎 ,取得了较好疗效 ,现将结果报道如下。材料和方法一、研究对象40例慢性重型乙型病毒性肝炎患者均为我院 1998年1月～ 2 0 0 0年 4月住院患者 ,其中男 37例 ,女 3例 ,年龄 2 0～ 6 5岁。治疗前 40例患者均有重度黄疸 (血清胆红素 >171μｍｏｌ/Ｌ) ;凝血酶原时间 (ＰＴ)明显延长 ,凝血酶原活动度 (ＰＴＡ)均 <40 %。 40例患者血清ＨＢｓＡｇ与ＨＢＶＤＮＡ(聚合酶链反应 )均阳性。甲、丙、丁和戊型肝炎病毒标…     

拉米夫定治疗慢性重型乙型肝炎近期临床疗效观察

目的 观察拉米夫定治疗慢性重型乙型肝炎的疗效。方法 31例患者给予拉米夫定100mg口服,每日一次,观察患者病死率、病毒量、血清病毒标志物及生化指标的改变。结果 治疗组病死率为32.2％,较对照组54.8％明显下降,病毒量明显减少,生化指标改善。结论 拉米夫定治疗慢性乙型重型肝炎似有一定的近期疗效。     

拉米夫定、强的松龙治疗慢性乙型重型肝炎5例报道

乙型慢性重型肝炎的治疗一直是临床治疗的难点,多数学者不主张应用皮质激素治疗.现将我科近来收治的5例乙型慢性重型肝炎在拉米夫定、强的松龙的治疗中,取得了满意疗效:     

拉米夫定治疗慢性乙型重型肝炎近期疗效观察

目的　观察拉米夫定治疗慢性乙型重型肝炎的近期疗效。方法　选择慢性乙型重型肝炎病人 2 3例 ,随机分成两组 ,拉米夫定组口服拉米夫定 ( 10 0mg/d) ,其它综合治疗措施与对照组相同 ,两组疗程均为 12周 ,观察其临床、生物化学、病毒学指标变化。结果　 ( 1)拉米夫定组TBIL、PTA、Child Pugh计分较对照组下降更显著 (P <0 .0 5 ) ,而ALT、AST、ALB下降和对照组无显著差异。 ( 2 )拉米夫定组HBVDNA阴转率显著高于对照组 ( 88.9%对 3 7.5 % ,P <0 .0 5 )。( 3 )拉米夫定组病死率与对照组无显著差异 ( 18.2 %对 3 3 .3 % ,P >0 .0 5 )。结论　拉米夫定治疗慢性乙型重型肝炎 ,可缓解病情 ,改善肝功能 ,抑制HBV复制 ,但对病死率无显著影响     

拉米夫定治疗慢性乙型重型肝炎近期疗效的观察

目的观察拉米夫定治疗慢性乙型重型肝炎的疗效。方法对25例慢性乙型重型肝炎患者临床资料进行回顾性分析。治疗组11例，对照组14例。对照组接受综合治疗，治疗组在综合治疗的基础上加用拉米夫定100mg口服，每日一次。结果治疗组存活9例(81．8％)，对照组存活4例(28．6％)。结论拉米夫定治疗伴有乙型肝炎病毒复制的慢性重型肝炎患者，可提高成活率。     

恩替卡韦治疗慢性重型乙型肝炎疗效观察

目的观察恩替卡韦治疗慢性重型乙型肝炎的疗效和安全性。方法36例慢性重型乙型肝炎患者随机分为2组。对照组16例给予常规的综合治疗;治疗组20例,在常规综合治疗的基础上,加用恩替卡韦0.5mg,每日一次,口服4周。分别观察2组治疗前后肝功能和凝血酶原活动度（PTA）、血清HBVDNA水平变化及疗效情况。结果治疗组的总有效率为85.0%,对照组为50.0%,P〈0.01。治疗后4周,与对照组相比,治疗组存活患者的总胆红素降低,凝血酶原活动度（PTA）升高、血清HBVDNA水平降低具有统计学意义P〈0.01。未发现明显的毒副作用。结论恩替卡韦治疗慢性重型乙型肝炎具有较好的疗效和安全性。     

