拉米夫定联合α-干扰素治疗慢性乙型肝炎对HBV YMDD变异的影响

目的探讨α-干扰素联合拉米夫定治疗慢性乙型肝炎对HBV YMDD变异的影响。方法40例患者被随机分为治疗组20例，给予口服拉米夫定100mg／d，同时予以αlb-干扰素5MU／d，肌肉注射，两周后改为隔日一次，疗程1年；对照组20例，单用拉米夫定100mg／d，疗程1年。结果疗程结束时，两组患者HBV YMDD变异率分别为15．0％和30．0％（P〈0．05），HBeAg血清转换率分别为40．0％和35．0%（P〉0．05）。治疗组发生YMDD变异率明显低于对照组。结论拉米夫定联合干扰素治疗慢性乙型肝炎，不能提高HBeAg血清转换率，但可降低YMDD变异率。     

拉米夫定联合干扰素α-2b治疗慢性乙型肝炎疗效观察

目的比较拉米夫定联合干扰素α-2b与单用拉米夫定治疗慢性乙型肝炎的疗效。方法26例慢性乙型肝炎患者接受拉米夫定联合干扰素α-2b联合治疗1.5年;34例单用拉米夫定1.5年。结果治疗结束时,联合组HBeAg/抗HBe转换率为65.4%,优于单用组的37.6%(P<0.001);两组HBV DNA转阴率分别是96.2%、94.1%(P>0.05);联合组完全应答率38.5%,优于单用组17.6%(p<0.01)。单用拉米夫定组3例出现YMDD变异。联合治疗组出现1例HBsAg转阴。结论拉米夫定与干扰素α-2b联合治疗慢性乙型肝炎,可提高HBeAg/抗Hbe血清转换率及综合应答率,并可防止或减少YMDD变异的发生。     

重组人干扰素α-2b联合拉米夫定治疗慢性乙型肝炎120例疗效观察

目的 研究重组人干扰素α-2b（安达芬）联合拉米夫定（LAM）对慢性乙型肝炎患者的疗效.方法 将120例慢性乙型肝炎患者按1∶1比例随机分为2组：联合组给予重组人干扰素α-2b和LAM治疗 单用组给予LAM治疗,疗程均为1年.结果 治疗1年后,联合组血清HBV-DNA转阴率和HBeAg/抗Hbe转换率均高于单用组（P均＜0.05）,单用组YMDD变异率高于联合组（P均＜0.05）.结论 重组人干扰素α-2b（安达芬）联合拉米夫定（LAM）治疗的1年疗效优于单用拉米夫定.     

胸腺肽α1、α干扰素和拉米夫定联合治疗HBV慢性携带者的临床研究

观察胸腺肽α1、α干扰素和拉米夫定联合治疗HBV慢性携带者的临床疗效。选择HBsAg、HBeAg、抗- HBc、HBV DNA阳性,肝功能正常的HBV慢性感染者72例,分为联合治疗组42例:拉米夫定0．1／d,口服,疗程52 周;胸腺肽α1 1．6mg／次,皮下注射,2次／周,连续26周;α干扰素500万单位／日,肌注,疗程26周。单用拉米夫定组 30例:剂量、疗程同联合治疗组。联合治疗组HBV DNA阴转率在26周时76．2％,52周时81．0%,拉米夫定组为 50．0％和66．7％。联合治疗组HBeAg阴转率26周时33．3％,52周时38．1％,拉米夫定组为10％和13．3％。HBeAg 血清转换率两组无统计学差异。联合治疗对HBV DNA和HBeAg的抑制作用显著优于单用药。     

