Circulating intercellular adhesion molecule-1 in chronic hepatitis C patients with normal or elevated aminotransferase before and after alpha-interferon treatment

OBJECTIVES: Intercellular adhesion molecule-1 (ICAM-1) plays a fundamental role during liver inflammation. In fact, weak ICAM-1 expression is physiologically restricted to the endothelium of portal vessels and to sinusoidal lining cells, but it becomes markedly evident on sinusoidal lining cells and at the surface of hepatocytes during inflammatory liver diseases. The aim of this study was to evaluate the behaviour of soluble ICAM-1 (sICAM-1) in chronic hepatitis C (CH-C) patients with persistently normal aminotransferase in comparison with patients with CH-C and elevated aminotransferase, and its changes during alpha-interferon (IFN) therapy. Immunohistochemical localization of ICAM-1 was also performed on liver tissue specimens of both groups. METHODS: Sixty subjects were divided into 3 groups: group A included 19 patients with CH-C and persistently normal aminotransferase; group B included 21 patients with CH-C and persistently elevated aminotransferase levels, and group C included 20 healthy subjects representing the control group. The first two groups were treated with recombinant alpha-IFN 2b at a dose of 6 MU 3 times a week for 3 months and followed up with 3 MU 3 times a week for another 3 months. RESULTS: Baseline values of serum ICAM-1 in groups A and B were significantly higher than those in group C (p < 0.0001). The median baseline value of sICAM-1 in group A (525.0 ng/ml) was lower than that of group B (561.0 ng/ml), but the difference was not statistically significant. Furthermore, there was a trend toward higher ICAM-1 values as histological severity increased (Mantel-Haenszel chi(2) 8.8, p < 0.003). Post-treatment sICAM-1 serum values showed a marked decrease in both groups, but only among responder patients, while ICAM-1 levels were unchanged in non-responders. Immunohistochemical localization showed no staining for ICAM-1 in normal liver specimens, while there was a quite similar staining for ICAM-1 in the two groups of patients, consistent with an inflammatory process. CONCLUSIONS: This study shows that circulating ICAM-1 levels in most patients with CH-C and persistently normal aminotransferase are higher than those in a control group and the fact that ICAM-1 molecules are also expressed on the hepatocyte membrane suggests that they could play an important role, in association with other molecules, in the intercellular adhesion processes during the induction and maintenance phases of the immune response. In both groups, only patients responding to alpha-IFN therapy showed a marked decrease in serum ICAM-1 below baseline values.     

丙肝患者治疗前后HCV RNA与抗-HCV及丙氨酸氨基转移酶水平的分析

目的分析丙型肝炎患者治疗前血清HCV RNA、抗-HCV和丙氨酸氨基转移酶(ALT)水平及治疗后HCV RNA和ALT水平的变化规律。方法对87例丙型肝炎患者血清进行实时荧光定量法(PCR)检测HCV RNA、ELISA法检测抗-HCV和酶速率法检测ALT浓度水平,并对所得数据进行统计学分析。结果丙型肝炎患者血清抗-HCV抗体滴度显著高于健康对照组,大部分患者的ALT水平均有显著性升高;HCV RNA含量与ALT水平具有显著相关性(r=0.673,P0.01),而与抗-HCV的S/OD值无显著相关性(r=0.122,P0.05);在治疗早期,患者HCV RNA含量在第2天显著性下降,而ALT浓度呈一过性上升。结论在HCV诊断与疗效观察中,血清HCV-RNA、抗-HCV和ALT指标各有利弊,3者有机结合在正确诊断和预测肝脏损伤及早期疗效观察中具有重要的临床意义。     

