非甲～庚型肝炎患者中TTV感染的调查

目的了解TTV在我院非甲-庚型肝炎患者中的感染状况。研究TTV感染对非甲-庚型肝炎临床表现的影响,探讨TTV在病毒性肝炎中的致病作用。方法采用聚合酶链反应(PCR)斑点杂交法对我院108例非甲-庚型肝炎患者血清标本进行TTV DNA检测。结果非甲-庚型肝炎患者TTV DNA阳性率为14.8％(16/108),急、慢性肝炎及重型肝炎患者中TTV DNA的检出率无统计学差异。TTV阳性组与TTV阴性组肝脏临床及生化指标无显著性差异。结论TTV可能并非是导致肝脏功能损害的真正病原。     

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。     

TTV在非甲～庚型肝炎患者中的检测及临床意义

目的 研究TTV在非甲～庚型肝炎中的临床意义。方法 用聚合酶链反应(PCR)方法检测了50例非甲～庚型肝炎的TTV DNA。结果 在50例肝炎患者中,TTV DNA阳性检出率为28.O％(14/50)。结论 TTV感染可能是非甲～庚型肝炎的病因之一。     

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。     

山东地区输血传播病毒(TTV)检测及部分基因克隆和序列测定

目的 了解TTV山东分离株感染状况及基因变异的情况。方法应用逆转录聚合酶链反应(PCR)检测26例山东地区非甲-庚型肝炎和12例肝细胞癌患者血清中TTV DNA,并对阳性扩增的产物利用PCR技术直接克隆和测序,分析其基因变异的情况。结果26例非甲-庚型肝炎中11例TTV DNA阳性(42％)。对其中两株(TTVSD4、TTVSD5)部分基因克隆测序,并与日本株(ABOO8394)相比较,其核苷酸旬同源性为99.9％和100％。而12例肝细胞癌患者中3例TTV DNA阳性(25％),对其中一株(TTVSD6)部分基因克隆与测序,与日本株(ABOO8394)相比较,其核苷酸序列同源性为99％;TTV山东株三株间核苷核同源性均为99％。结论本研究证实山东地区非甲-庚型肝炎和肝细胞癌患者中存在着较高TTV感染,TTV感染可能具有嗜肝性,而且可能与肝功能损害有关,是引起非甲-庚型肝炎的重要病原。     

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。     

山东泰安地区部分人群中TTV感染调查及TTV山东株部分基因序列分析

目的 了解山东地区输血后丙型肝炎和非甲～庚型肝炎病例中TTV感染及基因变异的状况。方法应用套式PCR方法检测41例输血后丙型肝炎和16例非甲～庚型肝炎患者血清中TTV DNA,并对其中阳性的2例扩增产物直接克隆测序,分析其基因变异的情况。结果 41例输血后丙型肝炎患者血消中TTVDNA阳性检出率为19.5％(8/41),而16例非甲～庚型肝炎患者血清中阳性检出率为31.3％(5/16)。TTV山东第一株序列和山东第二株序列相应位置核苷酸同源性与日本株和中国第一株相比较分别为94％和91％;山东TTV的两株序列间同源性为91％。结论 本项研究证实山东地区输血后丙型肝炎和非甲～庚型肝炎患者中存在较高TTV感染,输血可能为传播TTV感染途径之一,是否该地区存在着不同的TTV亚型还有待于进一步调查证实。     

山东泰安地区TTV检测和部分基因克隆及序列测定

目的 探讨山东非甲-庚肝炎和肝癌患者输血传播病毒(TTV)感染状况和基因变异情况。方法 应用逆转录聚合酶链反应(PCR)检测26例山东泰安地区非甲-庚型肝炎和12例肝细胞癌(HCC)患者血清中TTVDNA，并对阳性扩增的产物利用PCR技术片段直接克隆和测序，分析其基因变异的情况。结果 26例非甲-庚型肝炎中11例TTVDNA阳性(42．3％)。对其中两株(TTVSD4、TTVSD5)部分基因克隆测序，并与日本株(AB008394)相比较，其核苷酸序列同源性分别为99．9％和100％。而12例肝细胞癌患者中3例TTVDNA阳性(25．0％)，对其中一株(TTVSD6)部分基因克隆与测序，与日本株(AB008394)相比较，其核苷酸序列同源性为99％；TTV山东泰安三株问核苷酸同源性均为99％。结论 研究证实山东泰安地区非甲～庚型肝炎和肝细胞癌患者中存在着较高TTV感染，TTV感染可能具有嗜肝性，而且可能与肝功能损害有关，是引起非甲～庚型肝炎的重要病原。     

