树突状细胞表面特异性非整联蛋白同源物基因多态性与丙型肝炎病毒感染的相关性

目的 研究丙型肝炎患者树突状细胞表面特异性非整联蛋白同源物(DC-SIGNR)外显子4基因颈区重复序列的遗传多态性分布,探讨DC-SIGNR基因多态性与HCV病毒基因分型及HCV载量的关系. 方法采用PCR结合DNA测序对268例丙型肝炎患者DC-SIGNR重复序列多态性进行基因分型和测序分析,同时检测患者的HCV病毒载量及HCV病毒基因分型.组间两两比较用LSD法.结果 DC-SIGNR基因型或等位基因与HCV基因分型的相关性不显著.HCV载量携带7等位基因的患者为(4.6722±1.9766)log10拷贝/ml,携带9等位基因的患者为(5.3073±1.6795)log10拷贝/ml,P=0.036,两组差异有统计学意义.7/7基因型的患者HCV载量水平为(4.5974±2.0067)log10拷贝/ml,9/7基因型的患者组为(5.2771±1.8587)log10拷贝/ml,P=0.025,两组差异有统计学意义.提示HCV更易与携带较长DC-SINGR等位基因的患者结合.结论 DC-SIGNR遗传多态性可能与HCV在个体内的复制有关,但与HCV基因分型不相关.     

树突状细胞表面特异性非整联蛋白外显子4在中国裔丙型肝炎患者中的遗传多态性

目的探讨树突状细胞表面特异性非整联蛋白（DC—SIGN）及其同源物（DC-SIGNR）外显子4遗传多态性在中国裔丙型肝炎患者中是否存在遗传易感性。方法采用PCR结合DNA测序对300例丙型肝炎患者和520名健康人的DC-SIGN和DC-SIGNR外显子4重复序列多态性进行基因分型和测序分析。结果DC—SIGN外显子4基因型与等位基因频率在丙型肝炎患者和健康人群间差异无统计学意义（P〉0．05）。DC-SIGNR外显子4等位基因的频率差异也无统计学意义（P〉0．05）；但9／5基因型分布频率在丙型肝炎患者和健康人群间的差异有统计学意义（P〈0．05）。结论DC-SIGN外显子4遗传多态性与HCV感染易感性无明显相关性；9／5基因型DC-SIGNR外显子4在丙型肝炎患者中的分布频率较高，可能与HCV感染的易感性相关，值得进一步研究。     

干扰素联合利巴韦林治疗慢性丙型肝炎长期随访中的复发及其影响因素

目的 观察和分析慢性丙型肝炎患者经干扰素联合利巴韦林治疗获得应答后的复发情况及其影响因素.方法 收集长期随访资料完整的慢性丙型肝炎患者资料纳入回顾性统计分析.治疗方案为聚乙二醇干扰素或普通干扰素联合利巴韦林治疗,疗程依基因型分别为24周(非1b型)或48周(1b型).主要观察指标为血清HCV RNA载量,影响因素纳入了年龄、性别、HCV基因型、基线HCV RNA载量及干扰素类型.计量资料用t检验,计数资料用x2检验,影响因素的分析用二分类logistic回归分析.结果 146例慢性丙型肝炎患者抗病毒治疗结束后平均随访(33.5±16.4)个月,最短12个月,最长85个月,累计复发率为14.8％.随访第1～6个月内复发概率最大,为8.9‰第7～12个月为1.4％、第13～18个月为1.4％、第19～24个月为1.6％、第25～30个月为1.1,30个月后未见复发.65.0％(13/20)的复发病例发生于治疗结束后6个月内,但之后2年内仍有35.0％(7/20)病例复发.HCV基因1b型和非1b型患者复发率分别为20.4％和12.2％,两组比较,差异无统计学意义(P＞0.05).复发和未复发患者平均基线HCV RNA载量分别为(6.86±1.01)log10拷贝/ml和(6.60±1.21)log10拷贝/ml,两组比较,差异无统计学意义(P＞0.05);聚乙二醇干扰素α-2b,聚乙二醇干扰素α-2a及普通干扰素α治疗后复发率分别为12.1％、14.0％及15.0‰组间比较,差异无统计学意义(P＞0.05);复发患者的平均年龄为(46.15±11.89)岁,高于未复发患者的(37.41±10.65)岁,两组比较,差异有统计学意义(t=3.352,P=0.001).结论 接受病毒基因型指导的标准抗病毒方案的患者,只有年龄与复发显著相关,高龄患者容易复发.基因型指导的抗病毒方案基本上消除了病毒因素对治疗应答的影响.     

