拉米夫定治疗失代偿期乙型肝炎肝硬化患者疗效观察

目的观察拉米夫定用于失代偿期乙型肝炎肝硬化患者抗病毒治疗的疗效。方法将65例失代偿期肝硬化患者随机分为两组，治疗组35例，对照组30例。两组均采用常规内科综合治疗，治疗组加用拉米夫定100mg／d口服，疗程1年。结果治疗组在1年治疗结束时肝功能恢复情况及HEV DNA转阴率均优于对照组（P〈0．01），治疗组病死率8．57％，对照组为16．67％。结论抗病毒治疗能明显改善失代偿期肝硬化患者的肝功能及预后。     

阿德福韦酯联合拉米夫定治疗代偿期乙型肝炎肝硬化疗效观察

目的 观察阿德福韦酯联合拉米夫定及拉米夫定单用治疗代偿期乙型肝炎肝硬化的疗效和安全性.方法 62例患者在保肝、对症支持等综合治疗的基础上分为A、B两组.A组(32例)每13口服阿德福韦酯10 mg和拉米夫定100 mg联合治疗,B组(30例)每日仅口服拉米夫定100 mg,疗程均为48周.观察患者治疗前后临床表现、生化学指标、病毒学及肝纤维化指标改变情况及不良反应.结果 62例患者治疗后病情稳定,肝功能恢复正常;A组HBV-DNA<103cp/ml者占62.5%,HBeAg阴转率达37.5%,病毒耐药突破率仅为3.1%(1例),B组HBV-DNA<10 3cp/ml者占53.3%,HBeAg阴转率为23.3%,病毒耐药突破率为16.6%(5例);两组血清透明质酸酶、Ⅲ型前胶原、层粘连蛋白、Ⅳ型胶原治疗后均明显降低(P<0.01),无明显不良反应出现.结论 阿德福韦酯联合拉米夫定治疗代偿期乙型肝炎肝硬化,可迅速抑制HBV-DNA的复制,促进肝功能恢复,病毒突破率低,安全性好.     

拉米夫定治疗重度慢性乙型肝炎和失代偿期肝硬化

拉米夫定是一种新型的核苷类抗病毒药物 ,本文应用拉米夫定治疗 2 2例重度慢性乙型肝炎、失代偿期肝硬化和重型肝炎患者 ,现总结如下。资料与方法一、病例选择2 2例均为 1999年至 2 0 0 1年 2月期间的住院患者。诊断符合 1995年全国病毒性肝炎防治方案的标准。 2 2例病毒性肝炎中 ,急性重型肝炎 1例 ,肝硬化失代偿期 9例 ,重度慢性肝炎12例 ;年龄 2 5～ 79岁 ,平均 ( 4 5 .6± 13.2 )岁 ;男 2 0例 ,女 2例。病程最短半个月 ,最长 2 0年。所有的病例ＨＢｓＡｇ、抗 ＨＢｃ、ＨＢＶＤＮＡ均阳性 ,其中ＨＢｅＡｇ阳性 13例、抗 ＨＢｅ阳性 7…     

拉米夫定治疗失代偿期乙型肝炎肝硬化患者的临床分析

目的探讨拉米夫定治疗失代偿期乙型肝炎肝硬化的疗效和安全性。方法将60例HBeAg/HBV DNA阳性的失代偿期乙型肝炎肝硬化患者随机分为两组,对照组30例只接受一般保肝、利尿及对症支持治疗,治疗组30例患者加用拉米夫定治疗104周。结果在治疗104周结束时,治疗组患者肝功能明显改善,ALT从135.6±22.5U/L下降到30.9±10.7U/L,TBIL从58.6±16.2μmol/l下降到28.2±18.4μmol/l,HBV DNA转阴率为86.7%,以上指标均优于对照组。结论拉米夫定治疗失代偿期乙型肝炎肝硬化能够快速抑制HBV复制,显著改善肝功能。     

