慢性HBV感染孕妇妊娠期及分娩后病毒学 和肝功能变化的特点及机制

HBV感染的孕妇妊娠期间自身机体的变化(体内激素水平及免疫状态)或抗病毒治疗后停药等均可能会导致病毒学改变及肝功能异常,严重者可导致不良结局。因此,加强对慢性HBV感染孕妇妊娠期及分娩后的病毒学指标及肝功能的监测有助于及时发现孕妇机体变化情况,从而避免肝炎发作甚至重型肝炎等不良后果的发生。现就慢性HBV感染孕妇妊娠期及分娩后病毒学及肝功能变化的特点及机制的文献作一综述,为提高临床医生对慢性HBV感染的孕妇妊娠期及分娩后管理水平提供理论支持。     

无症状HBV感染儿童血清病毒标志物检测分析

1 材料和方法 287例检查者来自1989年～1995年我院儿科门诊儿童入托、入学体检或因其它疾病检查者。HBsAg、抗-HBs、HBeAg、抗-HBe、抗-HBc均用ELISA方法。 2 结果 2.1 基本模式(见表1)。     

慢性HBV携带者血清中肝功能相关蛋白检测的临床意义

目的了解慢性HBV携带者血清中肝功能相关蛋白胆碱脂酶(Ch E)、白蛋白(Alb)、前白蛋白(PA)、转铁蛋白(TRF)、铁蛋白(FRT)、C反应蛋白(CRP)、铜蓝蛋白(CER)的水平,并且探讨这些蛋白对慢性HBV携带者的诊断价值。方法选取2012年1月至2014年7月在重庆医科大学附属永川医院就诊的86例慢性HBV携带者作为观察组,另外选取102例健康体检者作为对照组,分别检测其血清中Ch E、Alb、PA、TRF、FRT、CRP、CER等生化指标,并对部分观察组人群进行肝穿刺活组织检查。计量资料组间比较采用独立样本t检验。结果观察组与对照组的CER水平分别为(0.20±0.04)g/L、(0.29±0.06)g/L,差异有统计学意义(t=2.03,P=0.03),其他指标差异均无统计学意义(P值均0.05);观察组中,肝脏炎症程度高或纤维化程度高的患者血清中CER水平下降明显,差异均有统计学意义[(0.23±0.01)g/L vs(0.18±0.02)g/L,t=-2.6,P=0.01;(0.22±0.02)g/L vs(0.17±0.04)g/L,t=-3.2,P=0.004)。结论血清中CER水平的变化能反映早期肝脏炎症和纤维化程度,并可能成为慢性HBV携带者早期诊断与治疗的重要指标。     

病毒性肝炎慢性HBV携带者血清中肝功能相关蛋白检测的临床意义

目的：了解慢性HBV携带者血清中肝功能相关蛋白胆碱脂酶（ChE）、白蛋白（Alb）、前白蛋白（PA）、转铁蛋白（TRF）、铁蛋白（FRT）、C反应蛋白（CRP）、铜蓝蛋白（CER）的水平,并且探讨这些蛋白对慢性HBV携带者的诊断价值。方法选取2012年1月至2014年7月在重庆医科大学附属永川医院就诊的86例慢性HBV携带者作为观察组,另外选取102例健康体检者作为对照组,分别检测其血清中ChE、Alb、PA、TRF、FRT、CRP、CER等生化指标,并对部分观察组人群进行肝穿刺活组织检查。计量资料组间比较采用独立样本t检验。结果观察组与对照组的CER水平分别为（0．20±0．04）g／L、（0．29±0．06）g／L,差异有统计学意义（t＝2.03,P＝0．03）,其他指标差异均无统计学意义（P值均＞0．05）;观察组中,肝脏炎症程度高或纤维化程度高的患者血清中CER水平下降明显,差异均有统计学意义[（0．23±0．01）g／L vs （0．18±0．02）g／L,t＝－2．6,P＝0．01;（0．22±0．02）g／L vs （0．17±0．04）g／L, t＝－3．2,P＝0.004）。结论血清中CER水平的变化能反映早期肝脏炎症和纤维化程度,并可能成为慢性HBV携带者早期诊断与治疗的重要指标。     