利巴韦林的应用时间和剂量与慢性丙型肝炎抗病毒疗效的关系

目的 探讨利巴韦林应用时间和剂量与慢性丙型肝炎抗病毒疗效之间的关系. 方法 收集69例聚乙二醇干扰素(Peg-IFN) α-2a联合利巴韦林治疗过程中的血红蛋白(HGB)降至100g/L的慢性丙型肝炎患者资料,将其分为2组:严格调整剂量组35例(简称限制组)和放宽调整剂量组34例(简称放宽组:当HGB≤80 g/L时减量,HGB≤60 g/L时停药),观察两组持续病毒学应答(SVR)、复发率、不良反应发生率等.应用独立样本的t检验、配对计数资料的x2检验等方法进行统计学分析. 结果 放宽组的持续病毒学应答明显高于限制组(91.17％比74.29％,x 2=3.425,P=0.048);继续随访观察至停药后2年,放宽组中有2例出现复发,限制组有6例出现复发,复发率差异有统计学意义(23.07％比6.45％,x 2=4.239,P=0.038);放宽组出现重度贫血及心脑血管事件的比例高于限制组,但差异无统计学意义(P＞ 0.05).对放宽组进行了亚组分析结果显示,基线HCV RNA＜5 log10拷贝/ml时,较基线HCV RNA ＞5 log10拷贝/ml的患者SVR明显升高(100％比76.92％,x2 =5.315,P=0.021),非基因1型HCV感染的患者利巴韦林达到足疗程后的SVR较基因1型的患者高(100％比70％,x2=7.897,P=0.005).结论 对采用Peg-IFN α-2a联合利巴韦林治疗慢性丙型肝炎过程中发生贫血者,放宽利巴韦林剂量调整指征可提高患者的持续病毒学应答,减少丙型肝炎复发率,并未明显增加利巴韦林的不良反应.对于病毒载量较低、非基因1型HCV感染的患者更适宜放宽利巴韦林剂量调整指征.     

慢性乙型肝炎患者HBVDNA载量与肝组织炎症及纤维化程度的相关性分析

目的研究慢性乙型肝炎(CHB)患者血清HBV DNA载量与肝组织炎症及纤维化程度间的相关性。方法将169例CHB患者根据血清HBeAg分为HBeAg阳性组(110例)和HBeAg阴性组(59例),回顾性分析血清HBV DNA载量与肝组织病理炎症分级、纤维化分期之间关系。结果 HBeAg阳性组与HBeAg阴性组血清HBV DNA载量分别为(6.9±1.3)log10拷贝/ml和(4.7±1.8)log10拷贝/ml,两组比较差异有统计学意义(P=0.024)。HBeAg阳性组患者肝组织炎症活动度G1组为9例、G2组为80例、G3~4组为21例,其血清HBV DNA载量分别为(5.7±1.4)log10拷贝/ml、(6.4±1.8)log10拷贝/ml、(7.2±1.1)log10拷贝/ml,3组患者血清HBV DNA载量比较,差异无统计学意义(P=0.069)。肝组织纤维化程度S1组为28例、S2组为50例、S3~4组为32例,其血清HBV DNA载量分别为(6.9±1.1)log10拷贝/ml、(6.9±1.4)log10拷贝/ml、(6.8±4.2)log10拷贝/ml,3组患者血清HBV DNA载量比较,差异无统计学意义(P=0.079)。HBeAg阴性组患者肝组织炎症活动度G1组为6例、G2组为19例、G3~4组为34例,其血清HBV DNA载量分别为(2.2±1.9)log10拷贝/ml、(4.9±1.5)log10拷贝/ml、(5.4±1.8)log10拷贝/ml,3组患者血清HBV DNA载量比较,差异有统计学意义(P=0.014);肝组织纤维化程度S1组为12例、S2组为30例、S3~4组为17例,其血清HBV DNA载量分别为(2.6±4.1)log10拷贝/ml、(5.3±1.3)log10拷贝/ml、(5.6±1.7)log10拷贝/ml,3组血清HBV DNA载量比较,差异有统计学意义(P=0.026)。结论 HBeAg阳性CHB患者血清HBV DNA载量与肝组织炎症及纤维化程度无显著相关。HBeAg阴性CHB患者血清HBV DNA载量较高者,其肝组织炎症及纤维化程度较高。     

