拉米夫定治疗慢性乙型肝炎36例临床观察

目的观察拉米夫定治疗慢性乙型肝炎的效果。方法36例患者,采取拉米夫定治疗,分别于12月和24个月时观察ALT复常率,HBV DNA转阴率及HBeAg转阴率,同时检测YMDD变异的情况。结果拉米夫定治疗1年的HBV DNA、HBeAg转阴率为别为54.5%、24.2%,HBeAg/抗HBe血清转换率12.1%,ALT复常率78.8%,YM-DD变异率5.6%。停药半年后血清HBV DNA复阳率为22.2%,YMDD变异率18.2%,ALT再次升高率33.3%,死亡1例。结论拉米夫定能够有效降低HBV DNA水平,随着用药时间的延长,YMDD变异的发生率逐渐升高,部份病例停药后出现病情反复或加重。     

拉米夫定治疗HBeAg阳性慢性乙型肝炎患者7年结果总结

目的 评估拉米夫定治疗乙型肝炎5年的长期疗效和安全性,以及对病毒变异发生率的影响.方法 429例HBsAg,HBeAg阳性的慢性乙型肝炎患者,先按3:1随机双盲分成拉米夫定组和安慰剂组,治疗共12周,以后所有患者均服拉米夫定100 mg/d,共5年.结果 服药治疗5年后,血清HBV DNA仍持续降低,在YMDD变异患者中则增高,中位值为107.5 Meq/nd.HBeAg阴转率和HBeAg/抗Hbe血清转换率分别为28.6%和27.5%.与治疗前ALT水平有显著关系.治疗前ALT基础值＞2×ULN(正常值上限)和＞5×ULN者,5年时HBeAg阴转率和血清转换率均为50%和67%.治疗前ALT增高的患者,5年治疗后,ALT的复常率为58%,治疗前ALT正常的患者,67.0%仍正常.1,2,3,4和5年的YMDD变异率分别为12.1%,49.7%,70.5%,67.0%和70.8%.发生变异后,HBV DNA大多仍可有一定程度抑制,在基线以下少部分可回升.在YMDD变异患者,继续有HBeAg阴转和血清转换,分别为18.4%和17.8%,低于非变异组患者.疗程中ALT增高＞5×ULN有22例,其中变异者16例,非变异者6例,经处理后均缓解.在5年治疗期间,不良反应24.8%.结论 长期应用拉米夫定可持久抑制HBV复制和促进血清转换,耐受性和安全性好,选择适合的患者,可取得最佳疗效.     

拉米夫定治疗慢乙肝的长期疗效及安全性评价

研究拉米夫定（lamivudine)对慢性乙型肝炎（慢乙肝）的长期疗效和安全性。49例患者均用拉米夫定100mg/d，疗程1－2年。疗效评估包括临床症状和体征、肝功能、HBV复制的指标。治疗3－6个月时，HBV－DNA阴转率为87．8％－75．5％，2年时降至40．9％。疗程结束时HBeAg的血清转换率为11．8％。6个月时ALT复常率为79．6％。疗程结束时ALT复常率为59．1％。拉米夫定治疗6－9个月后可出现YMDD变异，随着疗程的延长YMDD变异率升高，YMDD变异后病情急性发作者，多出现HBeAg的血清转换。拉米夫定能有效抑制HBV复制，迅速降低血清中HBV－DNA水平，提高HBeAg血清转换率，长期服用耐受性好，但疗程越长YMDD变异率越高。     

拉米夫定治疗慢乙肝所致YMDD变异的个体化治疗

回顾性调查48例HBV慢性感染者拉米夫定治疗中出现YMDD变异发生的时间,对其随访观察6～12个月,每1～3个月检查1次肝功和病毒学指标。结果48例患者服药10～37个月出现YMDD变异。无肝硬化者36例,其中YMDD变异后病情稳定的慢乙肝15例,继续服用拉米夫定或停药,患者预后均较好;YMDD变异后病情复发者21例,停拉米夫定者病情进一步恶化,而继续服用拉米夫定并加用保肝治疗或α-干扰素治疗者预后较好。有肝硬化者12例,3例停药后2例死亡;9例继续服用拉米夫定者3例死亡（33．3％）。认为拉米夫定治疗中出现YMDD变异后,应给予个体化治疗,以提高HBeAg的血清转换率,降低病死率。     

