慢性乙型肝炎患者ALT、HBV DNA及血清肝纤维化标志物与肝纤维化程度的关系

目的探讨ALT、HBV DNA以及血清纤维化标志物透明质酸(HA)、层粘连蛋白(LN)、Ⅲ型前胶原肽(PⅢP)、Ⅳ型胶原(CⅣ)与慢性乙型肝炎肝纤维化程度的关系。方法检测281例慢性乙型肝炎患者血清中ALT、HBV DNA和纤维化标志物(HA、LN、PⅢP及CⅣ)的水平,并行肝活检检测肝组织病理纤维化分期。结果 HBeAg阴性慢性乙型肝炎患者HBV DNA水平较低、纤维化程度较高。HBeAg阳性患者纤维化程度与HBV DNA呈负相关(r=-0.251,P<0.001),S≥3组水平最低。慢性乙型肝炎患者纤维化程度与PⅢP水平呈正相关,其水平随着纤维化程度的加重而明显升高。结论 PⅢP水平可能作为评估慢性乙型肝炎患者肝纤维化程度的血清学指标,血清HBV DNA与肝脏纤维化严重程度的关系仍需进一步深入探讨。     

血清纤维化指标联合肝生化检测对慢性乙型肝炎患者病情的评估

目的：探讨慢性乙型肝炎（CHB）及肝硬化患者血清纤维化指标透明质酸（HA）、层粘连蛋白（LN）、Ⅳ型胶原（Ⅳc）、人Ⅲ型前胶原（PCⅢ）含量及丙氨酸氨基转移酶（ALT）水平与病情严重程度的关系。方法以30例正常体检人员为对照,检测129例CHB及肝硬化患者血清HA、LN、Ⅳc、PCⅢ的含量及ALT水平,同时结合临床特点,运用统计学方法对上述血清学指标的诊断价值进行分析。结果 CHB患者血清 HA、LN、Ⅳc、PCⅢ较正常对照组升高,而低于肝硬化组,但当ALT＞800 IU/L时,CHB重度组血清 HA、LN、Ⅳc、PCⅢ并不低于肝硬化组。结论上述四项血清纤维化指标联合肝功能检测对全面评估慢性肝炎和肝硬化病情更具有临床诊断价值。     

慢性乙型肝炎和肝硬化患者血清HA、LN、PCⅢ和Ⅳ-C水平与肝组织纤维化程度的关系

目的 探讨慢性乙型肝炎和肝硬化患者血清透明质酸（HA）、层粘连蛋白（LN）、Ⅲ型前胶原（PCⅢ）和Ⅳ型胶原（Ⅳ－C）在肝纤维化诊断中的应用价值。方法 采用放射免疫法检测150例慢性乙型肝炎和肝硬化患者血清HA、LN、PVⅢ和Ⅳ－C水平，并与活检肝组织纤维化程度进行相关性分析。结果 各组慢性乙型肝炎患者血清HA、LN、PCⅢ和Ⅳ－C水平均高于正常对照组，与肝纤维化活动水平及程度呈密切正相关。结论 血清HA、LN、PCⅢ和Ⅳ－C水平能较好地反映乙型肝炎纤维化程度，联合检测可明显提高肝纤维化诊断的准确性和可靠性。     

透明质酸、层粘连蛋白、Ⅲ型前胶原和Ⅳ型胶原血清学指标对肝硬化诊断的价值

目的:评价血清纤维化指标对于诊断肝硬化的应用价值。方法:52例经肝穿刺确诊为慢性乙型肝炎及肝硬化患者,应用放射免疫法检测血清HA(透明质酸)、LN(层粘连蛋白)、PCⅢ(Ⅲ型前胶原)、CⅣ(Ⅳ型胶原)水平。结果:肝脏病理炎症及纤维化分级与血清HA、LN、PCⅢ、CⅣ水平有显著相关性,组间对比部分有统计学意义,炎症分级组较为明显。结论:检测血清HA、LN、PCⅢ、CⅣ水平对于判断肝脏炎症及纤维化程度有一定价值和意义。     