经胎盘感染HBV儿童患者的治疗

问：你能介绍一下有关经胎盘感染乙型肝炎病毒，伴有血清学和乙型肝炎病毒DNA（HBV DNA）滴度阳性，但肝功能正常的儿童患的治疗吗？假如能够治疗的话，您认为多大年龄治疗为好以及治疗方法和治疗时间？     

乙型肝炎病毒合并结核菌感染时的肝功能变化

每年全世界约有 1千万结核 (ＴＢ)新发病例 ,约有 3百万人死于结核病 ,是单因素所致的感染性疾病中病死率最高的疾病。乙型肝炎病毒 (ＨＢＶ)感染是人类最常见的病毒感染之一 ,全世界约有 3亿 ,我国ＨＢＶ感染率为 10 %～15 % ,因此相当一部分人有ＨＢＶ、ＴＢ菌混合感染。在长达6～ 8个月抗ＴＢ治疗过程中 ,其主要副作用为肝损害。为此 ,我们对混合感染时抗ＴＢ治疗肝组织损害发生率、肝组织病理情况和ＨＢＶ标记物的变化进行了研究。材料和方法一、病例选择80例近 3年ＴＢ菌感染病例 ,其中肺结核 5 0例 ,肠结核 12例 ,结核性腹膜炎 8例 ,…     

儿童HBV和HCV感染的临床研究

儿童ＨＢＶ和ＨＣＶ感染的临床研究王清图张益荣李树青孙群英王福民作者单位：２６１０１１山东省潍坊市妇幼保健院（王清图、李树青、孙群英、王福民）；潍坊市中心血站（张益荣）为评价我市儿童乙型肝炎病毒（ＨＢＶ）和丙型肝炎病毒（ＨＣＶ）感染的现状，自１９９４年...     

HBV感染所致慢加急性肝功能衰竭患者HBV变异的纵向研究

目的明确乙型肝炎病毒（HBV）变异与慢加急性肝功能衰竭（ACLF）发病之间的关系。方法采用纵向研究的方法 ,选取6例HBV感染者为研究对象,其中ACLF4例（P1～P4）,肝硬化（LC）2例（P5、P6）。分别留取每例患者不同疾病阶段血清2份,进行HBVDNA提取、扩增、克隆和测序,测序结果采用VectorNTISuite9.0软件分析,纵向对比HBV核苷酸序列变异情况。结果 6例患者均为基因C型。ACLF患者（P1～P4）在病程中HBV的核苷酸突变位点多于发生肝硬化患者（P5、P6）。ACLF患者中,nt53（C→T或T→C）、nt1846（A→T）、nt1896（G→A）的纵向突变见于2例或2例以上患者。C1913A或T突变可见于患者P1、P2,同时患者P2可见纵向突变。结论 nt53、nt1846、nt1896和nt1913四个核苷酸的突变可能与ACLF的发病相关。     

老年人慢性HBV感染的临床特点分析

目的探讨老年人慢性乙型肝炎病毒（HBV）感染的疾病谱及临床特点。方法比较53例老年慢性HBV感染者与相同例数的低年龄组慢性HBV感染者的性别、疾病谱、血清HBVDNA和ALT水平。结果老年组慢性HBV感染的疾病谱与低年龄组有显著不同,前者以非活动性HBsAg携带者为主（66.0%）,后者中HBeAg阳性慢性乙型肝炎患者较多（47.2%）。老年组慢性HBV感染者血清HBVDNA和ALT均明显低于低年龄组,差异有统计学意义（P〈0.05或P〈0.01）。两组总体性别组成差异无统计学意义。结论非活动性HBsAg携带者是老年慢性HBV感染的主要疾病谱,但HBeAg阳性或阴性慢性乙型肝炎（CHB）和乙型肝炎肝硬化的发生率仍较高,且存在HBV复制和肝脏病变。     

