兰州地区TTV感染的血清学及临床研究

研究兰州地区供血员 ,静脉毒瘾者和肝病患者中TT病毒 (TTV)的感染状况及致病性。采用套式PCR技术检测 12 0例供血员 ,5 6例静脉毒瘾者和 74例肝病患者血清中TTVDNA。供血员TTVDNA检出率为7 5 % (9/12 0 ) ;静脉毒瘾者中TTVDNA检出率为 2 6 8% (15 /5 6 ) ;肝病患者中TTVDNA检出率为 13 4% (10 /74)。肝病患者的感染率与供血员和静脉毒瘾者相比 ,无显著性差异 (P >0 0 5 )。在 10例TTVDNA阳性患者 ,6例为单一TTV感染 ,4例ALT增高 ,3例呈急性肝炎的临床症状。TTV感染可经血液和胃肠道传播 ,多呈病毒携带状态 ,也可单独引起急性肝炎 ,但致病性较弱。对TTV的病原学、流行病学和临床意义还有待进一步研究。     

南京地区TT病毒感染分子流行病学及临床研究

了解南京地区TTV(transfusion transmitted virus)感染情况,重叠TTV感染对慢性乙型肝炎病变程度和HBV复制的影响。采用巢式PCR(nested polymerase chain reaction)检测血清中TTV DNA。469份血清中,TTV DNA总检出率为21.1％,其中健康人群、献血员、血透患者、甲型肝炎、乙型肝炎、丙型肝炎、戊型肝炎、庚型肝炎、非甲-庚型肝炎检出率分别是9．4％、33．3％、30.8％、11.6％、19．9％、15.4％、8．7％、9．5％、34.1％;有28例慢性乙型肝炎合并TTV感染,轻度、中度和重度各组患者中TTV检出率无显著差异,TTV阳性与阴性组之间肝功能改变相近,HBeAg或TTV DNA阳性与阴性组之间TTV检出率相当。结论：南京地区存在TTV感染,TTV是导致非甲-庚型肝炎的重要原因,TTV可能存在非血源性传播途径;慢性乙型肝炎重叠TTV感染对病变程度和HBV复制无明显影响。     

输血传播性病毒的流行病学及临床研究

目的:观察分析不同人群中TTV(transfusion transmitted virus)感染状况及相关临床意义。方法:在TTVORF1设计引物,建立巢式聚合酶链反应,检测不同人群中血清TTV DNA,并对比观察肝炎病人的临床表现。结果:29例健康人群,27例职业献血员,56例乙型肝炎,31例丙型肝炎和47例非甲～非庚型肝炎患者中,TTV DNA阳性率分别为6.9％、3.7％、23.2％、25.8％和42.6％。3种肝炎病人中,TTV DNA阳性和阴性组间4项主要临床指标无显著差异。结论:健康人群和职业献血员存在TTV健康携带者。非甲～非庚型肝炎患者TTV感染率最高。乙型和丙型肝炎患者重叠TTV感染较常见。3种肝炎病人中,合并TTV感染组与非感染组临床表现无明显差异。TTV的致病性尚待深入研究。     

人类免疫缺陷病毒感染的静脉吸毒者TT病毒的检测和部分基因序列分析

目的 研究人类免疫缺陷病毒（HIV）感染的静脉吸毒者TT病毒（TTV）感染情况和基因序列变化。方法 用聚合酶链反应（PCR）对35例HIV感染的静脉吸毒者（IVDUs),64例HIV未感染的IVDUs及45例正常献血员进行TTV DNA检测。对其中2例HIV感染的IVDUs和1例HIV未感染的IVDUs的TTV DNA部分基因核苷酸序列进行测定。结果 TTV DNA在HIV感染的IVDUs中检出率为25．71％（9／35）,HIV未感染的IVDUs中检出率为17．18％（11／64）,两者差异无显著性（P＞0．05）,正常献血员中的检出率为2．2％（1／45）。对2例HIV感染的IVDUs TTV DNA部分基因核苷酸序列与日本株比较,其同源性分别为96．44％和95．79％,对1例HIV未感染的IVDUs的TTV DAN部分基因核苷酸序列与日本株比较其同源性为98．25％;HIV感染和HIV未感染的IVDUs TTV DNA核苷酸序列比较,HVI感染者在被测定序列的第299－309位碱基有较大的变 异。结论 静脉吸毒是TTV感染的高危因素,TTV在IVDUs中感染率与HIV感染无明显相关性;HVI感染和HIV未感染者TTV DNA序列可能存在一定差异。     

