恩替卡韦联合阿德福韦酯治疗高病毒载量慢性乙型肝炎的疗效观察

目的探讨恩替卡韦与阿德福韦酯联合治疗高病毒载量慢性乙型肝炎(CHB)的疗效及安全性。方法收集2008年12月至2011年12月收治的高病毒载量CHB初治患者80例,随机分为观察组和对照组各40例。对照组采用恩替卡韦(ETV)治疗,观察组采用ETV联合阿德福韦酯(ADV)治疗。观察2组患者治疗前和治疗3、6、12、24个月时的HBV DNA载量、HBsAg或HBeAg血清学转换、ALT复常及不良反应情况。计量资料2组间比较采用两独立样本t检验;计数资料2组间比较用χ2检验。结果观察组6、12、24个月时的HBV DNA载量(拷贝/ml)的对数值(3.4±0.4、2.6±0.3、1.2±0.4)比同期对照组降低程度更明显(3.7±0.3、2.9±0.4、1.6±0.7)(t值分别为3.339、5.657、2.806,P值均0.05)。观察组治疗12、24个月时HBV DNA阴转率(87.5%、95.0%)、HBeAg转阴率(80.0%、90.0%)明显高于对照组(70.0%、77.5%;55.0%、70.0%)(P值均0.05)。观察组治疗24个月时HBeAg血清学转换率及ALT复常率较对照组明显提高(77.5%vs 50.0%;82.5%vs 55.0%,P值均0.05)。治疗期间,2组不良反应发生率差异无统计学意义(P0.05),观察组病毒学突破发生率明显低于对照组(0 vs 10.0%,P0.05)。结论初始联合ETV、ADV治疗高病毒载量CHB具有较强的抗病毒作用,可减少应答不佳和耐药的发生,长期临床疗效比单一使用ETV好,且安全可靠。     

六味五灵片联合阿德福韦酯治疗慢性乙型肝炎临床研究

目的观察六味五灵片联合阿德福韦酯(ADV)治疗慢性乙型肝炎(CHB)的临床疗效及安全性。方法采用随机、双盲、双模拟方法,选择CHB患者156例,按照1:1比例随机分为治疗组与对照组各78例。治疗组给予六味五灵片联合ADV治疗,对照组单用ADV治疗。两组均给予常规保肝、对症、支持治疗,疗程均为48周,观察患者治疗前后临床症状、肝功能及HBVDNA变化。结果治疗后,两组患者临床症状、肝功能及HBVDNA指标均有所改善,且治疗组总有效率高于对照组(P<0.05)。结论六味五灵片联合ADV治疗慢性乙型肝炎临床疗效显著,且安全性良好。     

单用替诺福韦酯与恩替卡韦联合阿德福韦酯挽救治疗慢性乙型肝炎对比观察

目的:对比替诺福韦酯(TDF)与恩替卡韦(ETV)联合阿德福韦酯(ADV)治疗经治慢性乙型肝炎(CHB)患者的疗效。方法:通过回顾性病例对照研究,选取在本院经拉米夫定(LAM)或者替比夫定(LDT)分别联合阿德福韦酯(ADV)治疗疗效不佳CHB患者73例,其中28例换用TDF300mg/次,1次/d,对照组45例改用ETV0.5mg/次,1次/d,联合ADV 10mg/次,1次/d,观察患者在治疗12、24、36及48周时的HBV DNA水平、HBV标志物、肝肾功能等指标的变化并进行比较。结果:治疗12周、24周、36周和48周时,TDF治疗组HBV DNA转阴率分别为57.1%、82.1%、82.1%、89.2%,均显著高于对照组11.1%、33.3%、46.6%、53.3%,差异有显著性意义(P均0.05);基线病毒载量1.0×10~4IU/ml,治疗组患者在12周、24周HBV DNA转阴率与对照组相比差异有显著性意义(P0.05),而36和48周差异无显著性意义(P0.05);病毒载量≧1.0×10~4IU/ml,治疗组与对照组在12、24、36及48周时HBV DNA转阴率差异均有显著性意义(P0.05);治疗组患者中,基线高病毒载量与低病毒载量患者比较结果显示12、48周时HBV DNA转阴率无显著性意义(P0.05),而24、36周时HBV DNA转阴率有显著性意义(P0.05);对照组患者中,高病毒载量与低病毒载量患者在24、36及48周时HBV DNA转阴比较差异有显著性意义(P0.05)。结论:对于LAM或LDT分别联合ADV治疗病毒学疗效不佳的CHB患者,选择TDF较ETV+ADV疗效更佳,不仅起效较快,且随疗程延长至48周时,疗效不受基线病毒载量的影响。     

