Clinic-pathological features of metabolic associated fatty liver disease with hepatitis B virus infection

BACKGROUND Metabolic associated fatty liver disease(MAFLD)is a novel concept proposed in 2020.AIM To compare the characteristics of MAFLD and MAFLD with hepatitis B virus(HBV)infection.METHODS Patients with histopathologically proven MAFLD from a single medical center were included.Patients were divided into MAFLD group(without HBV infection)and HBV-MAFLD group(with HBV infection).Propensity score matching was utilized to balance the baseline characteristics between two groups.RESULTS A total of 417 cases with MAFLD were included,359(86.1%)of whom were infected with HBV.There were significantly more males in the HBV-MAFLD group than in the MAFLD group(P<0.05).After propensity score matching,58 pairs were successfully matched with no significant differences found in gender,age,body mass index,lipid levels,liver enzymes,and the other metabolic associated comorbidities between the two groups(P>0.05).The rank sum test results showed that the degree of liver steatosis in the MAFLD group was more severe than that in the HBV-MAFLD group,while the degree of inflammation and fibrosis in the liver was less severe(P<0.05).In multivariate analysis,HBV infection was associated with significantly lower grade of hepatic steatosis[odds ratio(OR)=0.088,95%confidence interval(CI):0.027-0.291]but higher inflammation level(OR=4.059,95%CI:1.403-11.742)and fibrosis level(OR=3.016,95%CI:1.087-8.370)after adjusting for age,gender,and other metabolic parameters.CONCLUSION HBV infection is associated with similar metabolic risks,lower steatosis grade,higher inflammation,and fibrosis grade in MAFLD patients.

Existence and significance of hepatitis B virus DNA in kidneys of IgA nephropathy

AIM: To investigate the existence and significance of hepatitis B virus (HBV) DNA in the pathogenesis of IgA nephropathy(IgAN).METHODS: Fifty cases of IgAN with HBV antigenaemia and/or hepatitis B virus antigens (HBAg, or HBsAg, HBcAg)detected by immunohistochemistry in renal tissues were enrolled in our study. The distribution and localization of HBV DNA were observed using in situ hybridization.Southern blot analysis was performed to reveal the state of renal HBV DNA.RESULTS: Among the 50 patients with IgAN, HBs antigenemia was detected in 17 patients (34%). HBAg in renal tissues was detected in 48 patients (96%), the positive rate of HBAg, HBsAg, and HBcAg was 82% (41/50), 58% (29/50),and 42% (21/50) in glomeruli, respectively; and was 94%(47/50), 56% (28/50) and 78% (39/50) in tubular epithelia,respectively. Positive HBV DNA was detected in 72% (36/50)and 82% (41/50) cases in tubular epithelia and glomeruli respectively by in Situ hybridization, and the positive signals were localized in the nuclei of tubular epithelial cells and glomerular mesangial cells as well as infiltrated interstitial lymphocytes. Moreover, 68% (34/50) cases were proved to be HBV DNA positive by Southern blot analysis, and all were the integrated form.CONCLUSION: HBV infection might play an important role in occurrence and progress of IgAN. In addition to humoral immune damages mediated by HBAg-HBAb immune complex,renal tissues of some IgAN are directly infected with HBV and express HBAg in situ, and the cellular mechanism mediated by HBV originating from renal cells in situ may also be involved in the pathogenesis of IgAN.