拉米夫定联合干扰素治疗慢性乙型肝炎的HBV清除动力学研究

比较拉米夫定联合干扰素和单用治疗慢性乙型肝炎对血清HBv清除动力学的影响，探讨联合治疗的安全性和抗病毒效果。88例HBeAg和HBV DNA均阳性慢性乙肝患者随机分为三组：联合组30例，给予拉米夫定100mg口服，每日1次，干扰素a3MU，肌肉注射，每周3次。拉米夫定组22例，干扰素组36例。疗程均为6个月。治疗结束时，ALT复常率联合组(100％)和拉米夫定组(95．4％)均明显高于干扰素组(44．4％)(P＜0．05)。治疗1个月时，血清HBV DNA下降幅度联合组和拉米夫定组均显著高于干扰素组(P＜0．05)。治疗结束时，血清HBV DNA阴转率联合组(100％)和拉米夫定组(100％)均明显高于干扰素组(44．4％)(P＜0．05)；血清HBeAg阴转率联合组(63．3％)明显高于拉米夫定组(31．8％)和干扰素组(38．9％)(P＜0．05)。血清HBeAg转换率联合组(56．7％)明显高于拉米夫定组(13．64)和干扰素组(27．78％)(P＜0．05)。拉米夫定和干扰素联合治疗慢性乙型肝炎是安全的，抗病毒效果优于单一药物治疗。     

拉米夫定联合胸腺肽治疗慢性乙型肝炎的疗效观察

目的 评价拉米夫定联合胸腺肽治疗慢性乙型肝炎(CHB)的近、远期疗效和安全性，探讨两者联合治疗的协同作用。方法 将207例HBV DNA及HBeAg阳性的CHB患者随机分为甲乙两组，甲组采用拉米夫定和胸腺肽联合治疗，乙组单用拉米夫定治疗。胸腺肽15mg口服，每日1次，疗程6个月。两组拉米夫定治疗均为100mg，每日1次，口服，其中甲组92例(92／124)、乙组70例(70／83)用药超过12个月。两组在治疗6个月、12个月时分别进行疗效评价，治疗结束后继续随访12个月。结果 治疗6个月时，甲乙两组ALT复常率分别为87．1％和74．7％，甲组显著高于乙组(P＜0．05)，但两组HBV DNA阴转率、HBeAg阴转率及HBeAg／抗—HBe血清转换率均无显著性差异(P＞0．05)。治疗12个月时，甲乙两组ALT复常率和HBV DNA阴转率无显著性差异(P＞0．05)，甲组HBeAg阴转率及HBeAg／抗-HBe血清转换率均显著高于乙组(P＜0．05)。随访结束时，甲组从量复常率、HBV DNA阴转率、HBeAg阴转率及HBeAg／抗—HBe血清转换率均显著高于乙组(P＜0．05)。结论 拉米夫定与胸腺肽联合治疗CHB，疗效明显优于单用拉米夫定，是CHB患者安全有效的治疗方法。     

干扰素联合拉米夫定治疗HBeAg阳性代偿期乙型肝炎肝硬化儿童患者疗效和安全性研究

目的研究干扰素(interferon,IFN)联合拉米夫定(LAM)治疗HBe Ag阳性代偿期乙型肝炎肝硬化儿童患者的疗效与安全性。方法给予26例入选患者IFN(3~6 MU/m2,隔日1次)联合LAM[3 mg/(kg·d)]治疗48周,观察基线和治疗12、24、36、48周的HBV血清学标志物、HBV DNA定量、生化指标及不良反应。结果治疗12、24、36、48周时HBe Ag清除率分别为30.8%、42.3%、53.8%和53.8%,HBe Ag血清学转换率分别为23.1%、34.6%、46.2%和46.2%,HBs Ag清除率分别为0、11.5%、19.2%和19.2%,HBs Ag血清学转换率分别为0、3.8%、19.2%和19.2%,HBV DNA低于检测下限率分别为38.5%、53.8%、73.1%和84.6%,ALT复常率分别为88.5%、92.3%、92.3%和96.2%。随着疗程的延长,HBe Ag清除/血清学转换率、HBs Ag清除/血清学转换率、HBV DNA低于检测下限率和ALT复常率均逐渐升高(P均0.05)。未见明显不可耐受的不良反应。结论 IFN联合LAM治疗HBe Ag阳性代偿期乙型肝炎肝硬化儿童患者具有良好的疗效和安全性。     

