血液透析患者与丙型肝炎的诊断及治疗特征

血液透析（Hemodialysis,HD）患者是丙型肝炎病毒（HCV）感染的易感人群,HCV可发展成慢性肝炎,最后引起肝硬化,严重者可称为肝癌,严重影响HD患者的生活质量和生存率,因此HCV是血液透析患者发病和致死的一个重要病因,我们旨对HD患者感染HCV的流行病学特征、实验窒诊断方法、治疗措施等进行综述。     

α1干扰素治疗慢性丙型肝炎的长期疗效及其与病毒血症关系

为观察α１干扰素（ＩＦＮａ１）治疗慢性丙型肝炎的长期疗效及其与ＨＣＶ病毒血症的关系,我对４２例经ＩＦＮａ１治疗的慢丙肝进行了长达３年的随访观察,并同时采用聚合酶链反应（ＰＣＲ）检测血清ＨＣＶＲＮＡ,现将结果报告如下。１临床资料１．１一般资料所选的４２...     

幽门螺杆菌毒力基因分型和宿主遗传多态性与胃病关系研究进展

幽门螺杆菌(Helicobacter pylori)感染能导致慢性胃炎、消化性溃疡、胃粘膜相关的淋巴样组织(Mu-cosa-associated lymphoid tissue,MALT)淋巴瘤和胃腺癌等疾病的发生。1994年世界卫生组织国际癌症研究中心(IARC)将H.pylori列为胃癌第一级因子。H.pylori感染引起的不同临床结局主要与H.pylori致病因子和宿主遗传易感性有关,大部分重大疾病发生在特定的细菌毒力因子(如cagA,vacA)与易感宿主遗传背景共同存在时。文章综述了H.pylori菌株的毒力基因的分型和宿主的遗传多态性对胃病发生的影响。     

TPOAbIgG亚型在慢性丙型肝炎抗病毒治疗中的分布及其意义

目的:探讨甲状腺功能正常但甲状腺过氧化物酶抗体(TPOAb)阳性的慢性丙型肝炎(CHC)患者干扰素治疗前后血清中TPOAb Ig G1、Ig G2、Ig G3、Ig G4的分布及其意义。方法:收集甲状腺功能正常但TPOAb阳性的CHC患者46例,按应用聚乙二醇干扰素(Peg-IFNα-2a)联合利巴韦林(RBV)抗病毒治疗过程中甲状腺功能(包括FT3、FT4、TSH)情况分为正常组和异常组。采用酶联免疫吸附测定法(ELISA)检测治疗前后患者血清中TPOAb Ig G各亚型的百分结合率,比较两组患者治疗前后TPOAb Ig G亚型的变化,进而分析该变化与合并甲状腺功能异常的相关性。结果:146例TPOAb阳性的CHC患者治疗过程中甲状腺功能异常者为35例,占76.09%,其中甲状腺功能减退(甲减)19例,占41.30%,甲状腺功能亢进(甲亢)3例,占6.52%,亚临床甲减12例,占26.09%,亚临床甲亢1例,占2.17%。2异常组抗病毒治疗前后TPOAb Ig G2亚型阳性率均高于正常组(P值分别为0.005和0.036),TPOAb Ig G1、Ig G3、Ig G4阳性率在正常组和异常组间的差异均无统计学意义(P0.05)。结论:伴TPOAb阳性CHC患者应用干扰素治疗前检测其血清中TPOAb Ig G2亚型可预示抗病毒治疗过程中甲状腺功能异常,尤其是甲减及亚临床甲减发生的可能性,有助于指导临床监测和及时检出甲状腺功能异常。     

恶性肿瘤的个体化治疗

当今所提的个体化医学一词最早见于1956年美国德州大学生化研究所所长威廉姆斯所著的《生化学个体性》一书,但一直未引起足够的重视,仅个别文献有所提及。直到2001年,基因组学工作的巨大进展才使人们重新认识到个体化医学的重要性,一个完全以每一位患者为中心的现代个体化医学的新时代才真正逐渐开始。     

延边地区丙型肝炎患者合并TT病毒感染的检测

检测丙型肝炎患者血清标本中的TT病毒 (transfusiontransmittedvirus,TTV) ,了解延边地区丙型肝炎患者合并TTV感染状况。采用ELISA检测抗TTVIgG和巢式PCR检测丙型肝炎病毒 (HCV)感染患者血清中TTVDNA。采用全自动生化分析仪检测患者血清谷氨酸氨基转移酶 (ALT)和谷氨酸草酰乙酸氨基转移酶 (AST)。 4 5例丙型肝炎患者抗TTVIgG阳性率为 37.8% (17/45 ) ,巢式PCR阳性率为 4 2 .2 % (19/45 )。延边地区HCV感染患者重叠感染TTV较常见。     