Treatment of hepatitis B virus-associated glomerulonephritis:A meta-analysis

AIM:To evaluate the efficacy of antiviral or corticosteroid treatment on hepatitis B virus-associated glomerulonephritis(HBV-GN) . METHODS:Six and five trials were used respectively to evaluate the efficacy of either antiviral or corticosteroid treatment on HBV-GN.Pediatric patients were pooled separately to assess their response to the above treatment modalities.The primary and secondary outcomes were remission of proteinuria and clearance of Hepatitis B e-antigen(HBeAg) ,respectively.A fixed or random effect model was established to collect the data. RESULTS:The remission rate of proteinuria(RR=1.69,95%CI:1.08-2.65) and the clearance rate of HBeAg(RR =6.44,95%CI:3.11-13.35) were significantly higher in antiviral treatment group than in control group.The proteinuria remission was significantly associated with HBeAg clearance(P=0.002) .However,the difference in proteinuria remission rate was not statistically significant between corticosteroid treatment group and controlgroup(RR=1.45,95%CI:0.68-3.11) .Antiviral therapy could significantly promote the HBeAg clearance in pediatric patients,but neither antiviral nor corticosteroid therapy could significantly decrease proteinuria in pediatric patients compared to controls. CONCLUSION:Antiviral but not corticosteroid treatment can decrease proteinuria and promote HBeAg clearance in HBV-GN patients.

Hepatitis B virus persistent infection-related single nucleotide polymorphisms in HLA regions are associated with viral load in hepatoma families

BACKGROUND Genome-wide association studies from Asia indicate that HLA-DP and HLA-DQ loci are important in persistent hepatitis B virus(HBV)infections.One of the key elements for HBV-related carcinogenesis is persistent viral replication and inflammation.AIM To examine genetic and nongenetic factors with persistent HBV infection and viral load in families with hepatocellular carcinoma(HCC).METHODS The HCC families included 301 hepatitis B surface antigen(HBsAg)carriers and 424 noncarriers born before the nationwide vaccination program was initiated in 1984.Five HBV-related single nucleotide polymorphisms(SNPs)—rs477515,rs9272105,rs9276370,rs7756516,and rs9277535—were genotyped.Factors associated with persistent HBV infection and viral load were analyzed by a generalized estimating equation.RESULTS In the first-stage persistent HBV study,all SNPs except rs9272105 were associated with persistent infection.A significantly higher area under the reciprocal operating characteristic curve for nongenetic factors vs genetic factors(P<0.001)suggests that the former play a major role in persistent HBV infection.In the second-stage viral load study,we added 8 HBsAg carriers born after 1984.The 309 HBsAg carriers were divided into low(n=162)and high viral load(n=147)groups with an HBV DNA cutoff of 105 cps/mL.Sex,relationship to the index case,rs477515,rs9272105,and rs7756516 were associated with viral load.Based on the receiver operating characteristic curve analysis,genetic and nongenetic factors affected viral load equally in the HCC family cohort(P=0.3117).CONCLUSION In these east Asian adults,the mechanism of persistent HBV infection-related SNPs was a prolonged viral replication phase.

HLA class Ⅱ associated with outcomes of hepatitis B and C infections

Several factors influence the clinical course of hepatitis B virus(HBV)and hepatitis C virus(HCV)infection.The human leukocyte antigen(HLA)system,the major histocompatibility complex(MHC)in humans,has been considered one of the most important host factors with respect to outcomes.To date,conventional genotyping studies have shown that HLA classⅡloci are mainly associated with spontaneous clearance of HBV and HCV.However,the specific HLA locus associated with the outcomes of hepatitis virus infection remains unclear.A recent genome-wide association study(GWAS)using a comprehensive approach for human genotyping demonstrated single nucleotide polymorphisms(SNPs)associated with the outcomes of hepatitis virus infection.Examination of large numbers of cohorts revealed that several SNPs in both HLA-DPA1 and HLADPB1 loci are associated with persistent HBV infection in Asian populations.To date,however,few studies have focused on HLA-DP because polymorphisms of HLA-DP haplotype do not vary greatly as compared with other loci of HLA.There are not enough studies to reveal the function of HLA-DP.GWAS additionally detected candidate SNPs within HLA loci associated with chronic HBV or HCV hepatitis,hepatic fibrosis,and the development of hepatocellular carcinoma.The results of one cohort were not always consistent with those of other cohorts.To solve several controversial issues,it is necessary to validate reported SNPs on HLA loci in global populations and to elucidate the HLA-allele-regulated molecular response to hepatitis virus infection.

