Antiviral therapy with nucleos(t)ide analogues for severe chronic hepatitis B

To the Editor:I read the paper by Chen et al[1]with great interest.The authors performed a retrospective study to evaluate the short-term efficacy of antiviral therapy with

Potent antiviral therapy improves survival in acute on chronic liver failure due to hepatitis B virus reactivation

Acute on chronic liver failure(ACLF)is a disease entity with a high mortality rate.The acute event arises from drugs and toxins,viral infections,bacterial sepsis,interventions(both surgical and non-surgical)and vascular events on top of a known or occult chronic liver disease.ACLF secondary to reactivation of chronic hepatitis B virus is a distinct condition;the high mortality of which can be managed in the wake of new potent antiviral therapy.For example,lamivudine and entecavir use has shown definite short-term survival benefits,even though drug resistance is a concern in the former.The renoprotective effects of telbivudine have been shown in a few studies to be useful in the presence of renal dysfunction.Monotherapy with newer agents such as tenofovir and a combination of nucleos(t)ides is promising for improving survival in this special group of liver disease patients.This review describes the current status of potent antiviral therapy in patient with acute on chronic liver failure due to reactivation of chronic hepatitis B,thereby providing an algorithm in management of such patients.

Importance of adequate immunosuppressive therapy for the recovery of patients with "life-threatening" severe exacerbation of chronic hepatitis B

AIM: Hepatitis B virus (HBV) re-activation often occurs spontaneously or after withdrawal of immunosuppressive therapy in patients with chronic hepatitis B. Severe exacerbation, sometimes developing into fulminant hepatic failure, is at high risk of mortality. The efficacy of corticosteroid therapy in "clinically severe" exacerbation of chronic hepatitis B has not been well demonstrated. In this study we evaluated the efficacy of early introduction of high-dose corticosteroid therapy in patients with lifethreatening severe exacerbation of chronic hepatitis B.METHODS: Twenty-two patients, 14 men and 8 women,were defined as "severe" exacerbation of chronic hepatitis B using uniform criteria and enrolled in this study. Eleven patients were treated with corticosteroids at 60 mg or more daily with or without anti-viral drugs within 10 d after the diagnosis of severe disease ("early high-dose"group) and 11 patients were either treated more than 10 d or untreated with corticosteroids ("non-early high-dose"group).RESULTS: Mean age, male-to-female ratio, mean prothrombin time (PT) activity, alanine transaminase (ALT)level, total bilirubin level, positivity of HBeAg, mean IgMHBc titer, and mean HBV DNA polymerase activity did not differ between the two groups. Ten of 11 patients of the "early high-dose" group survived, while only 2 of 11 patients of the "non-early high-dose" group survived (P＜0.001). During the first 2 wk after the introduction of corticosteroids, improvements in PT activities and total bilirubin levels were observed in the "early high-dose"group. Both ALT levels and HBV DNA polymerase levels fell in both groups.CONCLUSION: The introduction of high-dose corticosteroid can reverse deterioration in patients with "clinically lifethreatening" severe exacerbation of chronic hepatitis B,when used in the early stage of illness.

Immunological approaches to breakdown of hepatitis B viral persistence

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Hepatitis B virus genotypes:Global distribution and clinical importance

At least 600000 individuals worldwide annually die of hepatitis B virus(HBV)-related diseases,such as chronic hepatitis B(CHB),liver cirrhosis(LC),and hepatocellular carcinoma(HCC).Many viral factors,such as viral load,genotype,and specific viral mutations,are known to affect disease progression.HBV reverse transcriptase does not have a proofreading function,therefore,many HBV genotypes,sub-genotypes,mutants,and recombinants emerge.Differences between genotypes in response to antiviral treatment have been determined.To date,10 HBV genotypes,scattered across different geographical regions,have been identified.For example,genotype A has a tendency for chronicity,whereas viral mutations are frequently encountered in genotype C.Both chronicity and mutation frequency are common in genotype D.LC and progression to HCC are more commonly encountered with genotypes C and D than the other genotypes.Pathogenic differences between HBV genotypes explain disease intensity,progression to LC,and HCC.In conclusion,genotype determination in CHB infection is important in estimating disease progression and planning optimal antiviral treatment.

