Possible contribution of serum activin A and IGF-1 in the development of hepatocellular carcinoma in Egyptian patients suffering from combined hepatitis C virus infection and hepatic schistosomiasis

OBJECTIVES: The present study evaluated the role of activin A, insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein 3 (IGFBP-3) in Egyptian patients suffering from combined hepatitis C virus (HCV) infection and hepatic schistosomiasis. DESIGN AND METHODS: Four groups were included in the present study. Group I: 30 healthy subjects were included as controls; Group II (HCV): 30 patients with chronic liver disease due to HCV infection without evidence of schistosomiasis; Group III (SHF + HCV): 30 patients with combined disease, chronic schistosomal hepatic fibrosis (SHF) and chronic hepatitis C infection; Group IV (HCC): 30 patients with hepatocellular carcinoma associated with chronic hepatitis C virus and schistosomal infection. RESULTS: Patients with HCV, HCV + SHF and those with HCC had a significantly higher serum activin A compared with the control group (P < 0.001). Serum activin A level (mean +/- SD) was 5.7 +/- 2.76, 10.59 +/- 3.59, 15.39 +/- 4.61 and 19.93 +/- 5.43 ng/mL in controls, HCV patients, HCV + SHF patients and HCC patients, respectively. Serum IGF-1 was significantly lower in HCV patients, HCV + SHF patients and HCC patients compared to the control group (P < 0.001). Serum IGF-1 was 121.7 +/- 73.4, 76.7 +/- 23.5, 35.7 +/- 17.6 and 39.9 +/- 25.9 ng/mL in controls, HCV patients, HCV + SHF patients and HCC patients, respectively. Similarly, serum IGFBP-3 was significantly lower in HCV patients, HCV + SHF patients and HCC patients compared to the control group (P < 0.001). Furthermore, serum insulin-like growth factor binding protein 3 (IGFBP-3) was significantly lower in patients with HCC compared to patients with HCV or those with HCV + SHF (P < 0.01 and P = 0.024, respectively). The median (range) of serum IGFBP-3 was 4452 (352.2-8965), 3457 (1114-6000), 2114 (867-5901) and 1202 (576-3994) ng/mL in controls, HCV patients, HCV + SHF patients and HCC patients, respectively. Serum activin A correlated positively with Child-Pugh scoring in patients with HCV, HCV + SHF and those with HCC. The correlation coefficient was significant, at 0.001, in total cases. CONCLUSIONS: We conclude that patients with HCV, HCV + SHF and those with HCC have a significantly higher serum activin A when compared with controls. Serum activin A level was significantly higher in patients with HCV + SHF compared to those with HCV alone (P < 0.01) with a significant positive correlation between the serum activin A level and Child-Pugh scoring in patients with HCV, HCV + SHF and those with HCC. Furthermore, serum IGF-1 and IGFBP-3 levels were significantly reduced in patients with HCV, HCV + SHF and those with HCC compared to the control group. We suggest that this pattern (high activin A and low IGF-1 and its binding protein 3) may play a role in development of HCC in Egyptian patients suffering from combined hepatitis C virus infection and hepatic schistosomiasis.     

乳腺病中血清层粘连蛋白含量的变化

利用ＥＬＩＳＡ法检测了乳腺小叶增生、良性纤维瘤和恶性浸润性导管癌患者血清层粘连蛋白的含量，比较了乳腺良恶性病患者及正常人之间ＬＮ的差异。结果表明，恶性肿瘤病人ＬＮ值之间有显著差异（Ｐ〈０．０１），良性病人与正常人之间无显著差异，（Ｐ〉０．０５），本文还发现纤维瘤与正常人之间ＬＮ有显著差异（Ｐ≤０．０５），但小叶增生与正常人，纤维瘤之间ＬＮ无显著差异（Ｐ〉０．０５），由于乳腺病从良性转变为恶性，患者     

Effects of storage and viral load on hepatitis C viral genotyping.