人乳头状瘤病毒分型及病毒载量与宫颈病变的研究进展

宫颈癌作为目前妇女最常见的恶性肿瘤,新发病例在全球范围内仍处于上升趋势。已有实验证明,HPV感染是宫颈癌发生发展的必要条件。然而不同分型及其病毒载量高低仍会影响诊断率,从而影响病情,使之发展为持续性感染,最终演变为癌前病变或宫颈癌。目前,研究者对于高危型HPV病毒载量与宫颈病变之间是否存在依存关系尚存争议。研究表明,高病毒载量可能成为预测宫颈癌前病变进展的指标,然而对于病理诊断明确的宫颈癌患者而言,病毒载量并不能代表病理分期。本文综述了人乳头状瘤病毒,不同基因分型,病毒载量等因素对于宫颈病变及宫颈癌的相关性的近年研究进展,希望有助于指导临床工作。     

艾滋病合并丙型肝炎的抗病毒治疗临床观察

目的:观察艾滋病合并丙型肝炎的抗病毒治疗效果并回顾总结艾滋病合并丙肝的临床研究进展。方法:选择艾滋病合并丙型肝炎的患者33例,采用HAART疗法及干扰素联合利巴韦林治疗的方法,治疗4周后观察以上患者谷丙转氨酶(ALT)、谷草转氨酶(AST)、谷氨酸脱氢酶(GLDH)、总胆红素(TBIL)、白蛋白(ALB)和HCV-RNA检查结果,同时总结艾滋病合并丙肝的临床研究进展。结果:治疗4周后,以上患者ALT、AST、GLDH、TBIL、ALB和HCV-RNA阳性患者显著改善,治疗前后比较差异具有(高度)统计学意义(P<0.05,P<0.01)。结论:在对艾滋病合并丙型肝炎充分了解的同时,积极采取抗病毒治疗措施,可延缓疾病的发展。     

应用RNAi技术治疗HBV的研究进展

乙型肝炎病毒（hepatitis B virus,HBV）感染是一种全球性的健康问题。全球大约有4亿HBV慢性感染患者,尤其在中国,感染率高达9.8%。RNAi（RNA interference）技术具有特异性地抑制,甚至关闭基因表达的特点,在治疗HBV感染方面有很大的应用前景。近年来,研究者针对HBV基因设计或筛选有效siRNA靶点做了很多研究,最近还出现了针对与HBV代谢相关的宿主基因设计或筛选siRNA靶点治疗HBV的新策略。该文对RNAi技术在HBV治疗方面取得的研究进展作一综述。     

Pathology of hepatitis C

Abstract: The basic morphological patterns of acute or chronic viral hepatitides are very similar, irrespective of the causative hepatitis viruses A, B, C, D or E. In addition, however, acute and chronic hepatitis C shows characteristic, although not pathognomonic histological changes. These consist of lymphoid aggregates in portal tracts, sometimes with germinal centers, damage of bile duct epithelium, and micro- or macrovesicular steatosis of hepatocytes. A combination of two of these three characteristic alterations is seen in over half of the patients with chronic hepatitis C and is helpful in the histological diagnosis of the disease.     

The natural course of chronic hepatitis C

Abstract: In 1988, investigators from the Chiron Company (USA) detected the non-A, non-B agent and named it hepatitis C virus (HCV). An anti-HCV antibody assay (ELISA) and subsequently confirmation tests (immunoblot and polymerase chain reaction) were developed. HCV exposure results in a chronic infection in a majority of cases. This chronic infection is associated with slowly progressive chronic liver disease. Chronic HCV infection is, like HBV, also associated with the development of hepatocellular carcinoma. Most HCV carriers are infected by parenteral routes. Intravenous drug users have the highest risk of becoming infected. Intrafamiliar spread is seen in certain parts of the world but sexual and perinatal transmission does not play an important role in spreading the infection. Antiviral therapy (alpha-interferon) in patients with chronic hepatitis C will normalize liver function tests in about 25% of the cases.     