Hepatitis B virus and hepatitis C virus dual infection

Hepatitis B virus(HBV)and hepatitis C virus(HCV)share common mode of transmission and both are able to induce a chronic infection.Dual HBV/HCV chronic coinfection is a fairly frequent occurrence,especially in high endemic areas and among individuals at high risk of parenterally transmitted infections.The intracellular interplay between HBV and HCV has not yet been sufficiently clarified,also due to the lack of a proper in vitro cellular model.Longitudinal evaluation of serum HBV DNA and HCV RNA amounts has revealed that complex virological profiles may be present in coinfected patients.Dual HBV/HCV infection has been associated to a severe course of the liver disease and to a high risk of developing hepatocellular carcinoma.Despite the clinical importance,solid evidence and clear guidelines for treatment of this special population are still lacking.This review summarizes the available data on the virological and clinical features as well as the therapeutic options of the dual HBV/HCV infection,and highlights the aspects that need to be better clarified.

Relationship between HBV genotypes and anti-viral therapeutic efficacy of interferon-alpha

BACKGROUND: Much evidence demonstrates that the genotypes of hepatitis B virus (HBV) present differences in pathogenicity and outcomes owing to differences in genetic structure. This study aimed to investigate the influences of HBV genotypes on the anti-viral therapeutic efficacy of interferon-alpha (IFN-alpha) in chronic hepatitis B patients, and to determine the relationship between HBV genotypes and levels of viral replication or gene variations. METHODS: The chronic hepatitis B patients who were treated with IFN-alpha were selected randomly. Anti-viral therapeutic efficacy was monitored in these patients. The HBV genotypes were detected by PCR microplate hybridization ELISA. The levels of serum HBV-DNA were determined by fluorescence quantitative PCR. HBV gene variation at pre-C and basic core promoter (BCP) regions were assayed by gene chip technology. RESULTS: Genotypes B and C were predominant in 94 chronic hepatitis B patients. A, E and F genotypes were not found in these patients. The HBV-DNA levels of genotype C and mixed genotypes were significantly higher than those of genotype B. The response to IFN-alpha in patients with genotype B was markedly better than in those with genotypes C and D, and the complete response to IFN-alpha was only observed in genotype B. The response to IFN-alpha in patients with mixed genotypes was the least sensitive. The negative transition of HBeAg was correlated with variations in the HBV pre-C and BCP regions in patients with partial or no response to IFN-alpha. The variation rates of HBV pre-C and BCP regions were clearly higher in genotype C than in genotype B. CONCLUSIONS: The results suggest that HBV genotype is correlated with the serum levels of HBV-DNA, HBV gene variations and therapeutic efficacy of IFN-alpha. The regular detection of HBV genotypes in the clinic will be of benefit for disease prognosis and planning of anti-viral therapeutic strategies.

Recent advances in hepatitis B virus research:A German point of view

More than 30 years after the discovery of human hepatitis B virus (HBV) this virus remains to be one of the major global health problems. In infected adolescents or adults, 5%-10% will lead to a chronic carrier state, whereas in infected neonates up to 90% develop chronicity. It is estimated that about 370 million people are chronic carriers of HBV worldwide. In many regions of the world, chronic HBV infection is still the major cause of liver cirrhosis and hepatocellular carcinoma. During the last 30 years, many steps of the viral life cycle have been unravelled, mainly due to cloning, sequencing and expression of the genomic DNA extracted from HBV virions. This has lead to the development of a safe and efficient vaccine and sensitive tests for HBV surface protein (HBsAg) allowing reliable diagnosis and screening of blood products. More recently, a growing number of reverse transcriptase inhibitors have been developed. However, together with these improvements new deficiencies in prevention and cure of HBV infections are becoming apparent. Although HBV is a DNA virus, it is highly variable under immunity or drug induced selection pressure, resulting in vaccine-related escape mutants and drug resistance. To overcome these challenging problems new antivirals and optimised vaccines have to be developed.

