慢性乙型肝炎血清HBVDNA基因含量与临床的相关性研究

目的探讨慢性乙型肝炎（慢乙肝）患者病毒复制水平与HBV标志物（HBV—M）模式及肝损害程度的关系。方法360例慢性乙型肝炎（轻度160例、中度140例、重度60例）患者血清HBVDNA含量采用荧光标记（AmpliSensor）定量PCR方法检测,HBV—M检测采用ELISA法。结果血清HBVDNA含量与HBV—M模式有关,血清HBeAg阳性组HBVDNA含量（106．35±1．84）显著高于HBeAg阴性组（104．73±1．88）（P〈0．01）。慢乙肝轻度、中度患者HBVDNA含量[（105．58±1．92）,（106．27±2．05）]与慢乙肝重度患者HBVDNA含量（105．73±1．90）相比较无显著性差异（P〉0．05）,且不同HBVDNA水平患者的TBil、AI』、AST差别无显著性（P〉0．05）。结论血清HBeAg的存在影响HBVDNA的水平变化,随着肝损害程度的加重,慢性乙型肝炎轻度、中度、重度患者血清HBVDNA基因含量未发生显著变化,同时血清HBVDNA含量与TBil、ALT、AST水平无明显关系。     

乙型肝炎病毒C基因启动子热点变异的检测及分析

目的　探讨乙型肝炎病毒C基因启动子 (CP)热点变异的临床意义。方法　应用克隆测序的方法检测 2 0例HBV感染者HBVCP序列 ,并结合临床进行分析。结果　 10例HBeAg(+)患者中 ,CP的T176 2、A176 4联合变异有 2例 (2 0 % ) ;10例HBeAg(- )患者中T176 2、A176 4联合变异有 7例 (70 % ) ,χ2 =6 73,P <0 0 5 ,有显著性差异。结论　T176 2、A176 4联合变异多见于HBeAg(- )的慢性乙型肝炎患者。     

Adefovir dipivoxil in chronic hepatitis B infection

Adefovir dipivoxil, an acyclic nucleotide analogue, is effective for the treatment of chronic hepatitis B in both hepatitis B e antigen (HBeAg)-positive and -negative patients, with improvement in liver histology, hepatitis B virus (HBV) DNA levels, alanine aminotransferase levels, and HBeAg seroconversion (for HBeAg-positive patients). It is also effective against lamivudine-resistant strains of hepatitis B mutations. It has been studied in pre- and post-liver transplant patients. Compared to lamivudine, adefovir dipivoxil is associated with a much lower risk of emergence of drug-resistant HBV. Adefovir-associated resistant virus is susceptible to lamivudine therapy. The recommended dose of adefovir dipivoxil 10 mg is associated with low risk of nephrotoxicity. Adefovir dipivoxil can be recommended as a first-line treatment but can also be used in patients with chronic hepatitis B infection who are failing lamivudine therapy.     

Adefovir dipivoxil in chronic hepatitis B infection

Adefovir dipivoxil, an acyclic nucleotide analogue, is effective for the treatment of chronic hepatitis B in both hepatitis B e antigen (HBeAg)-positive and -negative patients, with improvement in liver histology, hepatitis B virus (HBV) DNA levels, alanine aminotransferase levels, and HBeAg seroconversion (for HBeAg-positive patients). It is also effective against lamivudine-resistant strains of hepatitis B mutations. It has been studied in pre- and post-liver transplant patients. Compared to lamivudine, adefovir dipivoxil is associated with a much lower risk of emergence of drug-resistant HBV. Adefovir-associated resistant virus is susceptible to lamivudine therapy. The recommended dose of adefovir dipivoxil 10 mg is associated with low risk of nephrotoxicity. Adefovir dipivoxil can be recommended as a first-line treatment but can also be used in patients with chronic hepatitis B infection who are failing lamivudine therapy.     