急性非甲-庚型肝炎病人血清TTV DNA检测分析

目的为了解非甲-庚型肝炎的病原学感染状况,对献血员24例、急性非甲-庚型肝炎31例血清采用PCR技术进行输血传播病毒(TTV)检测。结果献血员TTV DNA阳性率为12.5％(3/24);急性非甲-庚型肝炎阳性率为41.94％(13/31),两者差异有非常显著意义(P<0.001)。结论 TTV除导致肝炎外还能以携带方式存在,深入研究TTV对肝炎和携带者的防治具有重要意义。     

肝细胞癌患者血清TT病毒感染检测分析

目的 调查TT病毒在肝细胞癌患者及南通地区正常人群中的感染状况。方法 采用巢式聚合酶链反应(n—PCR)法，对145例肝细胞癌患者、143例献血员和375例体检者血清进行了检测分析。结果 145例肝细胞肝癌患者中有48例TTV DNA阳性(33．1％)，献血员中有13例TT病毒DNA阳性(9．1％)，正常体检人群中有39例TT病毒DNA阳性(10．4％)。肝细胞癌患者中TT病毒感染率明显高于献血员和正常人群。结论 TT病毒与肝细胞癌发生有一定的关系，是导致肝癌的一个危险因素。     

236例肝炎患者TT病毒感染情况分析

目的 了解广东地区肝炎患者TTV感染情况及TTV感染与肝功能关系。方法 用巢式聚合酶链反应,检测本院236例住院肝炎患者中TTV DNA阳性情况,并检测其肝功能指标。结果 在236例肝炎患者中TTV DNA检出率为5.9％(14/236),其中非甲～庚型肝炎TTV DNA阳性率为14.3％(5/35),乙型肝炎中TTV DNA阳性率为4.4％(7/140),乙型肝炎中TTV DNA阳性及TTV DNA阴性患者各项生化指标无差异。结论 TTV DNA在非甲～庚型肝炎中检出率明显高于其他肝炎,说明TTV可能为部分非甲～庚型肝炎的致病原因,TTV DNA在乙型肝炎中检出率较低,可能为乙型肝炎病毒影响TTV存在。乙型肝炎合并TTV感染未明显加重病情。重型肝炎中未检测到TTVDNA。     

成都地区新型肝炎病毒TTV的临床研究

目的了解成都地区是否存在新型肝炎病毒TTV感染，以及TTV感染后致病性探讨。方法对成都地区健康人群、非甲-庚型肝炎患者及甲-庚型肝炎患者采用PCR检测血清TTVDNA，并对单-TTV感染的急、慢性肝炎患者进行临床资料分析和随访。结果①成都地区健康人群中TTV DNA阳性率7．5％(3／40)，职业献血员中为21．9％(7／32)，非甲一庚型肝炎中为31．6％(42／133)。②单一TTV感染肝炎患者中76．2％(32／42)临床表现为急性肝炎，14．3％(6／42)慢性肝炎，7．1％(3／42)重型肝炎，2．4％(1／42)肝炎肝硬化。③随访观察单一TTV DNA急性肝炎12例，半年内临床症状及肝功能恢复正常，11例TTV DNA阴转，8．3％(1／12)TTV DNA持续阳性1年以上。随访慢性肝炎单一TTV DNA阳性4例，2例在2年内肝功恢复正常，TTV DNA阴转，另2例发展成重型肝炎和肝硬化，近期无死亡病例。结论①成都地区存在TTV感染。②单一TTV感染除可表现为健康携带和肝炎恢复期慢性携带状态外，可引起临床急性、慢性、重型和肝硬化等多种临床类型的肝脏病变，还可和其他已知的肝炎病毒形成二重或多重感染。研究结果支持TTV可能是另一种致肝损害的新型肝炎病毒，是至今原因不明的病毒性肝炎的病原学之一。     