Host susceptibility to persistent hepatitis B virus infection

基因传染病学研究象成双的研究那样，研究提供了的肝炎 B (HBV ) 感染研究和种族差别聚类家庭招待基因因素玩的证据在决定 HBV 感染的结果的一个重要角色。开的问题包括基因在感染是哪个人重要的并且怎么发现他们。尽管很多研究寻求了在 HBV 感染 / 坚持和基因多型性之间的基因协会，候选人基于基因的途径清楚地是不适当的充分解释疾病的基因基础。与新基因标记和自动化 genotyping 的来临，基因印射能被进行极其快速。这条途径在某传染病是成功的。连接分析能发现主人基因易受影响到 HBV 并且具有大临床的重要性。

Hepatitis C virus associated glomerulopathies

Hepatitis C virus(HCV)infection is a systemic disorder which is often associated with a number of extrahepatic manifestations including glomerulopathies.Patients with HCV infection were found to have a higher risk of end-stage renal disease.HCV positivity has also been linked to lower graft and patient survivals after kidney transplantation.Various histological types of renal diseases are reported in association with HCV infection including membranoproliferative glomerulonephritis(MPGN),membranous nephropathy,focal segmental glomerulosclerosis,fibrillary glomerulonephritis,immunotactoid glomerulopathy,IgA nephropathy,renal thrombotic microangiopathy,vasculitic renal involvement and interstitial nephritis.The most common type of HCV associated glomerulopathy is typeⅠMPGN associated with typeⅡmixed cryoglobulinemia.Clinically,typical renal manifestations in HCV-infected patients include proteinuria,microscopic hematuria,hypertension,acute nephritis and nephrotic syndrome.Three approaches may be suggested for the treatment of HCV-associated glomerulopathies and cryoglobulinemic renal disease:(1)antiviral therapy to prevent the further direct damage of HCV on kidneys and synthesis of immune-complexes;(2)B-cell depletion therapy to prevent formation of immune-complexes and cryoglobulins;and(3)nonspecific immunosuppressive therapy targeting inflammatory cells to prevent the synthesis of immune-complexes and to treat cryoglobulin associated vasculitis.In patients with moderate proteinuria and stable renal functions,anti-HCV therapy is advised to be started as pegylated interferon-αplus ribavirin.However in patients with nephrotic-range proteinuria and/or progressive kidney injury and other serious extra-renal manifestations,immunosuppressive therapy with cyclophosphamide,rituximab,steroid pulses and plasmapheresis should be administrated.

Potential mechanisms of hepatitis B virus induced liver injury

Chronic active hepatitis(CAH) is acknowledged as an imperative risk factor for the development of liver injury and hepatocellular carcinoma.The histological end points of CAH are chronic inflammation,fibrosis and cirrhosis which are coupled with increased DNA synthesis in cirrhotic vs healthy normal livers.The potential mechanism involved in CAH includes a combination of processes leading to liver cell necrosis,inflammation and cytokine production and liver scaring(fibrosis).The severity of liver damage is regulated by Hepatitis B virus genotypes and viral components.The viral and cellular factors that contribute to liver injury are discussed in this article.Liver injury caused by the viral infection affects many cellular processes such as cell signaling,apoptosis,transcription,DNA repair which in turn induce radical effects on cell survival,growth,transformation and maintenance.The consequence of such perturbations is resulted in the alteration of bile secretion,gluconeogenesis,glycolysis,detoxification and metabolism of carbohydrates,proteins,fat and balance of nutrients.The identification and elucidation of the molecular pathways perturbed by the viral proteins are important in order to design effective strategy to minimize and/or restore the hepatocytes injury.

慢性HBV感染与代谢相关脂肪性肝病:已知与未知

慢性HBV感染是全球病毒性肝炎疾病负担的主要原因。由于生活方式和饮食习惯的改变,代谢相关脂肪性肝病(MAFLD)的发病率不断上升,已成为全球第一大慢性肝病。慢性HBV感染合并MAFLD在临床上越来越常见,代谢因素而非病毒因素是慢性HBV感染合并MAFLD的主要原因。在疾病发展进程中,炎症、纤维化而非脂肪变性是合并患者发展为肝硬化、肝细胞癌的主要影响因素。对于慢性HBV感染和MAFLD同时存在的患者,抗病毒和代谢因素的联合管理至关重要。本文就慢性HBV感染合并MAFLD的相互作用、预后转归和临床管理等热点话题进行讨论。