拉米夫定治疗失代偿期乙型肝炎肝硬化34例疗效观察

目的观察拉米夫定治疗失代偿期乙型肝炎肝硬化的疗效及安全性。方法应用拉米夫定治疗失代偿期乙型肝炎肝硬化患者34例,观察144周时的疗效。结果本组患者在治疗后,ALB逐步提高,Child-Pugh评分逐步下降;治疗48周时HBV DNA阴转率为93.9%,96周后因耐药率的升高使HBV DNA阴转率下降为75%;本组患者在治疗48周时,死亡2例（5.9%）,在96周时死亡8例（23.5%）,在144周时死亡13例（38.2%）。结论应用拉米夫定治疗失代偿期乙型肝炎肝硬化患者可改善临床症状和肝功能。长期用药的安全性良好。     

干扰素治疗HBeAg阳性慢性乙型肝炎2年的疗效

我国是乙型肝炎病毒感染高发区,慢性乙型肝炎患者较多,干扰素仍是目前抗病毒治疗的首选药物之一,但短疗程疗效欠佳,应答率较低.我们对35例干扰素治疗有效者进行延长疗程治疗,观察其生物化学、病毒学指标及免疫学指标的变化,进一步观察其临床疗效.     

拉米夫定与阿德福韦酯联合治疗失代偿期乙型肝炎肝硬化患者临床疗效研究

目的 探讨拉米夫定与阿德福韦酯后续或初始联合治疗失代偿期乙型肝炎肝硬化患者的疗效差异。方法 2014年5月~2016年5月收治的失代偿期乙型肝炎肝硬化患者100例,分为A组50例和B组50例,分别给予拉米夫定治疗24 w后再联合阿德福韦酯或初始即两药联合治疗,比较治疗48 w末两组血清HBVDNA转阴和ALT复常情况。结果 B组患者Child-Pugh评分、血清ALT、TBIL和ALB水平分别为（7.6±0.6）分,（65.8±10.1）U/L,（25.4±5.6）μmol/L和（32.3±0.8）g/L,与A组的（8.9±0.8）分,（87.3±21.0）U/L,（27.9±7.4）μmol/L和（32.3±0.6）g/L比,除了血清ALT水平明显低于A组(P<0.05)外,均无显著差异（P<0.05）;B组门静脉内径、脾静脉内径和脾厚度分别为（12.7±0.7）mm、（7.9±0.6）mm和（45.4±6.5）mm,与A组的（12.2±0.9）mm、（7.6±1.0）mm和（45.7±7.4）mm比,无显著差异（P<0.05）;B组血清HBVDNA转阴率和ALT复常率分别为90.0%和88.0%,均显著高于A组的54.0%和60.0%（P<0.05）。结论 相对于后续加用阿德福韦酯,初始联合拉米夫定和阿德福韦酯治疗失代偿期乙型肝炎肝硬化患者,可能提高血清HBV DNA阴转率和血清ALT复常率。     

拉米夫定治疗干扰素无应答的儿童慢性乙型肝炎疗效分析

目的 对干扰素治疗无应答的儿童慢性乙型肝炎使用拉米夫定序贯治疗,探讨拉米夫定对儿童慢性乙型肝炎的疗效和安全性.方法 40例干扰素治疗无应答的慢性乙型肝炎患儿,口服拉米夫定每日3 mg/kg体质量,最大量100 mg/d,观察3年;定期检查血清生化学指标、HBV血清标志物、HBV DNA定量变化;并测身高、体质量,记录不...     

拉米夫定治疗失代偿期乙型肝炎肝硬化的随机对照研究

目的：用随机对照临床试验研究拉米夫定对失代偿期乙型肝炎后肝硬化患者生存率、肝功能生化指标、并发症及乙肝病毒学的影响。方法：107例患者随机分为治疗组（n=59)和对照组（n=48)。治疗组服用拉米夫定每日100毫克，对照组服用复方益肝灵每次四年，每日三次。结果：治疗组中位随访时间96周（17－161周），对照组为93周（12－160周），52周时治疗组HBV DNA转阴率78．7％（37／47），伴血清白蛋白显著升高，胆红素和谷丙转氨酶下降，P＜0．05。治疗组两年生存率为75．70％，对照组40．48％，P＜0．05。原发性肝癌发生率分别为8．5％和22．9％，P＜0．05。治疗组52周后11例（29．7％）HBV DNA转阳性，肝功能下降。结论：拉米夫定能改善乙型肝炎肝硬化失代偿期患者的肝功能，延长生存期，但长期疗效有限，应寻求更有效的治疗措施。     