艾滋病合并丙型肝炎病毒感染者抗反转录病毒治疗效果和肝脏损伤

目的 评价对AIDS合并HCV感染患者抗反转录病毒治疗(ART)的临床疗效和肝损伤.方法 将患者按有无HCV合并感染分为HIV和HCV合并感染组(HIV/HCV组)65例,HIV感染组(HIV组)52例,应用两个核苷类反转录酶抑制剂(NRTI)联合一个非核苷类反转录酶抑制剂(NNRTI)的ART方案,疗程1年.随访并检测血浆HIV载量、外周血CD4细胞数、ALT.结果 治疗前,HIV/HCV组和HIV组的HIV载量均值分别为5.59和5.89 log10拷贝/mL,治疗1年后,分别降至2.91 log10拷贝/mL(P＜0.05)和2.88 log10拷贝/mL(P＜0.05),两组分别有83.1%和78.9%的患者HIV载量＜500拷贝/mL.HIV/HCV组和HIV组CD4细胞均值由治疗前的73.9和72.4/μL,分别增至215.1/μL和214.8/μL(P值均＜ 0.05).1年内,HIV/HCV组与HIV组肝功能异常率分别为24.6%与7.7%(P＜0.05),但无因发生严重肝损伤而终止ART者.结论 联合应用NRTI、NNRTI治疗AIDS合并HCV感染患者,短期内能有效抑制HIV复制,促进免疫功能重建.HCV感染虽可加重肝损伤,但对ART疗效无明显影响.     

APOBEC3G基因多态性与HBV感染后疾病转归的关系

目的 研究中国汉族人群载脂蛋白B mRNA编辑酶催化多肽3G(APOBEC3G)基因多态性与慢性乙型肝炎和肝硬化的关系.方法 应用焦磷酸测序,检测202例HBV感染自然痊愈者(对照组)、217例慢性乙型肝炎患者和216例乙型肝炎肝硬化患者APOBEC3G基因rs8177832位点多态性,确定其基因型及等位基因分布.同时通过建立DNA池技术初步对APOBEC3G基因的另外4个标签单核苷酸多态性位点(tagSNP)rs17000736、rs17496046,rs9622924和rs2899313进行疾病相关性的初步筛选;HBV DNA检测采用实时定量PCR.结果 rs8177832在中国汉族人群中以A/A为主要存在形式,其基因型频率和等位基因频率在对照组、慢性乙型肝炎组和乙型肝炎肝硬化组中的分布差异无统计学意义.慢性乙型肝炎组中携带G等位基因的患者HBV DNA水平为6.25 log10拷贝/ml,携带A等位基因的患者为5.54 log10拷贝/ml,t=2.111,P=0.036.rs17000736和rs9622924两位点在中国汉族人群中分别只有G/G和C/C一种单一基因型存在,rs17496046和rs2899313两位点分别以G等位基因和A等位基因为主,这4个tagSNP(rs17000736、rs17496046、rs9622924和rs2899313)在对照组、慢性乙型肝炎组和乙型肝炎肝硬化组中等位基因频率差异均无统计学意义.结论 汉族人群APOBEC3G基因中rs8177832位点的多态性可能与HBV的复制有关,但这5个tagSNP可能与HBV感染后疾病的进展无关.     