干扰素联合微卡治疗慢性乙型肝炎

目的：探讨干扰素联合微卡治疗慢性乙型肝炎的作用机制及疗效。方法：按诊断标准选择慢性乙型肝炎患者80例，随机分为干扰素联合微卡为治疗组(40例)和干扰素为对照组(40例)，观察比较两组患者肝功能、HBeAg及HBVDNA的变化。结果：治疗组的肝功复常率、HBeAg及HBVDNA阴转率均明显高于对照组(P＜0.05)。结论：干扰素联合微卡治疗慢性乙型肝炎有协同作用，它能提高细胞免疫应答能力、促进HBeAg及HBVDNA的阴转，减少病毒的变异，延迟耐药性的发生。     

慢性乙型肝炎病情与乙型肝炎病毒标志物表达模式的关系

目的观察乙型肝炎病毒(HBV)标志物(HBsAg、HBsAb、HBeAg、HBeAb、HBcAb)表达模式与慢性乙型肝炎病情的关系。方法对582例5组慢性乙型肝炎和乙型肝炎后肝硬化患者,用酶联免疫吸附试验(ELISA)检测HBV标志物,用OlympusAU2700全自动生化分析仪检测血清总胆红素(TBIL)、白蛋白(ALB)、丙氨酸氨基转移酶(ALT)、前白蛋白(PA)。依据HBV标志物阳性情况分为6组:A组173例,为HBsAg、HBeAg、HBcAb阳性;B组218例,为HBsAg、HBeAb、HBcAb阳性;C组161例,为HBsAg、HBcAb阳性;D组13例,为HBeAb、HBcAb阳性;E组6例,为HBsAb、HBeAb、HBcAb阳性;F组11例,为HBsAb、HBcAb阳性。结果582例中,A组阳性率为29.7%;B组为37.4%;C组为27.7%;D组为2.2%;E组为1.0%;F组为1.9%。A、B、C模式组间阳性率有显著性差异(χ2=14.75,P<0.01),以B模式组的阳性率最高。5组慢性肝病间比较,A组阳性率有显著性差异(χ2=23.17,P<0.01),B组阳性率无显著性差异(χ2=3.72,P>0.05),C组阳性率有显著性差异(χ2=25.74,P<0.01)。HBeAg阳性的A组与HBeAg阴性的B、C组比较,TBIL、ALB、ALT、PA水平及其异常率均无显著性差异(F=1.91、2.48、0.58、1.37,P>0.05;χ2=2.09、5.97、2.35、2.26,P>0.05)。结论HBV标志物的表达模式与慢性乙型肝炎的病情无明显相关,临床上不能根据HBV标志物的表达模式来预测判断病情轻重和预后情况。     

Liver function and hepatitis markers in carriers of hepatitis B virus in New Zealand

AIMS: The Hepatitis Foundation has identified many chronic carriers of hepatitis B virus (HBV) in community surveys of schools and family contacts. This study reports the characteristics of carriers and the relationship between hepatitis markers and liver function. METHODS: Demographic data from confirmed chronic carriers of HBV in the North Island were correlated with liver function and hepatitis markers. Longitudinal data were obtained by following a cohort for two years with regular blood tests. RESULTS: Of 2778 confirmed carriers of HBV most were children or young adults and 56% were male. Sixty percent were Maori and 26% Pacific Island people. Loss of HBsAg occurred at less than 1% per year compared to 9% for HBeAg. Mean ages for 50% loss of HBeAg were 14 years for children of HBV negative mothers and 19 years for those of HBV carrier mothers. Fewer adult males than females were HBeAg positive. Alanine aminotransferase levels above 50 IU/L were found in 16% of HBeAg positive and 6% HBeAg negative cases. Other factors significantly associated with raised alanine aminotransferase were male gender (OR 1.8) and age more than 15 years (OR 2.0). Thirty five percent of HBeAg positive carriers with raised alanine aminotransferase levels spontaneously seroconverted to HBeAg negative in two years. However, raised alanine aminotransferase in HBeAg negative carriers was persistent in most cases and 38% had HBV-DNA detectable in serum. CONCLUSIONS: HBV carriage is less benign in adults than children, even after loss of HBeAg. It is recommended that all HBV carriers have regular checks of liver function. Those with persistent abnormality should be strongly advised to restrict alcohol and be assessed for possible antiviral treatment.     