TTV在非甲～庚型肝炎患者中的检测及序列分析

目的研究TTV在非甲-庚型肝炎患者中的感染状况及临床意义。方法 采用套式PCR法检测50例非甲-庚型肝炎患者血清标本中TTV DNA,并对其中一株TTV的部分基因序列进行了测定。结果 在50例肝炎患者中,TTV DNA阳性检出率为28.0％(14/50)。TTV序列分析与日本株的同源性为98％。结论TTV感染可能是非甲-庚型肝炎的病因之一。     

用微板核酸杂交—ELISA技术检测不同人群TTV感染状况

目的 用微板核酸杂交—ELISA技术检测皖北地区不同人群TTV感染情况。方法 用PCR法将病人血清标本中的TTV DNA扩增后,与两条特异性探针夹心杂交,通过酶联显色检测血清标本中的TTV DNA并进行分型。结果 TTV DNA在学生、血透患者、肝病患者中的阳性率分别为3.3％、16.7％和13.5％,前者与后两者比较差异均有显著性(P<0.05)。14例NA～NE肝炎的TTV DNA阳性率为14.3％。本地区流行的TTV可分为两个主要基因型,其中以Ⅰ型为主(66.7％),Ⅱ型次之(25％),少部分存在混合感染(8.3％)。结论 安徽省皖北地区一般人群、血透患者和肝病患者中均存在TTV感染,后两者为TTV感染的高危人群。TTV不是本地区NA～NE肝炎的主要病因。安徽省皖北地区流行的TTV的基因型以Ⅰ为主。     

武汉地区职业献血员血清TTV等病毒核酸的检测

目的 调查武汉地区既往职业献血员血清TTVV DNA及其他几种肝炎病毒基因的状况与特点。方法采用PCR或巢式PCR对74例既往乡村献血员进行血清TTV DNA及HCV RNA、HGV RNA的检测。结果 TTVDNA、HCV RNA及HGV RNA阳性检出率分别为43.2％、23.0％与2.7％,TTV DNA检出显著高于其他肝炎相关病毒,HCV RNA阳性率显著高于HGV RNA阳性率。结论 既往长期的献血已造成地区乡村职业献血员TTV与HCV感染率的显著升高。     

上海地区血液透析患者与供血者中输血传播病毒DNA检测及部分核苷酸序列分析

目的　了解上海地区暴露于血及血制品的血透患者中输血传播病毒（ＴＴＶ）感染率。方法　采用套式ＰＣＲ技术,检测了 ６例血透患者和 ４９例供血员血清中 ＴＴＶ ＤＮＡ,并对其中各 １例 ＰＣＲ产物（２７２ｂｐ）测］３。结果血透患者ＴＴＶ ＤＮＡ的检出率为 ３２．８％（２０／６１）,供血员的检出率为 ２４． ５％（１２／４９）。 ２０例 ＴＴＶＤＮＡ阳性血透患者中,６例为单纯ＴＴＶ感染,６例为ＴＴＶ、ＨＣＶ及ＨＧＶ重叠感染,４例为ＴＴＶ、ＨＣＶ和４例为ＴＴＶ、ＨＧＶ重叠感染。在所有ＴＴＶ感染者中,仅发现１例血清ＡＬＴ升高,该病例为ＴＴＶ、ＨＣＶ及ＨＧＶ重叠感染。对ＰＣＲ阳性扩增产物２７２ｂｐ测序结果显示,上海株（ＳＨＰ、ＳＨＤ）核苷酸的同源性为９９．６％,与深圳株、２株日本株核着酸的同源性分别为９７．４％、９８．７％和９８．７％,表明ＴＴＶ上海株与深圳株及日本株（Ｎ２２、Ｇ１ａ）属同一亚型,首次证实了上海地区的ＴＴＶ感染。结论ＴＴＶ感染可经血传播。其致病性较弱,对ＴＴＶ的研究尚属开始,ＴＴＶ的病原学、流行病学及临床意义等问题还有待进一步探索和阐明。     

