钠离子转运基因多态性及血清Na~+水平与朝鲜族女性原发性高血压相关性研究

目的探讨rs11643718、rs7187932、rs12447134和rs3743966位点多态性与血清Na~+与朝鲜族女性原发性高血压的相关性。方法对116例朝鲜族原发性高血压和109名朝鲜族健康者进行研究,运用LDR连接酶技术检测分析4个SNP位点多态性,全自动生化分析仪检测血清Na~+。结果朝鲜族女性原发性高血压组和正常对照组之间rs11643718高血压组和正常对照组GG基因型与GA和AA基因型频率及G,A等位基因频率分布差异有统计学意义(P0.01)。rs7187932、rs3743966位点高血压组和正常对照组基因型频率等位基因频率分布差异均无统计学意义(P0.05)。朝鲜族女性原发性高血压组和正常对照组之间血清Na~+水平差异无统计学意义(P0.05),而rs7187932位点对照组GG基因型组与高血压组GG基因型组及对照组GA+AA组血清比较Na~+水平差异有统计学意义(P0.05)。结论 rs11643718位点等位基因A是朝鲜族女性高血压的危险因素。rs7187932位点GG基因型组与血清钠离子水平正相关。     

HBV基因型与HBV感染慢性化、重症化的关系

目的 探讨HBV基因型与HBV感染后慢性化、重症化的关系.方法 应用型特异性引物聚合酶链反应法,对中国2922例HBV感染者进行HBV基因型检测,比较各临床类型HBV感染者基因型分布差异及各基因型HBV感染者肝功能和病毒学差异.结果 2922例HBV感染者中,基因型B、C、B/C、D分别占15.9%、83.5%、0.41%、0.21%.与慢性肝炎比较急性肝炎B基因型所占比例较高（P=0.003）,肝硬化和肝细胞性肝癌C基因型所占比例较高（P值均为0.000）,慢加急性肝衰竭与慢性肝炎比较基因型分布差异无统计学意义.急性肝炎和慢性肝炎B、C基因型患者HBeAg 阳性率、HBV DNA病毒载量、肝功能生化指标差异无统计学意义.慢加急性肝衰竭、肝硬化、肝细胞性肝癌组C基因型较B基因型患者HBeAg阳性率更高（P值分别为0.000、0.024、0.003）,肝细胞性肝癌C基因型患者HBV DNA病毒载量高于B基因型患者（P=0.025）,慢加急性肝衰竭和肝细胞性肝癌组C基因型较B基因型患者胆碱酯酶更低（P值为0.0004、0.02）.结论 中国HBV感染者的HBV基因型以B、C基因型为主,少量的B/C、D基因型;C基因型较B基因型HBV感染者更易发生慢性化和进展为肝硬化和肝细胞性肝癌,但未观察到基因型对慢加急性肝衰竭发生的差异.急性和轻症HBV感染者B、C基因型未显示对病情的明显影响,但重症和终末期HBV感染者C基因型较B基因型患者HBeAg阳性率、HBV DNA病毒载量更高,肝功能损害更严重.     

慢性HBV感染者甘露糖结合蛋白基因多态性与疾病进展及与HBV DNA相关性的研究

目的 探讨慢性HBV感染者甘露糖结合蛋白(MBP)基因多态性对慢性乙型肝炎患者疾病进展的影响及与HBV DNA载量的关系.方法 采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法和实时荧光定量PCR(FQ-PCR)技术对244例慢性乙型肝炎患者、151例肝硬化患者和88名正常对照者的MBP基因第54号密码子多态性和血清HBV DNA载量进行检测.结果 CHB轻、中度组患者MBP基因GGC/GAC基因型频率和GAC等位基因频率与正常对照组比较差异无统计学意义(P＞0.05);CHB重度组、代偿性LC组、失代偿性LC组MBP基因GGC/GAC基因型频率和GAC等位基因频率显著高于正常对照组(P＜0.05);其中失代偿性LC组突变率最高,为36.5％.慢性HBV感染者MBP基因GGC/GAC基因型频率和GAC等位基因频率不随HBV DNA载量而变化(P＞0.05).结论 MBP基因第54号密码子突变与HBV DNA载量无明显关系,而与慢性HBV感染进展有关.     

