Prevalence of occult HBV infection in haemodialysis patients with chronic HCV

AIM: To study the prevalence and clinical effects of occult HBV infection in haemodialysis patients with chronic HCV. METHODS: Fifty chronic hemodialysis patients with negative HbsAg, and positive anti-HCV were included in the study. These patients were divided into two groups: HCV-RNA positive and HCV-RNA negative, based on the results of HCV-RNA PCR. HBV-DNA was studied using the PCR method in both groups. RESULTS: None of the 22 HCV-RNA positive patients and 28 HCV-RNA negative patients revealed HBV-DNA in serum by PCR method. The average age was 47.2±17.0 in the HCV-RNA positive group and 39.6±15.6 in the HCV-RNA negative group. CONCLUSION: The prevalence of occult HBV infection is not high in haemodialysis patients with chronic HCV in our region. This result of our study has to be evaluated in consideration of the interaction between HBsAg positivity (8%-10%) and frequency of HBV mutants in our region.     

抗HBV特异性主动免疫治疗肝功能正常的慢性HBV感染5年随访

目的探讨抗HBV特异性主动免疫对肝功能正常的慢性HBV感染者的远期疗效。方法治疗组125例采用抗HBV特异性主动免疫治疗:乙型肝炎(乙肝)疫苗20μg、注射用重组人白细胞介素-220万U、沙格司亭75μg,分别行三角肌肌内注射,每月1次,12次为1个疗程。对照组75例,采用维生素B1200mg,注射方法同上。结果治疗组疗程结束时HBsAg、HBeAg阴转率与HBV DNA(<105copies/ml)例数分别为7(5.6%)、20(16.0%)及22(17.6%),明显高于对照组的0、4(5.3%)及3(4.0%)(P<0.05)。结论抗HBV特异性主动免疫对肝功能正常的慢性HBV感染者近期及远期均有一定的疗效。     

拉米夫定治疗HBeAg阴性的慢性HBV感染近期临床观察

观察和评价拉米夫定治疗ＨＢｅＡｇ阴性慢性ＨＢＶ感染的近期疗效。ＨＢｅＡｇ阴性／ＨＢＶ ＤＮＡ阳性的慢性ＨＢｖ感染者２６例（包括１１例乙肝肝硬化），ＨＢｅＡｇ阳性／ＨＢＶ　ＤＮＡ阳性的慢性ＨＢＶ感染者３０例（包括１０例乙肝肝硬化），均以拉米夫定治疗６个月后进行疗效评价，并继续观察５－１６个月。两组的ＡＬＴ／ＡＳＴ复常率分别为８４．７％／８８．５％和８６．７％／８６．７％（Ｐ＞０．０５），肝硬化患者Ｃｈｉｌｄ－Ｐｕｇｈ积分均明显下降，ＨＢＶ　ＤＮＡ全部阴转。ＨＢｅＡｇ阳性组３例发生ＹＭＤＤ变异，ＨＢｅＡｇ阴性组无１例变异。拉米夫定对于ＨＢｅＡｇ阴性／ＨＢＶ　ＤＮＡ阳性者，同样是十分安全有效的抗病毒治疗药物。ＨＢｅＡｇ阴性者的耐药发生率可能低于ＨＢｅＡｇ阳性者。     

Efficiency and safety of lamivudine therapy in patients with chronic HBV infection, dialysis or after kidney transplantation

