阿德福韦酯联合拉米夫定治疗乙型肝炎肝硬化的临床观察

目的探讨阿德福韦酯胶囊联合拉米夫定治疗拉米夫定耐药代偿期乙肝肝硬化的临床效果。方法对29例(观察组)对拉米夫定耐药代偿期乙肝肝硬化血清HBVDNA阳性患者,在综合治疗的基础上加用阿德福韦酯胶囊和拉夫米定口服。对照组21例仅用阿德福韦酯作治疗,治疗前及治疗后12、24、48周检测肝功能、HBVDNA定量和Child-Pugh评分观察。结果治疗组ALT恢复率为82.4%,明显高于对照组的57.1%(P0.05);治疗组血清HBVDNA复制改善情况显著优于对照组。治疗中未发现与服用阿德福韦酯相关的不良反应。结论阿德福韦酯加拉米夫定可有效抑制乙肝病毒、改善肝功能对拉米夫定的耐药,控制病情进展和改善预后。     

阿德福韦酯联合复方鳖甲软肝片治疗乙型肝炎肝硬化的临床观察

目的观察阿德福韦酯联合复方鳖甲软肝片治疗乙型肝炎肝硬化失代偿期的疗效和安全性。方法 78例乙型肝炎肝硬化失代偿期患者随机分为阿德福韦酯与复方鳖甲软肝片联合治疗组及单用阿德福韦酯对照组,观察48周时两组患者肝功能、Child-Pugh分级及血清HBV DNA自基线下降的水平。结果治疗48周后,治疗组肝功能、Child-Pugh分级及血清HBV DNA自基线下降水平与治疗前比较差异均有统计学意义（P〈0.01）;联合治疗组肝纤维化指标及脾门厚度的下降值均优于对照组（P〈0.01）。结论阿德福韦酯联合复方鳖甲软肝片治疗失代偿期乙型肝炎肝硬化明显优于单用阿德福韦酯。     

拉米夫定联合阿德福韦酯治疗失代偿期乙型肝炎肝硬化的临床观察

目的研究拉米夫定（LAM）联合阿德福韦酯（ADV）治疗失代偿期乙型肝炎肝硬化的临床疗效。方法92例失代偿期乙型肝炎肝硬化患者在综合护肝及对症治疗基础上,联合组30例给予拉米夫定100mg/d和阿德福韦酯10mg/d口服;LAM组28例给予拉米夫定100mg/d口服;34例给予阿德福韦酯10mg/d口服。在治疗前和治疗6个月时观察肝功能、HBVM以及血清HBVDNA水平的变化。结果拉米夫定和阿德福韦酯联合组与拉米夫定组和阿德福韦酯组HBVDNA阴转率分别为80%、53.6%和41.2%,联合组明显优于单用组（P〈0.05）;肝功能Child-Pugh计分分别为7.0±1.1、7.7±1.2和7.8±1.3,联合组明显优于单用组（P〈0.05）。结论拉米夫定联合阿德福韦酯抗病毒治疗失代偿期乙型肝炎肝硬化优于单用拉米夫定或阿德福韦酯治疗。     

安络化纤丸联合阿德福韦酯、拉米夫定治疗失代偿期乙肝肝硬化患者疗效观察

目的探讨安络化纤丸联合阿德福韦酯、拉米夫定治疗在延缓和逆转失代偿期乙肝肝硬化患者肝功能的效果。方法随机选取2013年10月至2016年10月我院感染性疾病科收治的失代偿期乙肝肝硬化患者60例为研究对象,采用随机数字表法分为观察组和对照组,每组30例。对照组患者使用阿德福韦酯、拉米夫定抗病毒治疗,观察组患者在对照组患者治疗基础上加用安络化纤丸治疗,治疗6个月后比较两组患者的症状评分、肝纤维化组织学改善程度和门静脉血流阻力等指标的变化情况。结果观察组患者症状评分显著低于对照组(P0.01);观察组患者门静脉最大血流速度显著大于对照组、门静脉内径显著小于对照组,差异有统计学意义(P0.05)。观察组患者Ig M水平显著高于对照组(P0.01)。观察组患者层黏连蛋白、透明质酸、Ⅲ型胶原蛋白和Ⅳ型胶原含量显著低于对照组(P0.01)。结论在使用阿德福韦酯、拉米夫定抗病毒治疗的基础上,辅助使用安络化纤丸治疗乙肝肝硬化患者,可有效改善患者肝纤维化程度,缓解病情发展。     