Relationships between lymphomas linked to hepatitis C virus infection and their microenvironment

The relationships between lymphomas and their microenvironment appear to follow 3 major patterns:(1)an independent pattern;(2)a dependent pattern on deregulated interactions;and(3)a dependent pattern on regulated coexistence.Typical examples of the third pattern are hepatitis C virus(HCV)-associated marginal zone lymphomas(MZLs)and mucosa-associated lymphoid tissue lymphomas.In these lymphomas,a regulated coexistence of the malignant cells and the microenvironmental factors usually occurs.At least initially,however,tumor development and cell growth largely depend on external signals from the microenvironment,such as viral antigens,cytokines,and cell-cell interactions.The association between HCV infection and B-cell lymphomas is not completely defined,although this association has been demonstrated by epidemiological studies.MZL and diffuse large B-cell lymphoma are the histotypes most frequently associated with HCV infection.Many mechanisms have been proposed for explaining HCV-induced lymphomagenesis;antigenic stimulation by HCV seems to be fundamental in establishing B-cell expansion as observed in mixed cryoglobulinemia and in B-cell lymphomas.Recently,antiviral treatment has been proved to be effective in the treatment of HCV-associated indolent lymphomas.Importantly,clinically responses were linked to the eradication of the HCV-RNA,providing a strong argument in favor of a causative link between HCV and lymphoproliferation.

The Expression of Sperm Membrane Peptide-Hepatitis B SurfaceAntigen Fusion Protein with Recombinant Vaccinia Virus

A synthetic oligonucleotide, HSD-2a, encoding a peptide segment of the extracel-lular domain of a human sperm membrane protein, YWK-II, was fused with hepatitisB surface antigen gene (HBs gene ). The fused gene was then cloned to pUC18plasmid. The fused gene was prepared from the recombinant pUC18 plasmid byBamH I and Eco R I digestion, and then cloned into the transfer vector pGJP- 5 underthe control of P;., promoter, designated as pGJP-HSD/HBs. CV-1 cells were co-transfected with vaccinia virus (Tian Tan strain) and pGJP-HSD/IIBs and homolo-gous re combination occurred between the vaccinia virus TK gene of the plasmid flank-ing the foreign gene and the same sequences within the virus genome. TK phen0tyPerecombinant virus, vv-HSD/HBs, were selected from trandected HuTK' cells byplaque purthcation technique. The eopressi0n of HSD-b in spent medium and cellu-lar protein of HuTK cells infected with vv-HSD/HBs was determined by ELISAand Western-blot analysis using anti-rwK-II antiserum. The present study indicatesthat the vv-HSD/HBs seems promising as an antdertility vaccine.

HBV-ACLF患者血清CCK-18、miR-122和HMGA2水平表达意义及预后影响因素分析

目的探讨血清角蛋白18(CCK-18)、微小核糖核酸122(miR-122)、高迁移率组蛋白A2(HMGA2)在乙型肝炎病毒相关慢加急性肝衰竭(HBV-ACLF)患者中的表达意义及预后影响因素分析。方法回顾性分析2019年1月至2022年1月148例在我院确诊为HBV-ACLF患者的临床资料并纳入HBV-ACLF组,另选取150例在我院行一般体检的健康人作为对照组;对比两组受试者血清CCK-18、miR-122、HMGA2表达差异;Spearman分析CCK-18、miR-122、HMGA2表达与HBV-ACLF发病关系;接收者操作特征曲线(ROC)分析CCK-18、miR-122、HMGA2单独及联合检测对HBV-ACLF的诊断价值;另外对148例HBV-ACLF患者随访1年,截止2023年1月,按照随访结果分为预后良好组(n=86)及预后不良组(n=62),单因素、多因素分析影响HBV-ACLF患者预后不良的独立危险因素;ROC分析CCK-18、miR-122、HMGA2单独及联合检测对HBV-ACLF预后预测价值。结果相比于对照组,HBV-ACLF组患者的CCK-18水平显著降低,而miR-122、HMGA2表达水平显著升高(均P<0.05);Spearman相关系数分析显示,miR-122、HMGA2表达与HBV-ACLF发病之间呈显著正相关,而CCK-18与HBV-ACLF发病之间呈显著负相关(均P<0.05);ROC显示,联合检测的曲线下面积(AUC)显著高于单一指标检测,灵敏度为93.33%,特异性为89.19%;多因素回归分析后显示并发症增多、miR-122及HMGA2表达水平上升是引发HBV-ACLF患者预后不良的独立危险因素,而CCK-18是保护因素(均P<0.05);ROC显示联合检测对预测HBV-ACLF患者的AUC显著高于单一指标检测,灵敏度为90.32%,特异性为81.40%。结论HBV-ACLF患者血清CCK-18、miR-122、HMGA2均具有特异表达水平,且作为影响该类患者预后的独立危险因素提示不良结局的发生,联合检测对于诊断疾病及预测疾病预后均具有较高的临床价值。