AIM: To analyze the effectiveness and safety of lamivudine treatment in patients with chronic HBV infection undergoing hemodialysis or after kidney transplantation, and to study the frequency of tyrosine - methionine - aspartate - aspartate (YMDD) mutation occurrence after lamivudine treatment. METHODS: We analyzed 91 patients with chronic hepatitis B, among whom, 16 patients underwent hemodialysis, 7 patients had kidney transplantation and 68 patients had normal function of kidney. The hemodialysis patients were treated by lamivudine 300 mg/wk. patients after kidney transplantation and patiente with normal function of kidney were treated with lamivudine 100 mg/d. Therapy lasted for 12 mo. HBV-DNA, HBsAg, HBeAg and anti-HBe, and anti-HCV antibodies were assessed in sera of patients. The analysis was performed before and 6 mo after the end of lamivudine treatment. Before, during and after the lamivudine therapy, the number of erythrocytes, leukocytes, platelets and hemoglobin concentration, ALT and AST activity, as well as bilirubin, urea and creatinine concentrations were analyzed in sera from patients. RESULTS: After the 12-mo lamivudine treatment, elimination of HBV - DNA was observed in 56% patients undergoing hemodialysis and in 53% patients with normal kidney function. Only 1 from 7 (14%) kidney-transplanted patients eliminated HBV-DNA. Furthermore, HBeAg elimination was observed in 36% hemodialysis patients, in 51% patients with normal function of kidneys and in 43% kidney transplanted patients. Among the patients undergoing dialysis, no YMDD mutation was found after 12 mo of therapy, while it was detected in 9 patients (13%) with normal function of kidney and in 2 kidney-transplanted patients (29%, P<0.006). We did not observe significant side effecte of lamivudine treatment in studied patiente. CONCLUSION: Effectiveness of lamivudine therapy in dialysis patients is comparable with that in patiente with normal function of kidney. Lamivudine treatment is well tolerated and safe in patiente with renal insufficiency undergoing hemodialysis and kidney-transplantation. However, in the latter group, high incidence of YMDD mutation after lamivudine treatment was observed.     

88例乙型肝炎病毒携带者前C区1 896位变异分析

目的 研究乙型肝炎病毒(HBV)携带者前C区1 896位变异情况.方法 采用聚合酶链反应(PCR)和酶联定量检测法分析,检测88例HBV携带者(其中HBeAg阳性50例,HBeAg阴性38例,HBV DNA均阳性)前C区1 896位变异.结果 50例HBeAg阳性患者中前C区1 896位变异率为8%,38例HBeAg阴性患者中,其前C区1 896位变异率为31.5%,88例HBV携带者总变异检出率为18.2%.HBV携带者HBeAg阴性组变异率明显高于HBeAg阳性组(P＜0.05).结论 HBV携带者普遍存在前C区1 896变异.     

慢性肝病患者血清HBV DNA含量与e系统关系的探讨

目的探讨慢性肝病患者血清HBVDNA含量与e系统的关系。方法分别用定量聚合酶链反应(PCR)法和酶标法(ELISA),检测207例乙型肝炎病毒慢性感染者血清HBV DNA含量与乙肝病毒血清标记物(HBVM)。结果 HBeAg阳性组与HBeAg阴性组血清HBV DNA含量分别为10~(7.4070±2.3830)拷贝/ml和10~(5.0797±3.5389)拷贝/ml,两组相比具有显著性差异(P<0.001)。结论HBeAg阳性是乙肝病毒体内复制的指标;但同时有56.04％(116/207)的HBeAg阴性患者仍可检出HBV DNA,提示HBeAg阴性不能认为乙肝病毒复制停止。     

组胺、内毒素对慢性HBV感染者免疫功能的影响

通过研究CHB(慢性乙型肝炎)患者血浆组胺、ET(内毒素)与Th1、Th2类细胞因子的关系,进而探讨其对CHB患者免疫功能的影响。以鲎试剂法测定血浆ET,以荧光法测定血浆组胺水平,分析ET、组胺与Th1、Th2类细胞因子的关系。CHB患者均有不同程度的Th1/Th2类细胞因子失衡,主要表现为:Th1类细胞因子减少而Th2类细胞因子增加,ET主要影响Th2类细胞因子,组胺影响Th1类细胞因子。     

The methylation status of the TMS1/ASC gene in cholangiocarcinoma and its clinical significance

BACKGROUND: TMS1/ASC is a bipartite protein comprising two protein-protein interactive domains: pyrin (PYD) and caspase recruitment domain (CARD). Proteins containing these domains play pivotal roles in regulating apoptosis and immune response pathways. The absence of TMS1/ ASC expression in some tumors is because methylation of the TMS1/ASC gene contributes to carcinogenesis and cancer development. We studied the methylation status of the TMS1/ASC gene and its clinical significance in cholangiocarcinoma. METHODS: Target DNA was modified by sodium bisulfite, coverting all unmethylated, but not methylated, cytosines to uracil, and subsequently by a nested amplification with primers specific for methylated versus unmethylated DNA. The PCR product was detected by gel electrophoresis and combined with the clinical records of patients. RESULTS: Aberrant methylation of the TMS1/ASC gene was detected in specimens of colorectal cancer tissues from 13 (36.1%) of 36 patients, and specimens of adjacent normal tissues from 3 patients (8.3%). No statistical differences were seen in the extent of differentiation and invasion, lymph node metastasis, and pathologic type between the methylated and unmethylated tissues (P>0.05). CONCLUSIONS: The frequency of TMS1/ASC gene methylation in cholangiocarcinoma is high, but it is not related to pathologic changes. The TMS1/ASC gene is probably suppressed by methylation, and is resistant to apoptosis and immunological surveillance. The gene epigenetically affected in methylated tissues could be associated with carcinogenesis of cholangiocarcinoma.     