拉米夫定联合心得安治疗乙肝肝硬化失代偿期的临床研究

目的观察拉米夫定联合心得安长期持续治疗乙肝肝硬化失代偿期的治疗效果。方法选择乙肝肝硬化失代偿期患者74例,随机分为两组,拉米夫定联合心得安治疗组(A组)、拉米夫定治疗组(B组)。两组均给予常规护肝、支持对症治疗。拉米夫定100mg/d,1次/d。心得安30～50mg/d,服用剂量以心率不低于55次/min为宜。两组治疗24个月后观察疗效。结果拉米夫定联合心得安治疗组肝血流量明显减少,肝门静脉内径、脾门静脉内径、脾厚度明显改善、再出血及腹水复发率优于拉米夫定组。拉米夫定联合心得安治疗组及拉米夫定组ALT、AST、TBiL、ALB、HBVDNA、Child-Pugh评分均降低。结论拉米夫定联合心得安治疗乙肝肝硬化失代偿期能有效改善肝功能,抑制乙肝病毒复制,使肝门静脉内径、脾门静脉内径、脾厚度明显改善、肝血流量明显减少,再出血及腹水复发率降低,二者通过协同作用减轻或阻止病情发展,提高患者的生活质量,减缓肝移植。     

阿德福韦酯和拉米夫定治疗乙型肝炎肝硬化失代偿期的临床观察

目的观察阿德福韦酯和拉米夫定治疗肝炎肝硬化失代偿期患者48周的疗效和不良反应。方法采用随机分组法,将62例肝炎肝硬化失代偿期患者,随机分为阿德福韦酯组32例,给予阿德福韦酯10mg/d,拉米夫定组30例,给予拉米夫定100mg/d,疗程均为48周。均给予常规护肝及支持、对症治疗。观察两组患者的肝功能、HBeAg、HBV DNA、肝纤维化标志物Ⅲ型前胶原、Ⅳ型胶原、层黏连蛋白、透明质酸、肾功能及Child-Pugh分级、药物不良反应。结果两组患者肝功能各项指标的复常率、血清HBV DNA下降水平及转阴率、HBeAg转阴率及HBeAg/抗-HBe转换率均随着治疗疗程的延长而增加,但两组比较,差异无统计学意义。治疗至48周时拉米夫定组有2例发生YMDD变异,变异率6.7%,阿德福韦酯组无病毒变异发生。两组患者血清肝纤维化标志物治疗至24周时与治疗前相比明显下降,且随着疗程的延长进一步降低,两组比较差异无统计学意义。两组患者治疗前后Child-Pugh分级比较,差异无统计学意义。两组患者均未发现药物相关的肾功能损害,两组中各有2例患者出现轻度不良反应,但均能耐受。结论肝炎肝硬化失代偿期患者48周的抗病毒治疗,阿德福韦酯的疗效与安全性均与拉米夫定相似,而病毒耐药突变率较拉米夫定低。     

阿德福韦酯联合扶正化瘀胶囊治疗活动性肝硬化临床观察

目的：观察阿德福韦酯联合扶正化瘀胶囊治疗活动性肝硬化的疗效和安全性。方法：95例活动性乙型肝炎肝硬化患者随机分为治疗组52例和对照组43例，两组均在保肝、对症等常规治疗基础上接受阿德福韦酯胶囊10mg／d治疗，治疗组在对照组基础上联合扶正化瘀胶囊3次／d，3粒／次，疗程24周。结果：两组患者治疗后ChildPugh评分下降，肝功能改善，HBVDNA载量下降，配对比较差异有显著性意义（P〈0．01）。治疗组患者肝纤维化指标及脾门厚度的下降值优于对照组，组间比较差异有显著性意义（P〈0．01或P〈0．05）。结论：阿德福韦酯联合扶正化瘀胶囊治疗活动性乙型肝炎肝硬化能显著提高肝纤维化的治疗效果，改善肝功能，临床应用安全。     

