2000年2月份全国疾病监测点35种法定传染病疫情动态分析

本研究通过对我国部分地区的自然人群和非甲非戊型肝炎病人进行HGV和TTV感染的分子流行病学研究,探讨这两种病毒在我国肝炎发病尤其是在非甲非戊型肝炎中的作用和地位.用建立的PCR方法检测血清标本中的HGV RNA和TTV DNA,对调查的自然人群和非甲非戊型肝炎病人血清标本进行检测.HGV RNA采用反转录PCR(RT-PCR)检测,TTV DNA则采用巢式PCR方法检测.结果表明,HGV在自然人群中HGV RNA携带率为0.6%～1.1%,TTV的病原携带率则高达7.1%～12.4%;非甲非戊型肝炎病人中HGV和TTV的阳性率分别为7.9%和28.1%.在所检测的非甲非戊肝炎病人中HGV和TTV的总感染率为35.9%(包括了HGV和TTV的混合感染).因此,HGV在自然人群中感染率低,而且在非甲非戊型肝炎病人中约为10%的病人是由HGV的感染所致,HGV不是非甲非戊型肝炎病人的主要病因.TTV DNA在自然人群中的携带率约为10%,类似于HBV DNA的携带率.虽然在非甲非戊型肝炎病人中TTV DNA的阳性率为28%,但仍然有高达60%的病人病因不明,TTV感染也不是非甲非戊型肝炎病人的主要致病病原.     

HGV和TTV不是我国非甲非戊型肝炎的主要病因

本研究通过对我国部分地区的自然人群和非甲非戊型肝炎病人进行HGV和TTV感染的分子流行病学研究 ,探讨这两种病毒在我国肝炎发病尤其是在非甲非戊型肝炎中的作用和地位。用建立的PCR方法检测血清标本中的HGVRNA和TTVDNA ,对调查的自然人群和非甲非戊型肝炎病人血清标本进行检测。HGVRNA采用反转录PCR(RT -PCR)检测 ,TTVDNA则采用巢式PCR方法检测。结果表明 ,HGV在自然人群中HGVRNA携带率为 0.6 %～ 1.1% ,TTV的病原携带率则高达 7.1%～ 12.4 % ;非甲非戊型肝炎病人中HGV和TTV的阳性率分别为 7.9%和 28.1%。在所检测的非甲非戊肝炎病人中HGV和TTV的总感染率为 35 9% (包括了HGV和TTV的混合感染 )。因此 ,HGV在自然人群中感染率低 ,而且在非甲非戊型肝炎病人中约为 10 %的病人是由HGV的感染所致 ,HGV不是非甲非戊型肝炎病人的主要病因。TTVDNA在自然人群中的携带率约为 10 % ,类似于HBVDNA的携带率。虽然在非甲非戊型肝炎病人中TTVDNA的阳性率为 2 8% ,但仍然有高达 6 0 %的病人病因不明 ,TTV 感染也不是非甲非戊型肝炎病人的主要致病病原。     

TTV病毒一例阳性报告

TTV是继甲、乙、丙、丁、戊及庚型肝炎病毒之后又发现的一种新型肝炎相关病毒。最初由日本学者于 1 997年底从一例输血后的非甲～戊型肝炎病人血清中分离 ,命名为TT病毒 ( Transfusion-Transmitted Virus)。TTV为一单链 DNA病毒 ,无胞膜 ,基因全长约为 3 .7kb,有 ORF1和 ORF2两个开放读码区 ,分别编码 770和2 0 2个氨基酸。TTV有两个基因型 ,四个基因亚型 ;呈全球型分布。我院 1 999年 9月开展了 TTV-Ig G病毒的检测 ,采用酶联法 (试剂 :北医大肝病研究所 ,北京肝炎试剂研制中心 )至今已检测 1 1 8例 ,检测阳性病人 1例。病人 :…     

HBsAg阳性肝病患者血清TTV抗体的检测

输血传播病毒(TTV)最早由Nishizawa等于1997年从1例不明原因的输血后非甲～庚型肝炎患者血清中发现。尽管在许多原因不明的重症肝炎和不明原因的ALT升高患者血清和肝组织中能够检测到TTV DNA，但关于TTV的致病性和在其他病毒性肝炎(甲～庚型)中的作用以及TTV是     