拉米夫定治疗慢性乙型肝炎失败的相关因素分析

目的探讨拉米夫定治疗慢性乙型肝炎（CHB）失败的相关因素。方法回顾性分析224例拉米夫定治疗CHB患者的临床资料,根据其疗效分为失败组和成功组,比较两组年龄、性别、用药前ALT、HBV DNA水平、治疗24周后HBV DNA阴转、规则用药、HBeAg性质及HBV YMDD变异等因素。结果拉米夫定治疗失败96例,成功128例;与成功组比较,失败组治疗前ALT水平、治疗24周后HBV DNA阴转率、HBeAg阳性患者治疗中阴转和血清转换率低（P〈0.01）,治疗前HBV DNA水平和HBV YMDD变异率高,患者不规则用药（P〈0.01）,两组在年龄和性别间的差异无显著性意义（P〉0.05）。结论ALT、HBV DNA基线水平,治疗24周后HBV DNA阴转、用药规则,HBV YMDD变异及治疗后HBeAg性质改变均是影响拉米夫定治疗CHB疗效的相关因素。     

拉米夫定治疗慢性乙型肝炎出现血清转换的持续性研究

目的观察拉米夫定治疗慢性乙型肝炎患者5年的血清转换率和持续血清转换率及多元因素对两者的影响。方法81例慢性乙型肝炎患者,每天服用拉米夫定100 mg,持续5年。出现血清转换后, 继续服拉米夫定6个月以上(每3个月随访1次,至少2次以上),仍为乙型肝炎e抗原(-)和抗-HBe( ), 则停药并继续随访6-12个月。所需观察项目有丙氨酸氨基转移酶、血清病毒学标志物、乙型肝炎病毒DNA 载量及基因分型、YMDD变异等。结果(1)共有26例患者出现血清转换。总血清转换率为32.10% (26/81)。第1-5年,每年累积的血清转换率为16.05%、19.75%、27.16%、28.40%和32.10%。(2)停药后4例出现复发,持续血清转换率为84.62%(22/26)。(3)经Logistic多元回归分析,得出近期血清转换率和持续血清转换率与治疗前丙氨酸氨基转移酶水平呈正相关,与治疗前乙型肝炎病毒DNA水平呈负相关。持续血清转换与血清转换后继续服药时间有相关性。结论慢性乙型肝炎患者出现血清转换后继续应用拉米夫定治疗6个月以上,大多数患者可达到持续转换。对持续血清转换的影响因素为治疗前丙氨酸氨基转移酶和乙型肝炎病毒DNA水平(P<0.05)。     

拉米夫定治疗慢性乙型肝炎过程中HBV YMDD变异与临床

目的:探讨拉米夫定治疗慢性乙型肝炎过程中HBV YMDD变异与临床的关系。方法:对应用拉米夫定治疗的19例慢性乙型肝炎患者进行肝功能、乙肝病毒血清学标志物、HBV YMDD变异检测,个别病例进行肝组织病理学检查。结果:ALT异常率为47％,HBeAg血清转换率为15.8％,HBV YMDD变异发生率为25％,肝组织中HBsAg和HBcAg依然阳性。结论:运用拉米夫定治疗慢性乙型肝炎6个月后可出现HBV YMDD变异,随着治疗时间延长,其变异发生率越高;该药远期降酶作用不够理想;HBeAg血清转换率不高;肝组织内仍处于炎症状态。     