慢性丙型肝炎患者血清甲状腺激素水平及甲状腺自身抗体的分析

目的探讨慢性丙型肝炎、代偿性丙型肝炎肝硬化、失代偿性丙型肝炎肝硬化时甲状腺激素水平的变化及甲状腺自身抗体存在状况。方法分别检测慢性丙型肝炎42例、肝硬化代偿期37例、肝硬化失代偿期36例、健康体检者30例的血清促甲状腺激素（TSH）、甲状腺素（T4）、三碘甲状腺原氨酸（T3）、游离甲状腺素（FT4）、游离三碘甲状腺原氨酸（FT3）、抗甲状腺过氧化物酶抗体（抗TPO）、抗甲状腺球蛋白抗体（抗TG）的含量。结果与正常对照组相比：T3,T4在各观察组均显著降低;FT3在肝硬化组,FT4在失代偿性肝硬化组显著降低;TSH在慢性丙型肝炎组降低,在肝硬化组升高;抗TPO、抗TG在各观察组均显著增高。结论慢性丙型肝炎患者甲状腺激素相关物质的检测可以帮助评估病情程度。     

病毒性肝炎患者血清中可溶性CD30检测的临床意义

目的检测病毒性肝炎患者血清中可溶性CD30（sCD30）的水平及其与血清丙氨酸氨基转移酶（ALT）的相关性及临床意义。方法采用酶联免疫吸附试验（ELISA）检测85例病毒性肝炎患者（包括43例乙型肝炎、19例丙型肝炎、23例戊型肝炎）血清中sCD30的水平,同时采用日立7600生化仪检测血清中ALT的水平。另取30例ALT正常的乙型肝炎病毒（HBV）携带者作为乙型肝炎对照,30名健康体检者作为正常对照。结果各型病毒性肝炎患者血清中sCD30和ALT水平均明显高于正常对照,ALT水平升高的乙型肝炎患者较ALT正常的HBV携带者血清中sCD30水平明显升高。各型病毒性肝炎患者血清中sCD30水平均与ALT呈正相关。结论病毒性肝炎存在Th2型细胞的活化,血清sCD30水平可以作为肝炎活动性的检测指标。     

慢性乙型肝炎患者血清补体C3b水平的研究

目的探讨慢性乙型肝炎患者血清补体C3b水平及其临床意义。方法选择乙型肝炎病毒（HBV）感染的慢性乙型肝炎患者140例,据患者血清中HBV e抗原（HBeAg）和丙氨酸氨基转氨酶（ALT）水平,将其分为6组：A组（HBeAg阳性,ALT正常）、B组（HBeAg阴性,ALT正常）、C组（HBeAg阳性,ALT轻、中度升高）、D组（HBeAg阳性,ALT高度升高）、E组（HBeAg阴性,ALT轻、中度升高）、F组（HBeAg阴性,ALT高度或重度升高）。另将20例健康者作为对照组。HBeAg采用酶联免疫吸附测定（ELISA）法,HBV-DNA采用荧光定量聚合酶链反应（PCR）法,ALT采用速率法,补体C3b采用ELISA-生物素亲和素抗体夹心法测定。结果 D组与F组患者血清C3b、ALT、天冬氨酸氨基转氨酶（AST）水平显著高于A、B、C、E组（P〈0.05）;而D组与F组比较,患者血清C3b、AST水平均无统计学差异（P〉0.05）。对照组受检者血清C3b水平显著低于A、B、C、D、E、F组（P〈0.05）。C3b水平与ALT、AST、HBsAg存在正相关（P〈0.05）,而与HBeAg和HBV-DNA无显著相关（P〉0.05）。结论补体C3b水平与HBV的感染及肝细胞损伤程度有关,而与病毒复制的活跃程度无关,可作为感染和预后的辅助检测指标。     

血清丙氨酸转氨酶正常的慢性丙型肝炎的治疗

丙型肝炎病毒（HCV）感染的流行较为广泛，呈全球性分布。慢性丙型肝炎患者如得不到及时和合理的治疗，可发展为肝硬化、肝细胞癌。对血清丙氨酸转氨酶（alanine aminotransferase，ALT）升高的慢性丙型肝炎患者的治疗早已取得共识，即应采取积极的抗病毒治疗；但对ALT正常的慢性丙型肝炎患者是否应该常规接受抗HCV治疗，长期以来一直存在分歧。本文对ALT正常的慢性丙型肝炎的流行病学、自然史和治疗等研究进展作简要的介绍。     

Monitoring depression in patients undergoing alpha-interferon and ribavirin therapy for hepatitis C.