健脾清化法联合阿德福韦酯治疗慢性乙型肝炎疗效分析158例

目的观察健脾清化法联合阿德福韦酯(ADV)治疗CHB的临床疗效及安全性。方法采用随机、双盲方法,选择CHB患者158例,随机分为治疗组80例,对照组78例。治疗组给予健脾清化煎剂联合ADV治疗,对照组单用ADV治疗。两组均给予常规保肝、对症、支持治疗,疗程均为24周,观察患者治疗前后临床症状、肝功能及HBV DNA变化。结果治疗后,两组患者临床症状及HBV DNA指标均有所改善,且治疗组总有效率高于对照组(P0.05)。结论健脾清化法联合ADV治疗CHB临床疗效显著,且安全性良好。     

聚乙二醇干扰素α-2a联合阿德福韦酯治疗HBeAg阴性慢性乙型肝炎的临床研究

目的 探讨聚乙二醇干扰素(Peg-IFN) α-2a联合阿德福韦酯(ADV)治疗HBeAg阴性慢性乙型肝炎(CHB) 96周的疗效及安全性. 方法 25例初治HBeAg阴性CHB患者接受Peg-IFN α-2a(135μg/周或180μg/周)联合ADV (10 mg/d)治疗.96周治疗结束时,如获得HBsAg血清学转换则停药随访,否则停用Peg-IFN α-2a,继续ADV维持治疗.所有患者随访至120周.基线和治疗过程中每12周检测HBV DNA和HBsAg水平.计数资料采用x2检验或Fisher's exact test检验. 结果 Peg-IFNα-2a联合ADV治疗48周时,100％ (25/25)的患者HBV DNA低于检测值(＜ 500拷贝/ml),且在治疗过程中始终保持不可检测水平;治疗48周时HBsAg血清学转换率为12％ (3/25),96周上升至28％ (7/25).随访至120周,HBsAg血清学转换率为32％ (8/25).延长治疗至96周未见新的不良反应发生,其安全性同48周.结论 Peg-IFNα-2a联合ADV并延长疗程可显著提高HBeAg阴性CHB患者的抗病毒疗效,尤其可以提高HBsAg血清学转换率,是值得探索的优化治疗策略之一.     

阿德福韦酯联合聚乙二醇干扰素α-2a治疗高病毒载量慢性乙肝的疗效观察

目的观察阿德福韦酯(ADV)联合聚乙二醇干扰素α-2a(Peg-IFNα-2a)治疗高病毒载量HBeAg阳性慢性乙型肝炎(CHB)的疗效。方法 73例HBV DNA≥1×107copies/ml的HBeAg阳性慢性乙型肝炎患者分为3组:联合治疗组25例,ADV治疗组24例和Peg-IFNα-2a治疗组24例,疗程为48周。对比分析在治疗48周时的HBsAg血清转换率、HBeAg血清转换率、ALT复常率和HBV DNA转阴率。结果联合治疗组HBeAg血清转换率明显高于ADV治疗组和Peg-IFNα-2a治疗组(P<0.05),联合治疗组ALT复常率明显高于Peg-IFNα-2a治疗组(P<0.05),联合治疗组HBV DNA转阴率显著高于Peg-IFNα-2a治疗组(P<0.05)。结论阿德福韦酯联合Peg-IFNα-2a治疗高病毒载量HBeAg阳性慢性乙型肝炎疗效优于单药治疗。     

