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.     

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.     

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.     

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.     

Durability of lamivudine-induced HBeAg seroconversion for chronic hepatitis B patients with acute exacerbation

BACKGROUND/AIMS: Lamivudine-induced hepatitis B e antigen (HBeAg) seroconversion in patients with chronic hepatitis B was reported to be durable by several studies but controversy still exists. The aim of this study was to evaluate the durability of the responses of lamivudine treatment. METHODS: Among 53 chronic hepatitis B patients who had acute exacerbation and had finished lamivudine therapy after at least 6 months of treatment, 31 patients achieved full HBeAg seroconversion twice at least 1 month apart, and subsequently stopped lamivudine therapy. Post-treatment monitoring was continued for up to 87 weeks. Alanine transaminase (ALT), HBeAg and hepatitis B virus (HBV) DNA were used as indicators for relapse. RESULTS: The cumulative relapse rates at 48 and 72 weeks post-treatment were 45.4% and 56.3%, respectively. During follow up, normal ALT levels precluded relapse while ALT levels over two times the upper limit of normal indicated relapse, which correlated well with HBeAg or HBV DNA reappearance. Patients older than 25 years were more likely to experience post-treatment relapse. CONCLUSIONS: Lamivudine-induced full HBeAg seroconversion was not durable in the Taiwanese population. ALT levels were useful for relapse detection. Age was the only independent predictive factor for relapse.     

拉米夫定治疗HBeAg阳性慢性乙型肝炎患者血清转换持久性的研究

目的观察拉米夫定长期治疗慢性乙型肝炎(CHB)3年以上患者的血清转换率和停药后持久率,及影响疗效的有关因素.方法167例CHB患者,每天服用拉米夫定100mg,持续3年以上,连续2次以上出现血清转换(间隔3个月),即HBeAg转阴和抗HBe转阳,继续服药6～12个月后,停药并随访1年以上.服药第1年每月,以后第3个月观察临床症状和血清病毒学标志、丙氨酸转氨酶(ALT)、HBV DNA定量及YMDD变异等项目.HBV基因分型应用型特异性PCR方法.结果共有45例患者出现血清转换(27.0%),继续服药6～12个月后停药并随访1年以上,9例出现血清学重新激活,血清转换持久率为80.0%.经单因素统计和Logistic多元回归分析,得出血清转换率和停药后持久率与基线ALT水平呈正相关,与基线HBV DNA水平和治疗后YMDD变异呈负相关.结论CHB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.对血清转换率和持久率有显著影响意义的因子为基线ALT、治疗后YMDD变异.     

拉米夫定联合胸腺肽加乙肝疫苗治疗慢性乙型肝炎的临床观察

目的观察拉米夫定联合胸腺肽加乙肝疫苗治疗慢性乙型肝炎的临床效果。方法100例未曾接受过抗病毒治疗的慢性乙型肝炎患者随机分为治疗组和对照组,治疗组50例,给予拉米夫定100mg,每日一次口服,同时乙肝疫苗10μg皮下注射,每两周一次,胸腺肽20mg肌肉注射,隔日一次,共计26周,随后继续使用拉米夫定和乙肝疫苗26周,总疗程52周;对照组给予拉米夫定100mg·d-1,疗程52周。结果治疗结束时治疗组ALT下降、HBeAg/抗-HBe血清转换率明显高于对照组,差异有显著性(P<0·01),但HBVDNA下降差异无显著性(P<0·01),停药后随访6月、12月,治疗组ALT及HBVDNA下降、HBeAg/抗-HBe血清转换率明显高于对照组比,差异有显著性(P<0·01)。治疗组的完全应答率与对照组比,差异有高度显著性(P<0·01)。结论拉米夫定联合胸腺肽加乙肝疫苗能明显提高临床疗效及HBeAg/抗-HBe血清转换率及HBVDNA阴转率,且无明显毒性反应。     

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患者的疗效与安全性。方法60例患者给予拉米夫定0．1口服，1次／日，疗程一年；其中13例患者进行治疗前后的肝组织病理学检查。结果治疗一年后肝组织学纤维化和炎症程度改善率为69．23％；36．3％的患者ALT复常；85％的患者HBV DNA水平由阳性转变为检测线以下，而HBeAg／抗-HBe血清转换率只有7．1％。结论拉米夫定可明显降低患者血清HBV DNA水平，并能改善肝组织学的炎症和纤维化程度，且用药安全，但HBeAg／抗-HBe血清转换率低。     