扶正化瘀胶囊联合阿德福韦酯治疗瘀血阻络型慢性乙型肝炎临床研究

目的:观察扶正化瘀胶囊联合阿德福韦酯治疗瘀血阻络型慢性乙型肝炎(CHB)的临床疗效。方法:对照组45例采用阿德福韦酯及一般保肝治疗,治疗组45例在对照组用药基础上加用扶正化瘀胶囊,治疗时间两组均为24周。结果:两组患者的症状、肝功能、乙肝病毒标志物、肝纤维化指标及B超(门静脉内径、脾肿大情况)均有改善,但在改善症状、肝纤维化指标及B超(门静脉内径、脾肿大情况)方面,治疗组优于对照组。结论:扶正化瘀胶囊联合阿德福韦酯对瘀血阻络型CHB患者能明显改善症状、较快改善肝功能,一定程度上提高HBV血清学指标的阴转率,并较好地改善肝纤维化及脾肿大程度。     

拉米夫定或阿德福韦酯选择性治疗失代偿性乙型肝炎肝硬化3年临床观察

目的观察拉米夫定或阿德福韦酯选择性治疗乙型肝炎肝硬化失代偿期患者长疗程疗效及治疗方案的选择。方法乙型肝炎肝硬化失代偿期患者65例,HBV DNA5 log10拷贝/mL者服用拉米夫定(100mg/d)或再联用阿德福韦酯(10mg/d);HBV DNA5 log10拷贝/mL者可单用拉米夫定或阿德福韦酯;病毒持续不下降或反弹要求拉米夫定联用阿德福韦酯。观察治疗前后患者临床症状体征、生化指标、病毒学改变情况。结果65例患者中43例生存至研究结束,3年生存率为66.1%。患者治疗后肝功能正常或好转,病情缓解稳定,生活质量改善,HBV DNA下降约3 log10拷贝/mL,Child-Pugh积分下降3。结论拉米夫定或阿德福韦酯选择性治疗乙型肝炎肝硬化失代偿期患者,可延长患者生存时间,改善肝功能,阻止病情进展,提高生活质量。     

国产阿德福韦酯治疗活动性失代偿肝硬化临床观察

目的观察国产阿德福韦酯片治疗活动性失代偿乙肝肝硬化的疗效和安全性。方法将44例活动性乙型肝炎失代偿肝硬化患者随机分为治疗组和对照组，均予以同样的保肝、对症及支持治疗，治疗组加用阿德福韦酯片10mg，口服、1次／d，疗程52周。分别观察两组治疗前后生存率、血清生化指标、HBV-DNA载量、Child-Pugh评分以及不良事件发生率。结果治疗组生存率、血清生化指标改善率、HBV—DNA载量下降幅度和阴转率均明显优于对照组（P〈0．05），不良反应少而轻。结论应用阿德福韦酯治疗有病毒复制的活动性失代偿乙肝肝硬化安全有效，值得推广应用。     

拉米夫定单药及其初始联合阿德福韦酯治疗失代偿期乙型肝炎肝硬化的疗效比较

目的 比较拉米夫定与阿德福韦酯初始联合或拉米夫定单药治疗失代偿期乙型肝炎肝硬化患者2年的疗效.方法 60例失代偿期乙型肝炎肝硬化接受初始拉米夫定(LAM)与阿德福韦酯(ADV)联合抗病毒治疗,为初始联合组;55例接受拉米夫定(LAM)单药抗病毒治疗,为LAM单药组每1～3个月检测患者肝功能、肾功能、甲胎蛋白、乙型肝炎病毒标志物、血清HBV DNA、凝血酶原时间(PT)、肝脏的超声或CT检查,分别在治疗12个月和24个月时比较疗效.组间均数比较用Mann-Whitney检验,相关性分析时采用Pearson双侧t检验.结果 初始联合组45例治疗12个月时血清HBV DNA阴转率为51.1%(23/45),而40例LAM单药组HBV DNA阴转率为47.5%(19/40);至24个月时,初始联合组HBV DNA阴转率达86.7%(39/45),LAM单药组为60.0%(24/40),两组间差异有统计学意义(P＜0.05).初始联合组治疗24个月时,HBeAg血清学转换率为43.5%(10/23),LAM单药组HBeAg血清学转换率为30.0%(6/20),两组间差异有统计学意义(P＜0.05).ALT复常率在初始联合组治疗12个月时为71.1%(32/45),LAM单药组为65.0%(26/40),至24个月时两组ALT复常率分别为88.9%(40/45)和75.0%(30/40),差异有统计学意义(P＜0.05).初始联合组在治疗12个月和24个月时,分别有4.4%(2/45)和6.7%(3/45)发生病毒学突破,但均未检测到病毒学变异,LAM单药组在12个月和24个月时分别有22.5%(9/40)和37.5%(15/40)发生病毒学突破,并分别有17.5%(7/40)和32.5%(13/40)的患者中检测到病毒学变异,均较联合治疗组高(P＜0.05).初始联合治疗更能改善肝功能,Child-Turcotte-Pugh评分和终末期肝病模型评分亦有更明显下降.随访24个月,LAM和ADV初始联合治疗组累计死亡或肝移植率为16.7%,LAM单药组累计死亡或肝移植发生率为20.0%.两组均未发现有血清肌酐超过正常值上限的病例.结论 LAM与ADV初始联合治疗失代偿期乙型肝炎肝硬化患者能更明显抑制HBV复制,改善肝功能各项指标,降低病死率,值得临床应用.