白细胞介素-17肝内表达与慢性乙型肝炎病毒感染所致肝纤维化的相关性

目的 探讨IL-17肝内表达与慢性HBV感染所致肝纤维化的相关性.方法 免疫组织化学法测定30例慢性HBV携带者、55例慢性乙型肝炎患者、20例乙型肝炎肝硬化患者肝组织内不同炎症程度分级和肝纤维化分期中IL-17的表达,ELISA法测定血清IL-17及肝纤维化指标HA、LN、PCⅢ、ⅣC的水平.组间差异性检验采用Kruskal-Wallis检验和Mann-Whitney检验,相关性分析采用Spearman分析.结果 肝组织IL-17表达水平在肝硬化组高于慢性乙型肝炎组(x2=25.3982,P=0.004),在慢性乙型肝炎组高于慢性HBV携带组(x2=11.5056,P=0.001);不同炎症程度及纤维化分级与IL-17表达强度呈正相关(r=0.718、0.693,均P＜0.01);肝组织IL-17主要集中于汇管区,其表达强度与血清HA、LN、PCⅢ、ⅣC呈正相关(r=0.793、0.834、0.722、0.883,均P＜0.01).结论 IL-17的肝内表达与肝内炎症程度分级及肝纤维化程度密切相关.     

多烯磷脂酰胆碱对慢性乙型肝炎患者细胞因子及肝纤维化指标影响

目的研究多烯磷脂酰胆碱对慢性乙型肝炎(CHB)患者肝纤维化指标及细胞因子的影响。方法选择98例CHB患者随机分为治疗组(50例)和对照组(48例),治疗前后检测患者血清转化生长因子β1(TGF-β1)、肿瘤坏死因子α(TNF-α)、透明质酸(HA)、Ⅳ型胶原(C-Ⅳ)、层粘连蛋白(LN)以及丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)水平。结果治疗组患者血清ALT、AST、HA、C-Ⅳ、LN和TGF-β1、TNF-α水平较治疗前及对照组比较,均显著降低(P<0.01),差异均有统计学意义。结论多烯磷脂酰胆碱具有很强的抗氧化、保护肝细胞、抗感染及抗肝纤维化作用。     

慢性肝病与肝纤维化指标的关系

目的:探讨肝纤维化指标包括透明质酸(HA),Ⅲ型前肢原(PCⅢ),层连蛋白(LN)及Ⅳ型胶原(Ⅳ-C)等与慢性肝病的关系。方法:应用放免法检潮103例慢性乙型肝炎,42例肝细胞癌和64例肝炎肝硬变患者及40例正常人的HA、PCⅢ、LN和Ⅳ-C的值。结果:慢性乙型肝炎轻、中、重度病人此4项血清学指标依次升高;慢性肝炎(重度)、肝硬变、肝细胞癌患者4项指标均有明显升高。结论:慢性乙型肝炎(重度)、肝炎肝硬变和肝细胞癌患者与肝纤维化有密切关系;联合检测HA、PCⅢ、LN和Ⅳ-C 4项指标,有助于慢性肝病肝纤维化的诊断。     

慢性病毒性肝炎患者血清中瘦素与肝纤维化指标的关系

研究血清瘦素水平与慢性病毒性肝炎和肝纤维化之间的关系。用放射免疫法检测 4 5例慢性乙型肝炎(CHB)患者血清中的瘦素和肝纤维化指标的水平。发现CHB患者血清瘦素水平 (7 6 3± 2 19)ng/ml显著高于正常对照组 (3 82± 1 0 9)ng/ml,其瘦素 /BMI值也显著高于正常对照组 ,CHB患者的血清瘦素水平与肝纤维化指标层粘蛋白 (LN)、透明质酸 (HA)、Ⅲ型前胶原 (PCⅢ )和Ⅳ胶原 (ⅣC)的水平呈正相关。瘦素与慢性病毒性肝炎肝纤维化的形成密切相关     