拉米夫定治疗慢性乙型肝炎的疗效影响因素

目的 探讨拉米夫定治疗慢性乙型肝炎患者的疗效影响因素,并初步评价基线特征、24周早期病毒学应答及治疗方案对疗效和病毒学突破(VB)发生率的影响.方法 对接受拉米夫定治疗的233例慢性乙型肝炎患者(其中90例治疗期间加用或换用阿德福韦酯)的专科门诊病历资料进行回顾性分析,采用聚合酶链反应法、酶联免疫吸附法分别检测HBV DNA水平与HBsAg、抗-HBs,HBeAg,抗-HBe水平.用SPSS17.0统计软件通过Kaplan-Meier法描述生存时间分布,并分析基线HBV DNA水平,HBeAg状态、ALT水平和疗效的关系.计量资料用t检验分析,计数资料用x2检验.结果 HBeAg阳性与HBeAg阴性患者HBV DNA阴转率分别为63.4%和84.6%,ALT复常率分别为83.8%和81.3%,VB发生率分别为31.0%和14.3%;60.6%的HBeAg阳性患者出现HBeAg阴转,28.9%出现HBeAg/抗-HBe血清学转换.HBeAg阳性患者中,与基线ALT<2.5×正常值上限(ULN)者比较,≥2.5×ULN者HBV DNA阴转率无明显变化(P>0.05),而HBeAg阴转率(66.7%与45.0%)和HBeAg血清学转换率(33.3%与17.5%)明显升高(P值均<0.05),VB发生率则明显下降(34.3%与50.0%,P<0.05),基线HBV DNA<1×106拷贝/ml者VB发生率为23.4%,与HBV DNA≥1×106拷贝/ml者的46.3%比较,差异有统计学意义(P<0.05).HBeAg阳性患者24周有初始病毒学应答(IVR)者的HBV DNA阴转率(76.3%与45.5%)、HBeAg阴转率(72.4%与43.9%)和HBeAg血清学转换率(40.8%与12.1%)均明显高于无IVR者(P值均<0.01),VB发生率较低(28.9%与45.5%,P<0.05).出现VB后,与单一拉米夫定组比较,加药或换药组中HBeAg阳性者HBV DNA阴转率(40.6%与16.7%)、HBeAg血清学转换率(21.9%与0)较高,HBeAg阴转率(37.5%与41.7%)较低,ALT复常率无差别(均为75%);而HBeAg阴性患者的HBV DNA阴转率、ALT复常率较高.结论 拉米夫定抗病毒疗效确切,基线ALT≥2.5×ULN和(或)HBV DNA水平<1×106拷贝/ml的患者疗效较好,VB发生率较低,24周IVR对拉米夫定疗效有预测价值;出现VB后,加用或者换用阿德福韦酯比继续单用拉米夫定治疗的效果好.     

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)。     

Pretherapy alanine transaminase level as a determinant for hepatitis B e antigen seroconversion during lamivudine therapy in patients with chronic hepatitis B. Asian Hepatitis Lamivudine Trial Group.

In the reported Asian lamivudine trial, the rate of hepatitis B e antigen (HBeAg) seroconversion, defined as HBeAg/hepatitis B virus (HBV) DNA seroclearance and development of anti-HBe, during 52 weeks of treatment was only 13% to 16%. To evaluate whether any factors influenced HBeAg seroconversion, data from 345 patients in that trial were reanalyzed to correlate HBeAg seroconversion with variables including treatment, age, gender, body build, histology, baseline HBV-DNA levels, and alanine transaminase (ALT) levels. Exploratory analysis using stepwise modeling revealed that HBeAg seroconversion correlated highly with pretherapy ALT (P <.001) followed by lamivudine therapy (P =.013), but only marginally with baseline HBV-DNA (P =.071) and cirrhosis (P =.066) for lamivudine 100 mg and placebo comparison. Among these four variables, only pretherapy ALT still had a highly significant (P <.001) correlation and lamivudine therapy had a borderline association (P =.066) for lamivudine 25 mg and placebo comparison. Categorical analysis revealed that HBeAg seroconversion occurred earlier and the cumulative rate was significantly higher in patients with pretherapy ALT values over 2 times the upper limit of normal (ULN) as compared with treated patients with lower ALT levels or untreated control patients with the same ALT levels (P <.001, respectively). The highest HBeAg seroconversion rate was observed in 100 mg lamivudine-treated patients with ALT levels greater than 5 times the ULN (64%) compared with patients with ALT 2 to 5 times the ULN (26%, P =.03); and ALT less than 2 times the ULN, (5%, P <.001). These results suggest that pretherapy ALT is the strongest determinant for HBeAg seroconversion during lamivudine therapy, and should be considered in selecting patients for treatment.     