HBV-前C区基因变异与乙肝病毒复制的相关性

目的 研究乙型肝炎病毒(HBV)前C区G1896A变异与乙肝病毒复制的相关性.方法 选取38例慢性轻度,57例慢性中度,29例慢性重度的乙型肝炎患者为研究对象.采用突变特异PCR技术检测HBV前C基因nt1896位点突变情况,并对血清中HBVDNA进行测序.同时检测乙型肝炎病毒HBeAg/抗-Hbe、HBVDNA定量、肝纤维化指标.结果 (1)抗Hbe阳性者在单纯变异株感染的慢性乙型肝炎患者中所占的比例(84.61%)高于单纯野生株感染者(24.32%).(2)随着变异株感染率的增加,HBVDNA的含量增高.(3)随着变异株感染率增加,肝脏纤维化分期的逐渐加重.结论 前C区G1896A变异与乙肝病毒的复制程度相关.     

乙肝病毒C基因启动子和前C／C基因变异与慢性乙肝发作及病情严重性的关系

目的 研究乙型肝炎病毒（HBV）C基因启动子（CP）和前C/C基因变异与无症状慢性HBV携带者（ASC）的肝炎发作及慢性乙肝病情严重性的关系。方法 通过PCR及其产物直接测序,检测4例ASC、27例慢性乙肝和3例慢性重型乙肝病人血清的HBVCP和前C/C基因序列,并定量检测HBV DNA。结果 （1）CP主要变异为nt1726-1730聚集变异（1726A→C、1727A→T、1730C→G）和nt17621764双变异（1762A→T和1764G→A）。前C区主要变异为1896G→A。C基因变异常使C蛋白aa5、13、27、60、87、97及130发生置换,（2）CP聚集变异与ASC首次肝炎急性发作有关,11例中,8例出现CP聚集变异。（3）CP聚集变异合并CP双变异的乙肝病人。临床上或表现为重型肝炎或迅速进展为活动性肝硬化,HBVDNA高水平,、HBeAg/抗HBe转换。结论 同前C/C基因比较,CP变异与慢性乙肝病人的临床表现可能更为密切。     

慢性乙型肝炎乙肝病毒基本核心启动子变异的实验与临床研究

目的 研究乙型肝炎基本核心启动子(BCP)变异与慢性乙型肝炎病情的关系.方法 通过PCR及其产物直接检测128例慢性乙型肝炎(CHB)患者HBV,同时检测患者HBV定量及血清生化指标.结果 128例标本中nt1762、1764变异(双变异)共检出56例,nt1753、1762、1764变异(三变异)共检出10例,肝炎肝硬化(LC)组中双变异明显高于其他CHB组(P＜0.05);双变异组的HBeAg、ALB明显低于无变异组(P＜0.05),三变异组HBeAg明显低于双变异组(P＜0.05).结论 BCP区双变异可减少HBeAg的表达,引起肝功能受损严重并导致肝硬化的发生,BCP区尚有新发现的变异如三变异也可影响HBeAg的表达.     

乙肝康治疗慢性乙型肝炎近期疗效分析

目的 :评价中药复合制剂乙肝康对慢性乙型肝炎治疗作用。方法 :选择HBeAg、HBV DNA阳性 ,肝功能异常的 31例慢性乙型肝炎作治疗对象 ,给予乙肝康 10mL加入 5 %葡萄糖 2 5 0mL内每日滴注 1次 ,疗程 3个月 ,并与 2 5例静滴甘利欣 ,泰特病人作对照。结果 :完全应答 11例 ,部分应答 13例 ,无应答 7例。HBV DNA14例阴转 ( 45 .1% ) ,HBeAg11例阴转 ( 35 .5 % ) ,其中 9例HBeAg/抗HBe血清转换 ( 2 9% )。 结论 :乙肝康具有治疗慢性乙型肝炎肝功能的作用 ,同时具有清除体内病毒的作用 ,值得进一步研究。     