Individuals with hepatitis C virus (HCV) constitute a growing segment of the US population, with most new infections attributable to intravenous drug use. Commonly, there is a 10- to 30-year delay from time of infection to diagnosis. Current treatment is with interferon, alone or in combination with ribavirin. A concerning side effect of both monotherapy and combination therapy is depression, which can become severe and lead to suicide. In patients with liver disease and those who have used intravenous drugs, depression is highest among those who are also positive for HCV. Use of a standardized short form depression self-rating tool would provide the advantages of increased accuracy in patient assessment, improved documentation, and cost-effective monitoring of depression in patients with HCV receiving interferon/ribavirin therapy. This article discusses the importance of screening and monitoring patients for depression as they undergo treatment for HCV infection with interferon alone or in combination therapy with ribavirin.     

Detection of replicative intermediates of hepatitis C viral RNA in liver and serum of patients with chronic hepatitis C.

The hepatitis C virus is a positive stranded hepatotropic RNA virus. We describe a method of detecting positive and negative strands of hepatitis C viral RNA using the polymerase chain reaction. We tested serum and liver tissue from nine patients with chronic hepatitis C. The positive RNA strand of HCV was detected in the sera and livers of all nine, the negative strand was detected in the livers of eight (89%), and in the sera of five (55%). Titers of both strands of HCV RNA were determined by serial endpoint dilutions. The amount of the negative strand in the serum and liver was usually 10-100 times less than the positive strand. Predigestion of serum with ribonucleases did not alter the detection of the negative strand. This suggests that the negative strand found in the serum may be protected from digestion by being associated with virions.     

甲状腺功能亢进患者治疗前后血清脂联素和游离脂肪酸水平的变化

目的分析甲状腺功能亢进(简称甲亢)患者治疗前后血清脂联素(adiponectin,ADPN)和游离脂肪酸(free fatty acid,FFA)水平变化,探讨其与甲亢发生、发展过程中的相关性。方法对甲亢患者初诊组32例,复诊组32例(经他巴唑治疗时间大于1年),对照组20名(健康体检人群),进行血清ADPN、FFA、空腹血糖(fastingblood-glucose,FBG)和糖化血红蛋白(glycolated hemoglobin,GHb)检测分析。结果 (1)血清ADPN和FFA水平:甲亢患者明显高于对照组,且治疗前明显高于治疗后(P<0.05);(2)FBG水平:甲亢患者明显高于对照组(P<0.05),且其治疗前后差异无统计学意义(P>0.05);(3)GHb水平:甲亢患者治疗前后与对照组均差异无统计学意义(P>0.05)。结论 (1)甲亢治疗前后ADPN和FFA水平存在差异,甲亢的药物治疗对患者血清ADPN和FFA水平有下调作用,其产生及下降的机制尚有待进一步的研究。(2)检测血清ADPN和FFA水平对甲亢患者的诊断和预后具有重要价值。     

Association of human platelet antigens polymorphisms with the levels of serum fibrosis marks in chronic hepatitis C patients

BackgroundHost genetic polymorphisms influence the fibrosis progression of chronic hepatitis C (CHC) patients. Previous studies have shown the association of human platelet antigens (HPAs) polymorphisms with CHC. However, little is known regarding the association of HPAs polymorphisms with the fibrosis progression of CHC. The aim of this study was to determine the association of HPA -2, -3, -5 and -15 polymorphisms with the levels of serum fibrosis marks in CHC patients.MethodsThe HPA -2, -3, -5 and -15 were genotyped by 5ˊ-nuclease assay in 211 CHC patients, while the serum concentration of hyaluronic acid (HA), collagen IV (CIV), amino-terminal pro-peptide of type III procollagen (PIIINP), and laminin (LN) from the same samples were measured by time resolved fluorescence immunoassay.ResultsThe level of serum LN was significantly lower in CHC patients with HPA-15aa genotype compared to those with HPA-15ab/bb (P = 0.032) but did not differ among HPA-2, -3 and -5 genotypes. There were no difference in HA, CIV and PIIINP levels among HPA-2, -3,-5 and -15 genotypes.ConclusionsThis study demonstrates that HPA-15 aa polymorphism is associated lower serum LN in CHC, which suggests that HPA -15 aa may be involved in the fibrosis progression of CHC.     