慢性乙型肝炎患者肝功能及血清HBeAg和HBV DNA载量与肝组织病理相关性的研究

目的 探讨慢性乙型肝炎患者肝功能、HBeAg及HBV DNA水平与肝组织病理炎症分级和纤维化分期的关系.方法 选择233例慢性乙型肝炎患者进行肝穿病理学检查,同时所有患者检测HBV DNA、HBeAg及肝功能,比较患者的肝功能、HBeAg及HBV DNA水平在不同病理炎症分级及纤维化分期中的差异情况.结果 不同的炎症分级患者中,ALT以C3组最高,G0～1组最低,各组间比较差异有统计学意义(P =0.016);TBil以G4组最高,G0～1组最低,各组间比较差异有统计学意义(P=0.000);HBV DNA载量各组间差异无统计学意义.不同的纤维化分期患者中,ALT各组间比较差异无统计学意义;TBil以S4组最高,S2组最低,各组间比较差异有统计学意义(P=0.039);HBV DNA载量各组间差异无统计学意义.炎症分级为G3～4的患者比例在HBeAg阳性组与阴性组差异无统计学意义.纤维化分期S3～4的患者比例在HBeAS阳性组(38%)比HBeAg阴性组(53%)低,两组差异有统计学意义(P=0.025).结论 慢性乙型肝炎患者血清HBV DNA水平的高低不能反映其肝脏炎症及纤维化程度,HBeAg阴性慢乙肝患者肝组织纤维化程度较高,TBil水平与肝组织炎症分级及纤维化分期均有良好的相关性,ALT水平与炎症分级有一定的关联性,但与纤维化分期无关.     

聚乙二醇干扰素α-2a联合基因重组酵母乙肝疫苗治疗HBeAg阳性CHB的疗效观察

目的 探讨聚乙二醇干扰素α-2a联合基因重组酵母乙肝疫苗治疗HBeAg阳性的慢性乙型肝炎患者疗效.方法 总75例HBeAg阳性慢性乙型肝炎纳入本研究,其中单用聚乙二醇干扰素α-2a治疗的45例（A组）;聚乙二醇干扰素α-2a联合基因重组酵母乙肝疫苗的HBeAg阳性慢性乙肝患者30例（B组）.对比分析两组在治疗0、24、48和72周时ALT、HBsAg水平、HBeAg血清转换率和HBV DNA阴转率的差异.结果 治疗前（0周）时两组患者的年龄、ALT、HBsAg和HBV DNA水平差异均无统计学意义（P＞0.05）,其中联合治疗组（B组）HBeAg水平明显高于对照组（A组）,差异具有统计学意义（P＜0.05）.第24周和48周时,两组患者的ALT、HBsAg水平、HBeAg血清学转换率和HBV DNA阴转率差异并无统计学意义（P＞0.05）.在治疗结束随访至72周时,A、B两组ALT、HBeAg血清转换率和HBsAg水平差异没有统计学意义（P＞0.05）,但B组HBV DNA阴转率高于A组,差异具有统计学意义（P=0.032）.结论 聚乙二醇干扰素α-2a联合基因重组乙肝疫苗治疗HBeAg阳性的慢性乙型肝炎患者可以提高48周治疗结束后72周时的HBV DNA阴转率,但是与HBeAg血清学转换和HBsAg水平降低无关.     