阿德福韦酯治疗拉米夫定失效慢性乙型肝炎的疗效分析

慢性乙型肝炎(CHB)治疗的关键是抗病毒,拉米夫定(LAM)的5年耐药发生率约为70%,耐药的发生严重影响CHB的治疗效果及其预后.由于阿德福韦酯(ADV)与LAM无交叉耐药位点而被用于LAM失效的CHB的挽救治疗.本研究对ADV作为LAM失效CHB的挽救治疗药物在临床应用的疗效及其耐药发生方面进行探讨.     

血清HBsAg水平检测在干扰素联合阿德福韦酯治疗慢性乙型肝炎患者疗效评估中的意义

目的探讨血清HBs Ag水平检测在干扰素联合阿德福韦酯(ADV)治疗慢性乙型肝炎(CHB)患者疗效评估中的临床价值。方法应用化学发光法检测60例CHB患者在干扰素联合ADV治疗前和治疗过程中HBs Ag水平,以聚合酶链反应技术检测HBV DNA,并以连续监测法监测ALT水平并分析HBV DNA与HBs Ag的相关性。结果观察组30例CHB患者治疗前HBV DNA水平为(7.1±0.6)log10 IU/ml,HBs Ag水平为(3.5±0.4)log10 IU/ml。经干扰素联合ADV治疗3个月后HBs Ag下降,6个月后显著下降(P=0.000);治疗6个月后HBV DNA显著下降(P=0.000);治疗12个月后HBs Ag和HBV DNA均降至较低水平,分别为(2.1±0.3)log10 IU/ml和(2.7±0.3)log10 IU/ml;治疗3个月后ALT水平显著下降,治疗6个月后基本正常;治疗12个月无CHB患者产生耐药;患者HBs Ag水平与HBV DNA水平呈正相关。结论干扰素联合ADV治疗可显著降低慢性乙型肝炎患者血清ALT水平、提高HBe Ag低于检测下限的比率及HBV DNA低于检测下限的比率。定期检测HBs Ag浓度有助于评估ADV联合干扰素治疗CHB的疗效、及时发现耐药及是否需延长疗程。     

不同策略治疗rtN236T位点变异的HBeAg阳性慢性乙型肝炎的疗效观察

目的 观察rtN236T位点变异的阿德福韦酯(ADV)耐药HBeAg阳性的慢性乙型肝炎(CHB)患者,ADV分别联合聚乙二醇干扰素(Peg-IFN) α-2a及拉米夫定(LAM)进行治疗的疗效及安全性,并分析影响疗效的因素.方法 收集rtN236T位点变异的ADV耐药HBeAg阳性CHB患者65例,随机分为A组(33例)和B组(32例),A组ADV联合Peg-IFN α-2a治疗,连续48周后停用.B组ADV联合LAM治疗,连续48周后,继续使用24周.在治疗前、治疗后24、48周及随访24周,比较两组HBV DNA载量下降≥2log10拷贝/ml和HBV DNA≤500拷贝/ml患者数及HBeAg阴转率、HBeAg血清学转换率、ALT复常率.比较两组行肝穿刺活组织检查患者治疗前后的肝脏炎症分级、纤维化分期及肝组织学活动指数(HAI)评分.根据数据类型用t检验或x2检验进行统计分析.结果 治疗后24、48周及随访24周时,HBV DNA载量下降≥2log10拷贝/ml的患者,A组分别为81.8％、90.9％、75.8％,B组分别为53.1％、56.2％、59.4％;HBV DNA≤500拷贝/ml的患者,A组分别为48.5％、60.6％、42.4％,B组分别为31.3％、34.4％、31.3％;HBeAg阴转率,A组分别为39.4％、60.6％、54.5％,B组分别为12.5％、37.5％、37.5％;HBeAg血清学转换率,A组分别为27.3％、54.5％、48.5％,B组分别为6.3％、15.6％、18.8％;ALT复常率,A组分别为72.7％、84.8％、78.8％,B组分别为46.9％、56.3％、46.9％;A组均明显高于B组,差异有统计学意义(P值均＜0.05).治疗48周后,A组的肝组织HAI积分、炎症分级及纤维化分期改善情况均明显优于B组(P值均＜ 0.05).除肌酐升高发生率差异无统计学意义外,A组的不良反应发生率均高于B组(P值均＜ 0.05),但未发生终止治疗或危及患者安全的不良反应.A组停药随访24周,5例患者HBVDNA升高≥2log10拷贝/ml,其中4例治疗期间HBV DNA≤500拷贝/ml,此4例患者均发生ALT升高,且均未发生HBeAg血清学转换.结论 rtN236T位点变异的ADV耐药HBeAg阳性CHB患者,ADV联合Peg-IFN α-2a的疗效优于联合LAM,但不良反应发生率更高;未发生HBeAg血清学转换的患者,停药后易出现病毒反跳及ALT升高.     

