苦参素胶囊对慢性乙型肝炎患者血清TNF-α、IL-6和HBV标志物的影响

目的　观察苦参素胶囊对慢性乙型肝炎患者血清肿瘤坏死因子 α、白细胞介素 6和乙型肝炎病毒标志物的影响。方法　将 47例慢性乙型肝炎患者 (轻度 2 8例、中度 17例、重度 5例 )分别于治疗前和治疗 3月、6月后采集静脉血作TNF α、IL 6、HBV标志物和肝功能的检测。结果　慢性乙型肝炎肝损害的程度与血清INF α、IL 6水平密切相关 ,肝损害越重其值升高越明显。经苦参素胶囊治疗 3个月后 ,其值下降明显 ,与治疗前相比有显著性差异 (P <0 .0 5 ) ,肝损害较轻者变化不明显 ,治疗前后无显著性差异 (P >0 .0 5 ) ;单用苦参素胶囊对慢性乙型肝炎患者HBeAg、HBVDNA转阴率较低 ,但肝功能复常率均在 80 %以上。结论　苦参素胶囊能显著降低慢性乙型肝炎患者血清炎性细胞因子INF α、IL 6水平 ,从而保护肝细胞膜的稳定性 ,有较好的降酶退黄作用 ,但单用苦参素胶囊对HBV标志物的影响则不甚理想     

血清IL-17水平及其基因多态性与HBV感染临床转归之间的关系研究*

目的 探讨血清白介素（IL）-17水平和IL-17-197A/G基因单核苷酸多态性与乙型肝炎病毒（HBV）感染临床转归之间的关系。方法 2015年3月~2017年8月在我院就诊的乙型肝炎肝硬化40例,慢性乙型肝炎120例,无症状慢性HBV携带者60例和自限性HBV感染者80例。采用酶联免疫吸附试验检测血清IL-17水平,使用全自动生化仪检测血浆丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）和总胆红素（TBIL）水平,采用多聚酶链反应结合荧光探针DNA扩增技术检测血清HBV DNA载量,使用单核苷酸检测试剂盒检测IL-17-197A/G基因单核苷酸多态性。结果 乙型肝炎肝硬化组血清IL-17水平显著高于慢性乙型肝炎组、无症状慢性HBV携带者组和自限性HBV感染组（F_3,296=102.8,P均<0.05）;慢性乙型肝炎组血清IL-17水平显著高于无症状慢性HBV携带者组和自限性HBV感染组（P均<0.05）;在乙型肝炎肝硬化组,血清高HBV DNA载量组（>1×10⁵ copies/mL）血清IL-7水平更高（t=5.1,P<0.05）,血清ALT>40 U/L组血清IL-7水平更高（t=10.7,P<0.05）;在慢性乙型肝炎组和乙型肝炎肝硬化组,血清AST>40 U/L组血清IL-7水平更高（t=24.5,P<0.05;t=22.4,P<0.05）,血清TBIL>20 μmol/L组血清IL-7水平更高（t=7.3,P<0.05;t=12.8,P<0.05）;肝硬化患者IL-17-197 AA、AG和GG基因型分别为75.0%、10.0%和15.0%,等位基因A分布频率为57.5%,G分布频率为42.5%,而慢性乙型肝炎患者则分别为25.8%、16.7%、57.5%和34.2%、65.8%,组间差异显著（P<0.05）,乙型肝炎肝硬化组以IL-17-197 AA基因型和A等位基因分布频率为主,慢性乙型肝炎组以GG基因型和G等位基因分布频率为主,HBV携带者组以AA基因型和A等位基因分布为主,自限性HBV感染者以GG基因型和G等位基因分布为主。结论 宿主免疫水平和遗传背景的相互作用决定了HBV感染的临床转归,IL-17在乙型肝炎病毒感染慢性化进程中发挥了重要作用。IL-17-197A/G位点的AA基因型和A等位基因可能是HBV易感的宿主基因,增加了HBV感染的不良转归。     

肿瘤坏死因子α基因多态性与慢性乙型肝炎病毒感染的相关性

乙型肝炎病毒（HBV）感染后临床表现的多样性，除与病毒因素有关，还与宿主的遗传因素密切相关。细胞因子在宿主清除病毒的免疫应答中发挥着重要作用，其基因多态性可影响细胞因子的整个转录，翻译和分泌过程，导致不同人群中细胞因子水平的差异，从而影响HBV感染后的转归。肿瘤坏死因子（TNF）α基因启动子区存在有多个多态性位点，分别为-1031（T／C）、-863（C／A）、-857（C／T）、-376（G／A）、-308（G／A）、-238（G／A）和-163（G／A）。     