肝病患者血清中抗-TTV的检测及临床意义

迄今 ,已发现的可导致人类肝炎的嗜肝病毒有甲、乙、丙、丁、戊五种肝炎病毒〔1〕 ,但仍有 3 .5～ 2 0 %的肝炎病人病因不明。 1 995年美国学者发现了庚型肝炎病毒( HGV) 〔2〕。新近研究表明 HGV不是非甲～戊型肝炎病人的主要致病因素。提示在非甲～庚型 6种肝炎病毒之外 ,还存在其它尚未被发现的病原体 ,1 997年底日本学者Okamoto等〔3〕从 1例输血后肝炎病人血清中分离到一种新的肝炎相关病毒基因 ,命名为 TT病毒 ( trarsfusiontransmitted virus)。为了解肝病患者 TTV感染情况 ,本文对 1 98例肝炎病人和 1 0 0名供血员血清中抗 -T…     

TT病毒DNA PCR-ELISA检测方法的建立

目的:建立检测TT病毒(TTV)DNA快速、敏感、特异的PCR-ELISA方法。方法:将生物素标记的PCR产物与地高辛标记的特异性探针杂交。通过酶免疫显色反应测出A值,判断TTV感染情况。优化反应条件,与PCR电泳结果比较,测定方法的敏感性,并检测325份正常人群、甲～庚型肝炎、非甲～庚型肝炎血清标本,确定该方法的特异性。结果:本实验的最佳杂交时间为45min,最佳探针浓度为4pmol/mL。该方法的检测阈值为50fg/μL TTV DNA,其灵敏度是PCR电泳法的10倍,检测TTV在正常人群、甲～庚型肝炎、非甲～庚型肝炎血清标本中的阳性率分别为2.4%、29.3%、25.0%,与PCR电泳检出结果差异无显著性(P>0.05)。结论:PCR-ELISA是一种快速、敏感、特异的检测方法,可用于临床TTV感染的诊断。     

盐城地区不同人群TTV DNA和抗-TTV IgG的调查

近年来 ,人们发现除甲、乙、丙、丁、戊五种肝炎外 ,尚有 1 0 %～ 1 5 %的肝炎原因不明。1 997年底日本学者 Nishizawa等 [1 ]报道从输血后肝炎病人血清中分离出一种新的肝炎相关病毒 ,暂命名为输血传播病毒 (Transfusion transmitted virus,TTV) ,1 998年 Okamoto报道了 [2 ] TTV全序列 ,我国学者周育森等 [3]证实了我国存在 TTV。笔者应用 PCR-微孔板杂交显色法和 ELISA法对不同人群进行TTV DNA及抗 -TTV Ig G调查 ,现报告如下。材料与方法1　标本来源　正常人群 1 0 1例为本院健康体检者 ,其中男 68例 ,女 3 3例 ,年龄 2 2…     

TTV研究进展

肝炎病毒学研究表明 ,肝炎病毒的种类繁多并不断发生变异。目前 ,国际病毒分类与命名委员会将具有明确的血清学和可靠分子生物学诊断方法的五种肝炎病毒命名为甲型肝炎病毒、乙型肝炎病毒、丙型肝炎病毒、丁型肝炎病毒及戊型肝炎病毒。然而 ,人们在对肝炎进行诊断及治疗过程中发现 ,除了已明确的五种肝炎病毒所至的肝炎外 ,还有10 %～ 2 0 %的肝炎病因不明 ,称为非甲～戊型肝炎。随后 ,发现了庚型肝炎病毒使得非甲～戊型肝炎中的部分病因得以明确。然而 ,仍有部分肝炎病因不明 ,人们对肝炎的病因仍在不断探索之中。1　 TTV的发现及流行趋…     