阿德福韦酯单用或联合拉米夫定治疗YMDD变异的慢性乙型肝炎的疗效比较

目的 探讨阿德福韦酯(ADV)单用或联合拉米夫定治疗YMDD变异的慢性乙型肝炎(CHB)的疗效及安全性.方法 40例研究对象随机分为ADV组(20例)和联合组(20例),分别换用或加用ADV片10mg/d治疗.结果 两组ALT、AST、TBil值在治疗1、2年时分别与同组治疗前比较差异均极显著(P＜0.01),1年时两组间比较差异无显著(P＞0.05);治疗2年时联合组ALT、AST值显著低于ADV组(P＜0.01),两组TBil值差异无显著(P＞0.05).两组HBV DNA转阴、ALT复常、耐药率在治疗1年时差异均无显著(P＞0.05),2年时差异显著(P＜0.05);两组HBeAg转阴率及血清转换率治疗1、2年时比较差异均无显著(P＞0.05);治疗过程中两组均无严重不良事件发生.结论 ADV联合拉米夫定治疗YMDD变异CHB在病毒学、生化学方面长期疗效优于单用ADV治疗,近期疗效相似,前者耐药发生率低,两组安全性均良好.     

Overview of hepatitis B and transplantation in the hepatitis B patient

Hepatitis B is a disease that infects 300,000 people in the United States each year, resulting in 15,000-30,000 cases of chronic hepatitis. Outcomes include death; development of chronic carrier state, chronic hepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. Hepatitis B surface antigen (HBsAg) carriers, especially those with cirrhosis, are at high risk for development of hepatocellular carcinoma. Histologically, chronic carriers of HBsAg may have a range of degree of tissue changes, ranging from normal, to varying degrees of portal or lobular inflammation, to significant cell injury with widespread necrosis, fibrosis and cirrhosis. Current histological grading systems reflect both graded inflammation and stage of fibrosis.     

Precore and core promoter mutations of hepatitis B virus and hepatitis B e antigen-negative chronic hepatitis B in Korea

BACKGROUND/AIMS: The aims of this study were to determine the frequency of precore/core promoter mutations and hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (e-CHB) in Korea. METHODS: Patients with chronic hepatitis B virus (HBV) infection were tested for HBeAg, anti-HBe, liver profile and HBV-DNA by a branched DNA (bDNA) assay. Serum HBV-DNA was amplified by a polymerase chain reaction and the precore/core promoter sequence was determined. RESULTS: Among the 413 consecutive HBeAg-negative patients, 19.6% were bDNA-positive. Evidence of liver disease was found in 90.1% of bDNA-positive and 41.7% of bDNA-negative patients. Overall, 17.7% of HBeAg-negative patients had e-CHB. Precore mutation (A1896) was detected in 93.7% of HBeAg-negative bDNA-positive and 93.9% of HBeAg-negative bDNA-negative patients. In 59 HBeAg-positive patients, 78% had wild-type and 22% had a mixture of wild-type and A1896 mutant. Core promoter TA mutation was detected in 89.9% of HBeAg-negative bDNA-positive patients, 89.8% of HBeAg-negative bDNA-negative patients, and 74.6% of HBeAg-positive patients. No correlation was found between the presence of precore/core promoter mutations and HBV-DNA levels or disease severity. CONCLUSIONS: In Korean patients infected with HBV genotype C, precore mutation occurred almost invariably along with HBeAg seroconversion and core promoter TA mutation was frequent irrespective of viral replication levels or disease severity.     