Chronic Carriage of Hepatitis B Virus at the University Teaching Hospital Yalgado Ouedraogo: Therapeutic Aspects and Outcome in a Cohort of HBeAg+ Outpatients

Introduction: The HbsAg prevalence in Burkina Faso was 9.1%. We aimed at describing the therapeutic features and the clinical outcome for the patients taking antiretroviral treatment. Materials and Methods: We implemented a cross-sectional study from January 1st, 2004 to December 31st, 2015. Patients aged more than 15 years with positive hepatitis B surface antigen for over six months and positive hepatitis B e-antigen were included. Results: We analyzed the data of 148 participants for a sex ratio of 3;sixty-three patients including 49 men (77.8%) were on treatment. and 81.5% had inflammatory activity greater than one. Under tenofovir, the normalization of ALT was observed in 42 (84%) patients while HBV-DNA became undetectable in 24/33 patients. HBeAg negativation was observed in 16/25 (64%) patients after seven years of treatment. With lamivudine, 2/9 patients had a complete virologic response and six had a normalization of their ALT. Two and 9 patients lost HBeAg after 7 and 9 years of treatment, respectively. Overall 63% and 27% of the patients were in the high or low-adherence group, respectively. In the low-adherence group, all patients had normal or abnormal ALT, but detectable HBV DNA. Ten patients taking lamivudine developed resistance including primary resistance in three patients. No resistance has been observed with tenofovir. Conclusion: The management of the viral hepatitis B includes often a long follow up period without any medication. When antiviral is indicated, the adherence to the treatment is crucial to a long-term control of the virus. In our setting, the low purchase power of the patients may jeopardize their therapeutic future and there is a need to support this group of patients with free-of-charge medicines as it is provided for the HIV infected people.

恩替卡韦治疗血清HBeAg阳性高病毒载量乙型肝炎病毒携带者合并肺结核患者预防抗痨治疗引起的药物性肝损伤效果研究

目的探讨在抗痨治疗过程中应用恩替卡韦预防治疗血清HBeAg阳性高病毒载量的乙型肝炎病毒(HBV)携带者合并肺结核(PTB)患者对预防药物性肝损伤(DILI)的效果。方法2019年1月~2022年1月我院收治的96例血清HBeAg阳性高病毒载量的HBV携带者合并PTB患者,被随机分为观察组48例和对照组48例。两组均接受标准的抗痨治疗,观察组在抗痨治疗的基础上应用恩替卡韦进行预防性抗HBV治疗,均持续治疗6个月。采用PCR-荧光免疫探针法检测血清HBV DNA载量。结果在治疗1个月、3个月和6个月,观察组DILI累计发生率分别为12.5%、16.7%和18.8%,显著低于对照组的29.1%、45.8%和54.2%(P<0.05);在治疗3个月,8例观察组发生DILI患者血清ALT、AST和HBV DNA水平分别为(67.7±8.5)U/L、(57.1±4.7)U/L和(1.1±0.2)lg IU/mL,均显著低于22例对照组【分别为(104.5±13.9)U/L、(96.9±15.3)U/L和(6.6±1.4)lg IU/mL,P<0.05】;在治疗过程中,观察组肝区不适、胃肠道症状、血清肌酸激酶升高、药疹和中止抗痨等不良反应发生率为10.4%,显著低于对照组的27.1%(P<0.05);在治疗结束时,观察组均获得治愈(100.0%),而在对照组治愈41例(85.4%,P<0.05),其中7例患者在延长疗程后才获得PTB的治愈。结论应用恩替卡韦可有效降低血清HBeAg阳性高病毒载量的HBV携带者合并PTB患者在抗痨治疗过程中DILI发生率,保证抗痨治疗的顺利进行,而使患者获益。