Hepatitis C virus (HCV) genotyping is important for determining the treatment protocol for hepatitis C patients. Since amplified material from the Roche HCV Monitor kit is compatible with the Innogenetics INNO-LiPA HCV II kit (line probe assay), amplicons from the Monitor assay can be used to identify the HCV genotype. The Monitor package insert recommends using amplicons within a 7-day period (at 4 degrees C) following amplification. It was hypothesized that storage of amplicons for 4 weeks and longer (at -20 degrees C) would not affect the sensitivity of the genotyping assay. After denaturation, amplicons from two genotypes were stored for 7-386 days prior to performing the genotyping assay. Storage of amplicons did not hamper the ability to identify the genotype. Additionally, the sensitivity of the assay was evaluated by analyzing five genotypes with low viral loads. HCV genotypes were detected most consistently at viral levels of 10,000 copies/mL. In conclusion, the Innogenetics genotyping assay can use stored amplicons, thus reducing the cost of the assay by avoiding additional PCR reactions. Determining the sensitivity of this assay facilitates the efficient use of this test by incorporating a sensitivity cutoff of >or=10,000 copies/mL.     

丙肝病毒核心抗原检测对于丙型肝炎诊断的价值

目的通过同时检测丙型肝炎病毒核心抗原(HCV-cAg)和丙型肝炎抗体(HCV-Ab)两项指标,且对HCV-cAg阳性但HCV-Ab阴性的标本进一步做HCV-RNA定量检测,探讨HCV-cAg检测对于丙型肝炎诊断的意义。方法对90例HCV-Ab阳性的感染者血清以及391例丙氨酸氨基转移酶(ALT)升高但HCV-Ab阴性的高危人群血清同时检测HCV-cAg,其中高危人群组中有2例为阳性,对其做HCV-RNA定量检测。结果 90例丙肝抗体阳性组中,34例为HCV-cAg阳性,阳性率为37.78%;391例丙肝抗体阴性的高危人群组中,2例为HCV-cAg阳性,阳性率为0.51%,此2例经HCV-RNA定量检测确证为1例阳性,1例阴性。结论丙型肝炎病毒核心抗原检测能够有效缩短窗口期,操作简便,费用低廉,在临床上具有很好的推广前景。     

Advanced liver fibrosis and care continuum in emergency department patients with chronic hepatitis C

Background

FIB-4, a non-invasive serum fibrosis index (which includes age, ALT, AST, and platelet count), is frequently available during ED visits. Our objective was to define 1-year HCV-related care outcomes of ED patients with known HCV, for the overall group, and both those with and without advanced fibrosis.

New approaches to in vitro diagnosis of hepatitis C infection a reason for post transfusion hepatitis: Diagnostic value of determination of hepatitis C virus core antigen

In between the dates of February 2008–March 2009, by applying to Istanbul University CTF Microbiology and Clinical Microbiology Basic Sciences Branch and Duzen laboratories, 123 cases, where HCV RNA and anti-HCV positivity are identified with molecular (real-time PCR) and serologic (ELISA) methods as a positive control group, and 48 cases where HCV RNA and anti-HCV negativity are identified as a negative control group are established. The values of sensitivity, specificity, positive and negative approximation of recently developed HCV Core Ag (Abbott Diagnostics, Germany) kit are determined successively as 94.3%, 97.9%, 99.1%, 87%, 95.3% and 88%. Although the new HCV Ag assay is clearly not sensitive enough to replace HCV NAT it may serve as a valuable tool in the HCV diagnostic algorithm as it is able to pick up a great majority of anti-HCV and HCV RNA positive samples, thus allowing a timely and less expensive serological diagnosis of an active HCV infection. This may be an advantage for labs that do not have access to PCR easily.     