Association between polymorphisms in OAS2 and CD209 genes and predisposition to chronic hepatitis C in Russian population

Chronic hepatitis C is a severe liver disease caused by positive-strand RNA virus. Previously, we reported an association between seven single nucleotide polymorphisms (SNPs) in four innate immunity genes (OAS2, OAS3, CD209, and TLR3) and human predisposition to tick-borne encephalitis, caused by a virus from the same Flaviviridae family, in a Russian population. Currently, genotype and allele frequencies for these SNPs were analyzed in 75 chronic hepatitis C patients and compared with the population control (269 Novosibirsk citizens). Data obtained suggest that the OAS2 rs1293762 and CD209 rs2287886 SNPs are associated with predisposition to chronic hepatitis C in Russian population.     

Single nucleotide polymorphism rs1800872 in the promoter region of the IL10 gene is associated with predisposition to chronic hepatitis C in Russian population

Previously, we studied an association of two IL28B gene single nucleotide polymorphisms (SNPs) and three IL10 gene SNPs with predisposition to tick-borne encephalitis in a Russian population. In this study, a possible involvement of these SNPs in the development of predisposition to chronic hepatitis C (caused by structurally similar, related virus from the Flaviviridae family) was investigated in the same population. Only the IL10 promoter rs1800872 SNP was associated with predisposition to chronic hepatitis C. This SNP seems to be a common genetic marker of predisposition to two diseases caused by hepatitis C and tick-borne encephalitis viruses in Russian population.     

Interferon therapy in chronic hepatitis C virus infection

Abstract: Antiviral treatment of chronic hepatitis C with interferon is reviewed. Alpha-interferon, both recombinant alpha-2a, -2b and human lymphoblastoid interferon given at a dose of ≥3MU t.i.w. for 6–12 months will result in normalisation of ALT levels complete response) in some 50–60% of treated patients with chronic hepatitis C virus (HCV) infection. Approximately half of the complete responders to interferon will relapse within 6 months once treatment is withdrawn (non-sustained response). Longer treatment schedules (6 vs. 12 months) seem to diminish the relapse rate and increase the percentage of sustained response. In patients with sustained response to interferon treatment with continuously normal ALT levels ≥6 months after treatment stop a concomitant eradication of the viraemia is usually seen, whereas a non-sustained or non-response to interferon usually will indicate a continuous viraemia. Factors predictive of a favourable response are low pretreatment HCV RNA levels in serum, genotypes other than type II according to Okamoto, short disease duration, female gender and less pronounced liver damage, whereas high serum HCV RNA levels, having genotype II and cirrhosis, are predictive of a less favourable response. Patients with a sustained response and eradication of the viraemia will also improve their liver inflammation with diminishing scores for portal inflammation, piecemeal necrosis, lobular inflammation and also fibrosis after treatment. For non-responders and non-sustained responders to interferon, ribavirin especially in combination with interferon will offer some hope for the future.     

Osteopontin gene polymorphisms as predictors for the efficacy of interferon therapy in chronic hepatitis C Egyptian patients with genotype 4

This study aimed to determine the relationship between osteopontin gene polymorphisms and its protein level and the efficacy of interferon‐based therapies in Hepatitis C virus (HCV) patients. Hundreds HCV patients genotype 4, treated with pegylated interferon alfa‐2b plus ribavirin and 60 healthy subjects were enrolled. All individuals were subjected to clinical and laboratory parameters, including hepatitis markers and HCV quantitation by real‐time polymerase chain reaction. Single nucleotide polymorphisms (SNPs) of osteopontin (OPN) gene (nucleotide ?155, ?443 and ?1748) were analysed by direct sequencing in addition to estimation of serum level of OPN. SNP at ?443 (C/C versus C/T, T/T) was found to represent predictors for treatment response by univariate logistic regression analysis. OPN serum level was independent predictors for treatment response by both univariate and multivariate logistic regression analysis. SNP at nucleotide ?443 and serum OPN protein levels could be used as useful markers to predict the efficacy of treatment. Copyright © 2013 John Wiley & Sons, Ltd.     

Increased serum oxysterol concentrations in patients with chronic hepatitis C virus infection

Oxidative stress and dysregulated cholesterol metabolism are characteristic features of chronic hepatitis C virus infection (CHC). Therefore, we analyzed serum oxysterol profiles in CHC patients and examined the significance of oxysterols in CHC. The concentrations of 7α-hydroxycholesterol, 4β-hydroxycholesterol and 25-hydroxycholesterol as determined by LC–ESI–MS/MS were significantly elevated by +236%, +29% and +44%, respectively, in CHC patients compared with controls. Moreover, the elevated levels were significantly decreased by anti-viral therapy using PEGylated-interferon and ribavirin for 3 months. In contrast, 24S-hydroxycholesterol, 27-hydroxycholesterol and 7α-hydroxy-4-cholesten-3-one concentrations were not affected by CHC or anti-viral treatment. These results suggest that some oxysterols that are elevated in CHC are produced by cholesterol autoxidation due to oxidative stress or inflammation in the liver. Oxysterols may represent novel targets for the inhibition of disease progression and the prevention of hepatocarcinogenesis in CHC patients.     