Long-term lamivudine therapy for chronic hepatitis B in patients with and without cirrhosis

STUDY OBJECTIVE: To evaluate the effects and safety of 52-week lamivudine therapy in Korean patients with chronic hepatitis B virus (HBV), with and without cirrhosis. DESIGN: Long-term retrospective study. SETTING: Ajoo University Medical Center, Soowon, Korea. PATIENTS: Twenty-seven men and two women who had received oral lamivudine 100 mg/day for 52 weeks for treatment of biopsy-proven chronic HBV; 11 patients had cirrhosis, 18 did not. MEASUREMENTS AND MAIN RESULTS: All 29 patients were positive for HBV DNA and hepatitis B surface antigen (HBsAg) before treatment began; 25 (86%) patients were positive for hepatitis B e antigen (HBeAg). Lamivudine therapy suppressed serum HBV DNA to undetectable levels in 26 (90%) patients within a median of 4 weeks. Serum HBV DNA of 28 patients (97%) fell significantly to undetectable levels within 12 weeks and remained undetectable in 24 (83%) patients after 52 weeks, and HBeAg had converted to negative in 10 (40%) of the 25 patients who were positive. Mean serum alanine aminotransferase (ALT) levels of the 29 patients decreased to within the normal range by 12 weeks and remained at 33-48 IU/L thereafter. Differences in responses of HBV DNA and ALT to lamivudine therapy in HBeAg-positive and -negative patients were negligible (p = 0.786 and p = 0.225, respectively). Pretreatment HBV DNA and ALT levels had no effect on the efficacy of lamivudine (p = 0.9116). Furthermore, differences in responses of HBV DNA (p = 0.641), HBeAg seroconversion (p = 0.386), and ALT (p = 0.689) and in development of drug resistance (p = 0.617) between patients with and without cirrhosis were negligible. No serious adverse effects were reported. CONCLUSION: Lamivudine is an effective and well-tolerated therapeutic agent for treating chronic HBV in patients with and without cirrhosis.     

Short report: prednisolone withdrawal followed by lymphoblastoid interferon in the therapy of adult patients with presumed childhood-acquired chronic hepatitis B virus infection

Eighteen patients with presumed childhood acquisition of chronic hepatitis B virus infection were initially entered into this randomized controlled trial. Twelve were treated with prednisolone for 4 weeks followed, after a 2-week gap, by thrice weekly lymphoblastoid a-interferon for 12 weeks. Two of these had previously acted as untreated controls. Three of the 12 patients (25%) [who were initially hepatitis B virus (HBV) surface antigen (HBsAg),‘e’ antigen (HBeAg) and HBV-DNA positive] became HBeAg and HBV-DNA negative during therapy and remained so after 12 months post-therapy follow-up. One of these also lost HBsAg. A further two patients lost HBeAg and HBV-DNA during therapy but relapsed 6 and 9 months later. Two additional patients were HBV-DNA negative but HBeAg positive at the end of follow-up. None of the eight untreated control patients seroconverted during an identical follow-up period. Two further patients were HBsAg and HBeAg positive but HBV-DNA negative at the start of therapy. These were omitted from the final analysis: both subsequently lost HBeAg. The treatment response was associated with a rise in aspartate aminotransferase, peaking 2–6 weeks after prednisolone withdrawal, loss of HBV-DNA 0–8 weeks later and subsequent normalization of liver function tests. Treatment was well tolerated.     