慢性乙型肝炎患者肝脏病理特点与血清HBeAg和HBV DNA的关系

目的 了解慢性乙型肝炎患者病理特点与血清HBeAg和HBVDNA的关系.方法对1057例慢性乙型肝炎患者进行肝脏病理检查,采用荧光定量PCR法检测血清HBV DNA,用化学发光法检测血清HBeAg.结果 HBeAg阴性的慢性乙型肝炎患者的炎症及纤维化程度(G4和S4分别为7.83%和12.17%)较HBeAg阳性的慢性乙型肝炎患者高(G4和S4分别为3.39%和5.44%);HBeAg阳性的患者中HBV DNA滴度低的患者炎症及纤维化程度较高(HBV DNA 104～105 G3G4和S3S4分别为45.64%和30.20%),而HBeAg阴性的患者则是HBV DNA滴度高的炎症及纤维化程度较高(HBV DNA106～107 G3G4为54.55%和HBV DNA 108～109S3S4为42.85%).结论慢性乙型肝炎患者的肝脏病理与血清HBeAg及HBV DNA水平有不同相关性,对HBeAg阴性的慢性乙型肝炎患者要及早进行肝脏病理检查和抗病毒治疗.     

VDR和GSDMB基因多态性与湖北地区儿童哮喘的易感性研究

目的:探讨湖北地区儿童VDR基因(rs2239185、rs7975232、rs2525046、rs2228570)和GSDMB基因(rs2305480)单核苷酸多态性(SNP)与儿童哮喘的易感性。方法:采用前瞻性研究方法,纳入158例哮喘患儿(哮喘组)和156例健康儿童(对照组),运用Sequenom MassArray质谱芯片微列阵技术对两组对象VDR和GSDMB基因的多个SNP位点进行基因分型,分析上述各位点在两组间分布的差异,筛选湖北地区儿童哮喘易感SNP位点。结果:GSDMB基因rs2305480位点GG、AG、AA 3种基因型频率在哮喘组中分别为64.56%、4.43%、31.01%,在对照组中分别为51.28%、8.97%、39.74%,两组间GG基因型分布频率差异具有统计学意义(P<0.05);GSDMB基因rs2305480位点的等位基因G、A在哮喘组中的分布频率分别为80.06%、19.94%,在对照组中的分布频率分别为71.15%、28.85%,两组间的等位基因A分布频率差异具有统计学意义(P<0.05);GSDMB基因rs2305480位点不同基因分布...     

白细胞介素1α基因单核苷酸多态性与甲型H1N1流感易感性的关系

目的 探讨白细胞介素1d(IL-1α)基因单核苷酸多态性(SNP)与甲型H1N1流感易感性的关系.方法 从IL-1α基因启动子区域中选取4个SNP位点rs1800587、rs2856836、rs2856838、rs3783525,针对以上位点建立基于飞行时间质谱分析技术(TOF-MS)鉴定SNP的方法,对167例H1N1流感患者(H1N1组)和192例健康对照人群(对照组)进行检测.确定各SNP位点的等位基因和基因分型;对比两组等位基因和各基因型的频率.结果 rs1800587、rs2856836、rs2856838位点具有T和C两种等位基因,包括TT、TC、CC 3种基因型.rs3783525具有A和T两种等位基因,包括AA、AT和TT3种基因型.H1N1组和对照组rs 1800587位点的等位基因频率差异有统计学意义(x2=12.69,P=0.000,OR=2.424,95％CI=1.472 ～ 3.993),rs2856836,rs2856838,rs3783525等位基因频率在H1N1组和对照组中差异则无统计学意义.H1N1组rs1800587位点CC纯合子频率低于对照组[72.5％(121/167)比87.0％(167/192),P＜0.05],杂合子(TC)频率高于对照组[25.1％(42/167)比12.5％(24/192),P＜0.05],而两组TT纯合子频率差异则不具有统计学意义.H1N1组rs2856836位点杂合子(TC)频率高于对照组[25.7％(43/167)比17.2％(33/192),P＜0.05],TT基因型与CC基因型频率在两组间差异均没有统计学意义.rs2856838位点对照组TT纯合子频率低于H1N1组[4.2％(8/192)比10.8％(18/167),P＜0.05],其余2种基因型TC与CC在两组间差异没有统计学意义.H1N1组rs3783525位点TTT纯合子频率高于对照组[21.0％ (35/167)比13.0％(25/192),P＜0.05],两组间的另两种基因型TC与CC差异也没有统计学意义.结论 IL-1α基因多态性位点rs1800587、rs2856836、rs2856838、rs3783525与甲型H1N1流感易感性相关.     