乙型肝炎病毒YMDD变异后病情进展的临床研究

目的研究慢性乙型肝炎经拉米夫定(LVD)治疗出现YMDD变异后,病情的进展及观察继续服用LVD并加强保肝治疗的疗效及安全性。方法78例YMDD变异患者采用继续服用LVD并加用双环醇片或水飞蓟素胶囊治疗48周,观察病情变化及转归。结果出现YMDD变异后,HBV DNA反弹的患者占93.6%(73/78),ALT升高者89.7%(70/78);轻度黄疸者25.6%(20/78);7例患者中途自行停用LVD,5例于停药后3~5个月出现重型肝炎的表现,其中2例死亡。本组治疗48周后ALT水平虽有下降,但ALT复常率为12.7%(9/71),HBV DNA较基线下降0.45log10copies/ml,无HBeAg/HBeAb血清转换。结论YMDD变异后大部分患者临床表现轻微;变异后继续LVD及保肝治疗短期内未见病情恶化,但患者ALT复常率、病毒学应答率、血清学应答率低,在无有效抗病毒药物继续治疗的情况下,停止LVD治疗存在病情恶化的风险。     

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。     

阿德福韦酯治疗慢性乙型肝炎患者的临床疗效观察

目的观察阿德福韦酯对慢性乙型肝炎患者的临床疗效。方法随机选择慢性乙型肝炎患者39例,其中12例为拉米夫定治疗后出现YMDD变异者。治疗48周,检测血清HBV DNA及HBV血清学标志物和ALT。结果治疗48周时,全组血清HBV DNA水平下降到1.3×103copies/ml,HBV DNA转阴率为56.4%,HBeAg转阴率为35.9%,HBeAg/抗-HBe转换率12.8%,ALT复常率为69.2%;YMDD变异组血清HBV DNA水平下降到7.9×103copies/ml,HBV DNA转阴率为50.0%,HBeAg转阴率为25.0%,HBeAg/抗-HBe转换率8.3%,ALT复常率为58.3%;HBV DNA>108copies/ml组,血清HBV DNA水平下降到6.8×103copies/ml,HBV DNA转阴率为0.0%,无HBeAg转阴和抗-HBe血清转换,ALT复常率为50.0%。结论阿德福韦酯是一有效的抗HBV药物。对HBV DNA野生株、拉米夫定耐药变异株均有抑制作用,HBV DNA基线水平低者疗效好,HBV DNA>108copies/ml者,疗效差。     

Extended lamivudine retreatment for chronic hepatitis B: maintenance of viral suppression after discontinuation of therapy.

In patients with chronic hepatitis B, brief lamivudine therapy suppresses hepatitis B virus (HBV) DNA but results infrequently in sustained losses of virus replication posttreatment. We evaluated treatment response and its posttreatment durability during up to 18 months of lamivudine therapy (100 mg/d) in 24 patients who had hepatitis B e antigen (HBeAg) despite 1 to 3 months of prior therapy. Therapy was to be stopped after HBeAg loss or seroconversion (acquisition of antibody to HBeAg); posttreatment monitoring continued for 6 months. During therapy, which was well tolerated, HBV DNA became undetectable in all evaluable patients, accompanied by reduced alanine transaminase (ALT) activity. The cumulative 18-month confirmed loss of HBeAg during therapy was 9 of 24 (38%) and seroconversion was 5 of 24 (21%). Therapy was discontinued after HBeAg loss/seroconversion in 7 patients, and HBeAg status was maintained in all. Four of the patients with HBeAg responses lost HBsAg at least once. In 10 (43%) of 23 patients tested, we identified HBV polymerase YMDD mutations, 3 with detectable HBV DNA (2 with ALT elevations) and 7 without virological/biochemical breakthrough. In conclusion, up to 18 months of lamivudine therapy was well tolerated, suppressed HBV replication consistently, and tripled the frequency of HBeAg losses observed during brief-duration therapy; HBeAg loss/seroconversion remained durable posttreatment. The emergence of YMDD-variant HBV was relatively common but occurred typically without reappearance of detectable HBV DNA or ALT elevation. Our observations suggest that lamivudine can be stopped after confirmed HBeAg loss or seroconversion.     