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.

Host genetic factors affecting hepatitis B infection outcomes:Insights from genome-wide association studies

The clinical outcome of hepatitis B virus(HBV) infection depends on the success or failure of the immune responses to HBV,and varies widely among individuals,ranging from asymptomatic self-limited infection,inactive carrier state,chronic hepatitis,cirrhosis,hepatocellular carcinoma,to liver failure,depending on the success or failure of immune response to HBV.Genome-wide association studies(GWAS) identified key genetic factors influencing the pathogenesis of HBV-related traits.In this review,we discuss GWAS for persistence of HBV infection,antibody response to hepatitis B vaccine,and HBV-related advanced liver diseases.HBV persistence is associated with multiple genes with diverse roles in immune mechanisms.The strongest associations are found within the classical human leukocyte antigen(HLA) genes,highlighting the central role of antigen presentation in the immune response to HBV.Associated variants affect both epitope binding specificities and expression levels of HLA molecules.Several other susceptibility genes regulate the magnitude of adaptive immune responses,determining immunity vs tolerance.HBV persistence and nonresponse to vaccine share the same risk variants,implying overlapping genetic bases.On the other hand,the risk variants for HBV-related advanced liver diseases are largely different,suggesting different host-virus dynamics in acute vs chronic HBV infections.The findings of these GWAS are likely to pave the way for developing more effective preventive and therapeutic interventions by personalizing the management of HBV infection.

HBV相关性肾炎患者肾组织氧化应激指标SOD、HO-1、8-OHdG的表达及临床意义

目的 探讨氧化应激指标超氧化物歧化酶(SOD)、血红素加氧酶(HO-1)、8-羟基脱氧鸟苷(8-OHd G)在HBV相关性肾炎(HBV-GN)患者肾组织中的表达情况,分析其与HBV-GN发生、发展的关系。方法 选取2010至2019年中国医科大学附属盛京医院收治的HBV-GN患者18例为观察组,留取患者肾组织石蜡切片为研究材料。另择2011至2019年本院收治的因肾脏肿瘤或外伤行肾组织切除术患者25例为对照组,留取切除的距病灶最远端的切缘肾组织标本为研究材料。收集两组患者肾功能指标资料,包括24 h尿蛋白、肾小球滤过率、血清肌酐、尿素氮水平。采用免疫组化法检测两组患者肾组织SOD、HO-1、8-OHd G表达水平并进行比较。分析观察组患者肾组织SOD、HO-1、8-OHd G表达水平与肾功能指标的相关性。结果观察组患者肾组织SOD、HO-1、8-OHd G表达水平分别为(1.28×10^(5)±6.37×10^(4))、(1.13×10^(5)±5.05×10^(4))、(2.33×10^(5)±1.26×10^(4));对照组分别为(324.20±155.08)、(296.67±116.40)、(214.58±42.92)。观察组患者肾组织SOD、HO-1、8-OHd G水平均明显高于对照组(均P<0.05)。观察组患者24 h尿蛋白定量、肾小球滤过率、血清肌酐、尿素氮水平分别为(4.79±2.44)g、(95.51±23.39)ml·min-1·1.73 m^(-2)、(86.32±28.10)μmmol/L、(5.94±1.76)mmol/L,SOD、HO-1、8-OHd G表达水平与以上指标相关性分析显示,观察组患者肾组织HO-1表达水平与肾小球滤过率呈正相关(r=0.667,P<0.05),其余指标间均无相关性(均P>0.05)。结论 SOD、HO-1、8-OHd G在HBV-GN患者肾组织中表达增强,与疾病的发生、发展有关。HBVGN患者肾组织HO-1表达水平与肾小球滤过率呈正相关。