拉米夫定治疗慢性乙型肝炎患者的疗效观察

目的探讨拉米夫定治疗慢性乙型肝炎(CHB)患者的疗效。方法按治疗前血清 ALT 水平将 CHB 患者分为二组:A 组26例 ALT>200IU,B 组34例 ALT<200IU。C 组为30例 HBV 携带者。所有受试对象均接受拉米夫定治疗一年,并加中西药辅助治疗。采用荧光定量 PCR 法检测血清 HBVDNA 含量,采用 ELISA 法检测血清乙肝五项指标。结果治疗后 A 组血清 HBV DNA 含量2.96±0.74,显著低了 C 组(P<0.01),血清 HBV DNA 阴转率84.6%、HBeAg 阴转率 69.2%、HBeAb 转换率61.5%,均显著高于 C 组(P<0.05,P<0.01)。治疗后 B 组血清 HBV DNA 含量3.33±1.20,显著低于 C 组(P<0.05),血清HBeAg 阴转率58.8%、HBeAb 转换率50.0%,均显著高于 C 组(P<0.05)。治疗后 C 组血清 HBV DNA 含量4.22±1.81,HBV DNA 阴转率56.7%,HBeAg 阴转率33.3%,HBeAb 转换率23.3%。结论拉米夫定对CHB 患者治疗效果好,对 HBV 携带者也有一定疗效;治疗前 ALT 水平高的 CHB 患者对拉米夫定治疗更为敏感。     

拉米夫定治疗慢性重型乙型肝炎短期临床疗效观察

慢性重型乙型肝炎病情凶险，死亡率高，其抗病毒治疗，目前临床上无突破性进展。用拉米夫定治疗慢性重型乙型肝炎，初步观察其短期临床效果，结果如下：     

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.     

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。     

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.     

Four years of lamivudine treatment in Chinese patients with chronic hepatitis B

BACKGROUND AND AIMS: This study assessed the efficacy and safety of up to 4 years of lamivudine treatment and the clinical relevance of the emergence of YMDD-variant hepatitis B virus (HBV). METHODS: Fifty-eight Chinese adult patients with chronic hepatitis B (CHB) were randomized to lamivudine 100 mg/day for up to 5 years and were monitored for YMDD-variant HBV, hepatitis B e antigen (HBeAg) seroconversion (loss of HBeAg and detectable antibody to HBeAg) and serum alanine aminotransferase (ALT) concentrations. Four-year data are reported here. RESULTS: The rate of HBeAg seroconversion increased with extended therapy and also with higher baseline ALT concentrations. YMDD-variant HBV was detected in 67% (39/58) of patients at some point during treatment. After 4 years, a total of 47% (27/58) of patients achieved HBeAg seroconversion. Thirty-three per cent (13/39) of patients with YMDD-variant HBV achieved HBeAg seroconversion; this increased to 57% (8/14) in patients with moderately elevated (>2-5 x upper limit of normal) pre-treatment ALT concentrations. The proportion of patients that achieved normal serum ALT increased from 29% (17/58) at baseline to 69% (31/45) following 4 years of treatment. That included 68% (23/34) of patients with YMDD-variant HBV and 73% (8/11) of those without the variant. All patients receiving lamivudine had reduced serum concentrations of HBV-DNA compared with baseline, despite the emergence of YMDD-variant HBV in 39 patients. Lamivudine was generally well tolerated; there was little change in the number or type of drug-related adverse events in the fourth year of the study. CONCLUSIONS: Despite the emergence of YMDD-variant HBV, Chinese patients showed increased HBeAg seroconversion and improvement in ALT levels with an increased duration of treatment with lamivudine.     

阿德福韦酯单药挽救治疗对拉米夫定耐药的慢性乙型肝炎患者3年疗效观察

目的总结阿德福韦酯(ADV)单药挽救治疗拉米夫定(LAM)耐药慢性乙型肝炎患者效果,分析疗效影响因素,探讨单药挽救LAM耐药的可行性。方法 60例慢性乙型肝炎应用LAM耐药后入组挽救治疗。收集患者的基本特征:如年龄、性别、肝生化指标、HBV DNA及HBV M。纪录治疗持续时间及应答,并进行分组对照。结果 60例中,HBV DNA定量反弹≥1log10拷贝/ml 20例,HBV DNA测序rtM204I/V、rtL180M位点变异40例。生化学突破的LAM耐药患者,给予ADV单药治疗。完成156周治疗者42例。HBV DNA低复制组(基线水平HBV DNA 103～105拷贝/ml)治疗后第12至156周HBV DNA转阴率均为80.0%,高复制组(基线水平HBV DNA≥106拷贝/ml)转阴率为40.7%～44.7%,两组相比差异有统计学意义(P<0.01)。HBV DNA转阴率随治疗时间延长渐增加。治疗156周时,HBeAg阳性血清学转换率24.1%。4例因检测出rtA181V/I/S位点变异改用恩替卡韦(ETV)。结论 ADV单药挽救治疗LAM耐药慢性乙型肝炎,具有一定的疗效,且更适合于低病毒载量患者。     