低水平丙氨酸氨基转移酶慢性乙型肝炎病毒感染者肝组织病理学变化研究

目的研究血清ALT≤3ULN的乙型肝炎病毒感染者肝组织病理学改变情况。方法选取血清ALT≤3ULN的乙型肝炎病毒感染者71例,在B超引导下行肝穿刺活检术,进行肝组织炎症活动度和肝纤维化程度检查。结果在71例HBV感染者,HBeAg阳性54例,HBeAg阴性17例。血清HBV DNA定量在1×103~105copies/ml 19例(26.8%),106~107copies/ml 34例(47.9%),≥108copies/ml 18例(25.3%)。ALT≤40U/L17例(23.9%),40U/L相似文献   

慢性丙型肝炎患者病毒因素及宿主细胞免疫对干扰素治疗应答的影响

目的：探讨丙型肝炎病毒（HCV）因素及机体细胞免疫因素对干扰素疗效的影响。方法：对40例慢性丙型肝炎患者进行干扰素治疗，分析HCV基因型，准种多样性，血清HCV RNA水平及肝组织HCV特异性细胞毒T淋巴细胞（CTL）活性与干扰素应答的关系。结果：经过6个月的干扰素治疗，21例获得治疗终点应答，其中10例呈持续应答，19例无应答，HCV1型患者应答率（43．3％）明显低于非1型患者（80％，P＜0．05），应答患者中治疗前血清HCV准种数目及HCVRNA水平明显低于无应答患者（P＜0．05，P＜0．01），而其肝组织HCV特异性CTL活性阳性率则显著高于无应答者（P＜0．05），结论：病毒因素和宿主因素均是影响慢性丙型肝炎干扰素治疗效果的重要因素，非1型感染，低准种数目，低病毒血症水平及肝组织HCV特异性CTL活性阳性者预示对干扰素应答良好。     

慢性乙型肝炎病毒感染者外周血自然杀伤细胞免疫效应分子的表达

目的 研究慢性HBV感染者外周血自然杀伤细胞(NK细胞)免疫效应分子表达与感染状态的相关性.方法 健康人作为对照组,慢性HBV感染者根据感染状态分为肝功正常高病毒复制组、肝功能正常低病毒复制组、肝功能异常高病毒复制组、肝功能异常低病毒复制组.应用流式细胞法检测外周血NK细胞的穿孔素(PF)、颗粒酶B(Gr B)、颗粒溶素(GNLY)、肿瘤坏死因子(TNF)α和干扰素(IFN)γ的表达,分析其与感染状态的相关性.组间比较用单因素方差分析;相关性分析采用直线相关Pearson分析.结果 阳性细胞百分比同对照组(31.50%±27.64%)相比,肝功能正常高病毒复制组(59.74%±30.82%)和肝功能正常低病毒复制组(61.89%±33.30%)的GNLY表达增加有统计学意义;同对照组(57.38%±23.69%)相比,肝功正常高病毒复制组(39.89%±21.30%)、肝功能异常高病毒复制组(37.54%±18.79%)的IFN γ表达降低,P值均<0.05,差异有统计学意义;肝功能正常高病毒复制组的PF、Gr B、GNLY(阳性细胞百分比分别为56.98%±38.34%、81.53%±19.58%、59.74%±30.82%)和肝功能正常低病毒复制组的PF、Gr B、GNLY(阳性细胞百分比分别为62.95%±31.98%、84.51%±14.57%、61.89%±33.30%)表达高于肝功能异常高病毒复制组 (阳性细胞百分比分别为35.47%±29.64%,66.55%±22.92%,42.03±33.17%),P值均<0.05,差异有统计学意义;除了TNF α和GNLY不具有相关性外,PF、Gr B、GNLY、TNF α和IFN γ之间呈两两正相关关系.结论 高病毒复制水平的HBV感染者外周血NK细胞表达的IFN γ明显低于正常对照组;肝功能正常的HBV感染者外周血NK细胞表达的PF、Gr B、GNLY水平明显高于肝功能异常者.     