IL-28B基因多态性与丙型肝炎易感性的关系

目的:探讨白介素-28B(interleukin-28B,IL-28B)单核苷酸多态性位点rs8099917与中国丙型肝炎易感性的关系.方法:采用TaqMan SNP基因分型的方法检测中国天津地区263名丙型肝炎患者和244名健康人IL-28B rs8099917基因型和等位基因分布情况,并统计分析rs8099917基因型和等位基因在2组中分布的差异.结果:在263名丙型肝炎患者中,TT基因型223人(84.8%),TG基因型39人(14.8%),GG基因型1人(0.4%).T等位基因频率为92.2%.244名健康对照者中,TT基因型222人(91.0%),TG21人(8.60%),GG1人(0.40%),T等位基因频率为95.3%.丙型肝炎患者和健康人群TG/GG基因型频率差异有统计学意义(OR=1.810,95%CI:1.042-3.145;P=0.033).丙型肝炎患者G等位基因频率也高于健康人(OR=1.709,95%CI:1.010-2.893;P=0.044).结论:中国人群IL-28B rs8099917基因多态性与丙型肝炎病毒(hepatitis C virus,HCV)感染易感性相关联.G为HCV感染的风险等位基因.     

丙型肝炎

聚乙二醇干扰素α-2b联用利巴韦林治疗慢性丙型肝炎的临床安全性研究；丙型肝炎病毒多表位基因核酸疫苗的构建及其免疫原性;DC-SIGNR基因多态性与丙型肝炎病毒载量的相关性研究;精氨酸酶Ⅰ在HCV转染肝癌细胞增殖中的作用;丙型肝炎病毒NS4B对p53表达及细胞凋亡的影响.     

HLA-G 14 bp基因插入/缺失多态性和HCV病毒载量的关系

目的:探讨人类白细胞抗原G(HLA-G)14 bp插入/缺失多态性与慢性丙型肝炎病毒(HCV)载量的相关性。方法:联合采用聚合酶链反应技术(PCR)及荧光毛细管电泳技术,对196例慢性丙型肝炎患者进行HLA-G 14 bp插入/缺失多态性的检测;采用实时PCR方法检测患者血清HCV病毒载量。结果:慢性HCV患者HLA-G基因型(+14 bp/-14 bp)、(-14 bp/-14 bp)及(+14 bp/+14 bp)的频率分别为41.8%、47.5%、10.7%,HCV载量分别为9.405×10~6(1.012×10~6～4.715×10~7)IU/mL、8.200×10~6(1.465×10~6～3.28×10~7)IU/mL、1.080×10~(11)(7.995×10~5～5.300×10~7)IU/mL。携带不同HLA-G基因型患者的HCV病毒载量差异无统计学意义(P0.05)。结论:HLA-G14bp基因插入/缺失多态性与HCV病毒载量无相关性。     

The tandem-repeat polymorphism of the DC-SIGNR gene in HCV infection

The C-type lectin DC-SIGNR has been shown to bind hepatitis C virus (HCV). Here, we analysed the tandem-repeat polymorphism of the DC-SIGNR gene with respect to intraindividual HCV replication. In a cross-sectional comparison HCV-infected patients (n = 430) and healthy subjects (n = 100) were genotyped for the DC-SIGNR polymorphism using PCR. The distribution of DC-SIGNR alleles did not differ significantly between the two groups. However, HCV-infected patients with 5-, 6-, and 7-repeat alleles had higher HCV-RNA levels when compared with carriers of 4- and 9-repeat alleles (P < 0.05). Thus, the DC-SIGNR polymorphism might affect HCV loads supporting the concept that DC-SIGNR contributes to HCV replication efficacy.     

白细胞介素-12p403'非翻译区基因多态性与丙型肝炎病毒感染的相关性

目的 探讨丙型肝炎患者IL-12p40 3'非翻译区rs3212227位点基因多态性与HCV感染的关系.方法 应用聚合酶链反应-限制性片段长度多态性分析(PCR-RFLP)和DNA测序的方法榆测127例丙型肝炎患者IL-12 p40 3'非翻译区rs3212227位点的基因型,采用荧光定量PCR技术测定丙型肝炎患者血清HCV RNA水平.组间基因型及等位基因分布频率比较采用χ2检验.结果 丙型肝炎患者IL-12 p40 3'非翻译区rs3212227位点AA、AC、CC基因型分布频率分别为34.6%、40.9%和24.4%.等位基因A、C分布频率分别为55.1%、44.9%.丙型肝炎患者中HCVRNA≥2.0×106拷贝/mL组IL-12 p40 rs3212227位点C等位基因携带者分布频率明显高于HCVRNA<2.0×106拷贝/mL组(χ2=7.367,P=0.007).IFN无应答组IL-12 p40 rs3212227位点C等位基因分布频率明显高于IFN应答组(χ2=4.942,P=0.026).结论 IL-12p40 3'非翻译区rs3212227位点基因多态性与HCV感染具有相关性,携带C等位基因的个体可能更利于HCV复制,而不利于IFN治疗.