感染HIV并有外周血细胞减少儿童的骨髓特点

据医学空间网5月17日报道(原载J Trop Pediatr 2005 Apr：51(2)：114—9)，HIV感染能同时影响髓系和淋系，产生许多异常。     

慢性乙型肝炎患者血细胞计数与肝脏组织学的关系

目的研究乙型病毒性肝炎患者血细胞计数与肝组织炎症和纤维化的关系。方法398例慢性乙型病毒性肝炎患者按肝组织纤维化分期分为S0-S4五组,按肝组织炎症分级分为G1-G4四组;常规方法检测外周血红细胞（RBC）、白细胞（WBC）和血小板计数（PLT）,并进行相关统计学处理。结果RBC、WBC、和PLT与肝组织纤维化和炎症程度均呈负相关（P〈0.05）,PLT相关性最好;PLT与肝纤维化分期和炎症分级的相关系数分别是0.743、0.688。PLT分别在S0-S4、G1-G4各组间差异均有统计学意义（P〈0.05）,在S4期下降到正常值以下（95.08±20.57）。RBC、WBC二项指标在S3、S4与S0、S1和S2之间有统计学意义（P〈0.05）,在G4与G1、G2、G3之间有统计学意义（P〈0.05）。结论RBC、WBC和PLT与肝组织纤维化和炎症程度负相关,PLT相关性最好,PLT降至正常界值以下,提示肝组织存在早期肝硬化,PLT下降接近正常界值下限时,提示肝组织的炎症活动和纤维化程度均很严重。     

慢性乙肝患者HBV-DNA、肝功能指标与肝纤维化的关系

[目的]探究慢性乙型病毒性肝炎患者乙肝病毒脱氧核糖核酸(HBV-DNA)、肝功能指标与肝纤维化的关系.[方法]入选65例慢性乙肝患者为患者组;同期选取肝功能合格的体检者65例作为对照组;检测2组肝纤维化指标[血清透明质酸(HA)、层粘连蛋白(LN)、Ⅲ型胶原(PCⅢ)、Ⅳ型胶原(Ⅳ-C)],HBV-DNA,肝功能指标[...     

慢性乙型肝炎患者血清脂联素水平与肝功能及相关因素的关系

目的探讨慢性乙型肝炎（CHB）患者血清脂联素水平与肝功能及相关因素的关系。方法选择77例不同类型CHB患者,应用ELISA法检测血清脂联素水平;同时检测肝功能、血脂、空腹血糖（FBG）、HBVDNA等。测量人体身高、体重,计算体重指数（BMI）。30例健康体检者为正常对照组。结果各组CHB患者血清脂联素水平明显高于正常对照组（P〈0.01）,随肝损害加重而上升。脂联素与AST、TBil和ALP均正相关,与白蛋白（ALB）负相关。结论CHB患者血清脂联素水平升高与肝脏炎症活动有关,可能是机体抵抗炎症的一种机制。     

Clinical significance of liver biopsy in chronic hepatitis B patients with persistently normal transaminase

OBJECTIVE: The aim of this study was to study the clinical significance of liver biopsy for individuals who had chronic hepatitis B virus infection and persistently normal serum transaminases for more than 6 months. METHODS: A total of 452 patients with positive hepatitis B surface antigen for over 6 months underwent percutaneous liver biopsy. All liver biopsy specimens were assessed by experienced liver pathologists blinded to the liver biochemistry, and were scored according to the modified criteria of grade and stage of chronic hepatitis. Patients were divided into four groups: group A and group C patients had normal transaminases, and were hepatitis B e antigen (HBeAg) positive and HBeAg negative, respectively; group B and group D patients had elevated transaminases, and were HBeAg positive and HBeAg negative, respectively. RESULTS: All patients had necrosis and inflammation in the liver. Patients with increased serum transaminases had a significantly higher grade (G) of hepatic necrosis and inflammation and more severe (S) fibrosis compared with patients with normal transaminases (P < 0.05). However, in the latter patients, G3 was seen in 10 (5.5%) and 13 cases (9.1%), S3 in seven (3.8%) and 16 cases (11.1%), and S4 in three (1.6%) and seven cases (4.9%) in Group A and Group C, respectively. Moreover, in patients with normal transaminases, the HBeAg‐negative group had more severe fibrosis than the HBeAg‐positive group (P < 0.05). CONCLUSION: Although more severe pathological changes were more frequent in patients with elevated transaminases, significant hepatic pathology could still be found in cases with persistently normal transaminases. Liver biopsy in cases of chronic hepatitis B virus infection is helpful to accurately assess both the activity of the disease and the degree of fibrosis, and to estimate if antiviral therapy is justifiable. Patients with normal transaminases and serious hepatic necrosis, inflammation and fibrosis need proper management.     