HBV基因型及肝脏组织学对聚乙二醇干扰素α治疗HBeAg阳性慢性乙型肝炎疗效的影响

目的 探讨聚乙二醇干扰素α治疗HBeAg阳性慢性乙型肝炎的疗效及HBV基因型和肝脏组织学对HBeAg血清学转换的影响.方法 54例经肝活检证实的、基因型明确的HBeAg阳性慢性乙型肝炎(CHB)患者根据体质量分别皮下注射聚乙二醇干扰素α-2a 135 μg或180 μg,或者聚乙二醇干扰素α-2b 50 μg、80 μg或者100 μg,每周一次,疗程为48周,停药后随访24周.治疗结束后统计HBeAg的血清学转换情况,分析HBV基因型及肝脏组织学对e抗原血清学转换的影响.结果 54例患者随访结束时HBeAg血清学转换率为29.63％ (16/54).基因B型患者HBeAg血清学转换率为35.29％,高于C型患者的27.03％,但差异无统计学意义(x2=0.382,P=0.537).肝脏炎症活动度较高者(＞G2)、纤维化程度较重者(＞S1)HBeAg血清学转换率较高(50.00％ vs.25.00％,40.90％ vs.21.88％),但均无统计学意义(x2=1.391、1.444,P=0.238、0.229).经多变量Logistic回归分析显示HBV基因型、肝脏炎症活动度、肝脏纤维化程度等诸因素中,仅肝脏炎症活动度为HBeAg血清学转换的重要影响因素.结论 肝脏炎症活动度是聚乙二醇干扰素α治疗HBeAg阳性慢性乙型肝炎疗效的重要影响因素,而HBV基因型和肝脏纤维化程度可能意义不大.     

HBV-LP与HBV-DNA联检的临床应用

目的：探讨血清乙型肝炎病毒大蛋白与HBV-DNA联检在乙型肝炎患者诊治中的意义。方法：对162例HBV感染者及47名健康对照组血清采用ELISA检测乙型肝炎病毒大蛋白及乙型肝炎病毒标志物;FQ-PCR定量检测HBV-DNA。结果：162例HBV感染者血清中,HBV-LP浓度与HBV-DNA拷贝数间具有良好的正相关性（rs=0.64,P〈0.001）,不同HBV-DNA拷贝数组别间HBV-LP浓度存在差异显著性（P〈0.01）;HBV-LP与HBV-DNA、HBeAg间均关联显著（P〈0.01）。HBV-LP与HBV-DNA、HBeAg间阳性率均存在差异显著性（P〈0.05）,HBV-LP阳性率为84.57%,较HBV-DNA、HBeAg均敏感。其中HBV-LP在HBV-DNA阳性组中阳性率为91.18%（93/102）,DNA阴性组中阳性率为73.33%,均较HBeAg高;在58例HBV-DNA和HBeAg共同阴性的HBV感染血清中,HBV-LP检出42例阳性。结论：血清HBV-LP浓度与HBV-DNA联检有利于提高HBV感染者体内病毒复制、疾病进程、疗效与预后判断的血清学诊断与监测水平。     

Evaluate the relationship between polymorphisms of OAS1 gene and susceptibility to chronic hepatitis C with high resolution melting analysis