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。     

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1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。     

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。     

Impact of TT virus infection in acute and chronic, viral- and non viral-related liver diseases

BACKGROUND/AIMS: The prevalence and pathogenicity of TT virus, recently identified in patients with non A-non G post-transfusional hepatitis, are questioned. METHODS: We investigated the impact of this new viral infection in a large series of patients with non A-non G, cryptogenic, non-viral and viral-related, acute and chronic liver diseases (n=577) and blood donors (n=300). TTV DNA was detected in serum by hemi-nested polymerase chain reaction. Phylogenetic analysis was performed in 13 isolates. RESULTS: TTV DNA was detected in 6/25 and 15/127 patients with cryptogenic non A-non G acute and chronic liver disease, respectively. TTV DNA positive subjects with post-transfusional acute hepatitis scored negative before transfusion. TTV prevalence was increased in patients with cryptogenic non A-non G acute and chronic liver disease compared to blood donors (6/300; p<0.001) and non-viral-related chronic liver diseases (6/137; p<0.05). TTV/HBV coinfection was frequently identified (35/147), but this was not the case for HCV-infected subjects (4/77). Transaminase activity or liver histological score was not significantly increased among TTV positive, HBV infected or non A-non G patients. The HBV infection and Mediterranean origin were the risk factors associated with TTV infection. The majority of analysed sequences clustered in genotype 1 (8=1b; 3=1a). Two isolates showed homology to genotype 2. CONCLUSIONS: These results support the view that TTV is a widely spread infectious agent with a weak pathogenicity. It raises the possibility, however, that TTV might be implicated in a few cases of acute and chronic non A-non G hepatitis. TTV-DNA-analysed sequences are related to genotypes 1 and 2 described in Europe.     

TT virus infection in Thailand: prevalence in blood donors and patients with aplastic anemia

Aplastic anemia has been reported to occur after viral hepatitis of unknown etiology. Recently, TT virus (TTV), a novel DNA virus, was identified in a Japanese patient with posttransfusion non-A-E hepatitis. The prevalence of TTV infection was investigated among blood donors and patients with aplastic anemia in Thailand. Of 99 blood samples from blood donors, 37 tested positive for TTV DNA via semi-nested polymerase chain reaction (PCR) using TTV-specific primers. Seventeen percent of samples from blood donors younger than 20 were positive for TTV DNA, whereas 48% from donors older than 20 were positive. The high prevalence of TTV infection in Thailand is comparable to that reported in China (28%), Mongolia (43%), and Egypt (29%). Forty-two percent of newly diagnosed aplastic anemia patients tested also had TTV DNA in blood. The detection rate of TTV DNA in aplastic anemia patients does not differ significantly from rates in normal blood donors. Our present data thus argue against the role of this novel hepatitis-associated virus in the pathogenesis of aplastic anemia in Thailand. However, larger epidemiological studies may be needed to further evaluate their association.     

High prevalence of G1 and G2 TT-virus infection in subjects with high and low blood exposure risk: identification of G4 isolates in Italy