Abstract：

Objective To compare the efficacy of Lamivudine (LAM) monotherapy and combination therapy with Adefovir Dipivoxil (ADV) for patients with hepatitis B virus (HBV) -related decompensated cirrhosis for 2 years.Methods A total of 115 patients with HBV-related decompensated cirrhosis were erolled in this study,among 60 patients were treated with LAM combined with ADV and 55 were treated with LAM.The liver and kidney functions,HBV DNA,HBV-M,AFP,Ultrasond or CT scan of liver were tested every l-3months.the treatment efficacy was evaluated by month 12 and 24.Results By month 12,the HBVDNA negative rates of combination therapy group and LAM monotherapy group were 51.1% (45 cases) and 47.5% (40 cases) respectively,by month 24 the rates were 86.7% and 60.0% respectively.By month 24 the HBeAg negative rates of combination therapy group and LAM monotherapy group were 43.5% and 30.0%respectively,with significant difference existed between the two therapy groups (P ＜ 0.05).By month 24,the ALT normalization rates of the two groups were 88.9% and 72.5% respectively.Viral breakthrough happened in 2 cases (4.4%) by month 12 and 3 cases (6.7%) by month 24 in LAM and ADV combination group,but no viral resistance observed.Viral breakthrough happened in 9 cases (22.5%) by month 12 and 15 cases (37.5%)by month 24 in LAM monotherapy group with viral resistance observed in 7 cases (17.5%) by month 12 and 13 cases (32.5) by month 24.Significant difference existed between the two groups (P ＜ 0.05).Improvement of liver function was more obviously in the combination group.The accumulative total mortality or liver transplantation rate were 16.7% and 20.0% respectively in combination therapy group and LAM monotheapy group.No renal dysfunction observed in both groups.Conclusion LAM combined with ADV is better choice for patients with HBV-related decompensated cirrhosis as compared to LAM monotherapy.     

De novo combination therapy with lamivudine and adefovir dipivoxil in chronic hepatitis B patients

AIM: To investigate the appropriate time for combination therapy in HBeAg positive chronic hepatitis B (CHB) patients with decompensated cirrhosis.METHODS: Thirty HBeAg positive CHB patients with decompensated cirrhosis were enrolled in the study. All of the patients were given 48 wk combination therapy with lamivudine (LAM) and adefovir dipivoxil (ADV). Briefly, 10 patients were given the de novo combination therapy with LAM and ADV, whereas the other 20 patients received ADV in addition to LAM after hepatitis B virus (HBV) genetic mutation.RESULTS: Serum alanine aminotransferase and total bilirubin were both improved in the two groups at 4, 12, 24 and 48 wk after treatment. Serum albumin was also improved at 24 and 48 wk after combination therapy in both groups. The serum HBV DNA level was still detectable in every patient in the two groups at 4 and 12 wk after combination treatment. However, in the de novo combination group, serum HBV DNA levels in 4 (40%) and 9 (90%) patients was decreased to below 1×10³ copies/mL at 24 and 48 wk after the combination treatment, respectively. In parallel, serum HBV DNA levels in 2 (20%) and 8 (40%) patients in the add-on combination group became undetectable at 24 and 48 wk after combination treatment, respectively. Furthermore, 6 (60%) patients in the de novo combination group achieved HBeAg seroconversion after 48 wk treatment, whereas only 4 (20%) patients in the add-on combination group achieved seroconversion. Child-Pugh score of patients in the de novo combination group was better than that of patients in the add-on combination group after 48 wk treatment. Moreover, patients in the de novo combination group had a significantly decreased serum creatinine level and elevated red blood cell counts.CONCLUSION: De novo combination therapy with LAM and ADV was better than add-on combination therapy in terms of Child-Pugh score, virus inhibition and renal function.     