The aim of this was to investigate the relationship between single-nucleotide polymorphisms (SNPs) in the OAS1 gene and the susceptibility to chronic hepatitis C virus (HCV) infection in a population from the Liaoning Province of China. High resolution melt (HRM)-PCR analysis was conducted to examine three OAS1 SNPs: rs2660 G/A, rs10774671 G/A, and rs3741981 G/A in 298 chronic HCV-infected patients and in 305 healthy controls and to identify a relationship between SNP genotype and susceptibility to chronic HCV infection using a case–control study design. These three OAS1 SNPs were in strong linkage disequilibrium (rs2660 vs. rs10774671: |D’|=1.000, r ² =1.000; rs2660/rs10774671 vs. rs3741981: |D’|=0.938, r ² =0.569). The frequency of AG + GG genotypes in both rs2660 and rs10774671 and the AA + AG genotype in rs3741981 was significantly higher among chronic HCV-infected patients than among control (P < 0.001); the A allele in all three SNPs was found more frequently in the chronic HCV-infected group than in the control group (rs2660 and rs10774671: P = 0.02; rs3741981: P < 0.001). Moreover, individuals carrying the A allele in these SNPs exhibited an increased risk for chronic HCV infection (rs2660 and rs10774671: OR = 1.356 [1.051–1.749]; rs3741981: 1.363 [1.085–1.712]). The haplotype created by the G allele at both rs2660 and rs10774671 and the A allele at rs3741981 increased the risk of chronic HCV infection by 3.394-fold (95 % CI 1.406–8.201). Our results identify OAS1 SNP rs2660, rs10774671, and rs3741981 as genetic risk factors for chronic HCV infection. Polymorphisms of the OAS1 gene might affect the susceptibility to chronic infection with HCV.     

Correlation between HBV DNA detection by polymerase chain reaction and Pre-S1 antigenemia in symptomatic and asymptomatic hepatitis B virus infections

The presence of hepatitis B virus (HBV) genome in sera from 73 symptomatic and asymptomatic HBsAg carriers was studied by the polymerase chain reaction (PCR) with primers specific for the S and C regions. Pre-S proteins of the HBV envelope were detected in serum by a specific monoclonal antibody in a double immunoradiometric assay. Out of twenty-five symptomatic patients with chronic active hepatitis (14 with HBeAg and 11 with anti-HBe), all were positive for HBV DNA by PCR, while 14/14 HBeAg and 2/11 (18%) of the anti-HBe patients were positive by dot blot hybridization. All but one anti-HBe patient (96%) carried Pre-S1 proteins. Among the asymptomatic HBsAg carriers, HBV DNA was detected by PCR in 14/14 (100%) HBeAg positive patients and in 25/34 (73%) anti-HBe positive patients. Pre-S1 proteins were found, respectively, in 14/14 (100%) and 11/22 (50%) of the same cases tested in parallel. The 20 healthy blood donors devoid of HBV markers and with normal transaminases tested were found negative for HBV DNA using PCR. Out of 12 patients who recovered from acute hepatitis B, all were found negative by PCR analysis after a mean follow up of 1 year after seroconversion to anti-HBs. When serial samples from 2 patients (one with acute hepatitis B, the other with chronic hepatitis B) were tested for the presence of HBV DNA and of Pre-S1 proteins, both markers showed parallel development.(ABSTRACT TRUNCATED AT 250 WORDS)     

Presence of hepatitis B virus core promoter mutations pre-seroconversion predict persistent viral replication after HBeAg loss.

BACKGROUND: In patients with chronic hepatitis B virus (HBV) infection DNA levels do not always fall after anti-hepatitis B e (anti-HBe) seroconversion. OBJECTIVES: To follow longitudinally through HB e antigen (HBeAg) loss HBV DNA levels and core promoter/precore sequences in a cohort of 21 chronic HBV carriers. STUDY DESIGN: Treatment-na?ve HBeAg seropositive HBV carriers were monitored through HBeAg loss for between 2 and 22 years (mean 9.3). Core promoter/precore sequences, genotypes, HBV DNA levels and HBe status were determined. RESULTS: Patients were grouped into those in whom serum/plasma HBV DNA remained high after HBeAg loss (group 1, n=11; HBV DNA>5log(10)IU/ml) and those in whom HBV DNA declined (group 2, n=10). Re-appearance of HBeAg was seen in seven group 1 patients. Pre-seroconversion mutations in the core promoter region including A1762T and/or G1764A were detected more frequently in group 1 (P=0.031). Overall sequence changes at sites other than 1762/1764 were more common post-seroconversion in group 1 than group 2 patients (P=0.037). CONCLUSIONS: The presence of core promoter mutations prior to HBeAg loss identified those patients in whom HBV DNA persisted at high levels and was associated with temporary re-emergence of serum HBeAg. These patients may benefit from early anti-viral treatment.     