Increased Levels of AIM2 and Circulating Mitochondrial DNA in Type 2 Diabetes

Background: Chronic inflammation has critical role in Type 2 diabetes (T2D), in which IL-1β contributes in insulin resistance and beta cell dysfunction. The activation of NLRP3 and AIM2 by endogens ligands, such as mtDNA can lead to the release of active form of IL-1β. Objective: To evaluate AIM2 expression and activation as well as circulating mtDNA levels in T2D patients. Methods: AIM2 expression was analyzed by flow cytometry, it’s activity was assessed by measuring in vitro release of IL-1β induced by Poly (dA:dT), and mtDNA copy number was determined by quantitative real-time polymerase chain reaction. Results: Increased percent of AIM2+ cells were detected in monocytes from patients with T2D. Moreover, increased levels of IL-1β in monocytes cultures from T2D patients compared to healthy controls were observed. Also, association between AIM2+ cells and hyperglycemia (r=0.4385, P=0.0095) and triglycerides levels (r=0.5112, P=0.002) and waist-hip ratio (r=0.4710, P=0.0049) were detected. Likewise, the mtDNA copy number was augmented in T2D patients compared to control group. The mtDNA copies number was associated with body mass index (r=0.4231, P=0.0008) and TNF-α levels (r=0.5231, P=0.0005). In addition, increased levels of IL-12p70, TNF-a, IL-10, IL-6, IL-8 and IL-1β were detected in a serum from T2D patients. Conclusion: These results suggest the involvement of AIM2 and mtDNA in the inflammatory process seen in T2D.     

低病毒载量HBeAg阴性慢性HBV感染者肝组织学特点及不同诊断指标对非活动携带的诊断价值

目的探讨低病毒载量HBeAg阴性慢性HBV感染者的肝组织学特点,评价不同临床标准对非活动HBsAg携带(IC)的诊断价值。方法选择HBV DNA4.3lg IU/mL、ALT2×正常值上限(ULN)、HBeAg阴性的慢性HBV感染者为研究对象,观察其肝组织特点,炎症活动指数(HAI)≤3或病变轻微定义为病理学的IC。临床诊断标准:A组为2015年中国指南标准(ALT正常,HBV DNA2.3 lg IU/mL),B组为2015年亚太与美国指南标准(ALT正常,HBV DNA3.3 lg IU/mL),C组为ALT2×ULN、HBV DNA2.3 lg IU/mL,D组为ALT2×ULN,HBV DNA3.3 lg IU/mL)。以肝组织学结果为"金标准"评价四组IC临床诊断标准的价值。结果 171例患者入选,其中男性125例,女46例,年龄22~69岁,平均(45.5±4.2)岁。HAI 1~11分,平均(4.3±2.1)分,其中≤3分者94例,占55.0%;纤维化积分(S)0~4分,平均(2.0±1.6)分,其中0~1分101例,占59.1%。不同临床IC诊断标准筛选的病例与病理IC的符合率没有显著差异。四种筛查方法的约登指数为0.08~0.11,AUC为0.544~0.558,判断IC的价值有限。所有入选病例中符合中国、亚太与欧美指南IC临床诊断的患者,仅有50%~60%符合病理IC,而临床非IC的患者中,有33.3%~51.4%符合病理学的IC诊断。结论低病毒载量HBeAg阴性慢性HBV感染者中有50%~60%的患者符合病理的IC诊断,而临床非IC的患者中,有33.3%~51.4%符合病理学的IC诊断。若以病理结果为IC诊断的"金标准",现有指南推荐的临床标准诊断IC的效率不高,判断价值有限,亚太与美国指南(2015)略有优势。     