Efficacy of combined therapy in patients with hepatitis B virus-related decompensated cirrhosis

AIM: To investigate the efficacy and safety of combined de novo lamivudine (LAM) and adefovir dipivoxil (ADV) therapy in hepatitis B virus (HBV)-related decompensated liver cirrhosis patients. METHODS: One hundred and forty patients with HBVrelated decompensated cirrhosis were recruited, 70 patients were treated with combined LAM and ADV de novo therapy, and the other 70 patients were treated with LAM alone as controls. The follow-up period was 144 wk. All patients with LAM resistance were shifted to ADV. RESULTS: The percentage of HBV-related decompensated cirrhosis patients with undetectable HBV DNA inde novo combination group was 51.6% (33/64), 84.2% (48/57), and 92.3% (49/53) by weeks 48, 96, and 144, respectively. In monotherapy group, HBV DNA negativity rate was 46.1% (30/65), 56.1% (32/57), and 39.2% (20/51) by weeks 48, 96 and 144, respectively. There was a significant difference between the two groups by weeks 96 and 144 (P = 0.012 and 0.001). The hepatitis B e antigen seroconversion rate was 28.1% (9/32), 40.0% (12/30), and 53.6% (15/28) in the combination group by weeks 48, 96 and 144, respectively, and 24.2% (8/33), 31.0% (9/29), and 37.0% (10/27) by weeks 48, 96 and 144, respectively, in monotherapy group. A total of 68.6% (44/64), 84.2% (48/57), and 92.5% (49/53) patients achieved alanine aminotransferase (ALT) normalization by weeks 48, 96 and 144, respectively in the combination group. In monotherpy group, the ALT normalization rate was 64.6% (42/65) by week 48, 73.7% (42/57) by week 96, and 80.4% (41/51) by week 144. No patients in the combination group exhibited detectable resistance for at least 144 wk. The cumulative resistance rate in monotherapy group at weeks 48, 96, and 144 was 20.0%, 36.8%, and 56.9%. Both combination group and monotherapy group demonstrated an improvement in Child-Turcotte Pugh and Model for End-Stage Liver Disease scores at weeks 48, 96, and 144. All patients tolerated both combination and monotherapy. The ceratinine levels and glomerular filtration rate remained norma     

拉米夫定耐药慢性乙型肝炎患者改用或加用阿德福韦酯治疗48周疗效比较

目的观察拉米夫定(LAM)与阿德福韦酯(ADV)联合应用和单用ADV治疗LAM耐药HBeAg阳性慢性乙型肝炎患者的疗效及安全性。方法收集2006年1月至2011年12月在本院就诊的LAM耐药HBeAg阳性慢性乙型肝炎患者40例,单药组与联合组各20例,分别以ADV与LAM联合或单用ADV进行治疗。观察治疗24周、48周时的血清HBV DNA水平及转阴率、HBeAg转阴率、ALT复常率以及治疗过程中药物的不良反应和耐药性。组间比较计量资料采用t检验,计数资料采用卡方检验。结果两组患者在性别、年龄、治疗前的HBV DNA及ALT水平上差异均无统计学意义(P0.05);治疗结束时联合组的血清HBV DNA转阴率和ALT复常率分别为90%及95%,而单药组的血清HBV DNA转阴率和ALT复常率分别为60%及65%,两组比较差异有统计学意义(P0.05);治疗结束时联合组血清HBeAg转阴率为45%,单药组为35%,两组比较差异无统计学意义(χ2=0.417,P=0.519)。结论 ADV联合LAM或ADV单药治疗LAM耐药HBeAg阳性慢性乙型肝炎患者均有较好的临床疗效,但ADV与LAM联合治疗可提高HBV DNA转阴率及ALT复常率,其安全性良好,值得借鉴。     