老年抑郁症患者治疗前后血清脑源性神经营养因子水平动态观察

目的 探讨5-羟色胺再摄取抑制剂治疗老年抑郁症患者的临床疗效及治疗前后血清脑源性神经营养因子水平的变化,为研究老年抑郁症的发生机制以及抗抑郁治疗的生物学指标提供依据.方法 将35例老年抑郁症患者设为病例组,抽取同期健康体检者50名设为对照组.病例组口服5-羟色胺再摄取抑制剂治疗,观察8周;于治疗前及治疗8周末采用汉密顿抑郁量表评定临床疗效.病例组于治疗前及治疗8周末,对照组于入组时检测血清脑源性神经营养因子水平,并进行对比分析.结果 (1)病例组治疗8周末汉密顿抑郁量表评分较治疗前显著下降(t=13.02,P＜0.01),显效率71.4%,总有效率88.6%.(2)病例组治疗后血清脑源性神经营养因子水平较治疗前显著升高(t=6.94,P＜0.01),治疗前显著低于对照组(t=8.02,P＜0.01),治疗后与对照组差异无显著性(t=1.62,P＞0.05).(3)病例组不同性别患者治疗前后血清脑源性神经营养因子水平差异均无显著性(P＞0.05).(4)病例组治疗前血清脑源性神经营养因子水平与病程、年龄、治疗前汉密顿抑郁量表评分均无明显相关性(P＞0.05).结论 脑源性神经营养因子可能参与老年抑郁症的病因与治疗机制,并可能成为预测老年抑郁症抗抑郁疗效的生物学指标之一.     

Detection of hepatitis C virus RNA in patients with chronic hepatitis C virus infections during and after therapy with alpha interferon.

In 24 patients with hepatitic C virus (HCV) infection who participated in a randomized trial with alpha 2B interferon, HCV RNA analysis by the polymerase chain reaction with two separate primer sets was performed at weeks 0, 4, and 24 and during a follow-up period of 6 to 9 months. Prior to therapy all patients were HCV RNA positive. During therapy, HCV RNA decreased to an undetectable level (< 1 chimpanzee infectious dose per ml) in nine patients at week 4. After week 4, no additional cases of HCV RNA disappearance (< 1 chimpanzee infectious dose per ml) were observed. During follow-up, HCV RNA could not be detected in four of the six patients with a sustained alanine aminotransferase response. These results suggest the probable predictive value of HCV RNA levels for detecting the failure of therapy in an early stage of HCV infection.     

Cytokine system in patients with chronic hepatitis C during treatment with interferon-alfa

AIM: To study changes in serum levels of interleukine-1 beta (IL-1b), IL-6, TNF-alpha (TNFa), HM-HMF and TFR-1 beta (TFR-1b), expression of surface antigens CD14 and CD95 on blood monocytes from patients with chronic hepatitis C (CHC) treated with interferon-alpha (INFa). MATERIAL AND METHODS: Examinations covered 25 CHC patients and 25 healthy controls. Concentrations of proinflammatory cytokines and growth factors in blood serum were measured with ELISA (kits by "R&D systems", USA). CD14 and CD95 antigen expression on monocytes of venous blood were studied using flow cytoflowmeter (Partes, USA) before and after a 12-week course of INFa. RESULTS: Before INFa treatment CHC patients had significantly elevated serum concentrations of TNFa, HM-KSF and TFR-1b. Coexpression of antigens CD14+ and CD95+ was found on 61% of blood monocytes. Three-month INFa treatment lowered levels of TNFa, GM-KSF and CD95+ expression on monocytes as well as TFR-1b concentration in the serum which correlated with a positive trend in the standard clinicolaboratory and virusological indices in the examinees. CONCLUSION: Changes in serum indices of proinflammatory cytokines and growth factors, in expression of CD95 on blood monocytes from CHC patients treated with INFa show an important role of cytokines system activation and mechanisms of programmed cell death in pathogenesis of chronic HCV infection.     

