Detection of TT virus in hemodialysis patients]

Recently a newly discovered DNA virus, transfusion transmitted virus (TTV), was introduced as a cause of post-transfusion hepatitis. We studied the frequency of TTV viremia in 60 hemodialysis patients in Yamaguchi, Japan. TTV DNA was detected by heminested PCR, using primers described by Okamoto et al. TTV DNA was detected in 18 patients (30%). There was no differences in clinical characteristics, including age, gender, history of blood transfusion, and double infection of other hepatitis viruses, between TTV DNA positive patients and negative patients. Also the frequency of TT viremia was not associated with the duration of hemodialysis. These results suggest that the routes of TTV infection may be different from those of infection by HBV, HCV, or HGV.     

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。     

Prevalence and infectivity of hepatitis G virus and its strain variant, the GB agent, in volunteer blood donors in Taiwan

BACKGROUND: The prevalence of hepatitis G virus (HGV) and its strain variant, the GB agent (GBV-C) is high in non-virus-inactivated plasma products, but, persistent infection in recipients is relatively low. STUDY DESIGN AND METHODS: Stored samples from transfusion donors and recipients in a prospective study of posttransfusion hepatitis were tested for HGV RNA and antibody to the E2 protein (anti-E2). RESULTS: Thirty-two (2.1%) of the 1500 qualified donors were positive for HGV RNA. Twenty-four persons had received a transfusion of blood from one of these 32 viremic donors. Of these 24 recipients, 3 were positive for HGV RNA before transfusion. Of the remaining 21 recipients, 8 became viremic after transfusion, while the other 13 were not infected. Four of the eight infected recipients were persistently positive for HGV RNA, while four became negative in 1 to 3 years. Three of the four patients with HGV clearance seroconverted to anti-E2 positivity. Comparison of the viral titer, viral sequences at E2, storage period of blood donations, and clinical data in the infected and noninfected recipients revealed no significant differences. However, the noninfected recipients seemed to have a higher prevalence of anti-E2 before transfusion. CONCLUSION: The prevalence of HGV viremia in volunteer blood donors in Taiwan is 2.1 percent, and blood from 0.6 percent of them actually causes HGV infection in the recipients. In half of infected recipients, clearance of HGV occurs. Anti-E2 appears in most recipients whose viremia is cleared.     

深圳市一般人群HGV和TTV感染的研究

为探讨深圳市一般人群中HGV和TTV感染状况及其影响因素。方法采用随机抽样法选取研究对象 ,对HGV感染的检测先用ELISA法检测样本中的抗 -HGV ,对其中阳性样本再用反转录PCR(RT -PCR)进行检测 ;TTVDNA则采用巢式PCR方法检测。结果表明 ,深圳市一般人群中HGVRNA和TTVDNA阳性率分别为 2 33%和 14 77% ,男女阳性率HGVRNA为 2.45%和2.20% ,TTVDNA阳性率为 17.86%和 12.0%。年龄组间HGVRNA及TTVDNA阳性率差异均无显著性 ;单因素和Logistic回归分析未显示肝炎病史、近期手术史、注射史、拔牙史及乙型肝炎疫苗接种史等因素与HGV及TTV感染有关 ;HBsAg、抗 -HBS和抗 -HBc与HGV及TTV感染无统计学意义。不同职业人群中HGVRNA阳性率以中学生和教师较高 ;TTVDNA阳性率则以税务干部和教师高于其他人群 ,因此证明 ,深圳市一般人群中HGV和TTV感染率较高 ,但其流行因素有待进一步研究。     