慢性乙型肝炎和肝炎肝硬化患者血浆内皮素-1水平与血清肝纤维化指标和门静脉宽度的关系

目的探讨慢性乙型肝炎和肝炎肝硬化患者血浆内皮素-1（ET-1）水平的变化及其与肝纤维化血清指标和门静脉宽度的关系。方法采用放射免疫法测定急性乙型肝炎、慢性乙型肝炎和肝炎肝硬化患者血浆ET-1、血清透明质酸（HA）、层粘蛋白（LN）、Ⅲ型胶原肽（PⅢP）和Ⅳ型胶原（Ⅳ-C）水平。结果23例急性乙型肝炎肝纤维化血清指标中仅HA水平较正常对照组明显升高；81例慢性乙型肝炎和64例肝炎肝硬化患者。血浆ET-1、血清HA、LN、PⅢP和Ⅳ-C水平均较正常对照组明显升高。在慢性乙型肝炎中血浆ET-1、血清HA、LN、PⅢP和Ⅳ-C水平随着肝脏损害程度（轻、中、重度）的加重而逐步升高。在慢性乙型肝炎和肝炎肝硬化患者中。血浆ET-1水平与血清HA、LN、PⅢP和Ⅳ-C水平明显相关；同时ET-1还与患者门静脉宽度明显相关。结论ET-1、HA、LN、PⅢP和Ⅳ-C与慢性乙型肝炎肝脏损害相关：ET-1与慢性乙型肝炎和肝炎肝硬化患者肝纤维化程度和门静脉高压有一定的关系。     

干扰素-α1b治疗慢性乙型肝炎患者对血清肝纤维化标记物的影响

目的 评价干扰素-α1b(赛若金)的抗肝纤维化作用及其与抗病毒疗效的关系。方法 干扰素-α1b治疗57例慢性乙型肝炎患者,对照组用常规方法治疗,检测治疗前后血清透明质酸(HA)、Ⅲ型前胶原(PCⅢ)、层粘连蛋白(LN),Ⅳ型胶原(ⅣC)的含量变化。结果 治疗组疗程结束后,HA、PCⅢ、LN和ⅣC均有不同程度下降,血清HBV DNA阴转者降幅显著大于未阴转者,与对照组比较有显著差异(P<0.05)。结论 赛若金可减轻慢性乙型肝炎患者肝纤维化程度,其抗肝纤维化作用与抗病毒作用呈一致关系。     

慢性乙型肝炎病毒携带者肝组织学特点与临床特征的关系

目的研究慢性HBV携带者的肝组织学特点与其临床特征的关系。方法对以“慢性HBsAg携带者”入院的142例患者行肝脏活体组织学检查,平均年龄（24．8±8．7）岁;其中129例血清HBV DNA阳性,符合“慢性HBV携带者”诊断,余13例符合“非活动性HBsAg携带者”诊断。肝穿刺获取标本（2．2±0．8）cm以进行组织学检查;同时进行血清病毒学、纤维化指标及蛋白质电泳、超声检查。按血清HBV DNA是否阳性及病理学诊断分组比较。结果病理学检查肝组织正常（G0S0）36例,慢性肝炎[炎症分级≥G1和（或）纤维化分期≥S1]106例,其中包括早期肝硬化（G4S4）1例;按HBV DNA是否阳性分组比较,差异无统计学意义。血清HBV DNA均值为（7．58±0．99）log10拷贝／ml,HBeAg阳性123例。45．8％（49／107）γ-球蛋白增高;37．1％（23／62）血清纤维化指标增高;40．1％（57／142）彩色多普勒超声检查显示异常。按病理学诊断分组比较,慢性肝炎组的血清PCⅢ均值高于正常组（P〈0．05）;PCⅢ与炎症分级呈正相关（r=0．391, P〈0．01）。结论本组病例具有高病毒载量及炎症轻微的特征;组织学炎症分级、纤维化分期与HBV DNA水平及HlBeAg状态无相关性,血清PCⅢ增高与炎症分级有关。     

A complete genomic analysis of hepatitis B virus genotypes and mutations in HBeAg-negative chronic hepatitis B in China