Extended lamivudine treatment in patients with chronic hepatitis B enhances hepatitis B e antigen seroconversion rates: results after 3 years of therapy

A study in Chinese patients with chronic hepatitis B showed that treatment with lamivudine for 1 year significantly improves liver histology and enhances hepatitis B e antigen (HBeAg) seroconversion compared with placebo. Fifty-eight patients from this 1-year study have received long-term treatment with lamivudine 100 mg; the outcome of 3 years of lamivudine is reported here. Before treatment, all patients had detectable HBeAg. HBeAg seroconversion (HBeAg-negative, anti-HBe-positive), hepatitis B virus (HBV)-DNA suppression, alanine transaminase (ALT) normalization, emergence of YMDD variant HBV, liver histology, and long-term safety were assessed. After 3 years of continuous treatment with lamivudine 100 mg daily, 40% (23 of 58) of patients achieved HBeAg seroconversion. In patients with baseline serum ALT >2 x upper limit of normal (ULN), the rate of HBeAg seroconversion was 65% (17 of 26). Median serum HBV-DNA concentrations were below the level of detection, and median ALT concentrations were within the normal range throughout 3 years of treatment. YMDD variant HBV emerged in 33 of 58 (57%) patients during the 3 years, of whom 9 (27%) achieved HBeAg seroconversion (6 after emergence of YMDD variant HBV). ALT levels and histologic scores after emergence of YMDD variant HBV did not show major deterioration. Lamivudine was well tolerated during 3 years of therapy. In conclusion, these data in Chinese patients with chronic hepatitis B show enhanced seroconversion rates with extended lamivudine treatment. Up to two thirds of patients with moderately elevated pretreatment ALT achieved HBeAg seroconversion after 3 years of therapy.     

A 7‐year study of lamivudine therapy for hepatitis B virus e antigen‐positive chronic hepatitis B patients in China

OBJECTIVE: To evaluate the long‐term efficacy and safety of lamivudine treatment for chronic hepatitis B and the impact of emergence of YMDD mutation of hepatitis B virus (HBV). METHODS: A total of 429 patients with serum HBsAg, HBeAg and HBV DNA positive were randomized to receive either lamivudine 100 mg daily or a placebo in a 3:1 ratio for the first 12 weeks. Thereafter, all patients were administered with lamivudine 100 mg/d for 5 years and followed up for 2 years. RESULTS: After 12 weeks of the lamivudine treatment, serum HBV DNA levels decreased rapidly and HBV DNA negativity (<1.6 pg/mL) was 92.2%, whereas it was only 14.1% (P < 0.01) in the placebo group. At the end of 5 years, serum HBV DNA continued to be substantially suppressed. The loss of HBeAg and seroconversion were significantly correlated with baseline alanine aminotransferase (ALT) levels, in patients with baseline ALT > 2 × upper limits of normal, the loss of HBeAg was 54% and seroconversion rate was 50%, respectively. YMDD mutation developed in 70.8% of the patients at years 5. In YMDD mutant patients, HBV DNA levels were increased moderately and with mild to moderate elevations of ALT. ALT flares (ALT > 5ULN) occurred in 22 patients, 16 with YMDD variants and six with non‐variants. One year durability of seroconversion after stopping lamivudine was 80%. CONCLUSION: Lamivudine is effective and tolerable for chronic hepatitis B.     

Durability of serologic response after lamivudine treatment of chronic hepatitis B