乙型肝炎e抗原阴性与阳性慢性重型乙型肝炎临床分析

目的 分析乙型肝炎e抗原(HBeAg)阴性与HBeAg阳性慢性重型乙型肝炎患者的临床特点.方法 2001年1月至2006年9月在重庆医科大学附属二医院收治的353例慢性重型乙型肝炎患者分为HBeAg阴性组236例(66.8%),HBeAg 阳性组117例(33.2%),HBeAg阴性患者平均年龄高于HBeAg阳性患者,分别为(43.5±12.4)岁和(40.8±11.3)岁,两组比较差异有统计学意义(t=-1.988,P=0.048).对两组生化指标、HBV DNA、肝硬化基础、并发症、预后等进行分析.结果 HBeAg阴性患者血清HBV DNA低于HBeAg阳性患者,分别为(5.49±2.02)log10拷贝/mL、(6.64±1.41)log10拷贝/mL,两组比较差异有统计学意义(t=6.46,P<0.001);且HBeAg阴性患者血清HBV DNA<5 log10拷贝/mL的病例教比例为41.8%,远高于HBeAg阳性患者(11.9%),两组比较差异有统计学意义(X2=30.055,P<0.001).两组在肝脏生化指标、肝硬化基础及发生感染、腹水、肝性脑病、消化道出血等并发症及近期预后方面比较,差异均无统计学意义.结论 HBeAg阴性患者血清HBV DNA低于HBeAg阳性患者.HBeAg阴性慢性重型肝炎的肝脏生化指标、并发症发生率及近期预后与HBeAg阳性的慢性重型肝炎相似.应重视低水平病毒复制的HBeAg阴性慢性乙型肝炎患者的治疗、随访,早期抗病毒治疗,减少重型肝炎的发生率.     

Economics of chronic hepatitis B and hepatitis C

Although not all patients develop progressive liver disease, chronic hepatitis B and chronic hepatitis C infections cause substantial morbidity and mortality worldwide. To address this need, many new antiviral treatments have become available over the past 10 years. While safety, efficacy, and therapeutic indications have been well established for these agents, the economics of antiviral treatment have become increasingly a focus of discussion for physicians, policymakers, and health payers. In this paper, we will elucidate some economic principles using examples from the treatment of hepatitis B and C. In particular, we will examine the considerations in estimating drug costs, methods for performing economic analyses and lastly summarize published cost-effectiveness analyses for antiviral treatments of chronic hepatitis B and chronic hepatitis C. This review should help clinicians understand economic issues regarding new drugs and answer questions about whether the clinical benefit provided by a medication justifies its expense.     

Differential distribution of hepatitis B surface antigen and hepatitis B core antigen in the liver of hepatitis B patients.