A novel noninvasive algorithm for the assessment of liver fibrosis in patients with chronic hepatitis B virus infection

Several noninvasive blood biomarkers have been established for the assessment of liver fibrosis in patients with chronic hepatitis B virus (HBV) infection, but their clinical performance remains inconclusive. Here, we compared the diagnostic performance of these biomarkers and developed a novel algorithm for assessing liver fibrosis. Six hundred and sixteen chronically HBV‐infected and treatment‐naïve patients who underwent liver biopsy were enrolled and randomly divided into training (N=410) and internal validation cohorts (N=206). One hundred and fifty‐nine patients from another centre were recruited as an external validation cohort. Receiver operating characteristic (ROC) curves were used to analyse the performance of the gamma‐glutamyltransferase‐to‐platelet ratio (GPR), red cell volume distribution width‐to‐platelet ratio (RPR), FIB‐4 index, aspartate aminotransferase‐to‐platelet ratio index (APRI) and HBV DNA level against liver histology, and a novel algorithm was developed using the recursive partitioning and regression tree (RPART) method. In the training cohort, the area under the ROC curve of FIB‐4 was significantly higher than that of APRI (P=.038) but was comparable to those of GPR, RPR and HBV DNA; however, the performance of the biomarkers was similar among the validation cohort. The established RPR‐HBV DNA algorithm performed better in the training cohort than any individual blood biomarker, and the corresponding sensitivity, specificity, positive predictive value and negative predictive value were 63%, 90%, 72% and 80%, respectively. In the internal and external validation cohorts, the performance of the algorithm in assessing liver fibrosis was also superior to that of other biomarkers. These results suggest that the established RPR‐HBV DNA algorithm might improve the diagnostic accuracy of liver fibrosis in treatment‐naïve patients with chronic HBV infection, although additional studies are warranted to confirm these findings.     

Potential of laparoscopy in chronic liver disease with hepatitis B and C viruses

Aim: The definitive diagnosis of chronic liver disease is made either by a histological examination of a biopsy specimen or upon visualization of the liver surface at laparoscopy. The aim of this retrospective cohort study is to assess whether histological or laparoscopic findings are associated with hepatocellular carcinoma (HCC) development. Methods: A retrospective review of paired laparoscopy and histology reports was performed on 4124 hepatitis virus-positive patients who underwent laparoscopy: 2804 patients had hepatitis C virus (HCV group) and 1320 patients had hepatitis B virus (HBV group). Based on the irregularities of the liver surface, the laparoscopic findings were classified into three groups in progression order: smooth, irregular, or nodular. The histological findings were classified according to the extent of fibrosis into four stages (stages 1-4) in progression order. Results: The number of patients with HCC development was 565 in the HCV group and 115 in the HBV group. The Coxregression hazard model showed that HCC appearance in the HCV group was independently associated with laparoscopic findings (relative risk based on every progression of one rank [RR], RR = 4.31, P < 0.0001) and histological findings (RR = 2.56, P < 0.0001). In the HBV group, however, HCC appearance in was mainly associated with laparoscopic findings (RR = 2.12, P < 0.0001) compared to histological findings (RR = 1.13, P = 0.403). Conclusion: Our data indicate that laparoscopic findings of the liver are dominant predictors for HCC development compared with histological findings in patients with HBV.     

Composition of peripheral blood lymphocyte populations during different stages of chronic infection with hepatitis B virus

To characterize the immunological populations associated with different stages of chronic infection with hepatitis B virus (HBV), we performed flow cytometric analyses on the peripheral blood leucocytes of 29 patients with various forms of chronic hepatitis B. The clinical spectrum of the patients ranged from asymptomatic infections, in the presence of high virus production, to intermittent or recurrent exacerbations of liver injury alternating with relatively normal liver function. Patients with partial resolution of disease who experienced an initial acute flare followed by prolonged seroconversion showed decreased percentages of CD3⁺ cells during the seroconversion phase when levels of serum alanine transferase (ALT) had normalized. These CD3⁺ cells were predominantly CD4⁺ cells bearing the αβ⁺ T-cell receptor (TCR). In addition, we saw an increase in CD4⁺ and CD8⁺ cells bearing the γδTCR in those patients who had seroconverted. No significant differences were seen between any of the groups with respect to percentage of cells with a naive (CD45RA) or memory (CD45RO) phenotype, or of cells displaying the activation markers CD38, HLA-DR or CD57. Longitudinal analyses of 15 patients failed to show any consistent pattern of changes in the immunophenotypic profile during acute flares and their resolution. Our results indicate that the turnover of circulating T lymphocytes during the apparent quiescent phase of chronic infections is higher than that during acute exacerbations, suggesting an active immunosurveillance role of T-cell subpopulations in maintaining low virus levels during seroconversion.     