Forty subjects with chronic hepatitis B and hepatitis B e antigen (HBeAg) seroconversion following lamivudine therapy in previous trials were monitored after treatment to assess the durability of serologic responses. Patient follow-up began a median of 4.3 months after completion of therapy in previous trials. At months 2, 4, 6, 9, and 12 of year 1, and every 6 months thereafter, we tested for HBeAg and hepatitis B surface antigen (HBsAg), hepatitis B virus (HBV) DNA, and alanine aminotransferase (ALT). After a median (range) of 36.6 (4.8-45.6) months of follow-up monitoring, HBeAg seroconversion was demonstrated at the last visit by 77% (30 of 39) of patients. In a post hoc analysis of a slightly different population of all 65 patients with HBeAg seroconversion in previous trials, the 3-year durability of HBeAg seroconversion measured from the time immediately after discontinuing lamivudine therapy was 64%. Nine (9 of 40, 23%) patients were HBsAg negative at the last assessment. Seventy-four percent (17 of 23) of patients with baseline undetectable HBV DNA and normal ALT maintained these responses at the last visit. Eight patients (8 of 40, 20%) initiated retreatment for reappearance of HBV markers, and 7 showed biochemical and/or virologic improvement (including regained HBeAg seroconversion in 2). No safety issues of concern emerged. In conclusion, most HBeAg responses achieved during lamivudine therapy were durable, and most responders experienced prolonged clinical benefit after HBeAg seroconversion and subsequent discontinuation of lamivudine. Lamivudine retreatment for reappearance of hepatitis B markers can achieve resumption of viral suppression.     

Effects of extended lamivudine therapy in Asian patients with chronic hepatitis B. Asia Hepatitis Lamivudine Study Group

BACKGROUND & AIMS: One-year lamivudine therapy significantly suppressed hepatitis B virus (HBV) replication, improved hepatic necroinflammatory activity, and prevented progression of fibrosis. However, the effects of prolonged therapy are unknown. METHODS: A total of 334 Asian patients with chronic hepatitis B from a previously reported 1-year study were randomized to receive either lamivudine (100 or 25 mg) or placebo for another year. The effects of treatment on serum HBV-DNA suppression, alanine transaminase (ALT) normalization, and hepatitis B e antigen (HBeAg) seroconversion were measured. The presence of YMDD variant HBV and its effect were also determined. RESULTS: A significantly greater proportion of patients achieved sustained HBV-DNA suppression and ALT normalization with 100 mg lamivudine daily for 2 years compared with lamivudine for 1 year followed by placebo for the second year (P<0.001). Daily lamivudine therapy for 2 years was safe and resulted in incremental HBeAg seroconversion from 17% at week 52 to 27% at week 104. HBeAg seroconversion during continued lamivudine therapy increased linearly with increasing pretherapy ALT levels (P< 0.001). Despite the emergence of YMDD mutant in 38% of the patients, they continued to clear serum HBeAg and maintain lower median serum HBV-DNA and ALT levels than baseline values. In contrast, ALT levels increased 8-12 weeks after switching from lamivudine to placebo, but returned to normal once lamivudine treatment was resumed. CONCLUSIONS: Treatment with lamivudine for 2 years is both well tolerated and efficacious in patients with chronic hepatitis B.     

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。     

Determinants for sustained HBeAg response to lamivudine therapy

There are inconsistent data on the durability of hepatitis B e antigen (HBeAg) seroconversion after lamivudine is discontinued. The aim of this study was to examine the determinants for sustained HBeAg response to lamivudine therapy. Both host and viral factors as well as the drug factor were compared between 43 patients with sustained HBeAg response and 39 patients whose response was not sustained. All of them received a mean period of 16 months (range, 3-55 months) lamivudine therapy and had achieved complete response (HBeAg seroconversion plus HBV DNA seroclearance by hybrid capture assay and normal alanine aminotransferase [ALT]) and were followed-up for a mean period of 44 months (range, 12-88 months). Stepwise logistic regression model was used to estimate the sustained response on the presence of the following variables: age; gender; pretherapy ALT; total bilirubin and HBV DNA levels; time to HBeAg seroconversion; additional lamivudine treatment after HBeAg seroconversion; total duration of treatment; hepatitis activity index scores; periportal, intralobular, and portal inflammation and fibrosis scores; scores excluding fibrosis; status of precore mutation; basal core promoter mutation; and genotype. The results showed that genotype (OR, 5.922; 95% CI, 1.611-21.768; P =.007), age (OR, 0.943; 95% CI, 0.891-0.997; P =.040), and additional treatment (OR, 1.097; 95% CI, 1.028-1.171; P =.005) were independent factors to sustained HBeAg response. Further categorical analysis disclosed that patients with genotype B, age < or =36 years, and additional lamivudine treatment over 8 months have higher sustained response. In conclusion, HBV genotype, age, and additional treatment are the major determinants for the sustained HBeAg response to lamivudine therapy.     