中国河南TTV分离株部分基因的克隆及序列测定

TTV是1997年底由日本学者首先发现的一种单链DNA病毒。随后的研究表明它与转氨酶异常有密切关系,并认为是一种与输血后肝炎有关的病毒。今年2月军事医学科学院的研究者首先证实我国人群中存在这种病毒的广泛感染。河南省历来是肝炎高发的地区之一,以往的研究表明存在大量的非甲非戊型肝炎病人和病原不明的输血后肝炎病例。为了证实我省是否存在TTV的感染以及了解TTV的感染状况,我们检测了部分非甲非戊型肝炎病人和献血员的标本并对河南株TTV的部     

TTV感染研究进展

自 198 9年人类克隆成功丙型和戊型肝炎病毒 ,病毒性肝炎被分为甲、乙、丙、丁、戊型 ,并建立了特异性的检测手段 ,但仍有 10 %～ 2 0 %病毒性肝炎的病例不能分型。 1995年Ｓｉｍｏｎｓ[1] 等和ｋｉｍ等分别用代表性差异分析法 ,从非甲—非戊型肝炎患者血清中获得庚型肝炎病毒 (ＨＧＶ)克隆。虽庚型肝炎病毒部分地解释了非甲—非戊型肝炎的病因 ,但ＨＧＶ感染更多地发生于ＨＢＶ或ＨＣＶ感染患者[2 ,3] ,且对肝脏的致病性尚未完全得到证实 ,提示尚有甲戊型肝炎病毒以外的病毒引起急、慢性肝炎。 1997年 ,Ｎｉｓｈｉｚａｗａ等[4 ] 应用代表…     

肝炎患者中TT病毒DNA及其IgG抗体的检测

目的：了解肝炎患中TTV的感染情况，方法：应用Nested-PCR对137份甲－庚型肝炎、31份非甲－庚型肝炎及104份献血员进行TTV DNA检测，同时用ELISA法检测抗TTVIgG。结果：TTV基因检出率分别为甲－庚型肝炎20．44％，非甲－庚型肝炎29．03％，献血员13．46％，抗TTVIgG检出率分别为甲－庚型肝炎27．74％，非甲－庚型肝炎35．48％，献血员14．42％；甲－庚型肝炎、非甲－庚型肝炎与献血组相比TTV DNA及抗TTV IgG均存在显性差异（P＜0．01）。结论：肝病中存在TTV感染，TTV存在健康携带状态。     

应用聚合酶链反应检测南京地区TT病毒感染

目的：了解南京地区TT病毒感染情况。方法：采用巢式PCR方法检测血清标本中TTV－DNA。结果：163例病毒性肝炎患者血清标本中,TTV－DNA总检出率为21.5％（35／163）,其中甲型肝炎13.3％（4／30）,乙型肝炎21.3％（16／75）,丙型肝炎20.0％（3／15）,戊型肝炎5.3％（1／19）,非甲－庚型肝炎45.8％（11／24）。结论：南京地区存在TTV感染,TTV是导致非甲－庚型肝炎的重要病因,TTV可能存在非血源性传播途径。     

TT virus infection does not affect the clinical profiles of patients with hepatitis B and C in Yanbian City,China

China is an area of high endemicity for viral hepatitis, and the molecular epidemiological investigation of TT virus (TTV) infection is of interest. In the present study, we investigated the epidemiology, clinical significance and molecular characteristics of TTV infection in patients with chronic hepatitis B and C in Yanbian City, China. Serum samples obtained from 74 patients with hepatitis B and hepatitis C who visited Yanbian Hospital, located in northeast China, were analyzed in this study. The study group included 22 cases of chronic hepatitis B (B-CH), 17 cases of liver cirrhosis B (B-LC), 7 cases of hepatocellular carcinoma (B-HCC), 16 cases of chronic hepatitis C (C-CH), 11 cases of liver cirrhosis C (C-LC) and 1 case of hepatocellular carcinoma (C-HCC). Detection of TTV DNA was performed as described by Nishizawa et al. The second-round PCR products from 7 subjects were sequenced, followed by investigation of nucleotide homology and phylogenetic analysis. TTV DNA was present in 18.2, 5.9, 28.6, 6.3, 9.1 and 0% of the patients with B-CH, B-LC, B-HCC, C-CH, C-LC and C-HCC, respectively. The highest prevalence of TTV infection was seen in the groups aged 40-50 and over 60 years. There was no significant correlation between the presence of TTV DNA and the clinical parameters in patients with hepatitis B and C. The various isolates showed 97.9-100% with isolates reported previously from Japan and 98.4-100% with isolates reported previously from China. Nucleotide sequence analysis revealed that the Yanbian isolates could be classified in the same group as the Japan and China isolates. We concluded that chronic coinfection with TTV did not affect the serological features of chronic hepatitis B and C in China, as found in Tokyo, Japan.     