Autoimmunity against pancreatic islets and other tissues before and after interferon-alpha therapy in patients with hepatitis C virus chronic infection

OBJECTIVE: The aim of the study was to investigate the prevalence of clinical and latent autoimmune diseases in Italian patients with hepatitis C virus (HCV) chronic infection before and after treatment with interferon-alpha (IFN-alpha). RESEARCH DESIGN AND METHODS: The evidence of clinical autoimmune disease and the presence of autoantibodies were assessed in 70 patients with HCV chronic infection. Autoantibodies to islet cell (ICA), glucagon-producing cells (GCA), parietal cell (PCA), adrenal cortex (ACA), adrenal medulla (AdMA), nuclei (ANA), liver-kidney microsomal (LKM-Ab), mitochondrial, and smooth muscle (SMA) were tested using the classic indirect immunofluorescence technique. Autoantibodies to GAD (GADAb), second islet cell autoantigen (IA2-Ab), and insulin (IAA) were tested by radioimmunoassay and thyroid microsomal autoantibodies (TMHA) and thyroglobulin autoantibodies (TGHA) were assessed by hemoagglutination test. RESULTS: None of the 70 patients studied showed evidence of clinical disease before treatment with IFN-alpha. However, 1 (1.4%) patient was positive for ICA, 2 (2.8%) were positive for GCA, 2 (2.8%) for GADAb, 5 (7.1%) for PCA, 2 (2.8%) for ANA, 3 (3.7%) for SMA, 4 (5.7%) for TMHA, and 2 (2.8%) for TGHA. These frequencies were not significantly different when compared with healthy control subjects. There were 29 (41%) patients who were positive for IAA at low titers compared with 2% of the control subjects (significantly different P < 0.0001). ICA titers of one patient positive for ICA/GADAb increased during the IFN-alpha therapy, and the patient developed type 1 diabetes 5 months after the beginning of treatment. IAA levels did not change during the course of treatment, and none of the IAA+ patients developed diabetes. Thyroid autoantibody titers increased in 3 of the 4 initially positive patients, with 1 patient becoming positive and 2 thyroid antibody-positive patients developing overt hypothyroidism during IFN-alpha treatment. PCA titers increased in 1 of 5 positive patients. Antibodies to other autoantigens did not change during the course of treatment. CONCLUSIONS: We have not found an increased frequency of clinical or latent autoimmune diseases in patients with chronic HCV infection. However, this study suggests that screening patients for autoantibodies (in particular, thyroid and pancreas) before and during IFN-alpha therapy may be useful in assessing the risk of patients developing autoimmune disease.     

慢性丙型肝炎病毒感染者血清中自身抗体检测结果分析

目的通过观察慢性丙型肝炎病毒（HCV）感染者血清中自身抗体的变化情况,探讨自身免疫反应在慢性丙型肝炎中的作用。方法用间接免疫荧光法对89例慢性HCV感染者血清测定抗核抗体（ANA）、可提取性核抗原抗体（ENA）、抗线粒体抗体（AMA）、抗平滑肌抗体（SMA）,并根据荧光反应模式判定结果。结果慢性HCV感染者89例中有34例出现自身抗体,检出率为38．2％,高于慢性乙型肝炎自身抗体检出率13．8％（P〈0．05）,也高于健康对照组检出率2．1％（P〈0．01）。其中慢性HCV感染者ENA阳性率为14．6％。结论HCV感染可触发机体自身免疫反应,自身免疫可能是HCV感染后组织损伤的重要因素。