Is the course of perinatal hepatitis B virus infection influenced by genetic heterogeneity of the virus?

We studied the relations between genetic heterogeneity of pre-C region of hepatitis B virus (HBV) DNA and outcome of HBV infection in 5 infants with perinatal infection, 3 born to antihepatitis B e antigen (HBeAg), and 2 to HBeAg positive mothers. HBV infection developed in the babies at 3–4 months of age, but it resolved with seroconversion to anti-HBs in infants born to anti-HBe positive mothers, while the infection became chronic in the 2 babies born to HBeAg positive mothers. HBV-DNA extracted from the first hepatitis B surface antigen (HBsAg) positive serum sample of each baby was amplified and directly sequenced for the pre-core region. HBV-DNA sequences from 3 babies born to anti-HBe positive mothers showed at position 1896 the contemporary presence of 2 nucleotides (G + A), indicating a mixture of wild-type and "e minus"variant HBV. These findings suggest a possible co-transmission of the 2 viruses from anti-HBe positive mothers to newborns. HBV-DNA from babies born to HBeAg positive mothers showed wild-type sequences only. The results of this study suggest that the outcome of HBV infection in newborns depends not only on the host's immunocompetence and on viremia level in maternal blood, but also on heterogeneity of HBV. Transmission of mixed HBV populations appears associated with an early immunoelimination of the virus, while infection with wild-type HBV alone contributes to induction of chronicity. © 1993 Wiley-Liss, Inc.     

阿德福韦酯治疗慢性乙型肝炎HBeAg血清学转换与基因型、HBV特异性CTL的关系

目的 探讨阿德福韦酯治疗慢性乙型肝炎患者发生HBeAg血清学转换与HBV基因型、HBV特异性CTL的关系.方法 70例慢性乙型肝炎患者HBV DNA阳性（HBV DNA≥1×104拷贝/ml）,HBeAg阳性45例,其中B基因型23例（51.11%）,C基因型22例（48.89%）.ALT＞2×正常参考值上限（ULN）、人白细胞抗原（HLA）-A2阳性,用阿德福韦酯（正大天睛药业公司生产）10 mg,口服,每日1次.观察治疗12个月后HBeAg血清学转换与HBV基因型、HBV特异性CTL的关系.结果 阿德福韦酯治疗12个月后,HBV特异性CTL（0.68%±0.11%）高于治疗前（0.33%±0.11%）,t=8.36 P＜0.001,HBV DNA（3.01±0.2）log10拷贝/ml低于治疗前[（6.27 ±0.70）log10拷贝/ml]t=12.63 P＜0.001,HBV DNA阴转（＜500拷贝/ml）43例（61.43%）.HBeAg阳性45例中发生HBeAg转阴13例（28.89%）,HBeAg血清学转换8例（17.78%）,HBeAg血清学转换者HBV特异性CTL（0.86 ±0.05%）高于无HBeAg血清学转换者（37例,82.22%）的HBV特异性CTL（0.61%±0.07%）,t=7.88,P＜0.001.HBeAg血清学转换8例中,B基因型7例（占B基因型30.43%）,C基因型1例（占C基因型4.55%）,x2=5.15,P＜0.05.结论 阿德福韦酯能提高CHB患者的HBV特异性细胞免疫功能,治疗后HBeAg血清学转换的发生与HBV特异性CTL水平升高有关,并可能与基因型有关.     