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。     

慢性丙型肝炎患者肝组织学改变及其影响因素分析

目的探讨慢性丙型肝炎患者肝组织学改变及其影响因素。方法选择经皮肝组织活检的慢性丙型肝炎患者102例,记录患者年龄、性别、体质指数(BMI)、感染途径等,检测ALT水平、AST水平、HCV基因分型、病毒载量和肝脏组织学改变。统计学处理采用t检验和Logistic回归分析。结果肝脏炎症活动指数( HAI)≥4的慢性丙型肝炎患者的ALT、AST水平较高,PLT较低,与HAI＜4的患者相比差异有统计学意义(t=2.209、2.298、2.565,均P＜0.05)。纤维化分期评分(F)≥3的患者平均年龄、ALT水平、AST水平以及感染时间均高于F＜3的患者（t=2.340、3.497、2.758、2.570,均P＜0.05）,而PLT则较低(t=2.761,P=0.007)。女性、ALT＞1×正常值上限(ULN)、AST水平、F≥3、HCV RNA≥6 lgIU/mL和PLT计数是HAI≥4的单因素预测因子;经多因素分析后,Ishak纤维化分期评分是HAI≥4的唯一独立预测因子(OR 3.098,95％ Cl1.884～5.092,P＜0.01)。单因素分析F≥3的预测因子为年龄、BMI≥24 kg/m2、ALT＞1×ULN、AST水平、HAI≥4、PLT计数以及感染年限≥15年;多因素回归分析显示,年龄(OR 1.074,95％CI1.006～1.146,P=0.033)、ALT水平(OR 1.035,95％CI 1.015～1.055,P＜0.01)、AST水平(OR0.969,95％CI 0.948～0.990,P=0.005)、感染年限≥15年(OR 37.215,95％CI 5.816～238.127,P＜0.01)和HAI≥4(OR 1.939,95％CI 1.426～2.636,P＜0.01)是F≥3的独立危险因素。结论年龄、ALT水平、AST水平、感染年限≥15年和HAI≥4是肝组织学显著纤维化的独立预测因子。     

Relevance of low viral load in haemodialysed patients with chronic hepatitis C virus infection

AIM: To identify predictors of sustained virological response in hemodialysed patients treated by PEGinterferon α for chronic hepatitis C, genotype 1.METHODS: The sustained virological response(SVR) rate, IL28 B genotype, IFNL4 genotype, initial viral load(IVL) and other pretreatment variables in 39 endstage renal disease patients(ESRD) on maintenance haemodialysis(HD) infected with hepatitis C virus(HCV), genotype 1b, were compared with a control group of 109 patients with normal kidney function treated within the same period. All the patients were treatment nave and had well compensated liver disease. The ESRD patients received 135 μg of PEGylated interferon α-2a(Peg IFN-α) weekly and a reduced dose of ribavirin(RBV) was administered to 23/39 patients with an initial haemoglobin level 10 g/d L. Control group patients were given standard doses of Peg IFN-α and RBV. SVR was assessed as HCV RNA negativity 24 wk post-treatment. A t-test or ANOVA were used for comparisons of the means and a χ2 testcompared the frequencies.Logistic regression was used to determine significant predictors of SVR.Cutoff values for continuous variables were obtained from Receiver Operating Characteristic analysis.RESULTS:The distribution of IL28B rs12979860 CC,CT and TT genotypes in the ESRD group was 28.2%,64.1%and 7.7%,respectively,and 19.3%,62.4%and18.3%in the controls.The IFNL4 genotype was in almost absolute linkage disequlibrium with IL28B.The proportion of patients with a low IVL(600000 IU/m L)was significantly higher in the ESRD group than in the controls(28/39,71.8%vs 51/109,46.8%,P=0.009),as was the proportion of patients with low IVL in IL28B CC carriers compared with non-CC carriers in the ESRD group(10/11,90.9%vs 18/28,64.3%,P=0.0035).This difference was not found in the controls(7/22,31.8%vs 44/87,50.6%,P=0.9).The overall SVR rate was 64.1%(25/39)in the ESRD group and 50.5%(55/109)in the control group(P=0.19).11/11(100%)and 19/22(86.4%)IL28B CC patients achieved SVR in the ESRD and control groups,respectively.A statistically significant association between SVR and IL28B and IFNL4 variants was found in both groups.The ESRD patients who achieved SVR showed the lowest IVL[median 21000,interquartile range(IQR):6000-23000IU/m L],compared with ESRD individuals without SVR(1680000,IQR:481000-6880000,P=0.001),controls with SVR(387000,IQR:111000-1253000)and controls without SVR(905000,IQR:451000-3020000).In ESRD,an IVL600000 IU/m L was strongly associated with SVR:24/28(85.7%)patients who achieved SVR had viraemia below this threshold.CONCLUSION:Haemodialysis decreases the viral load,especially in IL28B CC genotype carriers.A low IVL was the strongest predictor of SVR in ESRD patients identified in multivariate analysis.     