艾米替诺福韦片联合聚乙二醇干扰素α-2b治疗慢性乙型病毒性肝炎的临床疗效观察

目的 探讨艾米替诺福韦片联合聚乙二醇干扰素α-2b治疗慢性乙型病毒性肝炎(chronic hepatitis B, CHB)的治疗效果。方法 回顾性分析2021年8月—2023年6月于我院进行治疗的CHB患者110例。按照治疗方案的不同,将患者分为艾米替诺福韦组(56例)与联合治疗组(54例)。艾米替诺福韦组给予口服艾米替诺福韦片治疗。联合治疗组在艾米替诺福韦组治疗基础上加用聚乙二醇干扰素α-2b注射液。对比治疗24周和48周后2组患者的临床疗效。结果 治疗24周后,联合治疗组与艾米替诺福韦组的患者乙型肝炎病毒e抗原(hepatitis B e antigen, HBeAg)转阴率、乙型肝炎病毒表面抗原(hepatitis B surface antigen, HBsAg)清除率以及乙型肝炎病毒(hepatitis B virus, HBV)脱氧核糖核酸(deoxyribonucleic acid, DNA)转阴率比较,差异均无统计学意义(P均> 0.05);治疗48周后,联合治疗组患者HBe Ag转阴率为38.9%,HBs Ag清除率为22.2%,均显著优于艾米替诺福韦组(HBe Ag转阴率16.1%、HBs Ag清除率1.8%)(P均<0.05);联合治疗组与艾米替诺福韦组的患者HBV DNA转阴率分别为98.1%和92.9%,差异无统计学意义(P> 0.05);治疗24周后,联合治疗组与艾米替诺福韦组的患者总胆红素(total bilirubin, TBIL)、丙氨酸氨基转移酶(alanine aminotransferase, ALT)、天冬氨酸氨基转移酶(aspartate aminotransferase, AST)及谷氨酰胺转移酶(gamma-glutamyl transpeptidase, GGT)水平之间差异均无统计学意义(P均> 0.05);治疗48周后,联合治疗组患者的TBIL、ALT、AST及GGT水平均显著高于艾米替诺福韦组(P均<0.05)。艾米替诺福韦组的不良反应率为14.3%,显著低于联合治疗组的96.3%(P=0.000)。结论 艾米替诺福韦片联合聚乙二醇干扰素α-2b治疗CHB的临床疗效显著优于单独使用艾米替诺福韦片,但不良反应发生率较高。

HBV感染者病毒基因型分布特点及其与干扰素疗效的关系

目的研究HBV感染者病毒基因型分布特点及其与干扰素疗效之间的关系。方法选取急性乙型肝炎(Acute hepatitis B)8例,慢性乙型肝炎(CHB)120例,乙型肝炎肝硬化60例,肝细胞癌患者32例。提取血清HBV DNA,PCR扩增S区序列,对产物直接测序并上传至斯坦福大学HBV数据库,进行基因型分析;选取78例CHB患者(B基因型38例,C基因型40例),经干扰素-α治疗48周,分析干扰素治疗不同基因型病毒感染者的疗效。结果 HBV A、B、C、D基因型感染者分别为7.7%、35.9%、51.4%和5.0%,肝硬化和肝细胞癌患者B和C基因型感染者分别为95%和93.7%,显著高于A和D基因型感染的5%和6.3%(x2=11.364,P<0.01);在干扰素治疗48周后,B基因型感染者HBV DNA转阴率为60.5%,显著高于C基因型感染者的32.5%(x2=6.014,P<0.05);B基因型感染者HBeAg/HBeAb血清转换率为65.8%,显著高于C基因型感染者的27.5%(x2=10.564,P<0.01);B基因型感染者血清谷丙转氨酶复常率为97.6%,显著高于C基因型感染者的67.5%(x2=5.387,P<0.05)。结论 HBV基因型以B和C基因型为主,C基因型感染预示着不良的疾病预后和较差的干扰素治疗疗效。