High frequencies of HGV and TTV infections in blood donors in Hangzhou

AIM: To determine the frequencies of HGV and TTV infections in blood donors in Hangzhou. METHODS: RT-nested PCR for HGV RNA detection and semi-nested PCR for TTV DNA detection in the sera from 203 blood donors, and nucleotide sequence analysis were performed. RESULTS: Thirty-two (15.8%) and 30 (14.8%) of the 203 serum samples were positive for HGV RNA and TTV DNA, respectively. And 5 (2.5%) of the 203 serum samples were detectable for both HGV RNA and TTV DNA. Homology of the nucleotide sequences of HGV RT-nested PCR products and TTV semi-nested PCR products from 3 serum samples compared with the reported HGV and TTV sequences was 89.36%, 87.94%, 88.65% and 63.51%, 65.77% and 67.12%, respectively. CONCLUSION: The infection rates of HGV and/or TTV in blood donors are relatively high, and to establish HGV and TTV examinations to screen blood donors is needed for transfusion security. The genomic heterogeneity of TTV or HGV is present in the isolates from different areas.     

A prospective study on TT virus infection in transfusion-dependent patients with beta-thalassemia

A novel DNA virus designated TT virus (TTV) has been reported to be involved in the development of posttransfusion non-A-C hepatitis. We evaluated the frequency and natural course of TTV infection in a cohort of transfusion-dependent thalassemic patients in a 3-year follow-up study. Ninety-three serum hepatitis C virus (HCV) antibody-negative patients (median age of 8 years; range, 0 to 25) from eight centers were studied. Of them, 34 (37%) had an abnormal alanine-aminotransferase (ALT) baseline pattern, and the other 12 (13%) showed ALT flare-ups during the follow-up. TTV DNA in patient sera collected at the time of enrollment and at the end of follow-up was determined by polymerase chain reaction (PCR). In parallel, serum samples from 100 healthy blood donors were also tested. At baseline, 87 patient sera (93.5%) tested positive for the TTV DNA. Of these TTV DNA-positive patients, 84 (96.5%) remained viremic at the end of the study period. Of the 6 TTV DNA-negative patients, 3 acquired TTV infection during follow-up. However, no definite relation was observed between the results of TTV DNA determination and ALT patterns. TTV viremia was also detectable in 22% of blood donors. In conclusion, TTV infection is frequent and persistent among Italian transfusion-dependent patients. The high rate of viremia observed in healthy donors indicates that the parenteral route is not the only mode of TTV spread.     

A prospective study of transfusion-transmitted virus transmission by blood transfusion

Recently, a new single-stranded DNA virus (TT virus, TTV) has been isolated and related to post-transfusion hepatitis. The aim of this study was to investigate the prevalence of TTV in blood donors and blood recipients, and the incidence of TTV transmission by blood transfusion. TTV DNA and serum markers of hepatitis B virus (HBV) and hepatitis C virus (HCV), were examined in 130 blood recipients, and the presence of TTV was studied in their 340 corresponding blood donors. The prevalence of TTV infection was 10.6% (36/340) in donors and 8.5% (11/130) in blood recipients, before transfusion. Eighteen subjects (15.1%) were found to be TTV positive, after transfusion, in the 119 blood recipients without TTV before transfusion; at least one of the corresponding donors was TTV positive. There were 46 subjects with post-transfusion hepatitis virus infection, 45 with HCV infection (including seven co-infected with TTV) and two with HBV infection (including one co-infected with HCV and one co-infected with TTV). The recipient with TTV and HBV co-infection and three of the seven patients with TTV and HCV infection had alanine aminotransferase (ALT) levels higher than 90Ul^–1, but only two of the 10 isolated TTV infections had a mild ALT elevation. These results show that prevalence of TTV was high in blood donors and hospitalized patients, and isolated TTV infection is not related to significant ALT elevation.     

TT virus infection in chronic liver disease.