单用粒米夫定与联合α干扰素治疗慢性乙型肝炎的疗效观察

目的 观察和对比单用拉米夫定与拉米夫定联合α干扰素治疗慢性乙型肝炎的安全性和疗效。方法 拉米夫定组64例，单服拉米夫定，100mg或150mg，每日1次，其中54例（84．4％）用药超过12个月。联合组49例，拉米夫定用药2周后加用干扰素（甘乐能或罗尧愫），3MU－5MU肌肉或皮下注射，每周2次，24周后停干扰素，继续服拉米夫定，其中38例（77．6％）治疗超过12个月。两组在治疗6个月、12个月时分别进行疗效评价，并继续随访4－26个月。结果 拉米夫定组和联合组6个月时ATL／AST复常经分别为90．6％／92．2％和89．8％／93．9％（P＞0．05）；HBVDNA阴转率分别为96．9％和98．0％（P＞0．05）；HBeAg的血清转换率为20．3％和28．6％（P＞0．05）。12个月时两组ALT/AST 复常率分别为90．7％／90．7和89．5％／92．1％（P＞0．05）；HBVDNA阴转率为88．0％和89．5％（P＞0．05）；HBeAg的血清转换率则分别为31．5％（17／54）和55．3％（21／38），P＜0．05。HBeAg的血清转换率似乎与治疗前的转氨酶水平较高、HBeAg和HBVDNA水平较低有关。治疗9－24个月期间拉米夫定组9例（14．1％）、聚合组6例（12．2％）发生HBV多聚酶MDD变异。结论 拉米夫定和干扰素联合治疗慢性乙型肝炎，安全性和耐受性,1上后HBeAg的血清转换率显著高于单用拉米夫定组。     

干扰素α-1b联合其他抗病毒药物治疗慢性乙型肝炎的疗效比较

目的观察比较干扰素α-1b及联合拉米夫定、胸腺肽、苦参素治疗慢性乙型肝炎的疗效?方法将86例慢性乙型肝炎患者随机分成四组，采用干扰素α-1b及干扰素α-1b分别联合拉米夫定、胸腺肽、苦参素抗病毒治疗，随访至18个月，观察肝功能及乙型肝炎病毒标记物、HBV DNA变化情况。结果四组病例肝功能均恢复较好，18个月时HBV DNA阴转率分别为45％、45．5％、50％和75％，HBeAg阴转率分别为40．5％、40．9％、60％和62．5％，HBeAg／抗-HBe血清转换率分别为30％、31．8％、45．0％和45．8%。结论干扰素α-1b治疗慢性乙型肝炎有一定疗效，联合其他抗病毒药物后疗效有一定提高，但无统计学差异。     

阿德福韦酯治疗YMDD变异慢性乙型肝炎的临床观察

目的研究阿德福韦酯单用或联合拉米夫定治疗YMDD变异慢性乙型肝炎病人的疗效及安全性。方法120例发生YMDD变异的慢性乙型肝炎患者被随机分为拉米夫定组（A组）40例、阿德福韦酯组（B组）40例和阿德福韦酯联合拉米夫定组（C组）40例,均治疗48周。观察各组血清生化学、病毒学和血清学应答情况。结果治疗48周时,B、C组ALT复常率分别为77．5％和82．5％,HBV DNA水平分别下降3．54±0．97 lg copies／ml和3．46±0．94 lg copies／ml,HBV DNA阴转率分别为70％和75％,均明显优于A组;但3组HBeAg转阴率和HBeAg血清学转换率无显著性相差。结论阿德福韦酯单用或联合拉米夫定治疗YMDD变异慢性乙型肝炎的疗效肯定,安全性好。     

Combination of alpha-interferon with lamivudine reduces viral breakthrough during long-term therapy

BACKGROUND AND AIM: Viral breakthrough is frequently encountered during long-term lamivudine therapy, mostly associated with YMDD mutants. In this study, we investigated the effects of alpha-interferon (IFN-alpha) combined with lamivudine on the occurrence of viral breakthrough during long-term lamivudine therapy. METHODS: Eighty-three patients with biopsy-proven chronic hepatitis B were randomly allocated to a combination of lamivudine and IFN-alpha (LAM/IFN; n = 41) or lamivudine only (LAM; n = 42), and then followed up for >12 months. We calculated the cumulative rate of undetectable serum HBV-DNA and hepatitis B e antigen (HBeAg) loss, as well as the cumulative occurrence rate of viral breakthrough. We also evaluated the relationship between YMDD mutants and the occurrence of viral breakthrough. RESULTS: There was no difference in cumulative rates of undetectable serum HBV-DNA (100%vs 100% at 24 months, P = 0.13) and cumulative rates of serum HBeAg loss between the LAM/IFN group and the LAM group (49%, 61% and 67%vs 31%, 39% and 42%, respectively, at 12, 24 and 36 months; P = 0.07). The cumulative occurrence rate of viral breakthrough, however, was significantly lower in the LAM/IFN group compared with the LAM group (5%, 20% and 30%vs 10%, 55% and 58%, respectively, at 12, 24 and 36 months; P = 0.006). From the patients with viral breakthrough, YMDD mutants were detected in 82% (18 of 22) of the LAM group in contrast with 56% (five of nine) of the LAM/IFN group in their sera. CONCLUSION: IFN-alpha combined with lamivudine may reduce viral breakthrough during long-term lamivudine therapy, probably by suppressing the appearance of YMDD mutants.     