慢性乙型肝炎病毒携带者血清IL-1、IL-6和CRP水平与肝组织学相关研究

目的探讨慢性HBV携带者血清IL-1I、L-6和CRP水平与肝组织学变化的相关性。方法采用双抗体夹心ELISA法检测血清IL-1I、L-6;免疫比浊法检测血清CRP。采用在B超引导下快速肝穿刺活检术,肝组织炎症活动度分为轻度(G1-2/S0-2),中度(G3/S1-3),重度(G4/S2-4)。结果中、重度肝组织炎症活动者血清IL-1I、L-6和CRP水平显著高于轻度或无炎症改变者(P<0.05),轻度和无炎症改变者与正常对照组间比较无显著差异(P>0.05)。结论慢性HBV携带者血清IL-1I、L-6和CRP水平可以做为反应肝组织炎症活动程度的指标。     

The burden of HBV infection in HCV patients in Italy and the risk of reactivation under DAA therapy

Background

There is increasing awareness of HBV reactivation in HCV-RNA-positive/HBV-coinfected patients with chronic liver disease (CLD) treated with oral direct-acting antivirals (DAAs).

慢性乙型肝炎患者血清抗卯抗体检测及其与年龄变化、病毒载量和病毒基因型的关系分析

目的探讨幽门螺杆菌（HP）在慢性乙型肝炎中的作用。方法采用病例对照研究的方法分析376例慢性乙型病毒性肝炎患者的HP感染状况与年龄、乙型肝炎病毒（HBV）DNA定量和分型的关系。结果HP感染率随年龄变化无明显差异（P〉0．05），HP感染率在慢性乙型肝炎组（56．2％）、乙型肝炎肝硬化组（69．9％）、乙型肝炎合并肝癌组（75．0％）明显高于健康对照组（43．4％）（P〈0．01），各组与慢性胃炎组（57．9％）相比较无明显差异（P〉0．05），其中肝硬化组和合并肝癌组HP感染率均高于肝炎组（P〈0．05）。不同病毒载量慢性乙型肝炎患者的HP感染率均明显高于健康对照组（P〈0．01），但不同病毒载量之间无明显差异（P〉0．05）。慢性乙型肝炎患者B基因型、C基因型和D基因型HP感染率分别为61．3％、63．3％和50．0％，三组之间比较无统计学意义（P〉0．05）。结论慢性乙型肝炎患者HP感染率明显增加，且HP感染率随着肝病病变程度的进展而增加。     

Characteristics of co-infections by HCV and HBV among Brazilian patients infected by HIV-1 and/or HTLV-1

BackgroundThe human retroviruses HIV-1 and HTLV-1 share the routes of infection with hepatitis viruses B and C. Co-infection by these agents are a common event, but we have scarce knowledge on co-infection by two or more of these agents.ObjectiveTo evaluate the characteristics and risk factors for co-infections by HBV and HCV in patients infected by HIV-1 or/and HTLV-1, in Salvador, Brazil.MethodsIn a case–control study we evaluated patients followed in the AIDS and HTLV clinics of Federal University of Bahia Hospital. Clinical and epidemiological characteristics were reviewed, and patients were tested for the presence of serological markers of HBV and HCV infections. HCV-infected patients were tested by PCR to evaluate the presence of viremia.ResultsA total of 200 HIV-1, 213 HTLV-1-infected, and 38 HIV-HTLV-co-infected individuals were included. HIV-infected patients were more likely to have had more sexual partners in the lifetime than other patients’ groups. HIV-HTLV-co-infected subjects were predominantly male. Patients infected by HTLV or co-infected had a significantly higher frequency of previous syphilis or gonorrhea, while HIV infection was mainly associated with HPV infection. Co-infection was significantly associated to intravenous drug use (IVDU). HBV and/or HCV markers were more frequently found among co-infected patients. HBV markers were more frequently detected among HIV-infected patients, while HCV was clearly associated with IVDU across all groups. AgHBs was strongly associated with co-infection by HIV-HTLV (OR = 22.03, 95% CI: 2.69–469.7), as well as confirmed HCV infection (p = 0.001). Concomitant HCV and HBV infection was also associated with retroviral co-infection. Patients infected by HTLV-1 had a lower chance of detectable HCV viremia (OR = 0.04, 95% CI: 0.002–0.85).ConclusionsInfection by HCV and/or HBV is frequent among patients presenting retroviral infection, but risk factors and prevalence for each infection are distinct for each agent. Retroviral co-infection increases the risk of a positive AgHBs, but HTLV-1 infection seems to increase the likelihood of HCV spontaneous clearance.     