Abstract：

Objective To investigate the association between single nucleotide polymorphism (SNP) of interleukin-12 (IL-12) p40 3'untranslated region rs3212227 site and hepatitis C virus (HCV) infection. Methods Patients with hepatitis C (n=127) were genotyped and analyzed for the SNP of IL-12 p40 rs3212227 using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and DNA sequencing. The serum HCV RNA levels of patients with hepatitis C were detected using real time fluorescence quantitative-polymerase chain reaction (FQPCR). Inter-group comparisons of genotype and allele frequency were analyzed using chi-square test.Results In patients with hepatitis C, the frequencies of AA, AC and CC genotypes of IL-12 p40 rs3212227 site were 34. 6% ,40. 9% and 24. 4% , respectively,and the frequencies of allele A, C of IL12 p40 rs3212227 site were 55.1% and 44. 9%, respectively. The frequency of rs3212227 C allele in patients with HCV RNA ≥2. 0× 106 copy/mL was higher than that in patients with HCV RNA <2. 0 ×106 copy/mL (χ2 =7. 367, P = 0. 007). The frequency of rs3212227 C allele in responders to interferon (IFN) therapy was lower than that in patients with nonresponse to IFN therapy (χ2 =4. 942,P=0. 026). Conclusions The SNP of rs3212227 is correlated with HCV infection. The carriers with C allele may be susceptible to HCV infection, while resistant to IFN therapy.     

GNB3 C825T polymorphism and response to interferon-alfa/ribavirin treatment in patients with hepatitis C virus genotype 1 (HCV-1) infection

BACKGROUND/AIMS: The outcome of infection with the hepatitis C virus (HCV) has been shown to be influenced by genetic host factors. The G protein beta3 subunit (GNB3) C825T polymorphism has been shown to determine immune cell functions in vitro. We investigated the association of GNB3 genotypes with treatment response in HCV-infected patients. METHODS: We genotyped 1781 HCV-free blood donors and 232 HCV-infected patients treated with interferon-alfa/ribavirin. Sustained virologic response (SVR) was defined by undetectable HCV-RNA 24 weeks after discontinuation of therapy. Non-response (NR) was defined by positive HCV-RNA at the end of at least 24 weeks of treatment. GNB3 genotypes were determined by DNA restriction enzyme analyses. RESULTS: Genotype distribution was not significantly different in healthy controls and HCV-infected patients. Only in HCV genotype 1-infected patients a significant correlation between GNB3 CC genotype and NR could be observed (6 TT, 42 TC, 54 CC) versus SVR (11 TT, 25 TC, 19 CC) patients (P = 0.004). In a logistic regression analysis including biochemical and virologic characteristics, only GNB3 CC genotype was significantly associated with NR (OR 4.9; 95% CI = 1.4-16.5; P = 0.011). CONCLUSIONS: The GNB3 825 CC genotype is associated with NR in HCV-1-infected patients.     

慢性丙型肝炎患者病毒基因型与IL-28B基因型分布

目的：了解慢性丙型肝炎患者白细胞介素-28B（IL-28B）基因型多态性分布的特点及其临床意义。方法在27例慢性丙型肝炎患者,分离外周血细胞DNA,采用IPLEX Gold法检测宿主IL-28B基因多态性;分析患者IL-28B基因型与血清丙型肝炎病毒（HCV）基因型、HCV RNA载量和肝功能指标的相关性。结果在27例慢性丙型肝炎患者中,感染HCV基因1型1例（3.7%）,1b基因型7例（25.9%）,其它基因型19例（19/27,70.4%）;在IL-28B基因型中,rs12979860 CC基因型、rs12980275 AA基因型及rs8099917 TT基因型共24例（88.9%）,而IL28B rs12979860 CT基因型、rs12980275 GA基因型和rs8099917 GT基因型共3例（11.1%）;在HCV基因1型或1b型感染者中,IL28B rs12979860 CC基因型、rs12980275 AA基因型和rs8099917 TT基因型占62.5%（5/8）,而HCV其他基因型感染者IL28B rs12979860 CC基因型、rs12980275 AA基因型和rs8099917 TT基因型占100%（19/19）;HCV基因1型或1b型感染者与HCV其他基因型感染者比,其IL28B rs12979860位点、rs12980275位点和rs8099917位点基因型分布有显著性差异（P＆lt;0.01）;IL-28B基因多态性分布与患者血清HCV RNA载量或肝功能指标的变化无显著性相关。结论本组慢性丙型肝炎患者HCV基因型大多为非1型;大多数感染者IL-28B基因为rs12979860 CC、rs12980275 AA和rs8099917 TT基因型。     