拉米夫定联合阿德福韦酯初始治疗慢性乙型肝炎患者临床观察

目的探讨拉米夫定联合阿德福韦酯初始慢性乙型肝炎的临床疗效。方法将120例慢性乙型肝炎初始患者随机分为两组,分别给予拉米夫定联合阿德福韦酯治疗或拉米夫定单药治疗24周后,对HBV DNA未阴转者再加用阿德福韦酯治疗,观察48周。结果两组HBV DNA总体阴转率无显著性差异（P〉0.05）;对于HBVDNA≥107copies/ml患者,两组HBV DNA阴转率于第4和16周差异无显著性（P〉0.05）,但在第24周（x2=4.573,P〈0.05）和第48周差异具有显著性（x^2=4.289,P〈0.05）。结论对于高病毒载量的慢性乙型肝炎患者宜选用联合方案进行抗病毒初始治疗,以期达到更好的疗效。     

阿德福韦酯挽救治疗拉米夫定耐药患者的临床分析

目的观察阿德福韦酯挽救治疗拉米夫定治疗后HBVDNA突破患者的疗效。方法将49例拉米夫定治疗后HBVDNA突破的慢性乙型肝炎患者分为3组。A组12例患者直接改用阿德福韦酯治疗,B组25例患者先用拉米夫定与阿德福韦酯联合治疗,HBVDNA阴转后再单用阿德福韦酯治疗,C组12例患者持续应用拉米夫定与阿德福韦酯联合治疗。观察挽救治疗1年血清HBVDNA阴转情况。结果A组10例患者在治疗（3．50±2．07）个月（1～7个月）发生HBVDNA阴转;B组21例患者在治疗（2．05±1．36）个月（1～5个月）发生HBVDNA阴转;C组12例患者在治疗（1．33±0．65）个月（1-3个月）发生HBVDNA阴转。挽救治疗有效的患者维持应答〉12个月,治疗期间未发生肾功能损害等明显不良反应。结论拉米夫定治疗后HBVDNA突破患者直接改用阿德福韦酯治疗、先用拉米夫定联合阿德福韦酯再单用阿德福韦酯治疗以及持续拉米夫定联合阿德福韦酯治疗3种方案均是安全有效的。持续拉米夫定联合阿德福韦酯治疗可能是最快和最有效的挽救治疗方案。     

Add‐on combination therapy with adefovir dipivoxil induces renal impairment in patients with lamivudine‐refractory hepatitis B virus

Summary. Combination therapy with adefovir dipivoxil (ADV) and lamivudine (LAM) is recommended for patients infected with LAM‐refractory hepatitis B virus (HBV). However, the effects of such therapy on renal function and serum phosphorus levels have not been fully evaluated. Combination therapy with ADV and LAM was given to 37 patients infected with LAM‐refractory HBV, including 17 with hepatic cirrhosis. Serum HBV DNA levels decreased to below 2.6 log₁₀ copies/mL in 23 (62%) of 37 patients at 12 months, 25 (78%) of 32 patients at 24 months, and 16 (84%) of 19 patients at 36 months. Except for one cirrhotic patient, serum alanine aminotransferase levels were below 50 IU/L in all patients during combination therapy. Serum creatinine levels increased in 14 (38%) of 37 patients, and serum phosphate levels decreased to below 2.5 mg/mL in 6 (16%) of 37 patients during combination therapy. Patients who received combination therapy for 36 months or longer had a significantly incidence of elevated serum creatinine levels. Fanconi syndrome occurred in a 57‐year‐old woman with cirrhosis after ADV was added to LAM. Combination therapy with ADV and LAM can maintain biochemical remission in patients with LAM‐refractory HBV. However, the dosing interval of ADV should be adjusted according to renal function and serum phosphate levels in patients receiving long‐term treatment.     