Summary.  We aimed to study the distribution of hepatitis B virus (HBV) genotypes/subgenotypes in different parts of China and their clinical impact on the severity of hepatitis B e antigen (HBeAg)-negative chronic hepatitis B. Residual serum samples from a cohort of HBeAg-negative chronic hepatitis B patients in Hong Kong, Shanghai and Beijing were studied. Complete HBV genomic sequencing was performed for phylogenetic tree analysis and determination of HBV mutations was carried out. Mutations associated with severe liver fibrosis (Ishak score 4 or more) were selected by computerized information gain criteria. Genotype B (all subgenotype Ba) HBV was present in 19 of 45 (42%), 12 of 31 (39%) and 5 of 25 (20%) patients in Hong Kong, Shanghai and Beijing, respectively ( P  = 0.16). Ninety-seven per cent of genotype C HBV in Shanghai and Beijing belonged to subgenotype Ce whereas 69% of genotype C patients in Hong Kong belonged to subgenotype Cs ( P  < 0.001). Patients infected by subgenotype Cs had the lowest serum albumin and highest alanine aminotransferase levels compared with subgenotype Ce and Ba. Patients infected by subgenotype Cs also had more severe histological necroinflammation than subgenotype Ce. Two HBV mutations were identified to associate with severe liver fibrosis (G2858C and C2289A) and one mutation was protective against severe liver fibrosis (T2201C). The T2201C mutation was found exclusively among patients (21 of 46 patients, 45%) infected by HBV subgenotype Ce. The clinical differences in HBeAg-negative chronic hepatitis B in China may be influenced by different distribution of subgenotype C HBV.     

肝活检对HBV携带者的诊断意义

目的探讨肝活检对HBV携带者的诊断意义。方法回顾性分析134例HBV携带者,在B超引导下行1秒钟快速肝穿刺活检术,行肝组织病理学检查。结果在134例患者中,仅2例（1.49%）肝组织病理学检查完全正常（G0S0）;在105例HBV DNA≥10^5copies/ml（或HBeAg阴性者HBV DNA≥10^4copies/ml）的HBV携带者中,肝组织炎症活动度≥G2者80例（76.19%）,即可实施抗病毒治疗;在100例HBeAg（＋）与34例HBeAg（-）感染者,肝组织炎症活动度和纤维化程度比较无明显统计学差异（P=0.308）;在不同肝组织炎症活动度和纤维化程度感染者,HBV DNA载量无明显的统计学差异（P=0.557）,HBV DNA≥10^7copies/ml与HBV DNA〈10^7copies/ml感染者比,肝组织炎症活动度和纤维化程度存在统计学差异（P=0.007,P=0.001）。结论对于慢性HBV携带者,应及时进行肝组织活检。     

碱性成纤维细胞生长因子与慢性乙型肝炎及肝纤维化临床检测指标的关系

目的观察碱性成纤维细胞生长因子(b-FGF)在不同肝纤维化分期(S)肝组织中表达的差异性及其与临床检测常用的肝功能指标、肝纤维化指标、HBV DNA复制水平以及肝硬化Child-Pugh分级之间的关系。方法选取122例HBV引起的慢性肝炎及肝硬化患者,空腹静脉血检测:(1)肝功能指标:ALT、TBil、Alb;(2)肝纤维化指标:透明质酸(HA)、Ⅲ型前胶原(PCⅢ)、层粘连蛋白(LN)、Ⅳ型胶原(CⅣ);(3)HBV DNA复制水平;(4)对临床诊断肝硬化患者计算其Child-Pugh评分。行肝脏穿刺活检术后,经病理作纤维化分期(S1～S4)。免疫组织化学法测定肝组织中b-FGF在不同病理分期的表达及定位特点,半定量分析法计算b-FGF值,观察b-FGF与肝功能指标、肝纤维化指标、HBV DNA水平以及肝硬化Child-Pugh分级之间的关系。结果 (1)肝纤维化S1～S4期肝组织中b-FGF的表达部位及水平不同;(2)肝纤维化S1～S4期肝细胞中b-FGF的表达与肝纤维化分期(S1～S4)呈显著正相关(r=0.542,P<0.01);(3)不同肝纤维化分期中b-FGF的表达差异与患者ALT、TBil及Alb进行比较,其差异无统计学意义(P>0.05),不同肝纤维化分期患者,进行HBV DNA检测,其差异无统计学意义(P>0.05);(4)不同肝纤维化分期中,b-FGF与血清纤维化指标HA、PCⅢ、LN、CⅣ之间呈正相关;(5)b-FGF的表达与临床Child-Pugh分级无明显相关性。结论 b-FGF的表达与肝脏纤维化程度、肝纤维化指标有正相关关系,与患者ALT、TBil、Alb、Child-Pugh评分、及HBV DNA水平无关。     