血液透析患者丙型肝炎病毒型特异性PCR基因分型

目的 建立一种丙型肝炎病毒型特异性PCR基因分型方法。方法 对47份血液透析患者HCV RNA阳性的标本,用5’非编码区(5'-NCR)1、2、3、1b型特异性引物,进行逆转录巢式PCR扩增分型。结果 47份HCV RNA样本43例可以分型;优势株为1b亚型,1b及1b相关型占总样本数的87．23％(41／47);7例为混合感染,占可分型数的16．27％(7／43)。结论 本组血液透析患者感染的HCV基因型的分布可能与地区流行及医源性传播有关,其同源性有待核苷酸序列分析加以印证。     

丙型肝炎病毒基因型与慢性丙型肝炎患者病情严重程度之间关系的研究

目的分析丙型肝炎病毒(HCV)基因型与慢性丙型肝炎患者病情严重程度之间关系,为慢性丙型肝炎患者的临床诊断和治疗提供依据。方法采用直接测序法对HCV进行基因分型,并测量患者未治疗前HCVRNA水平、丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、清蛋白(ALB)、血红蛋白(Hb)、血小板计数(PLT)水平。结果共对321株HCV进行基因分型,其中1a型占1.2%,1b型占78.5%,2a型占8.7%,3a型占2.2%,3b型占4.7%,6a型占2.8%,6b型占1.9%。HCV1型患者ALT、HCV-RNA、AST/PLT比值指数(APRI)水平明显高于非1型患者,差异有统计学意义(P值分别为0.009,0.01,0.036);而AST、ALB、Hb、PLT、AST/ALT水平两者并无明显差异。结论 HCV1型患者HCV-RNA水平高于非1型患者,肝脏功能损害较非1型患者严重。     

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。     

Development and progression of gastroesophageal varices in patients with chronic hepatitis C

Evaluation of: Fontana RJ, Sanyal AJ, Ghany MG et al. Factors that determine the development and progression of gastroesophageal varices in patients with chronic hepatitis C. Gastroenterology 138(7), 2321–2331 (2010).

Hepatitis C virus infection is the leading cause of chronic liver disease in the western world. Chronic liver diseases may cause, through portal hypertension, the development of gastroesophageal varices, which can then bleed. We assess the findings of a study aimed at identifying the incidence of de novo varix development and their progression in patients with chronic hepatitis C and advanced fibrosis. This study was a substudy of the Hepatitis C Antiviral Long-Term Treatment against Cirrhosis (HALT-C) trial. The HALT-C trial was designed to determine whether pegylated interferon (PEG-IFN) at low dose can reduce the rate of disease progression in these patients. Approximately 26% of patients developed de novo varices and 35.2% of patients with varices at baseline had variceal progression or bleeding during the 4-year follow-up. The authors examine demographic, clinical, laboratory, virological, endoscopic and histological factors associated with the development and progression of gastroesophageal varices. PEG-IFN-α2a therapy did not reduce the risk of development or progression of gastroesophageal varices.     

不同诊断类型血吸虫病患者血清肾功能检测及其临床意义

目的 探讨不同诊断类型血吸虫病患者尿素氮(Urea)、肌酐、尿酸、胱抑素C(CysC)和β2微球蛋白(β2MG)的血清水平变化及各项检测指标的临床意义.方法 对80例慢性血吸虫病患者、72例巨脾型晚期血吸虫病患者、76例腹水型晚期血吸虫病患者和40例健康体检者进行肾功能检测和分析.结果 健康对照组、慢性血吸虫病组、晚期巨脾型血吸虫病组和晚期腹水型血吸虫病组患者血清β2MG、CysC、Urea水平呈逐渐升高趋势.血吸虫病各组血清β2MG水平与健康对照组之间差异均有统计学意义(P＜0.01).晚期腹水型血吸虫病组血清CysC水平与其余各组之间差异有统计学意义(P＜0.01).结论 血吸虫病患者随着病情的加重,CysC和β2MG水平会升高,加强对血吸虫病患者血清中CysC和β2MG的监测,有助于早期发现功能性肾衰竭,这对于该病的治疗具有一定参考价值.     

Hepatocellular carcinoma: clinical and radiological findings in patients with chronic B viral hepatitis and chronic C viral hepatitis

Aim

To compare clinical and radiological findings of newly diagnosed hepatocellular carcinomas (HCCs) in patients with chronic hepatitis B virus (HBV) and chronic hepatitis C virus (HCV) infections.