拉米夫定治疗慢性重型肝炎疗效观察

将45例慢性重型乙型肝炎患者随机分为治疗组22例、对照组23例.治疗组在综合保肝治疗的基础上口服拉米夫定100mg、每日1次,对照组仅用综合保肝治疗,疗程均为1年;观察症状、体征、肝功能、血清HBVM和HBVDNA的变化.结果显示,治疗后两组患者症状体征均有一定程度的改善;治疗结束时,治疗组治愈好转率(95.45%)高于对照组(73.91%),病死率(4.5%)低于对照组(17.39%),P均＜0.05.治疗前治疗组13例HBVDNA阴性、9例阳性(650.47±597.22fg/ml),治疗后阴性者持续阴性,阳性者均逐渐转阴;对照组15例HBVDNA阴性、8例阳性(579.52±542.86fg/ml),治疗后阴性者6例阳转,阳性者持续阳性.治疗3个月时,治疗组ALT复常率高于对照组;治疗8个月后治疗组复发率4.7%(1/21),对照组为57.14%(8/14),P＜0.01.提示拉米夫定治疗慢性重型乙型肝炎可使病毒持久转阴,复发率和病死率低.     

Hepatitis B surface antigen seroconversion is associated with favourable long-term clinical outcomes during lamivudine treatment in HBeAg-negative chronic hepatitis B patients

The aims of this study were to assess hepatitis B surface antigen (HBsAg) seroconversion and to determine its impact on the natural course of the disease in patients with HBeAg-negative chronic hepatitis B (CHB) during lamivudine (LMV) treatment. A total of 183 consecutive patients with HBeAg-negative CHB who were treated with LMV were included in the study. Data were retrospectively collected from outpatient visit charts. The primary endpoint was HBsAg seroconversion to anti-HBs. The secondary endpoint was to determine the development of cirrhosis. Loss of HBsAg was confirmed in 10 patients and seroconversion to anti-HBs in nine patients during LMV treatment or after its discontinuation. HBsAg seroconversion was achieved on-treatment in four patients after a median treatment duration of 30 months and off-treatment in the remaining five patients in a median 61 months after LMV discontinuation. The cumulative probability of HBsAg seroconversion increased from 0.6% at 1 year and 1.9% at 5 years to 21.5% at 10 years of LMV during and after LMV treatment. HBsAg clearance was preceded by undetectable serum hepatitis B virus (HBV) DNA. The majority of the patients responding to treatment had undetectable HBV DNA levels at 24 weeks of treatment. The cumulative probability of LMV resistance increased from 2.2% at 1 year to 37.3% at 5 years. No baseline parameter predicting either HBsAg seroconversion or the emergence of LMV resistance was identified. None of the patients with HBsAg seroconversion experienced virological breakthrough or disease progression during the follow-up period. These results indicate that HBsAg seroclearance can occur in patients with HBeAg-negative CHB under LMV therapy and predicts better clinical outcome.     

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。     

C ASE R EPORT: Dramatic response to lamivudine therapy following corticosteroid priming in chronic hepatitis B

A 21 year-old male patient with chronic hepatitis B was treated with lamivudine 150 mg daily after withdrawal of a short course of oral prednisolone (30 mg daily for 3 weeks, 15 mg daily for 1 week). Serum hepatitis B virus (HBV)-DNA increased during prednisolone pretherapy and serum alanine aminotransferase (ALT) was increasing after withdrawal of prednisolone. Clearance of HBV-DNA with hepatitis B e antigen seroconversion and ALT normalization occurred within 2 months after starting lamivudine therapy. If this dramatic response to lamivudine therapy after corticosteroid priming is confirmed by further studies, the regimens used in this particular case might become a powerful therapeutic tool for chronic HBV infection.