BACKGROUND/AIMS: The exact role of the novel hepatotropic TT virus regarding the etiology of viral hepatitis, as well as the progression towards chronic liver disease has as yet not been defined. Moreover, the contribution of TTV infection to the course of chronic hepatitis B or C virus infections also still awaits clarification. Hence, the aim of our study was to investigate the impact of TTV infection on clinical severity and histology of chronic liver disease originating from HBV and/or HCV infections in Thai patients concomitant with the determination of TTV's association with non-B, non-C chronic liver disease and compared to its prevalence among voluntary blood donors. METHODOLOGY: DNA was extracted from the sera collected from 115 hepatitis B patients, 41 hepatitis C, and 48 negative for either viral marker, who had all been diagnosed with chronic liver disease ranging from chronic hepatitis over cirrhosis to hepatocellular carcinoma. The sera obtained from 200 voluntary blood donors served as controls. TTV DNA was amplified by seminested polymerase chain reaction (PCR) employing primers derived from the genome's most conserved region. The PCR products were analyzed by gel electrophoresis. Liver function tests were performed by means of a chemical analyzer. RESULTS: TTV DNA was detected in 20% of the HBV-positive and 19.5% of the HCV-positive chronic liver disease patients. Within the group of patients seronegative for both viral markers, TTV was detected in 8.3%. Furthermore, its DNA was identified in 6.8% of the HCC patients and finally, in 7% of the blood donors. Yet, no significant differences between TTV infected and non-infected patients were found as to demographic data, assumed source of infection, biochemical abnormalities, or severity of liver histology. CONCLUSIONS: TTV appears to be highly prevalent on a worldwide scale but regarding etiology of and progression towards serious liver disease, its contribution seems to be minor if not altogether non-existent. Hence, regarding clarification of its clinical significance, further studies are certainly required.     

TT virus infection in screened Taiwanese blood donors

OBJECTIVE: TT virus (TTV) is a newly discovered human DNA virus of uncertain clinical significance. The aim of this study was to determine the prevalence of TTV infection among blood donors in Taiwan. METHODS: Viral DNA was studied in 224 healthy blood donors and 118 deferred donors. DNA was extracted from plasma and amplified by seminested polymerase chain reaction with reported primer sets from a conserved region of the TTV genome. RESULTS: The prevalence of TTV DNA in the deferred donors was 24.6%, significantly higher than in the healthy donors (11.9%). TTV was also more prevalent in those with hepatitis B surface antigen than in those without it (p = 0.002). CONCLUSION: In comparing normal with deferred Taiwanese blood donors, hepatitis B virus infection is linked to a higher prevalence of TTV infection.     

Prevalence of TT virus infection in blood donors with elevated ALT in the absence of known hepatitis markers

OBJECTIVE: Recently a novel DNA virus (TT virus) has been identified in Japan and shown to be associated with elevated aminotransferase levels after blood transfusion. The exact role of TTV in the pathogenesis of liver disease is yet to be established. Our aim was to determine the prevalence and role of TTV in the pathogenesis of elevated transaminases in healthy blood donors in the absence of markers for viral hepatitis A-C. METHODS: Stored sera were collected from 99 healthy blood donors with elevated alanine amino transferase (ALT) values that were discovered at the time of blood donation. A total of 146 samples were obtained from healthy donors with normal ALT values who were used as controls. None of the patients or controls had a history of blood transfusion or had clinical signs of acute or chronic hepatitis. Serological markers for hepatitis A, hepatitis B, and hepatitis C viruses were negative. TTV DNA was amplified and detected using polymerase chain reaction followed by gel electrophoresis. RESULTS: Five of 99 (5%) samples obtained from donors with elevated ALT had TTV DNA detected by PCR, as compared to one of 146 (0.7%) of those with normal ALT (p = 0.006). Among those with elevated ALT, mean ALT values in patients with TTV (296 +/- 305 U/L) were higher than in patients without TTV (95 +/- 37 U/L), but the difference was not statistically significant (p = 0.08). The two samples with highest ALT values (both >450 U/L) were among the five samples with detectable TTV DNA in serum. CONCLUSIONS: Although TTV is not likely to explain the majority of elevated ALT cases in otherwise healthy blood donors, TTV infection may potentially be associated with some cases. Based on these findings, we propose that the role of TTV in the pathogenesis of acute and chronic liver diseases merits further investigation.