Distribution of IL28B Genotypes in Iranian Patients with Chronic Hepatitis C and Healthy Individuals

Background

IL28B polymorphism is recognized as one of the most prominent predictors of hepatitis C spontaneous and treatment-induced clearance. Interestingly, the favorable genotypes of IL28B are found to be more frequent in Asian ethnicity than Caucasian and African populations, respectively. A few studies reported that there is a mysterious association between the IL28B polymorphism and the hepatitis C virus (HCV) genotype in patients with chronic hepatitis C but they did not give any reason for this phenomenon.

Objectives

The foremost purpose of this study was to compare the distribution of IL28B genotypes between Iranian healthy individuals and patients with chronic hepatitis C.

Patients and Methods

In this study, 921 patients with chronic hepatitis C and 142 healthy individuals were included. The IL28B rs12979860 and rs8099917 polymorphisms were genotyped using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method.

Results

The frequency of IL28B rs12979860 CC, CT, and TT genotypes in chronic hepatitis C patients was 38%, 48.8%, and 13.2% and in healthy individuals was 43.7%, 48.6%, and 7.7%. Also, the frequency of IL28B rs8099917 TT, GT, and GG genotypes in chronic hepatitis C patients was 58.3%, 37.1%, and 4.6% and in healthy individuals was 64.1%, 32.4% and 3.5%. The differences in the distribution of IL28B rs12979860 and rs8099917 genotypes between patients with chronic hepatitis C and healthy individuals were not statistically significant. When we compared the distribution of IL28B genotypes between the healthy group and the HCV infected patients by HCV genotype, we found 9.8% higher frequency of rs12979860 CC genotype in the healthy individuals than HCV genotype 1 infected patients (P = 0.03) however there was no significant difference in the distribution of rs12979860 genotypes between the healthy and HCV genotype 3 infected groups (P = 0.46).

Conclusions

It seems that the impact of IL28B polymorphism on the spontaneous clearance of HCV genotype 1 is more prominent than HCV genotype 3 which results in the observation of higher rs12979860 C allele frequency in chronic hepatitis C patients with HCV genotype 3 than HCV genotype 1.     

Association of interferon lambda-4 rs12979860 polymorphism with hepatocellular carcinoma in patients with chronic hepatitis C infection

BACKGROUND Hepatitis C virus(HCV) infection is a public health concern worldwide.Several factors,including genetic polymorphisms,may be evolved in the progression of HCV infection to liver diseases.Interferon lambdas(IFNLs) modulate the immune response during viral infections.IFNLs induce antiviral activity,interfering in the viral replication by promoting the expression of several genes that regulate immunological functions.The interferon lambda-4(IFNL4) rs12979860 polymorphism,which is characterized by a C to T transition in intron 1,is associated with spontaneous and treatment-induced clearance of HCV infection and may play a role in the development of HCV-associated liver diseases,including hepatocellular carcinoma(HCC).AIM To investigate the association of IFNL4 rs12979860 polymorphism with fibrosis,cirrhosis,and HCC in patients with chronic HCV infection.METHODS This study was comprised of 305 chronic HCV-infected patients(53 fibrosis,154 cirrhosis,and 98 HCC cases).The control group was comprised of 260 HCVnegative healthy individuals.The IFNL4 rs12979860 polymorphism was genotyped using the TaqMan assay.Fibrosis was diagnosed based on liver biopsy findings,while cirrhosis was diagnosed through clinical,laboratory,anatomopathological,and/or imaging data.HCC was diagnosed through imaging tests,tumor,and/or anatomopathological markers.RESULTS The T allele was observed in the three groups of patients(fibrosis,cirrhosis,and HCC) at a significantly higher frequency when compared with the control group(P=0.047,P 0.001,and P=0.01,respectively).Also,genotype frequencies presented significant differences between the control group and cirrhosis patients(P 0.001) as well as HCC patients(P=0.002).The risk analysis was performed using the codominant and dominant T allele models.In the codominant model,it was observed that the CT genotype showed an increased risk of developing cirrhosis in comparison with the CC genotype [odds ratio(OR)=2.53;95%confidence interval(CI):1.55-4.15;P 0.001] as well as with HCC(OR=2.54;95%CI:1.44-4.56;P=0.001).A similar result was observed in the comparison of the TT vs CC genotype between the control group and cirrhosis group(OR=2.88;95 % CI:1.44-5.77;P=0.001) but not for HCC patients.In the dominant T allele model,the CT+TT genotypes were associated with an increased risk for progression to cirrhosis(OR=2.60;95%CI:1.63-4.19;P 0.001) and HCC(OR=2.45;95%CI:1.42-4.31;P=0.001).CONCLUSION These findings suggest that the T allele of IFNL4 rs12979860 polymorphism is associated with the development of cirrhosis and HCC in chronic HCV-infected patients.     