病毒性肝炎树鼩动物模型研究与建模策略

病毒性肝炎是由肝炎病毒引起的肝脏疾病。在我国,病毒性肝炎高度流行,其中又以乙型肝炎病毒(Hepatitis B virus,HBV)和丙型肝炎病毒(Hepatitis C virus,HCV)危害较大。动物模型是研究疾病感染与发病机制,进行药物与疫苗研究的必要工具。目前病毒性肝炎实验动物模型的研究已取得长足的发展,主要集中于病毒在动物体内的感染特性及发病规律方面。本文仅就病毒性肝炎动物模型,尤其乙型、丙型肝炎树鼩动物模型的研究及建模策略进行综述。     

Ferritin and liver fibrosis among patients with chronic hepatitis C virus infection

IntroductionIn chronic hepatitis C virus (HCV) infection there is increased iron absorption leading to iron overload, a fact that may promote ferritin synthesis. Theoretically, increased ferritin should promote ongoing liver fibrosis but disparate results have been described.ObjectiveWe analyze the behavior of iron metabolism- related variables, comparing them with fibrosis and inflammatory activity in liver biopsy in HCV infected patients.Patients and MethodsWe analyzed among 90 HCV patients subjected to liver biopsy prior to antiviral treatment the relationships of serum levels of iron, ferritin, transferrin, transferrin saturation index (TSI) and total iron binding capacity (TIBC) with liver fibrosis and histological severity, assessed by Metavir-f, Metavir-a and Knodell indices, as well as with liver function, and also compared the aforementioned iron metabolism- related variables with 34 controls.ResultsPatients showed higher values of sideremia (T = 2.04; p = 0.044) and transferrin (T = 2.29; p = 0.004) compared with controls; but not ferritin, that was significantly higher among the 33 patients who also consumed alcohol (Z = 2.05; p = 0.041). Most patients showed a well preserved liver function (86 cases, Child A). Patients with Child B or C showed higher ferritin levels (Z = 2.68; p = 0.007) and TSI (Z = 2.41; p = 0.016), but lower transferrin and TIBC (Z = 3.25; p = 0.001) than Child A patients. Transferrin and TIBC were directly related to albumin (ρ = 0.24; p = 0.026), whereas bilirubin showed direct relationships with iron (ρ = 0.25; p = 0.016), TSI (ρ = 0.39; p < 0.001) and ferritin (ρ = 0.36; p < 0.001). Both ferritin (ρ = −0.22; p = 0.04) and TSI (ρ = −0.25; p = 0.016) were related to platelet count. No relationships were observed between iron variables and Knodell index, but serum iron, serum transferrin, and TSI were directly related to Metavir-f score (ρ = 0.28; p = 0.009, ρ = 0.22; p = 0.044, and ρ = 0.22; p = 0.044, in this order).ConclusionAlterations of iron related variables are relatively subtle in our series of 90 well compensated HCV patients. Serum ferritin was not related to liver fibrosis and increases only when alcoholism co-exists with HCV infection.     

联合疗法对慢性乙型肝炎患者红细胞免疫功能的影响

目的观察拉米夫定与氧化苦参碱单用及联合治疗对慢性乙型肝炎(CHB)患者红细胞免疫功能的影响.方法 77例CHB患者随机分成拉米夫定组、氧化苦参碱组和两者联合治疗组,分别对其红细胞膜CD35、CD44s分子定量、红细胞天然免疫粘附功能(CR1分子粘附活性)、红细胞CR1分子密度相关基因型进行测定.结果各组CHB患者红细胞粘附肿瘤细胞能力治疗后较治疗前明显上升(P＜0.05);3组药物对CHB患者红细胞CR1和CD44s分子数量有明显提高作用(P＜0.01),联合组最显著;77例CHB患者治疗前后CR1分子密度相关基因多态性表达型别比率无变化,但CR1分子数量发生明显变化(P＜0.05).结论联合疗法可明显提高CHB患者红细胞免疫功能.