血液病患者输血与庚型肝炎病毒感染的研究

目的：了解血液病患者输血后的庚型肝炎病毒（ＨＧＶ）感染情况。方法：对６３例血液病患者采用ＲＴＰＣＲ方法检测ＨＧＶＲＮＡ、丙型肝炎病毒（ＨＣＶ）ＲＮＡ，应用ＥＬＩＳＡ方法检测抗ＨＧＶ、ＨＢｓＡｇ。结果：ＨＧＶＲＮＡ阳性率为７．９％，抗ＨＧＶ阳性率６．３％；ＨＣＶＲＮＡ阳性率为４６．０％。ＨＧＶ感染通常伴有ＨＣＶ感染及丙氨酸转氨酶升高。ＨＧＶ感染与输血量有关，与血液病种类无关。结论：血液病输血可引起ＨＣＶ、ＨＧＶ的传播     

Evaluation of RNA and E2 antibodies in prospectively followed recipients of hepatitis G virus-infected blood

BACKGROUND: Hepatitis G virus (HGV) has recently been cloned and tests for HGV RNA and envelope antibodies (anti-E2) have been developed. HGV infection is widespread among blood donors worldwide, but the clinical and serologic outcome of transfusion-associated HGV infection has not been fully characterized. STUDY DESIGN AND METHODS: Consecutive blood donors (n = 2210) were investigated for HGV markers (RNA and anti-E2). The recipients of HGV RNA-positive blood were followed for 1 year after transfusion. RESULTS: Forty-two blood donors (1.9%) were positive for HGV RNA. Eight recipients of HGV RNA-positive blood were retrospectively identified within 2 weeks of transfusion and prospectively followed. In four patients, the presence of anti-E2 before transfusion or an early antibody response protected them from reinfection or prevented HGV persistence, while, in the remaining four patients, transient or persistent viremia was detected shortly after exposure. None of the infected recipients had any evidence of liver disease. CONCLUSION: These results do not support the screening of donors to prevent transfusion-associated HGV infection.     

TT virus genotype changes frequently in multiply transfused patients with hemophilia but rarely in patients with chronic hepatitis C and in healthy subjects

BACKGROUND: TT virus (TTV), a novel DNA virus, was originally thought to be transmitted by transfusion. However, nonparenteral transmission is recently suspected to be a major mode of transmission. To investigate the possibility of reinfection with TTV in multiply transfused patients and to evaluate the significance of transfusion transmission of TTV in patients with hemophilia, serial changes in TTV genotype were investigated in three groups. STUDY DESIGN AND METHODS: Serial changes in TTV genotype were investigated in 16 multiply transfused patients with hemophilia, 16 age-matched patients with chronic hepatitis C, and 16 age-matched healthy subjects. RESULTS: Mixed infection with multiple TTV genotypes was common in all groups. However, changes in TTV genotype were frequent in patients with hemophilia (15/16; 93.8%) but rare in patients with chronic hepatitis C and in healthy subjects (each group: 1/16; 6.3%). CONCLUSION: Changes in TTV genotype were frequently observed in multiply transfused patients with hemophilia but not in patients with chronic hepatitis or in healthy subjects without risk of transfusion transmission. This difference may suggest that exposure to TTV or even reinfection occurs frequently in patients with hemophilia, which could be evidence of transfusion transmission of TTV in this population.     

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。     

Detection of TT virus (TTV) in non-B, non-C hepatitis patients with hepatocellular carcinoma, and clinical features of these patients]

A novel human DNA virus, TTvirus (TTV), was identified from a patient with posttransfusion hepatitis of unknown etiology. It is thought to be a new hepatitis virus, but the clinical significance of this virus is uncertain. We investigated the frequency of TTV viremia by PCR in 39 non-B, non-C hepatitis (NBNC) patients with hepatocellular carcinoma (HCC), and clinical features of these patients. TTV viremia was detected in 20 (51.3%) of 39 NBNC hepatitis patients with HCC. Liver cirrhosis (LC) were found in 11 (55%) of 20 TTV-positive patients and 16 (84%) of 19 TTV-negative patients (p < 0.05). The levels of AST, LDH, LAP, gamma GTP in TTV-positive patients were significantly higher than those in TTV-negative patients (p < 0.05). (AST: 58 +/- 26 vs 42 +/- 23 IU/l, LDH: 468 +/- 127 vs 366 +/- 123 IU/l, LAP: 339 +/- 242 vs 206 +/- 80 IU/l, gamma GTP: 207 +/- 207 vs 105 +/- 107 IU/l) These results suggest clinical differences between TTV-positive and TTV-negative patients in NBNC hepatitis patients with HCC.     