转化生长因子β1信号肽区单核苷酸多态性与慢性丙型肝炎的相关性

目的 探讨HCV感染者转化生长因子β1(TGF β1)信号肽区密码子25基因多态性与HCV感染的相关性. 方法 采用扩增阻碍突变系统方法,分析106名健康对照者和85例慢性HCV感染者的TGF β1信号肽区密码子25基因多态性. 结果 TGF β1信号肽区密码子25的基因型分布与基因频数在HCV感染组和对照组之间,慢性丙型肝炎组和HCV相关肝硬化组之间的差异均无统计学意义.密码子25基因型分布在ALT正常组和ALT升高组之间的差异无统计学意义,但G基因频数在ALT升高组(G=108)较ALT正常组(G=47)高(P-0.040).密码子25基因型分布在尢病毒血症组(GG=18,CG=5,CC=3)和病毒血症组(GG=55,CG=4)之间的差异有统计学意义(P=0.005),且G等位基因更多出现干病毒血症组(P=0.000).结论 TGF β1信号肽区密码子25G→C突变影响HCV感染肝脏炎性反应,G等位基因与HCV感染病毒血症相关,TGF β1信号肽区密码子25G→C突变可能是影响HCV感染结局的因素之一.     

干扰素治疗慢性丙型肝炎的持续应答与复发相关因素的研究

目的 探讨丙型肝炎病毒（HCV）基因型、RNA含量与肝组织炎症活动的相关性，慢性丙型肝炎患者经干扰素治疗后复发的相关因素。方法 对慢性丙型肝炎患者的血清进行丙氨酸氨基转移酶（ALT）检测，采用Cobas Amplicor Monnitour Test．version 2．0试剂进行HCVRNA定量和Simmonds酶切分型方法进行HCV基因分型检测。对聚乙二醇化干扰素α-2a（PEG—IFN α-2a）与干扰素α-2a治疗24周结束时，取得病毒学应答的慢性丙型肝炎患者进行24周随访观察，对临床特征、病毒学特征、治疗药物等因素与复发的相关性进行分析。结果 208例丙型肝炎患者基础HCVRNA含量与ALT水平无相关性（r=0．093，P〉0．05），HCV基因1型与非基因1型之间ALT的水平差异无统计学意义，HCV基因型与RNA含量无相关性；在治疗结束取得病毒学应答的119例患者中，随访24周持续应答者61例（51．3％），复发58例（48．7％）。患者的性别、年龄、HCV感染途径、既往干扰素治疗史、天冬氨酸氨基转移酶／ALT比值、血小板计数和血清基础HCV载量等因素均与复发率无显著相关性。基因1型患者复发率（54．5％）显著高于非1型（32．1％）（x^2=4．265，P=0．039）。PEG-IFNα-2a组复发率（47．0％）低于IFNα-2a组（52．8％），但差异无统计学意义。结论 病毒基因型与慢性丙型肝炎干扰素治疗后的病毒复发显著相关。