乙型肝炎血清免疫标志物、乙型肝炎病毒核酸水平变化与HBV的关系及临床意义

目的：探讨乙型肝炎血清免疫标志物、乙型肝炎病毒核酸水平变化与HBV的关系及临床意义。方法选取本院2013年2月∽2014年2月收治的108例乙型肝炎患者为研究对象,按HBV DNA含量高低分为A（〈103拷贝/ml）、B（103∽105拷贝/ml）、C（106∽108拷贝/ml）3组,分别检测3组的乙型肝炎血清免疫标志物（HBV M）与乙型肝炎病毒核酸（HBV DNA）含量。结果 A组的HBeAg为（3.971±14.47）S/CO,B组为（446.7±785.8）S/CO,两组比较,差异有统计学意义（P〈0.05）;A组的抗-HBe、HBeAg、HBsAg与C组比较,差异均有统计学意义（P〈0.05）;B组的HBeAg与C组比较,差异有统计学意义（P〈0.05）;3组的抗-HBs、抗-HBc比较,差异均无统计学意义（P〉0.05）。HBV M阳性标本中抗-HBs、抗-HBc与HBsAg含量与HBV DNA无相关性,抗-HBe与HBV DNA呈负相关,HBeAg与HBV DNA呈正相关。结论定量检测HBV DNA可真实反映HBV的复制情况,对于传染性评价、乙型肝炎诊治及疗效观察均具有指导意义;定量检测HBV M虽在HBV复制程度的判断及传染性评价方面无明显价值,但可为乙型肝炎数据管理奠定基础。     

Treatment of chronic hepatitis B

Infection with the hepatitis B virus has switched over the last 20 years from the classical HBeAg positive serologic pattern to a HBeAg negative form that is linked, in the Mediterranean basin, with the epidemiologic replacement of the causative wild-type of virus B with mutant variants, whereby mutations in the core-promoter and in the pre-core region prevent the secretion of HBeAg. The wild-type pattern of infection (characterized by relatively high steady level ALT, high HBV-DNA levels and clinically overt liver disease) responds relatively well to Interferon: 3 to 5 mega units daily or 10 mega units every other day for 16 weeks induce anti-HBe seroconversion, normalize the ALT and possibly also eliminate the HBsAg in some 40% of the adults with a minimal (7%) risk of relapse. However, the mutant type infection (anti-HBe positive / HBe Ag negative) is less responsive to Interferon; this has led to the search for novel nucleoside analogues which has currently culminated in the advent of Lamivudine. This competitor of cytidine is 80% bioavailable and devoid of side-effects at the oral dose of 100 mg daily; tolerance continues for therapies up to 3 years. Lamivudine therapy shares with Interferon a rapid decline of ALT accompanied by improvement of histology; at variance with Interferon there is a delayed accumulating seronconversion to anti-HBe and the switch to anti-HBs is rare. Over the long term its activity is abolished by the emergence of specific viral mutations (YMDD mutants) that rekindle the disease. The indications to Lamivudine therapy in HBeAg negative chronic hepatitis B are currently under investigation. Lamivudine is highly efficacious in preventing HBV reinfection in liver transplants.     

Adefovir dipivoxil in chronic hepatitis B: history and current uses

INTRODUCTION: The nucleotide analogue adefovir dipivoxil (ADV) was approved in 2002 for the treatment of chronic infection with hepatitis B virus (HBV), in both hepatitis B e antigen (HBeAg)-positive and -negative patients. ADV 10 mg daily has been associated with improved liver histology, decreased levels of HBV DNA and alanine aminotransferase (ALT), and seroconversion of HBeAg. AREAS COVERED: This paper reviews the use of ADV as a first-line treatment for chronic hepatitis B and as an add-on therapy in chronic HBV-infected patients with lamivudine resistance. In the years since its launch, clinical resistance to ADV has emerged, and tenofovir and entecavir have shown greater efficacy in reducing viral load. EXPERT OPINION: Many patients who started antiviral therapy with ADV (either as monotherapy or in combination with lamivudine) remain on this agent because they have undetectable viremia, but its future use will probably diminish because of the availability of more potent drugs. ADV is generally well tolerated, though the 10 mg dose is associated with low risk of nephrotoxicity.     