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。     

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.     

Different models of HBeAg seroconversion predicated by on-treatment ALT and HBV DNA profiles

Summary.  Pretreatment alanine transaminase (ALT) elevation may be used as a predictor for higher hepatitis B e antigen (HBeAg) seroconversion in chronic hepatitis B patients. However, the role of dynamic changes of on-treatment ALT for seroconversion is unknown. A total of 170 naïve HBeAg-positive chronic hepatitis B patients were treated with a nucleoside/nucleotide analogues (NA), either lamivudine, adefovir, entecavir, or telbivudine, for at least 2 years and followed up for 1 more year. Clinical characteristics were detected and analysed at baseline and at 3-month intervals. On-treatment ALT predicted HBeAg seroconversion more accurately than baseline ALT. Among the patients with on-treatment ALT ≤1 × UNL, 1–≤2 × UNL, 2–≤5 × UNL and >5 × UNL, HBeAg seroconversion was 11.4, 5.4, 24.4 and 65.0% (odds ratio = 1.0, 0.4, 2.5 and 14.4, respectively), respectively. Moreover, two models/types of seroconversion were observed. Type I was characterized by rapidly decreased ALT and HBV DNA during the first 3-month interval, but with high HBeAg reversion rate (50%) after consolidation treatment. Type II was a slow decreased DNA procedure accompanied by significant elevated ALT with less reversion (23%). Receiver operating characteristic curve analysis showed a 1.9-fold increased ALT ratio (present visit ALT: previous visit ALT) accompanied by at least a 0.8 log decreased HBV DNA may be used to classify these two seroconversion types. We conclude that on-treatment elevated ALT levels is a better predictor for seroconversion after NAs treatment, and HBV DNA profiles may help to identify different models of seroconversion.     

Lamivudine therapy for children with chronic hepatitis B

AIM: To assess the effectiveness and side-effects of lamivudine therapy for children with chronic hepatitis B (CHB) who fail to respond to or have contraindications to interferon-α(IFN-α) therapy. METHODS: Fifty-nine children with CHB were treated with 100 mg lamivudine tablets given orally once daily for 12 mo. Alanine aminotransferase (ALT) activity was evaluated monthly during the therapy and every 3 months after its discontinuation. HBe antigen, anti-HBe antibodies, HBV DNA level in serum were evaluated at baseline and every six months during and after the lamivudine therapy. Sustained viral response (SVR) to lamivudine therapy was defined as permanent (not shorter than 6 mo after the end of the therapy), namely ALT activity normalization, seroconversion of HBeAg to anti-HBe antibodies, and undetectable viral HBV-DNA in serum (lower than 200 copies per mL). The analysis of the side-effects of the lamivudine treatment was based upon interviews with the patients and their parents using a questionnaire concerning subjective and objective symptoms, clinical examinations, and laboratory tests performed during clinical visits monthly during the therapy, and every 3 mo after the therapy. RESULTS: ALT normalisation occurred in 47 (79.7%) patients between the first and 11th mo of treatment (mean 4.4±2.95 mo, median 4.0 mo), and in 18 (30.5%) of them after 2 mo of the therapy. There was no correlation between the time of ALT normalization and the children's age, the age of HBV infection, the duration of HBV infection, inflammation activity score (grading), staging, ALT activity before treatment, serum HBV DNA level, and lamivudnie dose per kg of body weight. HBeAg/anti HBe seroconversion was achieved in 27.1% of cases. The higher rate of seroconversion was connected with lower serum HBV DNA level and longer duration of HBV infection. There was no connection between HBeAg/ anti HBeAb seroconversion and the children's age, age of HBV infection, grading, staging, ALT activity before treatment, and lamivudnie dose per kg of body weight. No complaints or clinical symptoms were observed during lamivudine therapy. Impairment of renal function or myelotoxic effect was noted in none of the patients. CONCLUSION: One year lamivudine therapy for children with chronic hepatitis B is effective and well tolerated. Seroconversion of HBeAg/HBeAb and SVR are connected with lower pre-treatment serum HBV DNA level.     