拉米夫定治疗失代偿期乙型肝炎肝硬化疗效观察

目的观察拉米夫定治疗失代偿期乙型肝炎肝硬化的疗效。方法37例失代偿期乙型肝炎肝硬化患者在保肝支持治疗基础上随机分成两组，治疗组19例加用拉米夫定100mg，口服，每日1次，疗程12个月。对照组18例不做任何抗病毒治疗。结果治疗组在治疗12个月后肝功能明显改善：丙氨酸氨基转移酶从89．6±22．8U／L下降到35．2±8．0U／L；总胆红素从61．4±17．3μmol／L下降到39．2±16．5μmol／L，HBV DNA转阴率为84．2％，HBeAg转阴率为47．4％；与对照组比，差异有统计学意义（P〈0．05）。结论拉米夫定通过抑制乙型肝炎病毒复制，可显著改善失代偿期肝硬化患者的肝功能，降低血清HBV DNA载量，使病情稳定，从而延缓肝硬化进展，提高生存质量。     

Long-term lamivudine treatment of children with chronic hepatitis B: durability of therapeutic responses and safety

Lamivudine has been demonstrated safe and efficacious in the short term in a large cohort of children with chronic hepatitis B (CHB), but optimal duration of treatment has not been elucidated and limited data on the safety of long-term lamivudine administration have been reported. In addition, the durability of favourable therapeutic outcomes after lamivudine therapy in children has not been well characterized. The aim of this study was to examine the safety of lamivudine and the durability of clinical responses in a group of children who received up to 3 years of treatment for CHB. One hundred and fifty-one children from centres in nine countries who had previously received lamivudine in a large prospective trial were enrolled. During the first year, children had been randomized to either lamivudine or placebo treatment. Subsequently, in a separate extension study, those who remained hepatitis B e antigen (HBeAg) positive were given lamivudine for up to 2 years and those who were HBeAg negative were observed for additional 2 years. Results of these studies have been previously reported. In this study, these children were followed for 2 additional years. Data gathered from medical record review included weight, height, signs and symptoms of hepatitis, alanine aminotransferase (ALT) levels, serologic markers, hepatitis B virus (HBV) DNA levels and serious adverse events (SAEs). Other pharmacological treatments for CHB were allowed according to the practices of individual investigators and were documented. Subjects were divided into two groups for analysis, those who had achieved virological response (VR), defined as HBeAg negative and undetectable HBV DNA by the bDNA assay by the end of the extension study at 3 years, and those who had not. In those who had achieved VR by the end of the extension study, long-term durability of HBeAg seroconversion was 82% and >90% in those who had received lamivudine for 52 weeks and at least 2 years respectively. This compares to 75% for those who had achieved seroconversion after placebo. In those who had not achieved VR by the end of the extension study, an additional 11% did so by the end of the study; they had all received lamivudine in the previous trial, and none had received further treatment during the study. Eight children lost hepatitis B surface antigen during the study and all had received lamivudine at some point during the previous trials. Evaluation of safety data revealed no SAEs related to lamivudine. There was no effect of treatment on weight or height z scores. Clinically benign ALT flares (>10 times normal) were seen in 2% of children. Favourable outcomes from lamivudine treatment of CHB in children are maintained for at least several years after completion of treatment. Up to 3 years of lamivudine treatment is safe in children.     

Three-phase sequential combined treatment with lamivudine and interferon in young patients with chronic hepatitis B