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 and TTV - new hepatitis viruses

AIM: To examine clinical, immunological and morphological features of HGV- and TTV-infections in patients with chronic hepatic diseases (CHD) and assess efficiency of treatment of HGV-seropositive patients. MATERIAL AND METHODS: 202 patients with CHD were examined for markers of HBV-, HCV-, HGV- and TTV-infections. Some patients were subjected to puncture biopsy of the liver. Efficiency of interferon-alpha treatment of HGV and HBV/HCV coinfection was studied. RESULTS: HGV RNA and TTV DNA were detected in 19.8 and 11.8% of cases, respectively. Biochemical indices in patients with HGV and TTV monoinfections significantly differed from those in the control group while morphological changes in most of them corresponded to those with hepatitis. INF-alpha was given to 7 patients with HGV + HBV/HCV infections. A response was achieved in 3 months in 2 of them. CONCLUSION: The role of HGV and TTV in hepatic diseases pathology is still unclear. Further studies on detection and examination of patients infected with G and TT viruses are necessary. When choosing therapy, the presence of HGV RNA and TTV DNA in blood serum, virus genome in hepatocytes and histological changes in hepatic tissue should be considered.     

Involvement of TTV, a new infectious factor in post-transfusion hepatitis, non A-non G]

Post-transfusion hepatitis developed in 6 of 447(1.3%) patients who received transfusion even after 1992 when HCV screening by PHA method was started. The six patients were suggested as hepatitis, non-B, non-C, non-G type. Of the six patients, 4 were found to be infected with TTV, which was identified in one of the patients. The patients became positive for TTV DNA before or almost the same time as the development of hepatitis and their amounts of TTV DNA were varied depending on the ALT level, suggesting that their hepatitis might be caused by TTV. The patients who presented hepatitis became positive for TTV DNA in the 6-10th week after transfusion, whereas more than half of the patients with a slight hepatic disorder became positive in the 2-4th week after transfusion. In addition, prolonged infection with TTV was only observed in nearly half of 23 patients.     

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.     

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.     

输血传播病毒感染与丙型肝炎病毒感染的相互影响

目的了解输血传播病毒(TTV)与丙型肝炎病毒(HCV)重叠感染的发生率,探讨TTV感染与HCV感染的相互影响。方法采用酶联免疫吸附试验(ELISA)法检测血清中人类免疫缺陷病毒(HIV)、乙型肝炎病毒(HBV)、HCV、庚型肝炎病毒(HGV)及TTV标志物,应用巢式聚合酶链反应(n-PCR)技术检测血清TTV DNA,用速率法或终点法检测血清肝功能指标,用放射免疫法检测血清肝纤维化指标,用超声诊断仪检查肝胆脾形态及动态指标;应用SPSS 11.0软件分析比较肝功能检测结果、肝纤维化指标检测结果及肝脾形态和动态指标改变的差异。结果TTV/HCV重叠感染占TTV感染的69.6%(39/56),占HCV感染的61.9%(39/63)。TTV、HCV感染与TTV/HCV重叠感染肝功能检测结果差异有统计学意义(P<0.05);肝纤维化指标检测结果差异有统计学意义(P<0.05)。结论TTV/HCV重叠感染存在很高的发生率,感染者肝损程度较重,临床进程加快,有肝纤维化趋势。     

Prevalence of the newly described human circovirus, TTV, in United States blood donors