Hepatitis B virus DNA is more powerful than HBeAg in predicting peripheral T-lymphocyte subpopulations in chronic HBV-infected individuals with normal liver function tests

AIM： To investigate the peripheral T-lymphocyte subpopulation profile, and its correlations with hepatitis B virus （HBV） replication level in chronic HBV-infected （CHI） individuals with normal liver function tests （LFTs）. METHODS： Frequencies of T-lymphocyte subpopulations in peripheral blood were measured by flow cytometry in 216 CHI individuals. HBV markers were detected with ELISA. Serum HBV DNA load was assessed with quantitative real-time PCR. Information of age at HBV infection, and maternal HBV infection status was collected. ANOVA linear trend test and linear regression were used in statistical analysis.
RESULTS： CHI individuals had significantly decreased relative frequencies of CD^3＋, CD^4＋ subpopulations and CD^4＋/CD^8＋ ratio, and increased CD^8＋ subset percentage compared with uninfected individuals （all P 〈 0.001）. There was a significant linear relationship between the load of HBV DNA and the parameters of T-lymphocyte subpopulations （ANOVA linear trend test P 〈 0.01）. The parameters were also significantly worse among individuals whose mothers were known to be HBV carriers, and those having gained infection before the age of 8 years. In multiple regressions, after adjustment for age at HBV infection and status of maternal HBV infection, log copies of HBV DNA maintained its highly significant predictive coefficient on T-lymphocyte subpopulations, whereas the effect of HBeAg was not significant.
CONCLUSION： HBV DNA correlates with modification in the relative T-lymphocyte subpopulation frequencies. High viral load is more powerful than HBeAg in predicting the impaired balance of T-cell subsets.     

慢性乙型肝炎患者肝功能与血清HBVDNA负荷及肝脏病理的关系

探讨慢性乙型肝炎患者肝功能与血清HBVDNA负荷及肝脏病理的相关性。随机选择207例慢性乙型肝炎患者,检测其血清ALT、HBVDNA含量,肝穿刺活检,光镜多视野观察其肝组织的病理情况。随着慢性乙型肝炎患者血清ALT的升高,HBVDNA复制程度的增高,其肝组织的炎症活动度、纤维化程度明显升高(P<0.01)。慢性乙型肝炎患者血清ALT、HBVDNA含量与肝组织的炎症活动度、纤维化程度有相关性。     

Quantitative testing of liver function in relation to fibrosis in patients with chronic hepatitis B and C

Abstract: Background/Aim: Quantitative tests of liver function may be superior to conventional tests to assess the prognosis of patients with liver diseases. There are insufficient data from quantitative testing of liver function (QTLF) for patients with chronic hepatitis B and C, particularly with regard to fibrosis. Therefore, we applied a broad panel of QTLF to these patients. Methods: Three hundred and sixty‐seven consecutive patients with chronic hepatitis B or C underwent liver biopsy and QTLF, which included tests for hepatic metabolism (aminopyrine breath test, galactose elimination capacity) and for hepatic perfusion (sorbitol clearance, indocyanine green clearance). QTLF values were correlated with liver histology (grading and staging for inflammation and fibrosis) and Child–Pugh classification for liver cirrhosis. Results: In patients with no and moderate fibrosis, metabolic liver function was significantly decreased, whereas hepatic perfusion remained normal. Severe fibrosis and cirrhosis showed a significant decline in all QTLFs. Hepatic inflammation only reduced metabolic liver function, irrespective of the inflammatory grade. Viral etiology and HCV genotypes did not change QTLF. Conclusions: In summary, viral damage compromises hepatic metabolism before perfusion. Therefore, tests of metabolic liver function (aminopyrine breath test, galactose elimination capacity) should be useful to search for drugs that restore liver function in viral hepatitis irrespective of the fibrosis stage.