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.     

Lamivudine monotherapy and lamivudine plus interferon alpha combination therapy in HBeAg negative chronic hepatitis B not responding to previous interferon alpha monotherapy

BACKGROUND AND STUDY AIMS: To investigate the efficacy of the combined therapy of lamivudine (LAM) plus alpha interferon (IFN) and LAM monotherapy in HBeAg negative chronic hepatitis B (CHB) patients who were unresponsive to previous IFN monotherapy, and the incidence of YMDD mutations. PATIENTS-METHODS: Forty-five HBeAg negative patients were enrolled in this study. 24 of these were treated with LAM (100 mg/day, PO, for 24 months) alone (group 1) and 21 with combined therapy (IFN-alpha-2b, 10 MU, tiw, SC, for 6 months plus LAM 100 mg/day, PO, for 24 months) (group 2). Normal alanine aminotransferase values and negativity of HBV DNA (molecular hybridization; Digene, USA) were accepted as treatment response. YMDD variants were analyzed at the end of treatment or when clinical breakthrough was observed (Inno-Lipa Innogenetic kit, Belgium). RESULTS: End of follow-up response rate was 29.2%, by ITT in group 1, 19% in group 2 (p > 0.05). Histological activity index was statistically decreased by LAM monotherapy as compared to combination therapy. YMDD mutation rates were 59% in group 1, 62.5% in group 2 (p > 0.05). CONCLUSIONS: Additional IFN-alpha therapy to LAM in HBeAg negative CHB not responding to previous IFN-alpha monotherapy does not increase the response rate compared to LAM monotherapy and does not also decrease the incidence of YMDD mutations.     

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.     

拉米夫定治疗儿童和青少年慢性乙型肝炎的长期临床观察

目的观察拉米夫定治疗儿童和青少年慢性乙型肝炎的疗效及安全性。方法27例5—18岁的慢性乙型肝炎患者给予拉米夫定片剂每天3mg／kg,最大剂量100mg／d,疗程不少于12个月。观察治疗前后肝功能、HBVDNA、HBeAg／抗一HBe变化;有HBVDNA复升者检测YMDD变异;记录不良事件;停药后定期随访。结果治疗12、24、36和48个月的生化应答率分别为92．6％、84．6％、100％和100％;HBVDNA阴转率为92,6％;HBeAg阴转率为60％;HBeAg血清学转换率为55％。YMDD变异见于治疗12个月后,累积变异发生率为14．8％。达到停药标准终止治疗者,复发率为21．4％。无严重不良反应事件。结论拉米夫定治疗儿童和青少年慢性乙肝安全有效,YMDD发生率低。可以扩大样本进一步观察。     

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.     

Early reduction of infected hepatocytes by activated immunity at the time of interferon withdrawal hepatitis followed by lamivudine administration resulted in higher seroconversion in hepatitis Be antigen-positive patients with chronic hepatitis B