BACKGROUND/AIMS: A non-enveloped single-stranded DNA virus (TTV) was detected in Japanese patients with fulminant hepatitis (47%) and chronic liver disease of unknown etiology (46%) more frequently than in blood donors (12%). Subsequent studies, however, questioned the association of TTV with liver disease. We further investigated the role of this novel virus in liver diseases. METHODS: We tested 106 patients and 102 blood donors for TTV by polymerase chain reaction using conserved region primers. RESULTS: TTV DNA was found in 19 of 102 volunteer blood donors (18.6%) and in 27 of 106 patients with liver disease (25.5%): 10 of 28 chronic hepatitis B (35.7%), 9 of 28 chronic hepatitis C (32.1%) and 8 of 50 (16%) cryptogenic liver disease patients. Previous interferon treatment was not associated with a significantly lower prevalence of TTV infection. TTV prevalence was higher in patients with blood exposure (42.8%, 6/14) than in patients without risk factors (21.4%, 18/84). Four of five patients (80%) with HBV familial infection and without blood exposure were also TTV positive. Partial nucleotide sequences from 3 Italian isolates diverged more than 30% from the 2 prototype genotypes G1 and G2 and were 88% homologous to the recently described genotype G4. CONCLUSIONS: G1 and G2 TTV are common in Italy and in the USA in liver disease patients and in blood donors. The prevalence is high in patients with blood exposure but also in subjects without risk factors; other routes of transmission should therefore be considered.     

长春地区TT病毒的基因分型及其临床意义

为调查各种急、慢性肝炎中TT病毒的感染状况及临床意义,并检测TTV基因的分型。利用半套式PCR（semi-nested PCR）方法检测了TTV-DNA。利用邻近丁（neighbor-joining）法画出系统树。TTV-DNA的阳性率在非甲非乙非丙型急性肝炎中为42.3%,在非乙非丙型慢性肝炎中为45.5%。基因型可分为1a、1b、2a、2b等型。TTV-DNA在非甲非乙非丙型急性非乙非丙型慢性肝炎中的感染率最高;在TT病毒与乙型、丙型肝炎病毒混合感染的慢性肝炎中,TT病毒干涉乙型及丙型肝炎病毒造成的肝细胞损伤的可能性很小。     

丙型及非甲-庚型肝炎患者血清TTV检测及临床分析

目的 了解郑州地区不同肝病患者中ＴＴＶ（ｔｒａｎｓｆｕｓｉｏｎ ｔｒａｎｓｍｉｔｔｅｄ ｖｉｒｕｓ）感染状况及其临床特点。方法 自行设计ＴＴＶ ＯＲＦ１保守区的两对引物,对２０例非甲－庚型肝炎和９７例丙型肝炎患者血清进行ＰＣＲ检测,并对３０例资料完整的丙肝患者是否合并ＴＴＶ感染及其临床特点进行分析。结果 丙型和非甲－庚型肝炎患者血清ＴＴＶ ＤＮＡ检出率分别为１６．５％（１６／９７）和２０％（４／２     

TT virus infection in acute and chronic liver diseases and in patients regularly receiving blood products in Belgium

BACKGROUND: TT viruses are single-stranded DNA viruses, suggested to be involved in non A-E hepatitis. We studied the prevalence of TTV infection in acute or chronic hepatitis in Belgium in comparison with that in blood donors and in patients regularly receiving blood products. METHODS: TTV-DNA was detected by PCR using the primer set of Takahashi et al (1998) or a nested-PCR specific for genotype-2, because it had been reported that this subtype might be more pathogenic (Tagger et al. 1999). RESULTS: TTV-DNA was present in 49% of 128 patients with chronic hepatitis C, in 54% of 54 with chronic hepatitis B and in 54% of 24 with acute liver failure. This prevalence is similar to the 47% in 127 patients with clotting disorders, or the 64% in 103 undergoing chronic haemodialysis, but lower than the 29.7% found in 340 healthy blood donors. Significant differences in clinical or biochemical characteristics between TTV- positive or TTV-negative patients could not be substantiated. The genotype-2 subgroup comprised 3.9%, but they also did not differ from non genotype-2 patients. CONCLUSIONS: The prevalence of TTV infection was higher in patients than in healthy blood donors. Its clinical significance remains questionable since clinical and biochemical characteristics were not different between TTV positive and TTV negative patients. The higher prevalence of TTV in patients might be related to parenteral transmission, but the relatively high prevalence in healthy blood donors points to an additional presumably faeco-oral infection. The presence of TTV in animals suggests that infection might also originate from food. Long term follow-up will have to define whether co-infection with TTV eventually alters the natural history of chronic hepatitis.     

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.