DETECTION AND SIGNIFICANCE OF HBV IN RENAL TISSUE OF HBV ASSOCIATED GLOMERULONEPHRITIS PATIENTS

Objective To study the pathogenesis of hepatitis B virus ( HBV ) on kidney tissues. Methods HBsAg and HBcAg in paraffin-embedded renal biopsy tissues from 27 cases of glomerulonephritis with positive serum HBV markers were observed by using immunohistochemistry. In addition, in situ polymerse chain reaction (IS-PCR) was performed in 5 cases with positive HBsAg and HBcAg in renal tissue of the 27-case glomerulonephritis to reveal the state of renal HBV DNA. Results Twenty cases (20/27,74.07%) were positive with HBAg which were mainly diffusely distributed in epithelial cells of renal tubule. Four cases (4/5,80% ) were positive with HBV DNA whose distribution was the same of that of HBAg. Conclusion Renal lesions due to HBV are not only the results of immunologic response, but also the outcome of direct invasion and duplication of HBV in epithelial cells of renal tubule.

乙肝相关慢加急性肝衰竭患者6个月预后影响因素分析及模型构建

目的分析乙肝相关慢加急性肝衰竭(Hepatitis B virus associated chronic acute liver failure,HBV-ACLF)患者6个月预后影响因素及预后模型的建立。方法以2017年5月-2022年5月新疆医科大学第一附属医院感染中心收治的131例HBV-ACLF患者为研究对象。随访6个月,根据患者预后结果分为死亡组(n=60)和存活组(n=71)。收集患者血常规、肝功能、肾功能及血气指标,采用Logistics回归分析筛选影响HBV-ACLF患者6个月预后的因素,并将筛选的因素使用R 4.3.0软件进行绘制列线图预测模型,绘制校准曲线和受试者工作特征曲线(Receiver operating characteristic,ROC)拟合度及预测效能评估,根据决策曲线评估预测模型的临床适用性。结果二元Logistics回归分析发现,血小板计数、白蛋白及凝血酶原时间是影响HBVACLF患者6个月预后的重要因素,建立的预后模型区分度和校准能力较好。自发性腹膜炎在存活组和死亡组HBV-ACLF患者并发症中占比均最高。结论通过白蛋白,血小板计数和凝血酶原时间建立的预测模型对HBV-ACLF患者6个月预后有较好的预测价值。

尿HBV DNA在乙型肝炎病毒相关性肾炎诊断中的价值

目的探讨尿HBVDNA在乙型肝炎病毒相关性肾炎的诊断价值。方法本研究共入组152例患者,分为3组:乙型肝炎病毒相关性肾炎组66例,非乙型肝炎病毒相关性肾炎组66例,慢性乙型肝炎无肾损害患者20例。应用PCR方法检测血尿HBV DNA;乙肝五项定量采用酶联免疫法检测。结果乙型肝炎病毒相关性肾炎患者中尿HBV DNA阳性率33%(22/66),两对照组中无1例阳性。尿HBVDNA在乙型肝炎病毒相关性肾炎的诊断特异性高达98%,具有良好的阳性预测值(0.96)和阴性预测值(0.60)。尿HBV DNA或尿HBV DNA与血清HBeAg联合诊断价值优于尿HBV DNA与血清HBV DNA、血清HBsAg、血清HBeAg联合对乙型肝炎病毒相关性肾炎的诊断价值。结论尿HBV DNA可能作为乙型肝炎病毒相关性肾炎的一种新无创辅助诊断指标。