Materials and Methods

Dynamic contrast-enhanced CT images in 532 patients with newly diagnosed HCC were retrospectively reviewed. Of these patients, 418 had chronic HBV infections and 114 had chronic HCV infections. The number, size, shape (nodular vs. non-nodular) and enhancement pattern (typical vs. atypical) of hepatic lesions were assessed. The presence of portal vein thrombosis and bile duct invasion were determined.

Results

The mean age of the HBV group (54.31 [range 27–85], median 54) was younger than that of the HCV group (64.21 [range 30–86], median 64) (P?5; P?P?=?0.023); non-nodular shape (P?P?=?0.047), association with portal vein thrombosis (P?=?0.004); association with bile duct invasion (P?Conclusions Clinical and radiological findings of HCC differ between patients with HBV and HCV infections.     

Cyclopheron pretreatment in opisthorchiasis management in patients with viral hepatitis C

AIM: To assess efficacy of cyclopheron (Polysan production) as opisthorchiasis pretreatment in patients with chronic viral hepatitis C (CHC). MATERIAL AND METHODS: Fifteen CHC patients received cyclopheron by 6 month scheme before dehelminthization. The effect was evaluated by dynamics of clinical symptoms, results of functional hepatic tests, levels of autoantibodies to antigens of native and denaturated DNA, CIC and lactoferrin. Fourteen control patients did not receive pretreatment with cyclopheron. RESULTS: The study group patients exhibited a relief of asthenovegetative and pain syndromes, aminotranspherases lowered to normal in 11 patients, minimal activity of cytolytic syndrome--in 4 patients. Lactoferrin normalized in all the patients, coefficient of autoantibodies to antigens of native and denaturated DNA fell two-fold. No significant improvement in the clinical and laboratory picture was seen in the controls. CONCLUSION: Cyclopheron in patients with CHC combination with chronic opisthorchiasis is recommended as pretreatment before dehelminthization.     

Serum L-carnitine levels and lipoprotein compositions in chronic viral hepatitis patients

OBJECTIVES: The aim of this study was to evaluate the serum L-carnitine levels and its effect on lipoproteins in chronic viral hepatitis B or C patients. DESIGN AND METHODS: Blood samples were taken from 41 patients and 30 healthy subjects after 12 h fasting. RESULTS: Patients' serum L-carnitine levels (11.19 +/- 6.67 mg/L) (p < 0.0001) and hepatic enzyme activities (AST and ALT) (49.02 +/- 42.80 and 58.35 +/- 57.51 U/L) (p < 0.0005) were significantly higher than controls'. Serum total (3.85 +/- 0.82 mmol/L), LDL (2.08 +/- 0.76 mmol/L) and HDL (1.02 +/- 0.29 mmol/L) cholesterol levels were significantly lower in patients (p < 0.01). On the other hand triglyceride levels (1.65 +/- 0.85 mmol/L) were significantly higher in patients (p < 0.05). CONCLUSIONS: The higher L-carnitine levels of patients may result from the leakage of hepatic cellular carnitine. If there is a decreased hepatic cellular carnitine levels, this may affect the transport of acetyl moiety for cholesterol synthesis and alter lipoprotein composition. Further investigation is needed for hepatic tissue L-carnitine levels.     