干扰素α-2b治疗HBeAg阳性慢性乙型肝炎的疗效观察

目的比较干扰素α-2b联合拉米夫定与单用干扰素α-2b及单用拉米夫定三种不同疗法,治疗HBeAg阳性慢性乙型肝炎（CHB）的疗效。方法三个治疗中心针对259名HBeAg阳性CHB进行抗病毒治疗的临床研究。其中单用干扰素α-2b（A）组82名患者;干扰素α-2b联合拉米夫定（B）组88名患者;单用拉米夫定（C）组89名患者。对照分析各组治疗12、24、36、48周时以及随访第72周时,血清ALT复常率、HBV DNA阴转率和血清HBV标志物的变化。观察不良反应以及乙型肝炎病毒耐药情况。结果 （1）三组患者治疗各时间点血清ALT复常率比较,差异无统计学意义（P〉0.05）。（2）干扰素α-2b联合拉米夫定组抗病毒治疗48周时,HBeAg阴转率和血清学转换率分别为39.67%和31.59%,与A组和C组比较差异有统计学意义（P〈0.05）。（3）单用干扰素α-2b组抗病毒治疗48周时,血清HBeAg阴转率和转换率分别为30.29%和29.27%,与单用拉米夫定组的6.74%和5.62%比较差异具有统计学意义（P〈0.05）;（4）干扰素α-2b联合拉米夫定组和单用拉米夫定组治疗12周即可获得较高的HBVDNA检测下限率,伴随治疗时间越长,单用拉米夫定的患者48周耐药率12.21%,而联合用药组仅为3.23%;（5）干扰素治疗期间可出现白细胞明显减少现象,没有发生一起严重不良事件,入组患者均完成疗程。结论三组不同治疗方法均可获得一定的抗HBV疗效。但干扰素α-2b联合拉米夫定抗病毒治疗较单独使用干扰素α-2b或拉米夫定的疗效高。适当延长抗病毒治疗时间,患者能获得较高的HBeAg阴转率和HBeAg血清学转换率。干扰素α-2b联合拉米夫定还可以减少乙型肝炎病毒耐药率     

乙型肝炎病毒YMDD联合前C变异及其临床意义

目的：研究拉米夫定治疗过程中乙型肝炎病毒（HBV）前C区，P区YMDD基序变异及其对疗效的影响。方法：对5例拉米夫定（100mg/d)治疗过程中HBeAg血清转换而HBV DNA仍阳性的慢性乙型肝炎患者，采用聚合酶链反应（PCR）产物直接测序方法分析HBV前C、P区的基因序列，结果：5例患者前C区均发现有G1896A变异，其中3例HBeAg血清转换前未发现此变异，2例已有此变异，同时5例患者在拉米夫定治疗后检测出YMDD变异，变异类型均为M5521，其中有1例在出现M5521变异40周后变为M552V变异，有2例M5521联合L528M变异，5例患者中有1例治疗无反应，另4例在治疗过程中HBV DNA突发，结论：拉米夫定治疗过程中YMDD变异的出现可导致HBV DNA突发，而前C区G1896A变异可致HBeAgbe阴转，因此在治疗过程中出现HBeAg血清转换后需结合HBV DNA检测，排除前C区变异的可能。     

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.     

拉米夫定治疗严重急性乙型肝炎患者的疗效分析

目的 观察拉米夫定治疗严重急性乙型肝炎患者的疗效.方法 80例严重急性乙型肝炎患者随机分为拉米夫定组40例和对照组40例.观察两组患者HBV DNA、ALT、TBil和凝血酶原活动度(PTA)的变化,比较两组患者HBsAg、HBeAg血清转换率、HBV DNA阴转率.数据行t和x 2检验.结果 治疗1、2周时拉米夫定组...