HCV基因型对慢性丙型肝炎干扰素疗效的影响

目的 探讨HCV基因型对慢性丙型肝炎的干扰素（IFN）治疗效果的影响。方法 采用随机、开放和对照的多中心临床试验设计。208例受试者按1：1随机分到聚乙二醇干扰素α—2a(Peg-IFN）组和IFN-α-2a组。在治疗之前，用Simmonds基因分型法酶切分型，在治疗24周结束和完成24周的随访后检测患者的ALT和HCV RNA，以HCV RNA的阴转率作为主要评价指标，经ITT人群的统计学分析。结果 202例患者确定了HCV基因型，基因1型158例（78.2%），非基因1型44例（21.8%），治疗结束病毒应答率（ETVR）和持续病毒应答率（SVR）基因1型患者分别为53.8%和25.3%，非基因1型患者分别为61.4%和43.2%，SVR两组患者差异有显著性，x^2=5.313,P=0.021。Peg IFN组基因1型和非1型患者的ETVR分别为76.8%和81.0%，SVR分别为35.4%和66.7%，SVR两组患者差异有显著性，x^2=6.735,P=0.01。病毒复发率基因1型和非基因1型患者分别为55.6%和23.5%，差异有显著性，x^2=5.496,P=0.02.IFN-α-2a组，ETVR和SVR基因1型患者分别为29.0%和14.5%，非基因1型患者分别43.5%和21.7%，差异无显著性。病毒复发率基因1型患者为72.7%，非基因1型患者为50.0%，差异无显著性。结论 IFN对基因1型丙型肝炎患者的疗效低于非基因1型，HCV基因型主要影响IFN对慢性丙型肝炎的持续应答，也与药物和IFN的疗程相关。     

80例慢性HBV感染者临床与肝组织病理学分析

目的探讨血清丙氨酸氨基转移酶（ALT）低于2倍正常值上限（ULN）的慢性乙型肝炎病毒（HBV）感染者临床特征和肝组织病理学的变化。方法在2010年7月至2013年11月住院行肝活检的80例慢性HBV感染者,常规检测血清HBeAg和HBV DNA水平,回顾性分析其临床资料和肝组织学改变。结果 50例HBeAg阳性和30例HBeAg阴性患者年龄分别为（28.52±9.10）岁和（39.37±10.14）岁,HBV DNA载量分别为（7.79±0.73）lg拷贝/毫升和（4.52±1.67）lg拷贝/毫升,差异均有统计学意义（P〈0.01）;两组肝组织炎症活动度分别为（1.00±0.57）和（1.27±0.45）,纤维化程度分别为（0.38±0.57）和（1.07±1.11）,差异均有统计学意义（P〈0.05）;两组肝组织HBsAg表达强度免疫染色评分（ISS）分别为（0.93±0.92）和（0.77±0.93）,HBcAg分别为（1.58±0.88）和（1.63±0.92）,差异均无统计学意义（P〉0.05）;22例患者年龄≥40岁和35例年龄〈30岁患者肝组织炎症活动度分别为（1.32±0.48）和（0.69±0.58）,纤维化程度分别为（1.00±1.27）和（0.40±0.50）,差异均有统计学意义（P〈0.05）;52例男性和28例女性患者肝组织炎症活动度分别为（1.12±0.55）和（1.07±0.54）,纤维化程度分别为（0.71±0.82）和（0.50±0.96）,肝组织HBsAg表达强度（ISS）分别为（0.89±0.89）和（0.82±1.00）,HBcAg分别为（1.44±0.94）和（1.24±1.09）,差异均无统计学意义。结论对年龄≥40岁且HBeAg阴性的血清ALT低于2×ULN的慢性HBV感染者,应及早行肝组织病理学检查,以进行正确的病情评估。     