Alpha-interferon (IFN) or lamivudine monotherapy are ineffective in treating chronic HBeAg positive patients with high viral load and low alanine aminotransferase (ALT) levels. We investigated whether priming lamivudine treatment might enhance the antiviral and immunostimulant action of lamivudine/IFN combination in young tolerant patients. Eleven chronic HBeAg positive patients received: 100 mg/day lamivudine for 3 months followed by IFN 5 MU/m2/tiw with lamivudine 100 mg/day for 6 months and then lamivudine alone 100 mg/day for 9 months. Quantitative hepatitis B virus (HBV)-DNA was evaluated during treatment and core-promoter, precore and polymerase HBV mutants were detected by direct sequencing at the end of therapy. Serum HBV-DNA levels dropped during lamivudine monotherapy and in combination with IFN. After IFN withdrawal, viraemia transiently increased to high levels in five of 11 (45%) patients who showed rt M204V/I lamivudine mutant resistant. Two patients cleared HBeAg without anti-HBe seroconversion. One patient presented core-promoter (A1762T/G1764A) and precore stop codon mutations. Hence, three-phase sequential combined lamivudine/IFN treatment reduced HBV-DNA serum level, but did not lead to HBeAg and HBV-DNA clearance in these highly viraemic, normal ALT patients. Lamivudine/IFN combination did not prevent the emergence of YMDD lamivudine resistance. New schedules of antiviral treatments must be evaluated in this population at risk of disease progression.     

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     

Efficacy of lamivudine re-treatment for relapsed patients after an initial lamivudine therapy in HBeAg-positive chronic hepatitis B

The efficacy of lamivudine re-treatment in chronic hepatitis B (CHB) patients who relapse after HBeAg seroconversion with lamivudine has not been investigated. The aim of this study was to evaluate the efficacy of lamivudine re-treatment in relapsed patients. Among 192 patients who had achieved HBeAg seroconversion with lamivudine at a dose of 100 mg/day, 121 patients discontinued lamivudine. Relapse occurred in 49 patients (40.5%). Thirty-three relapsed patients received lamivudine re-treatment for at least 6 months. The mean duration of lamivudine re-treatment was 16 months and the follow-up period was 8.9 months. HBeAg seroconversion was achieved in 23 patients (69.7%). The cumulative HBeAg seroconversion rates at 5, 9, and 12 months were 60, 64, and 67%, respectively. The mean time to HBeAg seroconversion in lamivudine re-treatment was shorter than that in the initial therapy (4.7 months vs. 9.7 months). Viral breakthrough occurred in six (18.2%) patients. All patients with viral breakthrough were accompanied by elevation of serum alanine aminotransferase (ALT) levels. Among 15 patients who discontinued lamivudine re-treatment after HBeAg seroconversion, relapse occurred in six patients (40%). All relapses occurred within 9 months after the discontinuation of lamivudine re-treatment. In conclusion, lamivudine re-treatment in relapsed patients after initial lamivudine therapy had a higher response rate and shorter duration to HBeAg seroconversion than during the initial therapy. However, HBeAg seroconversion induced by lamivudine re-treatment was not durable.     

联合治疗策略在应答不佳/耐药HBeAg阳性慢性乙型肝炎患者中的临床研究

目的比较采用聚乙二醇干扰素(pegylated interferon,Peg-IFN)+核苷(酸)类似物[nucleos(t)ide analogues,NAs]和NAs+NAs二种方案治疗NAs治疗应答不佳/耐药的HBe Ag阳性慢性乙型肝炎(chronic hepatitis B,CHB)的疗效和安全性,探求具有停药终点的优化治疗方案。方法选择NAs抗病毒治疗应答不佳/耐药的HBe Ag阳性CHB患者110例,根据既往NAs用药史、耐药检测结果及个人意愿,采用Peg-IFN+NAs(IFN组)或NAs+NAs(NA组)进行抗病毒治疗。比较2组在治疗48周和96周时完全病毒学应答(HBV DNA20 IU/ml)率、HBe Ag血清学转换率及HBs Ag清除/血清学转换率。结果 IFN组58例,NA组52例,2组分别有45例和42例完成96周疗程。在治疗48周IFN组和NA组完全病毒学应答率分别为96.55%(56/58)和67.31%(35/52);96周分别为100%(45/45)和71.43%(30/42),IFN组均高于NA组(P值均为0.001)。IFN组在治疗48周和96周HBe Ag血清学转换率(20.69%、46.67%)高于NA组(5.77%、21.43%),差异有统计学意义(P=0.023、0.013)。24、48、96周时IFN组HBs Ag水平明显低于NA组。截至96周IFN组8例(17.78%)HBs Ag清除,其中3例(6.67%)发生HBs Ag血清学转换。NA组在治疗96周出现1例(2.38%)HBs Ag清除。IFN组的HBs Ag清除率高于NA组(P=0.045)。结论对于NAs治疗应答不佳/耐药的CHB患者,采用Peg-IFN+NAs和NAs+NAs的治疗方案均可有效抑制病毒复制;在HBe Ag血清学转换及HBs Ag清除方面,Peg-IFN+NAs联合治疗方案更具优势。采用以IFN为基础的联合治疗可使NAs应答不佳/耐药患者获得可靠的停药终点。     