抗结核同时给予替比夫定治疗肺结核合并HBV携带者的临床疗效

目的观察抗结核同时给予替比夫定治疗肺结核合并HBV携带者的临床疗效。方法 82例HBV携带者合并肺结核患者予以(HRZE)2/(HRZ)4抗结核治疗。39例患者同时接受替比夫定抗病毒治疗,43例作为对照,观察肝功能损害情况。结果治疗6个月结束时,抗病毒组肝功能指标(ALT48.1±6.7U/L、AST 39.1±5.6U/L和TBil24.9±3.6μmol/L)显著低于非抗病毒组(ALT 77.7±9.8 U/L),AST 69.9±9.5U/L和TBil 32.1±6.7μmol/L,P<0.01);抗病毒组停药率为5.1%,非抗病毒组为9.3%(P>0.01)。结论给予替比夫定抗病毒对抗结核治疗过程中防止肝炎发作有明显的保护作用。

141例慢性重度乙型肝炎患者凝血功能与HBV标志物模式HBV-DNA载量相关性研究

目的:研究慢性重度乙型肝炎患者HBV标志物模式(HBV-M)、病毒载量(HBV-DNA)与凝血功能的关系。方法:测定141例慢性重度乙型肝炎患者血清凝血功能、HBV-M及HBV-DNA载量,运用SPSS17.0统计软件对结果进行统计学分析。结果:141例慢性重度乙型肝炎患者中,HBV-DNA阳性率为85.8%,依HBV-M及HBV-DNA载量分组的各组凝血功能四项指标与对照组比较,差异有统计学意义(P<0.05),并且慢性重度乙型病毒性肝炎患者的凝血功能与HBV-M及HBV-DNA载量变化具有相关性,凝血酶原时间(PT)、活化部分凝血酶时间(APTT)、凝血酶时间(TT)与HBV-M和HBV-DNA呈正相关性;纤维蛋白原(FIB)与HBV-M和HBV-DNA呈负相关性。结论:慢性重度乙型肝炎患者的凝血功能变化与其HBV-M及HBV-DNA载量有关,该三项指标的变化对此类患者的治疗及治疗效果的判定有重要意义。

恩替卡韦长期治疗核苷(酸)类药物初治HBeAg阳性慢性乙型肝炎患者的疗效和安全性

目的：了解恩替卡韦单药治疗至少5年对核苷（酸）类药物初治的 HBeAg 阳性慢性乙型肝炎患者的疗效和安全性。方法选择BMS463-012和BMS463-023研究项目在瑞金医院感染科入组的20例 HBeAg 阳性慢性乙型肝炎核苷初治患者。所有患者在第一阶段（第1～2年）口服恩替卡韦0．5 mg/d，第二阶段（第3～5年）口服恩替卡韦1．0 mg/d。检测并记录基线以及治疗48、96、144、192和240周时患者的ALT、HBV DNA、HBeAg和 HBsAg水平。如治疗240周时HBV DNA ≥300拷贝/mL，则进行基因序列测定以明确是否发生耐药。结果恩替卡韦治疗第48、96、144、192和240周，HBV DNA ＜300拷贝/mL的比例分别为60％、40％、50％、85％和85％，HBeAg消失率分别为15％、15％、20％、30％和65％。有3例患者在第192周发生 HBeAg 血清学转换。恩替卡韦治疗48周时血清 HBV DNA＜300拷贝/mL 与＞300拷贝/mL患者相比，240周病毒学应答率分别为100％和66．7％；240周 HBeAg 血清学转换率分别为27．3％和0。入组患者中基线ALT＞2倍和＜2倍患者相比，前者240周病毒学应答率为100％，后者为75％；前者240周 HBeAg 血清学转换率为37．5％，而后者为0。入组患者基线高病毒载量（＞10^8拷贝/mL）和低病毒载量（＜10^8拷贝/mL）比较，前者240周病毒学应答率为83．3％，后者为100％；前者240周 HBeAg血清学转换率为11．1％，而后者为50％。以上二者相比，均差异有统计学意义（P＜0．05）。基线、治疗48、96、144、192和240周血清 HBsAg 水平分别为（4．04±0．40）、（3．64±0．44）、（3．73±0．41）、（3．53±0．55）、（3．55±0．55）和（3．55±0．63）lg IU/mL。相对于基线，在第48周、144周、192周、240周 HBsAg效价有明显下降（P值分别为0．005、0．005、0．009、0．018）。治疗240周时 HBeAg消失和未消失的患者，其基线 HBsAg效价（3．95±0．54）lg IU/mL比（4．20±0．48）lg IU/mL，差异有统计学意义（P＝0．005）。在长达5年的恩替卡韦治疗过程中未出现任何严重不良事件。结论 HBeAg阳性慢性乙型肝炎核苷类初治患者接受恩替卡韦单药长期治疗能获得持久的病毒学抑制，5年未发生耐药。