Interleukin 28B polymorphisms as predictor of response in hepatitis C virus genotype 2 and 3 infected patients

Single nucleotide polymorphisms near the interleukin28B(IL-28B)gene have been identified as strong predictors of both spontaneous or Peg-interferon(Peg-IFN)and ribavirin(RBV)induced clearance of hepatitis C virus(HCV).Several studies have shown that,in patients with genotype 1(GT-1),rs12979860 C/C and rs8099917T/T substitutions are associated with a more than twofold increase in sustained virological response rate to Peg-IFN and RBV treatment.Although new treatment regimens based on combination of DAA with or without IFN are in the approval phase,until combination regimens with a backbone of Peg-IFN will be used,we can expect that IL28B holds its importance.The clinical relevance of IL28B genotyping in treatment of patients infected with HCV genotype 2(GT-2)and 3(GT-3)remains controversial.Therefore,after a careful examination of the available literature,we analyzed the impact of IL28B in GT-2 and-3.Simple size of the studies and GT-2 and GT-3 proportion were discussed.An algorithm for the practical use of IL28B in these patients was suggested at the aim of optimizing treatment.     

Serum mannan-binding lectin in egyptian patients with chronic hepatitis C: its relation to disease progression and response to treatment

Background

Chronic hepatitis C virus (HCV) infection is a major worldwide public health problem. Egypt has the highest prevalence of adult HCV infection in the world, averaging 15%–25% in rural communities. Mannan-binding lectin (MBL) is a liver-derived pluripotent serum lectin that plays a role in the innate immune system of the host. It is an acute-phase protein that is involved in the activation of the classical complement pathway. MBL may play a defensive role in HCV infection.

Objectives

To investigate the relationship between MBL concentration and HCV infection in Egyptian patients suffering chronic hepatitis C.

Patients and Methods

Serum samples obtained from 35 Egyptian hepatitis C patients and 30 normal controls were assayed for MBL. MBL concentrations were correlated to disease characteristics and treatment response.

Results

Serum MBL was significantly higher in HCV patients than in controls, but no relationship was found between MBL concentration and disease progression in terms of hepatic fibrosis and inflammation. Responders to interferon (INF)-based therapy had significantly higher serum MBL than non-responders.

Conclusions

We found no association between serum MBL concentration and progression of HCV related liver disease. Responders to INF-based therapy had significantly higher serum MBL than non-responders.     

Effects of exercise training on inflammatory markers in patients with heart failure

Cardiologists now recognize that the cardio-centric model of heart failure does not sufficiently explain the entire traits particular to chronic heart failure. Evidence accumulates, that many features of the syndrome can be explained by the known biological effects of inflammatory mediators. Indeed, when expressed in experimental models at concentrations commonly observed in heart failure, inflammatory mediators such as tumor necrosis factor-α, interleukin-6, and nitric oxide can produce effects that mimic features of heart failure, including (but not limited to) progressive left-ventricular dysfunction, pulmonary edema, left-ventricular remodeling, and cardiomyopathy. As we witness anti-cytokine therapies and other strategies to avoid an increase in cytokines we have been shown that acute bouts of exercise are associated with an increase in pro-inflammatory cytokines and markers of oxidative stress. As a consequence we have been warned exercise may thus even further contribute to the deterioration of heart failure. However, there are several randomized trials which unanimously document that chronic—as opposed to acute bouts of—exercise does not only lead to a reduction of cytokines and oxidative stress, but that patients dramatically benefit by the increase in maximal oxygen consumption, exercise capacity, quality of life, reduction in hospitalization, morbidity, and mortality. Over the past two decades it has become evident that cytokine research has come to stay and that we will continue to see anti-cytokine treatment strategies for our patients. It is the aim of this review to shed some more light on the most commonly investigated and most relevant cytokines.     