lnfluence of HLA-DRB1 alleles and HBV genotypes on interferon-α therapy for chronic hepatitis B

AIM: To investigate the influence of HLA-DRB(1) alleles and HBV genotypes on interferon-alpha therapy for chronic hepatitis B. METHODS: HLA-DRB1*03, *07, *09, *12, *15 alleles were determined using polymerase chain reaction/sequence specific primer (PCR/SSP) technique in 126 patients with chronic hepatitis B and 76 normal control subjects in Shandong Province, and HBV genotypes were determined by nested-PCR analysis using type-specific primers in 126 patients. RESULTS: The positivity of HLA-DRB1*07 allele in chronic hepatitis B group was significantly higher than that in normal control group (chi(2) = 6.33, P<0.025, RR = 2.37). Among the 126 patients, genotype B was found in 38 (30.2%), genotype C in 69 (54.8%), and mixed genotype (B+C) in 19 (15.0%), genotypes D-F were not found. Among the 46 DRB1*07(+) patients, 7 were responders and 39 were non-responders among them (chi(2) = 6.71, P<0.05). The positivity of HLA-DRB1*07 and prevalence of HBV genotype C were significantly higher in non-responders than in responders. CONCLUSION: High positivities of HLA-DRB1 *07 allele and HBV genotype C are closely associated with the lower response to interferon-alpha therapy for chronic hepatitis B.     

Tnfluence of HLA-DRB1 alleles and HBV genotypes on interferon-α therapy for chronic hepatitis B

AIM: To investigate the influence of HLA-DRB1 alleles and HBV genotypes on interferon-α therapy for chronic hepatitis B.METHODS: HLA-DRB1*03, *07, *09, *12, *15 alleles were determined using polymerase chain reaction/sequence specific primer (PCR/SSP) technique in 126 patients with chronic hepatitis B and 76 normal control subjects in Shandong Province, and HBV genotypes were determined by nested-PCR analysis using type-specific primers in 126 patients.RESULTS: The positivity of HLA-DRB1*07 allele in chronic hepatitis B group was significantly higher than that in normal control group (x2 = 6.33, P<0.025, RR = 2.37). Among the 126 patients, genotype B was found in 38 (30.2%), genotype C in 69 (54.8%), and mixed genotype (B+C) in 19 (15.0%),genotypes D-F were not found. Among the 46 DRB1*07(+)patients, 7 were responders and 39 were non-responders among them (x2 = 6.71, P<0.05). The positivity of HLADRB1*07 and prevalence of HBV genotype C were significantly higher in non-responders than in responders.CONCLUSION: High positivities of HLA-DRB1 *07 allele and HBV genotype C are closely associated with the lower response to interferon-α therapy for chronic hepatitis B.     

Association of TAP1 and TAP2 polymorphisms with the outcome of persistent HBV infection in a northeast Han Chinese population

Abstract

Objective. Transporter associated with antigen processing (TAP) plays a central role in a cellular immune response against HBV. Polymorphisms exist at the coding region of TAP and alter its structure and function. The aim of this study was to evaluate the potential relationship between polymorphisms of TAP and different outcomes of persistent HBV infection in a Han population in northeastern China. Material and methods. 189 HBV spontaneously recovered (SR) subjects, 571 HBV-infected patients including 180 chronic hepatitis B (CHB), 196 liver cirrhosis (LC) and 195 hepatocellular carcinoma (HCC) individuals were included in this study. TAP1-333 Ile/Val and -637 Asp/Gly, TAP2-651 Arg/Cys and -687 Stop/Gln were genotyped in all the samples by using a PCR-RFLP method. Results. The frequency of TAP1-637-Gly (allele G) was significantly higher in persistently HBV-infected individuals (CHB and LC) than that of SR subjects (OR = 1.58, 95% CI 1.12–2.45, p = 0.024; OR = 1.78, 95% CI 1.27–2.68, p = 0.002) by a logistic regression analysis. In addition, the statistically significant difference in the distribution of TAP2-651-Cys (allele T) was observed between HCC cases and SR controls (OR = 2.30, 95% CI 1.51–3.72, p < 0.001), and TAP2-687-Gln (allele C) in CHB patients was more common than that in SR subjects (OR = 1.41, 95% CI 1.13–1.97, p = 0.021). The data also revealed that haplotype 687 Gln-651 Cys-637 Gly-333 Ile was strongly associated with persistent HBV infection (CHB, LC and HCC) (p < 0.001, < 0.05 and < 0.001, respectively). Conclusion. These results suggested that TAP variants were likely to play a substantial role in different outcomes of persistent HBV infection in the studied population.     