拉米夫定治疗慢性乙型肝炎三年疗效观察

目的　评估拉米夫定治疗慢性乙型肝炎 3年的长期疗效和安全性 ,以及病毒变异的发生率和影响。方法　采用多中心双盲、随机、安慰剂、对照临床试验及开放试验。 4 2 9例HBsAg、HBeAg阳性的慢性乙型肝炎病人 ,先按 3∶1随机分成拉米夫定组和安慰剂组 ,治疗 12周 ,以后所有病人均服拉米夫定 10 0mg/d ,共 3年。结果　治疗 12周 ,拉米夫定组HBVDNA累计阴转率 (<1 6pg/ml)为 92 2 % ,安慰剂组仅为 14 1% (P <0 0 1)。服药 3年后 ,血清HBVDNA仍持续降低 ,非变异组病人其中位值 ,低于可检测水平 ,变异组则可有轻度或中度回升 ,中位值为 86mEq/ml (bDNA法 ,相当于液相杂交法的 10pg/ml)。第 3年结束时 ,HBeAg阴转率为 2 0 3% ,HBeAg/抗 HBe血清转换率为17 3%。此与治疗前ALT水平有显著关系。治疗前ALT基础值 >2倍正常值上限 (2ULN)和 >5ULN者 ,3年时HBeAg阴转率分别为 4 2 2 %和 6 6 7% ,血清转换率分别为 34 4 %和 6 1 1%。治疗前ALT增高的病人 ,3年治疗后 ,ALT的复常率为 5 8 8%。第 1、2和 3年的YMDD变异率分别为 12 1%、4 9 7%和 70 5 %。发生变异后 ,继续服药 ,HBVDNA大多仍抑制 ,少数可回升 ,中位值为 86mEq/ml,仍继续有HBeAg阴转和血清转换 ,分别为 2 0 0 %和 15 1% ,低于非变异组病人。ALT增     

Durability of HBeAg seroconversion following antiviral therapy for chronic hepatitis B: relation to type of therapy and pretreatment serum hepatitis B virus DNA and alanine aminotransferase

Background and aims: Interferon (IFN) induced hepatitis B e antigen (HBeAg) seroconversion is durable in 80-90% of chronic hepatitis B patients. Preliminary reports on the durability of HBeAg seroconversion following lamivudine are contradictory. We investigated the durability of response following IFN, lamivudine, or IFN-lamivudine combination therapy in a meta-analysis of individual patient data. PATIENTS AND METHODS: Twenty four centres included 130 patients in total with an HBeAg seroconversion (HBeAg negative, antibodies to hepatitis B e antigen positive) at the end of antiviral therapy: 59 with lamivudine, 49 with interferon, and 22 with combination therapy. Relapse was defined as confirmed reappearance of HBeAg. RESULTS: The three year cumulative HBeAg relapse rate by the Kaplan-Meier method was 54% for lamivudine, 32% for IFN, and 23% for combination therapy (p=0.01). Cox regression analysis identified pretreatment hepatitis B virus (HBV) DNA, alanine aminotransferase (ALT), sex, and therapy as independent predictive factors of post-treatment relapse; Asian race, previous therapy, centre, and type of study were not predictive of relapse. The relative HBeAg relapse risk of lamivudine compared with IFN therapy was 4.6 and that of combination therapy to IFN therapy 0.7 (p(overall)=0.01). CONCLUSIONS: The durability of HBeAg seroconversion following lamivudine treatment was significantly lower than that following IFN or IFN-lamivudine combination therapy. The risk of relapse after HBeAg seroconversion was also related to pretreatment levels of serum ALT and HBV DNA, but independent of Asian race.