慢血、晚血、慢性乙型肝炎和肝硬化病人凝血、抗凝血及纤溶功能的研究

目的探讨慢血、晚血、慢性乙型肝炎和肝硬化患者的凝血、抗凝血及纤溶功能。方法收集血防站诊治的慢性、晚期血吸虫病和南昌大学第一附属医院住院的慢性乙型肝炎和肝硬化患者各50例及同期健康体检者50例作为对照组,测定和分析血浆凝血功能(PT、APTT、TT、Fg)、抗凝血功能(AT-Ⅲ、PC、PS)及纤溶功能[纤溶酶原(PLG)、D-二聚体(D-D)]。结果1、与健康对照组相比:⑴慢血组凝血功能(PT、APTT、TT、Fg)差异无显著性,抗凝血功能(AT-Ⅲ、PC、PS)差异有显著性,纤溶产物D-D水平差异有显著性而PLG无统计学差异;⑵晚血组PT、TT、Fg差异有显著性而APTT差异无显著性,抗凝血功能(AT-Ⅲ、PC、PS)和纤溶功能(PLG、D-D)差异有显著性;⑶慢性乙型肝炎和肝硬化组凝血功能、抗凝血和纤溶功能差异均有显著性;2、慢血组与晚血组比较:PT、TT差异有显著性而APTT、Fg差异无显著性,AT-Ⅲ、PC差异有显著性而PS差异无显著性,D-D、PLG差异有显著性;3、慢血组和慢性乙型肝炎组比较:凝血功能和抗凝血功能差异非常显著,纤溶功能PLG差异非常显著而D-D差异无显著性;4、晚血组和肝硬化组比较:凝血功能除TT差异无显著性外PT、APTT、Fg差异有显著性,抗凝血功能和纤溶功能差异有显著性;5、慢性乙型肝炎和肝硬化比较:TT、Fg差异无显著性而PT、APTT差异有显著性,抗凝血功能和D-D差异有显著性,PLG差异无显著性。结论慢血、晚血、慢性乙型肝炎及肝硬化患者均存在一定程度的凝血、抗凝血和纤溶功能紊乱,且凝血、抗凝血及纤溶指标的检测有助于监测慢血、晚血、慢性乙型肝炎及肝硬化患者病情的出凝血功能。     

慢性病毒性肝炎患者血清抗氧化能力状况与乳果糖保护效应

目的研究不同内毒素水平的慢性病毒性肝炎患者血抗氧化能力差别,探讨乳果糖对慢性病毒性肝炎患者体内抗氧化能力的影响。方法 72例慢性病毒性肝炎患者根据内毒素水平分为两组,比较两组体内抗氧化水平;并随机分为乳果糖治疗组(n=36)和对照组(n=36),观察两组病人治疗前及治疗2周后血清抗氧化能力、血内毒素水平的变化。结果内毒素血症阴性患者(内毒素水平<45ng/L)与内毒素血症阳性患者(内毒素水平≥45ng/L)比较,丙二醛(MDA)水平降低,超氧化物歧化酶(SOD)活性明显升高,差异均有统计学意义(t分别=4.27、-3.47,P均<0.05),而一氧化氮合酶(NOS)活性在两组间比较,差异无统计学意义(t=1.26,P>0.05)。Pearson相关性分析显示,血内毒素水平与MDA水平呈正相关(r=0.57,P<0.05),内毒素水平与SOD和NOS水平呈负相关(r分别=-0.62、-0.30,P均<0.05)。乳果糖治疗组治疗后血中SOD水平和NOS水平明显升高,MDA和内毒素水平明显下降,治疗前后差异均有统计学意义(t分别=-3.88、-3.12、4.69、3.74,P均<0.05)。且与对照组治疗后比较,SOD水平升高,内毒素水平下降,差异均有统计学意义(t分别=-3.08、3.19,P均<0.05),但两组治疗后MDA和NO水平差异均无统计学意义(t分别=1.63、-1.54,P均>0.05)。结论乳果糖能改善慢性病毒性肝炎患者抗氧化系统损伤,可能与降低血清内毒素水平有关。     

慢性丙型肝炎患者HCV不同功能区抗体的随访研究

目的　探讨慢性丙型肝炎患者不同功能区抗体的免疫应答。方法　利用基因重组克隆表达丙型肝炎病毒HCV c、NS3、NS4、NS5和HVR1抗原 ,分别包被酶联板 ,以间接ELISA法检测 1991～ 2 0 0 2年采集的 5 8名丙型肝炎患者的 14 4份血清不同功能区抗 HCV。结果　其中 5 0名 (86 .2 0 % )慢性丙型肝炎患者血清 5种相应抗 HCV呈持续阳性。结论　慢性丙型肝炎患者体内HCV c、NS3、NS4、、NS5和HVR1抗体无明显变化 ,未发现这 5种抗体与自愈的关系。