Background It has been found that the efficacy of lamivudine (LAM) therapy can be improved by preceding administration with a short course of corticosteroid that induces a flare of the disease upon its withdrawal. Because of the side effects of corticosteroid, we tested the effect of a short course of interferon (IFN) as the primer instead of prednisolone, which was followed by LAM when the hepatitis flare occurred. The incidence of LAM resistance mutations and the effect of core promoter and precore mutations on the durability of the responses were also studied. Methods Patients treated with interferon (IFN)-LAM therapy (n = 73) were compared to those treated with IFN alone (n = 117). The IFN-LAM group received IFN-α MU/day, t.i.w. for a 3-month period. LAM (10mg/day during 1 year) was started when IFN withdrawal hepatitis occurred during 2–10 months after stopping IFN. The LAM-resistant, core promoter, and precore mutations were examined by sequencing. Results (1) The IFN-LAM group developed exacerbated hepatitis following IFN withdrawal in 63 patients before starting LAM therapy. The seroconversion (SC) rate was significantly higher in the IFN-LAM group than in the IFN-alone group (61% vs 26%, P = 0.0001). (2) The LAM resistance mutation rate was 31% at 1 year after initiating LAM therapy. (3) In a stepwise discriminant-function analysis, decreased level of HBeAg determined at 4 weeks after LAM administration and increased level of HBeAb before the start of LAM administration contributed significantly on seroconversion to anti-HBe (P = 0.0073 and 0.004, respectively). (4) The reappearance rate of HBeAg within 6 months after the therapy (relapse) was 33% in the IFN-LAM group and 10% in the IFN-alone group. The prevalence of core promoter and precore mutations did not change before and after the therapy, nor did these mutations correlate with the relapse after stopping IFN-LAM therapy. Conclusions (1) Our findings suggest that early reduction of infected hepatocytes expressed by HBeAg by LAM may contribute to a high SC rate of IFN-LAM therapy. (2) The emergence of LAM-resistant mutations was similar to the previously reported rate, and neither core promoter nor precore mutations correlated with relapse of seroconverters after IFN-LAM withdrawal.     

Combination therapy for children with chronic hepatitis B virus infection

BACKGROUND AND AIM: To compare the therapeutic efficacy of two different interferon (INF)-alpha and lamivudine (LAM) combination therapy regimens in childhood chronic hepatitis B (CHB) infections. METHODS: Thirty-two children with CHB infection were prospectively evaluated in two random groups. In the first group, patients received INF-alpha 10 MU/m2 and LAM 4 mg/kg (max 100 mg) simultaneously for 6 months, and then LAM alone was continued for 6 months. In the second group, LAM was started alone for the first 2 months, then INF-alpha added to LAM for 6 months, after which INF-alpha was stopped, and LAM alone was continued for 4 months. The same doses of LAM and INF-alpha were used in both groups. RESULTS: In the first group, the mean values of alanine aminotransferase (ALT) were 125 +/- 100 IU/L and 28 +/- 8 IU/L at the beginning of the treatment and at the end of the 12 months, respectively (P < 0.05). At the end of 6 months of the follow-up period, the mean ALT value was 36 +/- 37 IU/L. In group 2, mean ALT values were 111 +/- 63 IU/L, 35 +/- 2 IU/L and 34 +/- 2 IU/L initially, at the end of 12 months and at the end of 6 months of follow up, respectively (P < 0.05). At the end of therapy, the ratios of hepatitis B early antigen (HBeAg) clearance and antibody to HBeAg (anti-HBe) seroconversion were 65% and 47% in group 1 and 60% and 40% in group 2, respectively (P > 0.05). After 6 months from completion of therapy, rates of seroconversion to anti-HBe were found to be 64% and 47% in group 1, and 53% and 46% in group 2, respectively (P > 0.05). Hepatitis B virus (HBV) DNA was detectable by polymerase chain reaction in only one patient in group 1 at the end of therapy and 6 months after termination of therapy. Clearance of HBV DNA in group 2 was observed in all but one patient at the end of the therapy. However, two patients relapsed within 6 months of cessation of therapy. Complete response occurred in 47% and 40% of patients at the end of the therapy in group 1 and 2, respectively (P > 0.05). These ratios were changed to 47% and 46%, respectively, 6 months after discontinuation of drugs (P > 0.05). CONCLUSIONS: Comparison of our two different combination regimens disclosed similar results in the normalization of ALT, clearance of HBeAg and HBV DNA and seroconversion to anti-HBe. However, the most beneficial combination of LAM and INF-alpha treatment modalities needs to be further investigated.     

Clinical significance of hepatitis B e antigen level measurement during long-term lamivudine therapy in chronic hepatitis B patients with e antigen positive

INTRODUCTION Hepatitis B virus (HBV) infection is a serious public health problem worldwide and a major cause of chronic hepatitis, cirrhosis, and hepatocellular carcinoma[1]. Of the approximately 2 billion people who have been infected worldwide, more th…     

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.