乙型肝炎病毒相关性肾小球肾炎患儿血清中HBV-cccDNA水平检测及其临床意义

目的:分析血清中乙肝病毒共价闭合环状双链DNA (HBV-cccDNA)水平对乙型肝炎病毒相关性肾小球肾炎(HBV-GN)患儿肝肾功能、肾组织中HBV抗原的检出、肝组织病理分级和分期的影响,评价HBVcccDNA水平检测对HBV-GN患儿诊断的临床应用价值。方法:选取39例HBV-GN初治患儿作为研究对象(观察组),所有患儿均接受肝脏和肾脏穿刺;选取肝功能正常HBV携带患儿40例作为对照组。检测2组患儿丙氨酸氨基转移酶(ALT)和天门冬氨酸氨基转移酶(AST)水平,采用PCR荧光分子信标技术检测患儿血清中HBV-cccDNA水平,HE染色检测患儿肝脏和肾脏组织的形态表现,免疫荧光法检测患儿肾组织中HBsAg、HBeAg和HBcAg检出率,采用受试者工作特征(ROC)曲线及曲线下面积(AUC)评价HBV-cccDNA水平检测在HBV-GN诊断中的价值。以HBV-cccDNA的Ax荧光值>21判定为阳性,反之判定为阴性,将HBV-GN患儿分为HBV-cccDNA阳性组(n=24)和HBV-cccDNA阴性组(n=15)。在抗病毒治疗后第2、4、8和12周时检测患儿血清中HBV DNA及HBV-cccDNA水平。结果:HBV-cccDNA阳性组患儿ALT和AST水平异常率、HBeAg和尿蛋白阳性率均高于HBV-cccDNA阴性组(χ~2=4.454,P=0.035;χ~2=5.912,P=0.022;χ~2=8.770,P=0.007)。HBV-cccDNA阳性和阴性组HBV-GN患儿肝组织炎症和纤维化程度比较差异无统计学意义(P>0.05),HBV-GN患儿肾脏活检病理类型以膜性肾病(MN)为主,HBV抗原成分以HBeAg及HBcAg为主,HBV-cccDNA阳性组患儿HBeAg及HBcAg检出率明显高于HBV-cccDNA阴性组(χ~2=5.652,P=0.027;χ~2=12.523,P=0.001)。ROC曲线评价,HBV-cccDNA水平检测能有效鉴别观察组HBV-GN患儿和对照组患儿,AUC=0.804 (95%CI:0.709~0.883)。10例规范治疗且有完整追踪治疗资料的HBV-GN患儿在治疗第2周时其HBV-cccDNA水平明显降低,治疗至第12周时其中7例患儿HBeAg转阴,无蛋白尿、血尿症状,ALT和AST水平均正常;治疗无效的3例患儿血清中HBV-cccDNA水平均高于其余7例标本。结论:HBV-cccDNA高表达与HBV-GN患儿肝功能、蛋白尿及肾脏HBV抗原检出有密切关联,检测HBVcccDNA水平对儿童HBV-GN患儿的辅助诊断及疗效评估具有潜在的临床应用价值。

NF-κB/IκB信号通路在乙型肝炎病毒相关性肾炎肾组织中的表达

目的探讨核转录因子-κB(NF-κB)/IκB在乙型肝炎病毒相关性肾炎(HBVGN)肾组织中的表达及其在HBVGN发病机制中的可能作用。方法采用免疫组化染色法,检测42例HBVGN、20例原发性膜性肾病及5例正常肾组织中NF-κBp65、IκB-α蛋白的表达。结果NF-κBp65蛋白在HB-VGN组织中的表达,明显高于在原发性膜性肾病(P<0.01)及正常肾组织(P<0.05)中的表达,且细胞核和细胞质中都可检测到NF-κBp65的表达;相反IκB-α在HBVGN组织中的表达低于原发性膜性肾病肾组织(P<0.05)。结论HBVGN肾组织可能有IκB-α蛋白降解及NF-κB核转移。NF-κB/IκB可能参与了肾组织的病理损害过程。