恩替卡韦治疗HBeAg阴性代偿期慢性乙型肝炎肝硬化的效果分析

目的探讨恩替卡韦(ETV)治疗HBe Ag阴性代偿期慢性乙型肝炎肝硬化患者96周的临床效果及其对不同HBV DNA载量患者的影响。方法选取2009年1月-2013年6月于襄阳市中医医院就诊的HBe Ag阴性代偿期慢性乙型肝炎肝硬化患者共118例,Child-Pugh评分为A级,根据HBV DNA载量分为高载量组(A组):HBV DNA≥105拷贝/ml和低载量组(B组):HBV DNA105拷贝/ml。给予恩替卡韦0.5 mg/d治疗96周,所有患者治疗前后采用Child-Pugh评分评价肝功能,观察患者治疗前后ALT、白蛋白(Alb)、TBil变化。通过透明质酸、α2巨球蛋白、肝脏硬度测量值(LSM)评估肝纤维化情况。计量资料组间比较采用t检验,不同时间点组内和组间比较采用重复测量数据方差分析。计数资料组间比较采用χ2检验。结果两组血清ALT、Alb、TBil在治疗第12、24周显著下降(χ2值分别为9.241、6.428、11.134、5.139,P值均0.05),两组ALT复常率和HBV DNA阴转率在治疗第24、48周差异均具有统计学意义(t值分别为2.648、1.921、4.018、3.166、2.136、3.461,P值均0.05)。两组透明质酸、α2巨球蛋白和LSM在治疗后显著下降,差异均具有统计学意义(P值均0.05)。两组并发症如静脉曲张出血、腹水、肝细胞癌发生率比较差异均无统计学意义(P值均0.05)。结论恩替卡韦治疗HBe Ag阴性代偿期慢性乙型肝炎肝硬化患者可显著改善其肝功能,减缓肝纤维化及肝硬化进程,有效降低远期并发症。     

Efficacy of lamivudine treatment in Japanese patients with hepatitis B virus-related cirrhosis

Background Several clinical trials have suggested that lamivudine therapy is effective in patients with hepatitis B virus (HBV)-related cirrhosis. However, there are few studies of lamivudine therapy in Japanese patients with HBV cirrhosis. The aim of this study was to evaluate the efficacy of lamivudine therapy in Japanese patients with cirrhosis, and to evaluate the clinical course after the emergence of YMDD mutants.Methods Fifty-four consecutive adult Japanese patients with HBV-related cirrhosis were enrolled and continuously treated with lamivudine, daily for 6–35 months (median, 25 months). Twelve of the 54 patients were hepatitis B envelope antigen (HBeAg)-positive. The clinical courses of 21 of the patients were evaluated using the Child-Pugh-Turcott (CPT) score.Results Lamivudine suppressed serum HBV-DNA to undetectable levels (<3.7 LGE/ml) in 77.8% of patients at 12 months and in 61.3% at 24 months. Before the emergence of YMDD mutants, clinical improvement, defined as a decrease in the CPT score of 2 points or more, was apparent in 6 of 21 (29%) patients. No change in CPT score was evident in 14 of 21 patients (67%). YMDD mutants emerged in 19 of 54 (35%) patients. The cumulative emergence rates increased each year. The emergence rate of YMDD mutants in patients with HBV cirrhosis was higher than that in patients with chronic hepatitis. After the emergence of YMDD mutants, 3 of 12 (25%) patients with YMDD mutants showed CPT score increases of 2 points or more.Conclusions Lamivudine therapy improved the clinical course in some cirrhotic patients. However, in patients with Childs B and C cirrhosis, the emergence of YMDD mutants sometimes led to deterioration of liver function.     

Dynamics of hepatitis B e antigen index ratio correlate with treatment response in chronic hepatitis B patients.