Hepatitis B virus DNA in asymptomatic HBsAg carriers: comparison with HBeAg/anti-HBe status

Sera of 17 HBeAg positive and 104 anti-HBe positive asymptomatic HBsAg carriers from two cohorts were tested for HBV DNA. HBV DNA was found in 13 of 17 HBeAg positive carriers (76.5%) and in only 7 of 104 of anti-HBe positive carriers (6.7%). Eleven of the 17 HBeAg positive carriers were retested for HBV DNA over a period of 7 to 36 months after the initial test. HBV DNA disappeared from the serum in 2 patients in spite of persistence of the HBe antigen. Of the 104 anti-HBe carriers, 89 were retested for HBV DNA over a period of 6 to 52 months after the initial test. HBV DNA disappeared from the serum in 5 of the 7 who were previously positive for HBV DNA, and persisted in 2. These findings indicate that there is an inconstant relationship between the time of seroconversion of HBeAg to anti-HBe and the disappearance of HBV DNA. In one HBeAg positive patient, HBV DNA, which was absent in the serum on first testing, was present on retesting. This suggests that the presence of HBV DNA in the serum of some patients may be intermittent. The presence of HBV DNA in the serum of some anti-HBe positive carriers accounts for the finding that they may be infective. All but one of the HBV DNA positive anti-HBe carriers were born outside North America, most in Asia. HBV DNA were found more frequently in the serum of anti-HBe positive carriers who had biochemical and histological evidence of liver disease than in carriers without such evidence.     

Receptors for polymerized human serum albumin on hepatitis B virus particles detected by radioimmunoassay: changes in receptor activity in serum during acute and chronic infection

Receptor sites that bind polymerized human serum albumin on hepatitis B virus (HBV) particles were evaluated in purified virus particle preparations and in HBsAg positive sera, by using solid phase radioimmunoassay. The receptor, found in previous reports to be species-specific, was inhibited neither by native human serum albumin, nor by anti-human immunoglobulins or anti-C1q sera, indicating that these host components are not involved in the reaction. Differential receptor expression on various HBsAg particles was evaluated by relating levels of HBsAg to those of polyalbumin binding activity. This ratio was lower in HBsAg particles purified from hepatitis Be antigen (HBeAg) positive serum (mean ratio: 3.5) than in those obtained from anti-HBe positive serum (mean ratio: 20.1), suggesting that HBeAg/anti-HBe status influences the expression of the receptor on virus particles. Accordingly, during acute hepatitis type B receptor activity was high in sera obtained at the onset, but rapidly decreased afterwards, particularly at the time of anti-HBe seroconversion. A similar behavior of the receptor was observed in cases of chronic HBV infection, where mean receptor counts by radioimmunoassay were 3825±4422 (mean cpm ±SD) in HBeAg positive cases and 868±1196 cpm in anti-HBe positive cases (P<0.01). Seven HBsAg chronic carriers, all initially HBeAg positive, were followed up over a period of 1 to 4 yr and in all of them a progressive decrease in receptor activity was noted, independently of HBeAg persistence. These results indicate that the expression of the receptor for polymerized human albumin on HBV particles is an early event in the natural course of acute and chronic HBV infection, being followed by a progressive reduction in receptor activity, that parallels the reduction in virus replication, often independently of HBsAg serum levels.     

Efficacy of long-term interferon therapy in chronic hepatitis B patients with HBV genotype C