Polymorphisms in programmed death-1 gene are not associated with chronic HBV infection in Chinese patients

AIM:To investigate the association between the programmed death-1(PD-1) polymorphisms and genetic susceptibility of chronic hepatitis B virus(HBV) infection in Chinese patients.METHODS:Two single nucleotide polymorphisms(SNPs),PD-1.1 G > A and PD-1.2 G > A,were genotyped in 539 patients with chronic HBV infection and 353 other family members(HbsAg-) from 256 nuclear families using polymerase chain reactiorestriction fragment length polymorphisms assay.The associations between PD-1 polymorphisms and genetic susceptibilityof chronic HBV infection were analyzed usng the familybased association analysis method.RESULTS:No association or linkage was detected among 539 patients.Univariate(single-marker) familybased association tests demonstrated that PD-1 genotypes,alleles and transmitted haplotypes are not associated with chronic HBV infection(all with P value more than 0.05).Transmission/disequilibrium test and sibship disequilibrium test analysis showed no excess of the alleles from heterozygous parents to affected offspring(P = 0.688880,P = 1.000000 respectively).CONCLUSION:The data demonstrated that PD-1.1 and PD-1.2 polymorphisms are not associated with chronic HBV infection in Chinese patients.     

HBV携带者外周血中辅助性T淋巴细胞1/辅助性T淋巴细胞2相关细胞因子的研究

目的：研究慢性HBV携带者外周血中辅助性T淋巴细胞1（Th1）/辅助性T淋巴细胞2（Th2）相关细胞因子白细胞介素2（IL-2）、白细胞介素4（IL-4）及γ干扰素（γ-IFN）随患者体内病毒含量变化时的变化及其意义。方法：通过荧光定量方法检测86名慢性HBV携带者体内的病毒载量,而后根据病毒载量值将患者分为HBV DNA阴性组、HBV DNA低载量组、HBV DNA高载量组;通过ELISA方法检测86名慢性HBV携带者及39名正常人血清中IL-2、IL-4及γ-IFN的含量。结果：各患者组外周血清中IL-2的含量比正常组增高,且HBV DNA低载量组、HBV DNA高载量组与正常组比较,差异有统计学意义（F=3.055,P=0.031）;各患者组外周血清中IL-4的含量比正常组增高,HBV DNA高载量组与正常组比较,差异有统计学意义（F=2.486,P=0.064）;各患者组外周血清中γ-IFN的含量与正常组相比,差异无统计学意义（F=0.063,P=0.976）。结论：慢性HBV携带者体内存在Th1/Th2平衡紊乱,且可能Th1存在免疫功能障碍是形成的机制之一。     

前S1抗原诊断乙型肝炎病毒复制的临床探讨

目的分析前S1抗原与乙型肝炎病毒血清复制指标之间的关系。方法对651例乙型肝炎病毒标志物阳性血清,检测其HBV DNA、HBeAg和前-S1,分析检出率及相关性。结果HBV DNA、前-S1在HBsAg、HBeAg、HB-cAb阳性组中的检出率分别达98.5%、97.0%,HBsAg、HBeAb、HBcAb阳性组中为63.0%、62.4%,HBsAg、HBcAb阳性组中为49.1%、45.4%。HBV DNA≥103拷贝/ml的399例中HBeAg和前-S1的阳性率分别为34.1%、95.7%;HBV DNA<103拷贝/ml的252例中HBeAg和前-S1的阳性率分别为0.9%、2.4%。HBV DNA与HBeAg的检出率差异有显著性,与前-S1的检出率差异无显著性。结论前-S1抗原较HBeAg更敏感地反映HBV复制的情况。