One hundred liver biopsies from 100 patients with clinical presumptive diagnosis of hepatitis were examined by immunofluorescence for the presence of hepatitis B surface antigen (HBSAg) and hepatitis B core antigen (HBcAg). Of the 60 HBsAg-positive livers, 51 were diagnosed as chronic hepatitis on histological grounds, 6 as acute hepatitis, and 3 as "near-normal liver." From the 60 tissue-positive cases, 3 subjects were HBsAg seronegative. HBcAg was detected in 44 livers, all of which also had HBcAg in the localized in the cytoplasm and the membranes of the hepatocytes, and HBcAg in the nuclei and in 4 cases also in the cytoplasm. Predominant HBsAg expression in the cytoplasm was observed in near-normal liver, chronic persistent hepatitis, and cirrhosis with little activity. This correlated with the amount of ground glass hepatocytes in the biopsies. HBcAg and membrane-localized HBsAg were minimal in those conditions. HBcAg was most prevalent in patients with chronic aggressive hepatitis and active cirrhosis treated with immunosuppressive drugs, whereas the amounts of HBsAg and HBcAg in nontreated patients of those two groups and in acute hepatitis with signs of transition to chronicity were almost equal. HBsAg expression in liver cell membranes was most prominent in active forms of chronic hepatitis (chronic aggressive hepatitis and in active cirrhosis) and in acute hepatitis with signs of transition to chronicity. This observation correlated in the presence of HBcAg in the biopsies of those patients. In acute hepatitis both HBsAg and HBcAg were detected rarely and no membrane expression of HBsAg was observed. The over-all results show a significant relationship between the different degrees of accumulation of HBsAg and HBcAg in the liver and the various histological types of hepatitis and further suggest an interplay of both hepatitis B virus and host immune response in the development and pathogenesis of hepatitis B.     

The structure of hepatitis B envelope and molecular variants of hepatitis B virus

Summary. Accumulated evidence in recent years has shown that the variation of hepatitis B virus (HBV) genomes may have profound implications for our understanding of hepatitis B pathogenesis and prevention. Attention has focused on areas of the outer envelope coded by the S gene which are involved in the induction of a protective neutralising antibody response, and mutations which directly affect the production of C gene products, one of which is considered as a target for immune T cells involved in virus clearance. This review highlights recent experimental data which emphasizes the role of such mutations in the establishment and maintenance of chronic HBV infections and focuses attention on the significance of HBV variants with respect to the expanding use of HBV vaccines for mass immunization.     

乙型肝炎免疫球蛋白在乙型肝炎防治中的研究进展

自1977年乙型肝炎免疫球蛋白(HBIG)首次用于治疗HBsAg阳性患者后,HBIG作为被动免疫制剂被广泛应用于保护急性暴露或易受感染者、预防慢性乙型肝炎伴肝硬化行肝移植者术后乙型肝炎病毒(HBV)再感染,或作为联合被动主动免疫中的被动免疫制剂,用于保护HBsAg阳性母亲所生新生儿,阻断母婴传播。一、HBIG的应用(一)急性暴露者和易受感染者的应用早期报道,血液透析患者使用HBIG500U次,透析当日及间隔2个月共注射2次,其保护率高达80%。Palmovic[1]报道56例医护人员被意外HBsAg和(或)HBeAg污染针刺感染,3d内肌肉注射HBIG0.06ml kg,1个…     

Leprosy and hepatitis B

In 1966, B. S. Blumberg, investigating for carriers of the "Australia" antigen which he had discovered two years before, finds that the percentage is significantly more elevated in a group of leprous patients than in controls. In this initial work, realized at Cebu, Philippines, he mentions a higher percentage of this antigen carriers among the lepromatous than among the tuberculoid patients. He explains his findings by a genetic hypothesis and by the fact that lepromatous patients are more often hospitalized than the tuberculoid ones, thus narrowest contacts could favour the antigen transmission. Later, the established relation between Australia antigen and hepatitis B incites the authors to disregard the very deceiving genetic hypothesis and to build up the most important characteristic of lepromatous leprosy--cell immunity--as opposed to the tuberculoid form where cell immunity is normal. Investigation for seric markers of hepatitis B virus in patients with tuberculoid or lepromatous leprosy provides a model for the study on "cell immunity and hepatitis B". The juxtaposition of geographic areas with high prevalence of leprosy patients and of HBs Ag carriers is a supplementary argument for the study of their connection. Up to now, about fifty works have been published on this subject. Most of them investigate detection of HBs Ag and a few of HBe Ag and HBs Ac. This bibliographical study, including a personal study, reviews markers of hepatitis B virus replication in leprosy patients, incidence of hospitalization and age of these patients, as well as the methodology used.