BACKGROUND: A novel nonenveloped single-stranded circular DNA virus (TTV) was recently identified. The prevalence of TTV in blood donors in the United States is, however, still unclear. STUDY DESIGN AND METHODS: Viral DNA was detected in US blood donors from five cities by using two sets of TTV primers: NG059/NG061/NG063 primers, which amplified the conserved region of strains 1 and 2, and T801/T935 primers, which amplified the 5' end region of the TTV sequence. A TTV antibody assay system was based on the detection of the truncated open reading frame (ORF)-1 (amino acids 1-411) from type 1b. The truncated ORF-1 was expressed as a fusion protein in Escherichia coli, and the fusion protein was used as the antigen in the antibody assay system. RESULTS: Viremia was detected in 21 (8. 4%) of 250 donors by use of NG059/NG061/NG063 primers and 104 (41. 6%) of 250 by use of T801/T935 primers. There was little correlation among the assays, which suggests the preferential detection of different strains with the different primers. TTV antibody was detected in 38 of 100 donors: 32 (84%) of 38 with concurrent TTV viremia and 6 (16%) of 38 without TTV viremia. TTV viremia and/or TTV antibody-positive samples were detected in 52 (52%) of 100 of US blood donors. CONCLUSION: Evidence of infection or exposure to TTV appears to be common among blood donors in United States.     

Pathogenic significance and organic virus levels in patients infected with TT virus.

Previous reports documented the recovery of a DNA virus from a patient with posttransfusion non-A-G hepatitis and named TT virus (TTV). Although the virus was initially detected as a causative agent of hepatitis, there is doubt about its pathogenicity. The aim of this study was to clarify the relationship between TTV and liver diseases. Histopathological examination of liver biopsies from 14 patients with TTV genotype 1 positive non-B, non-C and non-G chronic hepatitis showed mild fibrosis and periportal/piecemeal necrosis. Using the real-time detection (RTD)-PCR method, we found that TTV DNA levels of genotype 1 in liver samples from 3 such patients were 100- to 1,000-fold higher than those in the paired serum samples. Further investigation using various tissues from 2 autopsies of patients with hepatitis C with hepatocellular carcinoma revealed that the concentrations of TTV DNA in the liver were also higher than in serum samples. However, the highest TTV DNA concentrations in these 2 autopsies were found in the lung and bone marrow, respectively. Our results suggest that TTV may replicate in various tissues including the liver and may cause only mild liver damage.     

The prevalence of TTV infection and the route of TTV transmission in hemodialysis patients--compared with HCV infection]

Recently a novel virus named TT virus (TTV), associated with posttransfusion hepatitis, was isolated. The prevalence of TTV infection and the route of TTV transmission in HD units was investigated. TTV was detected in 51.3% of patients on HD (59/115), as compared with 16.5% of healthy blood donors (15/91). The prevalence rate of TTV in the patients without history of blood transfusion was similarly high (51.6%), compared with that of those with history of blood transfusion (51.2%). The prevalence rate of TTV did not differ according to the duration of HD. These suggest that the risk of TTV infection is very high in HD units and there is another major route of TTV transmission than blood transfusion.     

Molecular virology of TT virus]

In 1997, a novel DNA virus was isolated from the serum of a patient with posttransfusion hepatitis of unknown etiology in Japan, and it was named TT virus (TTV) after the initials of the index patient. TTV is a nonenveloped, single-stranded and circular DNA virus, and its entire nucleotide sequence of 3.9 kb has been determined. For being a DNA virus, TTV has a wide range of sequence divergence, allowing the classification into at least 16 genotypes separated by an evolutionary distance of > 0.30. Nucleotide sequence of the noncoding region is conserved, whereas the coding region sequence is highly variable. TTV strains with extremely high sequence divergence prevail in infected individuals. An association of TTV genotypes, detectable by PCR with N22 primers or genotype 1-specific primers, with hepatitis of unknown etiology suggest that TTV of restricted genotypes would be clinically important.