隐匿性乙型肝炎病毒感染者临床特点和肝组织病理学检查

目的了解血清肝炎病毒标志物阴性、肝功能反复异常患者中HBV隐匿性感染的比例及其临床和病理学特点。方法对27例血清肝炎病毒标志物阴性、肝功能反复异常患者采用免疫组化法检测肝组织HBsAg、HBcAg和HCVAg，并进行常规的病理学检查。结果肝组织HBsAg和（或）HBcAg阳性9例（33．3％）；HBsAg和（或）HBcAg及HCVAg阳性10例（37．0％）；全阴性8例（29．6％）。在HBV隐匿性感染的19例患者中，慢性肝炎8例，肝硬化11例。结论HBV和HCV感染为血清肝炎病毒标志物阴性患者肝功能反复异常的主要原因之一，尤其是HBV感染。这种HBV隐匿性感染与慢性肝炎、肝硬化的发生关系密切，应引起重视。     

Predictive value of serum globulin levels for the extent of hepatic fibrosis in patients with chronic hepatitis B infection

The mechanism underlying disease progression in hepatitis B virus (HBV) infection is unknown. Immunoglobulins stimulate the proliferative activity of rat hepatic stellate cells in vitro. A strong association was found between serum immunoglobulin levels and hepatic fibrosis in patients with hepatitis C virus infection. Our objective was to determine if the same index could also be used in patients with chronic HBV infection. The records of 100 patients with biochemical, serological, virological and histological evidence of chronic HBV infection were reviewed for background factors and serum globulin and immunoglobulin levels. Mean (+/-SD) patient age was 44.0 +/- 14.7 years; 80 (80%) were male. Of the factors found to be significant on univariate analysis, the only significant predictors of severe hepatic fibrosis (stage > or = 2) on multivariate analysis were serum globulin level [odds ratio (OR) 5.97, 95% confidence intervals (CI) 1.82-19.53, P = 0.0004], platelet count (OR 0.98, CI 0.97-0.99, P = 0.001), and immunoglobulin G (IgG) level (OR 1.003, CI 1.000-1.007, P < 0.042) but not IgA, alkaline phosphatase, albumin or international normalized ratio. For each increase of 0.33 mg/dL in serum globulin, there was a 0.5 point increase in the stage of hepatic fibrosis. There appears to be a strong association between levels of serum globulin and IgG and extent of hepatic fibrosis in patients with chronic HBV infection. They can serve as noninvasive markers of hepatic fibrosis and, if confirmed, have important implications for the management of patients with chronic HBV infection.     

Serum measures of iron status and HFE gene mutations in patients with hepatitis B virus infection

Aim: We tested associations between HFE mutations and hepatitis B virus (HBV) infection. We also explored measures of total body iron status and their association with chronic HBV infection. Methods: Serum measures of iron status and HFE mutations (C282Y, H63D, and S65C) were assessed in 344 Iranian patients with chronic HBV infection (214 asymptomatic carriers, 130 patients with chronic progressive liver disease [CPLD]) and 302 controls. Results: Frequencies of HFE mutations did not differ between patients with chronic HBV infection and controls (C282Y: P=0.9, H63D: P= 0.8, S65C: P=0.9). By logistic regression, advanced hepatic fibrosis was associated with HFE H63D mutation (OR=13.1, P=0.006; 95% CI=2.0-84.1). Higher levels of serum ferritin and transferrin saturation were observed in patients with CPLD than in healthy controls (P=0.0001 and 0.01, respectively, adjusted for age and sex). None of the serum iron measures was related to liver fibrosis stage or necroinflammatory grade. Conclusion: Serum iron measures are associated with chronic progressive hepatitis B. Carriage of HFE mutations is not associated with the presence of chronic HBV infection or values of serum iron measures in this population, although HFE H63D is associated with more advanced hepatic fibrosis.     