APRI as a predictor of early viral response in chronic hepatitis C patients

AIM: To evaluate the aspartate aminotransferase (AST) to platelet ratio index (APRI) as a predictive factor of early viral response in chronic hepatitis C naive patients.METHODS: We performed an ambispective casecontrol study. We enrolled chronic hepatitis C naive patients who were evaluated to start therapy with PEGylated interferon a-2b (1.5 mg/kg per week) and ribavirin (> 75 kg: 1200 mg and < 75 kg: 1000 mg). Patients were allocated into two groups, group 1: Hepatitis C patients with early viral response (EVR), group 2: Patients without EVR. Odds ratio (OR) and 95% confidence interval (CI) were calculated to assess the relationship between each risk factor and the EVR in both groups.RESULTS: During the study, 80 patients were analyzed, 45 retrospectively and 35 prospectively. The mean ± SD age of our subjects was 42.9 ± 12 years; weight 70 kg (± 11.19), AST 64.6 IU/mL (± 48.74), alanine aminotransferase (ALT) 76.3 IU/mL (± 63.08) and platelets 209 000 mill/mm3 (± 84 429). Fifty-five (68.8%) were genotype 1 and 25 (31.3%) were genotype 2 or 3; the mean hepatitis C virus RNA viral load was 2 269 061 IU/mL (± 7 220 266). In the univariate analysis, APRI was not associated with EVR [OR 0.61 (95% CI 0.229-1.655, P = 0.33)], and the absence of EVR was only associated with genotype 1 [OR 0.28 (95% CI 0.08-0.94, P = 0.034)]. After adjustment in a logistic regression model, genotype 1 remains significant.CONCLUSION: APRI was not a predictor of EVR in chronic hepatitis C; Genotype 1 was the only predictive factor associated with the absence of EVR in our patients.     

HFE基因多态性检测判断慢性丙型肝炎患者疾病活动的价值*

目的 观察遗传性血色素沉着症候选基因HFE多态性检测判断CHC疾病活动的价值。方法 2016年11月～2018年11月我院收治的257例丙型肝炎病毒感染者,其中病毒感染者131例和慢性丙型肝炎(CHC)患者126例。采用酶结合免疫吸附法测定血清铁蛋白(SF)水平,使用ABIPrismsTM-7900实时荧光定量PCR仪和TaqMan-MGB荧光探针,以实时定量PCR法检测HFE基因rs2071303和rs9366637位点基因型。结果 病毒感染者SF水平为(97.5±4.1)μg/L,显著低于CHC患者【(202.1±24.5)μg/L,P＜0.05】,血清ALT水平为(34.0±4.5)U/L,显著低于CHC患者【(88.4±5.6)U/L,P＜0.05】,AST为(37.5±4.2)U/L,显著低于CHC患者【(70.0±5.4)U/L,P＜0.05】;病毒感染者HCV基因非Ⅰb型频率为29.8%,显著高于CHC患者13.5%(P＜0.05),病毒感染者HCV基因型中混合型频率为9.1%,显著低于CHC患者的21.4%(P＜0.05);病毒感染者rs2071303位点GG基因型患者SF水平为(97.6±4.2)μg/L,显著低于CHC患者【(199.5±45.4)μg/L,P＜0.05】,GA基因型SF水平为(97.6±4.1)μg/L,显著低于CHC患者【(207.5±34.7)μg/L,P＜0.05】,AA基因型SF水平为(96.7±3.7)μg/L,显著低于CHC患者【(198.0±44.8)μg/L,P＜0.05】;病毒感染者rs9366637位点TT基因型患者SF水平为(97.4±4.0)μg/L,显著低于CHC患者【(206.4±35.6)μg/L,P＜0.05】,TC基因型SF水平为(97.2±4.0)μg/L,显著低于CHC患者【(208.5±34.0)μg/L,P＜0.05】,CC基因型SF水平为(99.1±4.5)μg/L,显著低于CHC患者【(178.5±58.6)μg/L,P＜0.05】;病毒感染者rs2071303位点AA基因型频率为13.7%,显著低于CHC患者的21.4%(P＜0.05),病毒感染者AC单倍型频率为3.1%,显著低于CHC患者的8.3%(P＜0.05)。结论 HFE基因多态性与CHC疾病活动密切相关,临床应引起足够的重视。     

Effect of sustained virological response on long-term clinical outcome in 113 patients with compensated hepatitis C-related cirrhosis treated by interferon alpha and ribavirin