BACKGROUND/AIM: Hepatitis B e antigen (HBeAg) seroconversion is an important event in the natural history of chronic hepatitis B virus (HBV) infection. Whether early dynamics of HBeAg index ratio could predict therapeutic endpoint of HBeAg seroconversion in patients receiving lamivudine remains unclear and thus deserves investigation. METHODS: A total of 52 patients (males/females, 40/12; mean age, 31.1+/-7.5 years) with HBeAg-positive chronic hepatitis B and serum alanine aminotransferase (ALT) level > or = 5 x upper limit of normal were enrolled. They received daily 100 mg lamivudine for at least 1 year. Pretreatment HBeAg index ratio and the dynamics during treatment [early serologic response (ESR) and serologic breakthrough (SB)] between responders and non-responders were compared. RESULTS: Of these 52 patients, mean pretreatment serum ALT level was 580 IU/l and baseline HBeAg index ratio (S/N) was 37.9. The overall 1-year on-treatment combined response rate was 50%. By using linear regression analysis, HBeAg index ratio was positively correlated with serum HBV DNA level (Pearson's correlation coefficient: 0.62, P<0.0001). By using multivariate logistic regression analysis, ESR could predict the success of treatment response (P=0.0302), and SB had a 90% positive predictive value of treatment failure. CONCLUSIONS: HBeAg index ratio is closely correlated with serum HBV DNA level, and the dynamics of HBeAg index ratio may predict 1-year on-treatment combined response to lamivudine in HBeAg-positive chronic hepatitis B patients.     

恩替卡韦联合胸腺肽治疗HBeAg阳性慢性乙型肝炎患者的临床效果

目的研究HBe Ag阳性慢性乙型肝炎(CHB)患者应用恩替卡韦(ETV)联合胸腺肽治疗的临床疗效。方法纳入2012年3月-2015年3月于上海市第八人民医院传染病科就诊的HBe Ag阳性CHB患者108例,根据平行、单盲、随机对照原则分为对照组(54例)和观察组(54例)。两组均接受内科综合治疗,对照组单用ETV治疗,观察组应用ETV联合胸腺肽治疗。对比两组肝功能指标、病毒学指标、免疫指标及肝纤维化指标变化。计量资料组间比较采用t检验,计数资料组间比较采用χ2检验。结果治疗48周后,观察组的肝功能指标(Alb/Glo、ALT、AST、TBil)与对照组比较差异均有统计学意义[(1.73±0.57)vs(1.50±0.51)、(42.58±14.32)U/L vs(54.26±18.78)U/L、(35.79±10.33)U/L vs(49.97±17.84)U/L、(18.89±6.02)μmol/L vs(25.24±9.06)μmol/L,t值分别为2.210、3.634、5.055、4.290,P值均0.05];治疗48周后,观察组的肝纤维化指标(层黏连蛋白、透明质酸、Ⅳ型胶原片段、Ⅲ型前胶原)与对照组比较差异均有统计学意义[(65.34±11.02)ng/ml vs(102.57±16.41)ng/ml、(91.68±11.53)ng/ml vs(151.23±16.71)ng/ml、(81.02±12.64)μg/ml vs(118.47±18.01)μg/ml、(70.44±13.06)μg/ml vs(91.57±17.16)μg/ml,t值分别为13.840、21.555、12.507、7.200,P值均0.001];治疗12、24及48周时,观察组HBe Ag阴转率分别为29.63%、46.30%、57.41%,显著高于对照组的12.96%、22.22%、25.93%(χ2值分别为4.475、6.948、11.009,P值均0.05);治疗48周后观察组的血清IL-4为(2.69±1.23)pg/ml,显著低于对照组的(4.38±1.44)pg/ml(t=6.558,P0.001),IFNγ水平为(1.82±0.89)pg/ml,显著高于对照组的(1.12±0.56)pg/ml(t=4.812,P0.001);观察组的不良反应率为3.70%,与对照组的1.85%比较,差异无统计学意义(χ2=0.343,P=0.558)。结论 HBe Ag阳性CHB患者应用恩替卡韦联合胸腺肽治疗能够促进肝功能康复,调节免疫功能,提高HBe Ag阴转率并抑制肝纤维化进程。     

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.