TT virus infection in Japanese children: isolates from genotype 1 are overrepresented in patients with hepatic dysfunction of unknown etiology

The pathogenecity of the TT virus (TTV) especially during childhood remains obscure. We investigated the prevalence of TTV in 40 patients with non-A to C hepatic dysfunction (non-A to C hepatic dysfunction group). Five patients with fulminant hepatitis of unknown etiology were enrolled in this group. We also examined 380 children without a history of transfusion or liver disease (control group). Subsequently, the genotypes of TTV strains isolated were analyzed in terms of their nucleotide sequences including 222 bp in the open reading frame 1 region. The prevalence of serum TTV DNA was 10/40 (25%) in the non-A to C hepatic dysfunction group and 25/380 (7%) in the control group. Sixty-six percent (23/35) of all examined cases exhibited either genotype 1 or 2. However, assessment of genotype in the non-A to C hepatic dysfunction group (10 cases) revealed a higher prevalence of genotype 1 than of all other genotypes (80% vs. 20%). This result differed significantly from that of the control group (25 cases; 32% vs. 68%). Such overrepresentation of genotype 1 suggests that this type of TTV strain is associated with the development of hepatic dysfunction of unknown etiology in Japanese children.     

Detection of TT virus DNA in patients with non-A to G liver diseases]

A novel single-stranded DNA virus, TT virus(TTV), has been reported recently. We detected TTV viral sequences by polymerase chain reaction using primers derived from nucleotide sequences of ORF1 and the 5' noncoding region of ORF2. Using primers of the 5' noncoding region, TTV DNA was detected in 21 of 25(84%) healthy individuals, suggesting that most TTV strains detected by these primers are almost harmless. In contrast, using primers of ORF1, which detect genotype 1a TTV that was reported to be a causative agent of posttransfusion hepatitis, TTV DNA was detected in only 3 of 25 healthy subjects and 3 of 27 acute and 9 of 72(12%) chronic non-A to G hepatitis patients. Whether these TTV strains actually cause hepatitis remains to be determined.     

Roles of TT virus infection in various types of chronic hepatitis

An unenveloped single-stranded virus, which might be a causative agent for posttransfusion non-A-G hepatitis, was recently found and named "TT virus" (TTV). There is still controversy over the role of TTV in chronic hepatitis. Therefore, we have examined the prevalence of TTV in various types of chronic hepatitis in Japan. TTV DNA was detected in 11 of 40 patients (27.5%) with non-B, non-C chronic hepatitis, 13 of 46 patients (28.3%) with type B chronic hepatitis, 21 of 55 patients (38.2%) with type C chronic hepatitis, and 41 of 131 subjects (31.3%) with normal liver function tests. The positivity rate for TTV DNA tended to increase with age. The detection rate did not differ statistically between non-B, non-C chronic hepatitis and type B or type C chronic hepatitis, or normal subjects. The distribution of TTV genotypes was not significantly different among them. Clinical characteristics of the chronic illness were similar for patients with or without TTV in all hepatitis groups. The etiologic role of TTV in chronic hepatitis is not confirmed from the statistical and clinical standpoint.     

Prevalence of TT virus in serum and peripheral mononuclear cells from a CAPD population.