乙型肝炎病毒基因型用干扰素α-2b联合苦参素治疗的临床研究

目的：研究乙型肝炎病毒基因型用干扰素α-2b联合苦参素治疗慢性乙型肝炎疗效的关系。方法：应用免疫荧光定量方法检测60例慢性乙型肝炎（慢乙肝）的乙肝病毒基因型，患者均在常规保肝治疗基础上应用干扰素α-2b和苦参素联合抗病毒治疗，疗程6个月。随访6个月。结果：治疗结束及随访6个月时血清HBeAg／HBeAb转换率、HBVDNA阴转率、HBVDNA降低2—5logL率为B基因型组分别为83.3％、83.3％、16．67％；66．67％、75．00％、25．00％；C基因型组分别为45．83％、47．92％、45．65％；35．42％、39．58％、41．67％。B基因型组与C基因型组比较．血清HBeAg／HBeAb转换率、HBVDNA阴转率、血清转氨酶及肝纤维化指标下降均有统计学意义（P〈0．05）。结论：干扰素α-2b联合苦参素治疗慢性乙型肝炎疗效及随访观察疗效B基因型优于C基因型。     

拉米夫定治疗慢性乙型肝炎的临床和病理研究

目的 :探讨拉米夫定治疗慢性乙型肝炎病人后 ,病人的血清HBV指标和肝组织学的变化。方法 :选择 2 0例慢性乙型肝炎病人 ,口服拉米夫定 ,10 0mg ,qd× 1a。治疗前后 ,检测病人血清ALT ,HBV DNA ,HBeAg ;肝组织活检 ,作病理检查。结果 :治疗后ALT降低 2 0例 (10 0 % ) ;HBV DNA阴转 18例 (90 % ) ;肝组织炎症明显减轻 17例 (85 % ) ;治疗前后比较 ,差异有显著意义 (P <0 .0 5 )。HBeAg阴转 4例 (2 0 % ) ;病人肝组织纤维化减轻 2例 (10 % ) ;治疗前后比较 ,差异无显著意义 (P >0 .0 5 )。结论 :拉米夫定可以有效减轻慢性乙型肝炎病人的肝组织炎症 ,改善病人的肝功能 ,促使病人的血清HBV DNA阴转 ,但改善肝组织纤维化和促使HBeAg阴转效果不明显     

乙型肝炎患者血清中前S1蛋白、HBcAg及HBV DNA相关性临床研究

目的探讨乙型肝炎患者血清前Si(Pre-S1)蛋白、HBcAg、HBV DNA及HBV其他标志物的关系及临床意义,为评判HBV复制和病情发展提供新的思路与证据.方法对136例乙型肝炎患者血清中HBVDNA应用微板核酸杂交法;HBcAg采用ELISA间接法,两种抗体包被,反应孔内裂解Dane颗粒的酶标技术直接检测Pre-S1及HBV其他标志物同时进行ELISA检测. 结果血清中Pre-S1、HBcAg、HBV DNA检出率在HBsAg、HBeAAg抗-HBc组合中最高,分别为33.3%、74.6%、85.7%,与HBV-M其它组合比较P＜0.01;HBeAg和HBcAg阳性组的HBVDNA、Pre-S1检出率最高(91.7%、39.6%),其次为HBeAb和HBcAg阳性组;HBV DNA阳性组的Pre-S1、HBcAg检出率(27.5%、62.6%)明显高于阴性组(2.2%、8.9%),P＜0.001;Pre-S1阳性血清中HBcAg与HBV DNA检出率为96.4%、89.3%,与阴性组比较P＜0.001及P＜0.05;Pre-S1、HBcAg与HBV DNA检出率在各临床类型患者中,除慢性肝炎HBV DNA检出率高,且统计学意义(P＜.001)外,其它无特异性. 结论血清Pre-S1、HBcAg、HBV DNA和HBeAg均是反映乙肝病毒复制的敏感指标,具有较好的相关性.抗HBe的出现并不表示病毒复制停止,应参考其他病毒复制指标情况.乙型肝炎各临床类型HBV复制指标检出率仅HBVDNA具有特异性.