AIM： To assess the long-term clinical benefit of sustained virological response （SVR） in patients with hepatitis C virus （HCV） cirrhosis treated by antiviral therapy using mostly ribavirin plus interferon either standard or pegylated.METHODS： One hundred and thirteen patients with uncomplicated HCV biopsy-proven cirrhosis, treated by at least one course of antiviral treatment ≥ 3 mo and followed ≥ 30 mo were included. The occurrence of clinical events [hepatocellular carcinoma （HCC）, decompensation and death] was compared in SVR and non SVR patients.RESULTS： Seventy eight patients received bitherapy and 63 had repeat treatments. SVR was achieved in 37 patients （33%）. During a mean follow-up of 7.7 years, clinical events occurred more frequently in non SVR than in SVR patients, with a significant difference for HCC （24/76 vs 1/37, P = 0.01）. No SVR patient died while 20/76 non-SVR did （P = 0.002）, mainly in relation to HCC （45%）.CONCLUSION： In patients with HCV-related cirrhosis, $VR is associated with a significant decrease in the incidence of HCC and mortality during a follow-up period of 7.7 years. This result is a strong argument to perform and repeat antiviral treatments in patients with compensated cirrhosis.     

Effect of interferon alpha2b plus ribavirin treatment on selected growth factors in respect to inflammation and fibrosis in chronic hepatitis C

AIM: Growth factors (GF) that participate in regeneration and apoptosis have an important role in chronic liver diseases. We analyzed serum GF concentration during antiviral treatment and correlated it with morphological liver failure in chronic hepatitis C. METHODS: The levels of GF were determined in sera by ELISA method in 0,16,32 and 48 wk of therapy in 40 patients treated with IFNα2b (9 MU sc/wk) and RBV (1.2 g/d) and in 25 healthy subjects. Blind liver biopsies were done before treatment with histological grading and staging examination. RESULTS: The hepatocyte growth factor (HGF) and epidermal growth factor (EGF) were markedly elevated prior the treatment and decreased during the therapy, although they did not reach the normal level. In non-responding (NR) patients, HGF and EGF were higher than that in responders (R), however differences were not significant. Before the treatment thrombopoietin (TPO) level was significantly lower in R than in NR (P<0.03). Platelet-derived growth factor (PDGF) concentration was lower in chronic hepatitis C than in healthy subjects and decreased during the treatment. A significant positive correlation was observed between inflammatory activity in the liver tissue and the concentration of HGF (in R: r= 0.4, in NR: r= 0.5), TPO (R: r= 0.6), and a significant negative correlation between this activity and EGF (R: r = -0.6) and PDGF (R: r= -0.5). Serum HGF concentration was higher in more advanced fibrosis (R: r = 0.5, P<0.05; NR: r=0.4, P<0,03). CONCLUSION: The decrease in PDGF can be an effective prognostic marker of the treatment and HCV elimination. Decreasing HGF, EGF, and PDGF can influence the inhibition of inflammatory and fibrotic processes in the liver during the antiviral treatment.     

慢性丙型肝炎患者外周血IL-28B基因型多态性及其对持续病毒学应答的影响

目的 探讨慢性丙型肝炎（CHC）患者白细胞介素28B（IL-28B）基因型位点多态性及其对持续病毒学应答（SVR）的影响。方法 2011年3月～2016年3月收治的CHC患者285例,接受24～48周利巴林韦联合聚乙二醇干扰素治疗。采用双色荧光TaqMan技术检测患者外周血IL-28B rs12979860基因型位点多态性,常规检测HCV基因型。结果 在285例CHC患者中,发现HCV 1b型169例（59.29%）,2a型 99例（34.74%）,非1b/2a亚型 17例（5.96%）;IL-28B rs12979860基因型为CC基因型208例（72.98%）,CT基因型64例（22.46%）,TT基因型13例（4.56%）; CC型和CT/TT型感染患者血清HCV RNA水平无显著相差（Z=0.260,P>0.05）;获得SVR 183例（64.21%）,其中169例HCV 1b型获得SVR 23例（13.61%）,99例2a亚型获得SVR 76例（76.77%）,17例非1b/2a亚型获得SVR 7例（41.18%）,组间比较差异有统计学意义（x2=20.415,P<0.05）;208例IL-28B CC基因型获得SVR 192例（92.31%）,64例CT基因型获得SVR 12例（18.75%）,13例TT基因型中获得SVR 4例（30.77%）,组间比较差异有统计学意义（（x2=15.294,P<0.05）。结论 CHC患者获得SVR与IL-28B rs12979860基因位点多态性密切相关,CC基因型感染者可能更容易获得更高的SVR。