De novo combined lamivudine and adefovir dipivoxil therapy vs entecavir monotherapy for hepatitis B virus-related decompensated cirrhosis

AIM:To compare efficacy of combined lamivudine(LAM)and adefovir dipivoxil(ADV)therapy with that of entecavir(ETV)monotherapy for hepatitis B virus(HBV)-related decompensated liver cirrhosis.METHODS:A total of 120 na ve patients with HBVrelated decompensated cirrhosis participated in this study.Sixty patients were treated with combined LAM and ADV therapy(LAM+ADV group),while the other60 were treated with ETV monotherapy(ETV group)for two years.Tests for liver and kidney function,alpha-fetoprotein,HBV serum markers,HBV DNA load,prothrombin time(PT),and ultrasonography or computed tomography scan of the liver were performed every1 to 3 mo.Repeated measure ANOVA and theχ2test were performed to compare the efficacy,side effects,and the cumulative survival rates at 48 and 96 wk.RESULTS:Forty-five patients in each group were observed for 96 wk.No significant differences in HBV DNA negative rates and alanine aminotransferase(ALT)normalization rates at weeks 48(χ2=2.12 and 2.88)and96(χ2=3.21 and 3.24)between the two groups were observed.Hepatitis B e antigen seroconversion rate in the LAM+ADV group at week 96 was significantly higher in the ETV group(43.5%vs 36.4%,χ2=4.09,P<0.05).Viral breakthrough occurred in 2 cases(4.4%)by week 48 and in 3 cases(6.7%)by week 96 in the LAM+ADV group,and no viral mutation was detected.In the ETV group,viral breakthrough occurred in 1 case(2.2%)at the end of week 96.An increase in albumin(F=18.9 and 17.3),decrease in total bilirubin and in ALT(F=16.5,17.1 and 23.7,24.8),reduced PT(F=22.7 and 24.5),and improved Child-Turcotte-Pugh and the model for end-stage liver disease scores(F=18.5,17.8,and 24.2,23.8)were observed in both groups.The cumulative rates of mortality and liver transplantation were 16.7%(10/60)and 18.3%(11/60)in the LAM+ADV and ETV groups,respectively.CONCLUSION:Both LAM+ADV combination therapy and ETV monotherapy can effectively inhibit HBV replication,improve liver function,and decrease mortality.     

核苷（酸）类抗病毒药物对失代偿期乙型肝炎肝硬化患者肾功能的影响研究*

目的 评价核苷（酸）类药物（NUCs）对失代偿期乙型肝炎肝硬化患者肾功能的影响。方法 纳入失代偿期乙型肝炎肝硬化患者306例,其中接受抗病毒治疗者中包括拉米夫定（LAM）治疗者39例、阿德福韦（ADV） 73例、替比夫定（LDT）34例、恩替卡韦（ETV） 48例、LAM联合ADV 41例、LDT联合ADV 25例和未抗病毒治疗对照46例。随访3年。排除失访、随访时间小于3年和对照组中途开始抗病毒治疗者97例,最终209例患者纳入本研究。观察估算的肾小球滤过率（eGFR）、血清肌酐和尿素氮水平变化。结果 与对照组比,各抗病毒治疗组1年、2年、3年时eGFR较基线均无明显变化（P>0.05）,而LDT、LDT联合ADV组eGFR有逐年升高趋势（P>0.05）;本组失代偿期乙型肝炎肝硬化患者在基线时存在轻度肾功能损害者58例（27.8%）;在存在轻度肾损伤（基线eGFR<90 ml?min-1?1.73m-2）的患者,经LDT或LDT联合ADV治疗3年时患者eGFR复常率分别为55.6%和50%;各组患者血清肌酐和尿素氮水平与基线比无显著性差异（P>0.05）。结论 LDT单药或联合ADV可改善失代偿期乙型肝炎肝硬化患者的肾功能。     

联合核苷类药物治疗干扰素应答不佳的慢性乙型肝炎时机选择及疗效研究

目的：探讨干扰素治疗HBeAg阳性慢性乙型肝炎时,联合核苷（酸）类药物的不同时机对治疗应答的影响。方法：观察干扰素治疗患者分别在治疗起始时联合阿德福韦酯、12周应答不佳者及24周应答不佳者联合拉米夫定最终各组疗效。结果：48周时及停药后24周时,起始时联合阿德福韦酯治疗组及12周应答不佳者联合拉米夫定组患者的病毒转阴率、 ALT复常率、 HBeAg转阴率均高于对照组（ P＜0.05）,而HBeAg转换率并未有明显提高（ P＞0.05）。结论：治疗起始干扰素联合阿德福韦酯或根据12周应答情况加用拉米夫定治疗均能一定程度提高治疗应答率。