5例应用恩替卡韦治疗的慢性HBV感染者发生HBV逆转录酶区单独A181位点突变的分析

目的探讨恩替卡韦与HBV逆转录酶区单独A181位点突变的关系。方法对5例应用恩替卡韦治疗后逆转录酶区出现单独A181位点突变的慢性HBV感染者做回顾性调查与随访,并分析其突变前后病毒学指标的变化。结果 5例应用恩替卡韦治疗的慢性HBV感染者中,3例发生逆转录酶区A181V突变的病例均对恩替卡韦产生了应答,2例发生逆转录酶区A181T突变的病例血清HBV DNA也出现了明显下降。结论 5例应用恩替卡韦治疗的慢性HBV感染者逆转录酶区的单独A181位点的突变为自然产生,HBV逆转录酶区发生自然突变的临床意义需要进一步明确。

荧光定量检测HBV cccDNA在慢性乙型肝炎患者中的应用

目的:研究慢性乙型肝炎患者HBV共价闭合环状DNA(cccDNA)在外周血的分布、肝组织中含量及探讨抗病毒治疗对慢性乙型肝炎患者血清HBV cccDNA的影响。方法:随机选取HBV DNA阳性慢性乙型肝炎患者、肝硬化患者、重型肝炎患者共125例。使用实时荧光定量PCR法检测血清中cccDNA。选取36例慢性乙型肝炎患者肝组织和外周血样本,酶切后进行荧光定量PCR检测。60例慢性乙型肝炎患者,按1:1随机分配接受拉米夫定或干扰素治疗,所有患者均治疗24周以上;应用实时荧光定量聚合酶链反应技术检测慢性乙型肝炎患者0周、8周、12周、24周、HBV cccDNA及HBV DNA含量。结果:125例患者中cccDNA阳性率为71.2%,以肝硬化患者阳性率最低。肝硬化患者HBVcccDNA检出阳性率与慢性乙型肝炎患者及重型肝炎患者比较,差异有显著性意义(P<0.05)。肝组织中HBV cccDNA与肝组织总HBV DNA及血清HBV DNA存在相关性(P<0.05),HBeAg阳性组与阴性组患者比较差异有显著性意义(P<0.05)。患者接受抗病毒治疗后血清HBV DNA及HBV cccDNA下降。结论:乙型肝炎肝硬化患者外周血HBV cccDNA阳性率低,慢性乙型肝炎患者中HBeAg(+)组病毒复制较HBeAg(-)组活跃。抗病毒治疗对血清HBV cccDNA有抑制作用;血清HBV cccDNA可作为抗病毒治疗的重要监测指标。