FibroScan and ultrasonography in the prediction of hepatic fibrosis in patients with chronic viral hepatitis

Background  The aim of this study was to assess the diagnostic performances of liver stiffness measurement (LSM), ultrasonography (US) and their combined use in predicting the extent of hepatic fibrosis. Methods  Consecutive patients with chronic hepatitis B (HBV) or hepatitis C virus (HCV) infections, with indications for liver biopsy, were prospectively enrolled. LSM was performed on the same day as biopsy. US scores, including assessment of liver surface, liver parenchyma, intrahepatic vessels and spleen index, were used to assess the degree of hepatic fibrosis. The pathological findings were used as a reference standard and diagnostic accuracy was assessed and compared. Results  Three-hundred and twenty patients, including 199 men and 121 women, with a mean age of 50.8 years, were analyzed. There were 214 (66.9%) HCV patients, 88 (27.5%) HBV patients and 18 (5.6%) patients with both HCV and HBV. LSM correlated significantly with the hepatic fibrosis (F) scores, necro-inflammatory activity and US scores in multivariate analysis. The diagnostic accuracy of LSM is significantly superior to US, and equal to combined LSM with US, in the prediction of all HCV-related fibrosis scores. The cut-off value of LSM is 6 kPa for diagnosing F > =1, with a positive predictive value of 91%. Also, the cut-off value is 12 kPa for the prediction of cirrhosis, with a negative predictive value of 94%. Conclusions  LSM is useful for predicting hepatic fibrosis and excluding cirrhosis. A combination of LSM and US does not improve the accuracy in assessing hepatic fibrosis.     

戊型肝炎与慢性乙型肝炎重叠戊型肝炎病毒感染的临床特征比较

目的分析比较戊型肝炎与慢性乙型肝炎重叠戊型肝炎病毒感染患者的临床特征,并初步探索戊型肝炎慢性化问题。方法对66例戊型肝炎与37例慢性乙型肝炎重叠戊型肝炎病毒感染患者的临床资料进行回顾性分析比较及统计。结果慢性乙型肝炎重叠戊型肝炎病毒感染患者较戊型肝炎患者丙氨酸氨基转移酶(ALT)、天门冬酸氨基转移酶(AST)、总胆红素(TBIL)、直接胆红素(DBIL)升高水平及发生率无显著差异,而在白蛋白(A)、白蛋白/球蛋白(A/G)及凝血酶原活动度(PTA)降低与肝纤维化系列各项指标增高方面更突出,消化道症状更重。结论慢性乙型肝炎重叠戊型肝炎病毒感染后肝功能损害更严重,凝血酶原时间长,慢性肝病特征常见,但单纯戊型肝炎患者慢性化问题也值得重视。     

248例慢性乙型肝炎患者血清HBV DNA水平与肝组织HBsAg／HBcAg表达的相关性研究

目的 探讨慢性乙型肝炎患者血清HBV DNA水平与肝组织病理学损害和HBsAg／HBcAg表达的关系。方法 对248例慢性乙型肝炎患者进行肝穿刺活检,采用免疫组织化学法检测HBsAg和HBcAg,同时检测患者血清HBVDNA水平。结果 在肝脏炎症程度G1～G4四组患者之间血清HBV DNA水平无显著性差异（P〉0．05）,肝纤维化程度S1～S4四组患者之间血清HBV DNA水平也无显著性差异（P〉0．05）;在肝组织HBsAg表达强度-～＋＋＋四组患者之间血清HBV DNA水平无显著性差异（P〉0．05）,而肝组织HBcAg随血清HBV DNA水平的增高而表达增强。结论 慢性乙型肝炎患者肝组织炎症活动度和纤维化程度与血清HBV DNA水平无相关性。