Infection with Hepatitis B virus (HBV) genotype C predominates in Japan. We analyzed the efficacy of interferon (IFN) alpha or beta in the treatment of chronic hepatitis B patients with HBV genotype C and the clinical predictors for therapeutic response. Forty-three genotype C-infected, chronic hepatitis B e antigen (HBeAg)-positive patients (32 men and 11 women with a mean age of 35.6+/-10.1 years) who had been treated with IFN therapy were retrospectively studied. The patients were classified into two treatment groups. Short-term therapy group was administered a 5-6 MU dose three times weekly for 4 weeks, and the long-term therapy group for 24 weeks. At the end of the follow-up period, 4 (15%) of 27 short-term therapy group patients and 6 (38%) of 16 long-term therapy group patients had normalized serum ALT levels and seroconversion of HBeAg to anti-HBe (p=0.137). Multivariate analysis for parameters most important for the efficacy of IFN therapy was performed using Cox proportional hazard models in order to investigate the association between baseline characteristics of patients and the response to IFN treatment. As a result, the p-values of IFN treatment group and sex were <0.05, and both factors can be recognized as independent significant factors (relative risk, 2.93 and 2.53; p=0.027 and 0.040, respectively). Furthermore, the cumulative rates of seroconversion of HBeAg to anti-HBe analyzed by the Kaplan-Meier method was significantly higher in the female group (p=0.015) and in the long-term IFN therapy group (p=0.0046). In summary, long-term IFN therapy may be more effective than short-term IFN therapy for patients with chronic HBV genotype C infection.     

阿德福韦酯联合胸腺肽α1治疗拉米夫定无应答的HBeAg阳性慢性乙肝的疗效观察

目的 探讨拉米夫定无应答HBeAg阳性慢性乙肝病人进行胸腺肽α1与阿德福韦酯联合疗法的临床效果.方法 将拉米夫定无应答HbeAg阳性乙型慢性肝炎病人80例,按照随机数字表法分为研究组和对照组,各组40例.研究组进行胸腺肽α1与阿德福韦酯联合疗法,对照组仅进行胸腺肽α1治疗,治疗期为半年.比较两组治疗前后的谷丙转氨酶(ALT)、谷草转氨酶(AST)、γ-转肽酶(γ-GT)水平;比较两组治疗前后的HBeAg/抗-HBe转换、HBV DNA阴转情况.结果 治疗后两组的ALT、AST、γ-GT水平均有改善,但研究组治疗后的ALT、AST、γ-GT水平显著优于对照组,差异有统计学意义(P＜0.05);研究组治疗后的HBeAg/抗-HBe转换、HBV DNA阴转情况显著优于对照组,差异有统计学意义(P＜0.05).结论 拉米夫定无应答的HBeAg阳性慢性乙型肝炎病人进行胸腺肽α1与阿德福韦酯联合疗法,可显著改善病人的肝功能状态,临床效果确切,值得临床推广.     

抗HBc IgM阳性慢性乙型肝炎临床特性、病毒学和血清学研究

目的探讨抗HBcAg IgM阳性慢性阳性肝炎患者的临床特性及其与HBV病毒学和血清学的关系。方法收集河北省张家口市传染病医院和北京地坛医院2004—2006年经Abbott EIA检测试剂证实的所有抗HBcAg IgM阳性和同期随机抽样的抗HBcAg IgM阴性患者的临床资料,包括生化指标、血清HBV DNA载量和血清学指标,分析抗HBcAg IgM阳性和阴性患者的疾病程度和临床转归之间的差异及抗HBcAg IgM状态与HBV DNA载量和HBeAg状态的关系。结果收集了200例慢性乙型肝炎患者,其中抗HBc IgM阳性70例,阴性130例,轻、中和重度肝脏疾病患者分别为71、83、46例。抗HBc IgM阳性患者的年龄和发病年数高于抗HBc IgM阴性患者,抗HBc IgM阳性的轻度肝脏疾病患者百分比为45.71%,中重度患者为54.29%,低于抗HBc IgM阴性患者(30.00%和70.00%),差异有统计学意义(χ2=4.907,P=0.027)。抗HBc IgM阳性患者和阴性患者的HBV DNA载量,血清HBeAg/抗HBe状态、住院天数和转归差异无统计学意义。结论慢性乙型肝炎患者抗HBcAg IgM的状态与肝脏疾病的程度相关,但与HBV DNA载量和HBeAg/抗HBe状态无相关性。