BACKGROUND: A novel virus named TT virus (TTV) has been isolated recently from patients with posttransfusional hepatitis of unknown etiology. The prevalence of TTV in several groups at risk has been reported, however, there is no information about the prevalence of TTV in patients on continuous ambulatory peritoneal dialysis (CAPD) without blood transfusions or hemodialysis antecedents. OBJECTIVE: To study the incidence of TTV in serum and peripheral blood mononuclear cells (PBMC) of CAPD patients. DESIGN: TTV DNA was detected by polymerase chain reaction, using primers from the open reading frames (ORF) 1 and 2, in serum and PBMC from 22 CAPD patients who had not received blood transfusions or hemodialysis therapy prior to CAPD. As controls, sera from 20 patients with chronic viral hepatitis (10 with HBV and 10 with HCV) and 20 healthy donors were included in the study. RESULTS: TTV DNA was detected in the serum of 5 of 22 (22.7%) CAPD patients with both sets of primers. Four of the 5 (80%) patients with TTV DNA in their serum were TTV positive in their PBMC with primers from ORF1 and ORF2. Five of 20 (25%) patients with chronic viral hepatitis (2 patients with HBV and 3 with HCV) and 4 of 20 (20%) healthy donors were TTV DNA positive in serum. No relation was found between TTV infection and the underlying kidney disease, previous surgery, and abnormal alanine aminotransferase levels. CONCLUSION: We have found a relatively high prevalence of TTV that is similar to that found in healthy donors and in patients with chronic viral hepatitis.     

TT virus(TTV) infection in patients with acute hepatitis]

A novel DNA virus, TT virus(TTV), has been reported in patients with posttransfusion hepatitis of unknown etiology. However association between TTV and acute hepatitis has not been shown. We investigated the prevalence of TTV in acute hepatitis. TTV-positive rates in acute hepatitis A, B, C, cytomegalovirus infection, Epstein-Barr virus infection, and acute hepatitis of unknown etiology were 15.3%, 21.8%, 60.0%, 0%, 10.0%, 22.6%, respectively. There were no significant differences in TTV prevalence between each etiology and healthy blood donors(20.8%). Clinical data were similar between patients with or without TTV. In this study we could not find any difference in the prevalence of TTV between acute hepatitis with known etiologies and that with unknown etiology. TTV did not affect the clinical features of acute hepatitis with known etiologies.     

TT virus infection in patients with hepatocellular carcinoma associated with non-A to G hepatitis: histopathological study]

To study if TTV infection is involved in the development of hepatocellular carcinoma (HCC), we tested the sera of 19 patients with HCC associated with non-A to G hepatitis for the presence of serum TTV DNA, and compared the blood chemistry values and liver histology of the patients in the TTV DNA-positive and -negative groups. Detection of TTV DNA was performed described as Nishizawa, et al method. TTV DNA was detected in the sera of 47.4%. There were no significant differences in the blood chemistry results and other tests between the TTV-positive and -negative patients. Histological examination of the non-tumor regions of the liver showed that there were no significant differences in the number of areas and characteristics of the necro-inflammatory reactions, the degree of staging and irregular regeneration of hepatocyte between the two groups. These results suggest that the development of HCC in patients with non-A to G hepatitis is not associated with TTV infection.     

Frequency of hepatitis G virus and transfusion-transmitted virus infection in type II diabetes mellitus

The hepatitis G virus (HGV) and transfusion-transmitted virus (TTV) are recently defined hepatitis viruses that the pathogenic roles in liver diseases are still not clear. It has been well known that some hepatitis virus, such as hepatitis C, might have an affinity to pancreatic islet cells. To investigate the relationship between the newly defined hepatitis viruses and diabetes mellitus (DM), we studied the prevalence of TTV and HGV in a type 2 diabetic patient population. Serum samples of 60 patients with DM and 45 healthy volunteers as control were taken. HGV RNA and TTV DNA was investigated by polymerase chain reaction. HGV was detected in none of diabetic patients (0%) and only one in control group (2.2%). However, TTV DNA was detected in 16 patients with DM (26%) and in five controls (11%). TTV was more prevalent in diabetic patients, but the difference between groups was not statistically significant (p > 0.05). These results revealed that TTV is more common in diabetic patients than in controls. At present, we don't know if this result is only a coincidence or a sign of potential association between TTV and DM. Further studies are certainly needed to elucidate a potential relationship.