高病毒载量HBeAg阳性慢性乙肝孕妇应用抗病毒药物阻断乙型肝炎病毒母婴传播的有效性和安全性分析

目的观察高病毒载量HBeAg阳性慢性乙肝孕妇应用抗病毒药物阻断乙型肝炎病毒(HBV)母婴传播的有效性和安全性分析。方法将收治在院(2020年1月~2020年12月)的高病毒载量HBeAg阳性慢性乙肝孕妇(孕28周),经过纳入、排除筛选后共60例纳入研究,其中30例配合抗病毒药物阻断治疗至分娩后42 d止的孕妇为研究组,另30例未配合抗病毒药物阻断治疗的孕妇为对照组。孕妇的婴儿出生后均接受主、被动联合免疫,并在出生6 h内、1月龄和6月龄时,肌内注射乙肝疫苗各10μg,均于出生后6 h内和1月龄时肌肉注射乙肝免疫球蛋白各200 IU。比较两组孕妇在孕28周和分娩时血清HBV DNA载量,HBV DNA低于检测下限率并统计孕妇不良反应。检测婴儿出生后6 h内(于主、被动免疫前抽股静脉血)和7月龄血清HBsAg阳性率及HBV DNA载量。结果研究组孕妇在分娩时的血清HBV DNA载量明显低于对照组与同组在孕28周时,HBV DNA低于检测下限率高于对照组,差异具有统计学意义(P<0.05)。研究组不良反应率与对照组相比,差异无统计学意义(P>0.05)。出生6 h内,研究组新生儿HBsAg阳性率显著低于对照组,7月龄时,研究组婴儿HBsAg均为阴性,对照组73.33%为阴性,差异具有统计学意义(P<0.05)。研究组婴儿出生及7月龄时血清HBV DNA阳性率均为0.00%,两组婴儿出生后6 h内及7月龄时的HBV DNA阳性率,差异具有统计学意义(P<0.05)。结论分娩前的孕妇血清HBV DNA检查时的载量相对升高,孕妇危险性增加。而在HBV DNA高载量孕妇孕晚期时应用替诺福韦酯抗病毒治疗,可显著降低妊娠晚期孕妇血清HBV DNA载量,提升新生儿的血清HBsAg转阴率,对母婴均具有良好的安全性。

阿昔洛韦与IFN序贯抗HBV感染时血清HBVDNA含量变化

目的为探讨HBV感染者单用IFN或阿昔洛韦（Acy）联合IFN序贯治疗时，血中HBVDNA水平变化与疗效关系．方法血清HBsAg，HBeAg，抗HBc：和HBVDNA皆阳性HBV感染者33例．IFN组15例，用重组IFNa-1b300万U，im，1次／d×14，1次／2d×36，共 50支；合用组 18例，用 Acy25 mg／（kg·d），iv计×15，接着 IFNa-1b300万 U，用法同 IFN组，IFN治疗20 d时再用 Acy 15 d，方法同前采用信号引物能量转移定量PCR，测定患者治疗前。中、治疗结束时血清HBVDNA水平并判断疗效．结果完全反应老干扰素治疗前血清HBVDNA含量（拷贝／L）范围 5．03×107～4．58×109；部分反应和无反应者范围 5.68×107～2．37×1015．Acy能降低血中HBVDNA含量，Acy联合IFN序贯治疗组完全反应率（72．2％）明显高于单用IFN组（46．6％）．结论先用Acy降低患者血中HBVDNA含量。

慢性重型肝炎患者血中LPS、LBP和sCD14的水平及其临床意义

探讨LBP、sCD14水平在慢性重型肝炎 (慢重肝 )患者伴肠源性内毒素血症中的作用。应用基质显色法和ELISA双抗体夹心法 ,检测 2 4例慢重肝患者血中LPS、LBP和sCD14的水平 ,并以 10名献血员和 16例慢性乙型肝炎患者作为对照。结果慢重肝患者在早期、中期、晚期 ,其血中LPS、LBP和sCD14的水平均明显高于慢乙肝患者及献血员 ;慢重肝死亡者其LPS、LBP和sCD14的水平也显著高于存活者。提示慢重肝患者伴肠源性内毒素血症时 ,血清中LBP和sCD14的水平 ,可显著提高机体对内毒素的敏感性。在内毒素浓度较低时 ,仍可诱导Kupffer细胞释放TNF α,从而加剧肝细胞损伤。