Infection with an unenveloped DNA virus (TTV) in patients with acute or chronic liver disease of unknown etiology and in those positive for hepatitis C virus RNA

BACKGROUND/AIMS: An unenveloped single-stranded DNA virus (TTV) has been reported in association with elevated transaminase levels in patients with posttransfusion hepatitis and in those with acute or chronic liver disease of unknown etiology. To further evaluate the association of TTV with liver disease, TTV DNA was searched for in patients with acute or chronic liver disease of various etiologies. METHODS: TTV DNA was determined by polymerase chain reaction with hemi-nested primers in 64 patients with acute or chronic liver disease of unknown etiology and in 100 with acute or chronic liver disease positive for antibody to hepatitis C virus (HCV) as well as HCV RNA. RESULTS: TTV DNA was detected in two of the seven (29%) patients with acute hepatitis of unknown etiology, but in none of the four patients with acute HCV-associated hepatitis. It was detected in 27 of the 57 (47%) patients with chronic liver disease of unknown etiology at a frequency significantly higher (p<0.001) than that in 17 of the 96 (18%) patients with chronic HCV-associated liver disease. By contrast, RNA of hepatitis G virus was detected in none of the patients with acute hepatitis, and only in one of the 57 (2%) patients with chronic liver disease of unknown etiology as well as in six of the 96 (6%) patients with chronic HCV-associated liver disease. CONCLUSIONS: Based on the obtained results, TTV has a role in the development of acute and chronic liver disease of unknown etiology.     

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.     

Infection with a novel human DNA virus (TTV) has no pathogenic significance in patients with liver diseases

BACKGROUND/AIMS: A recently identified DNA virus, termed TT virus (TTV), has been associated with post-transfusional hepatitis, and a high prevalence of TTV infection in patients with acute or chronic liver disease of unknown etiology has been reported from Japan, but few data are available about TTV infection in other countries. METHODS: Using hemi-nested-PCR amplification to detect TTV-DNA sequences in serum, we investigated TTV infection in blood donors and in patients with liver diseases of varied etiology. RESULTS: The prevalence of TTV infection was 13.7% in blood donors (23/168), 18.6% in chronic hepatitis C (19/102), 28.6% in chronic hepatitis B (16/56), 29.9% in hepatocellular carcinoma (20/67), 9.1% in cryptogenic chronic liver disease (2/22) and 39.6% in fulminant hepatitis (19/48). The prevalence of TTV infection in patients with virus-induced or idiopathic fulminant hepatitis was similar. Comparison of TTV-infected and non-infected patients did not reveal significant differences concerning demographic, epidemiological or histopathological features. In patients with hepatitis C, response to interferon therapy was not related to TTV infection. Phylogenetic analysis of TTV isolates showed that at least three different types of TTV are present in Spain. CONCLUSIONS: Our data suggest that TTV infection is frequent among blood donors and patients with acute liver disease. However, pathogenic effects associated with TTV infection were not observed.     

TTV infection in children with and without liver disease.

BACKGROUND: TTV DNA has been reported in patients with a broad spectrum of hepatic disorders as well as in healthy people. AIM: To clarify the role of TTV in children with liver disease and in healthy children. METHODS: Degenerate primers designed to amplify a target sequence from the ORF 1 region of TTV genome were used for nested PCR, to detect TTV DNA in sera. RESULTS: TTV was detected in 3 of 18 children with chronic hepatitis B (16.7%), 2 of 17 hepatitis B carriers (11.8%), 2 of 17 children with cryptogenic chronic liver disease (11.8%), and 1 of 40 (2.5%) children without liver disease. The infection rate was similar among the various study groups and in the various age groups. There was no difference between TTV positive and negative children in respect to gender, history of surgery, parenteral treatment, transfusion of blood and blood products, presence of hepatomegaly, splenomegaly, jaundice, and transaminase values. CONCLUSION: TTV does not seem to have an etiologic role in cryptogenic liver disease in children and does not seem to influence the clinical course of liver disease.     

TT virus (TTV) is not associated with acute sporadic hepatitis

Summary A novel virus, TT virus (TTV), recently discovered byOkamoto et al. in the serum of a patient with posttransfusion hepatitis, is thought to be one of the causative agents of blood-borne acute hepatitis. The association of this virus with acute sporadic hepatitis was evaluated. TTV DNA was detected in 4 (4.9%) of 81 cases of acute hepatitis A, in 5 (16.7%) of 30 cases of acute hepatitis B, in 1 (25.0%) of 4 cases of acute hepatitis C, in 1 (9.1%) of 9 cases of cytomegalovirus and Eppstein-Barr infection, and in 8 (13.6%) of 59 cases of acute hepatitis of unknown etiology. These positive rates of TTV in various etiologies did not differ significantly amongst each other, and were similar to those of healthy volunteers, i.e. 12.0% (12/100). The comparison of levels of alamine aminotransferase, aspartate aminotransferase, total bilirubin, hepaplastin test and prothrombin time between TT virus-positive and- negative patients did not show any differences. This indicates that TTV is neither a main causative agent of acute sporadic hepatitis of unknown etiology, nor does it affect the clinical features of acute hepatitis with already known etiology.     

Transfusion-transmitted virus in association with hepatitis A-E viral infections in various forms of liver diseases in India

AIM: To describe the prevalence of transfusion-transmitted virus (TTV) infection in association with hepatitis A-E viral infections in different forms of liver diseases in North India. METHODS: Sera from a total number of 137 patients, including 37 patients with acute viral hepatitis (AVH), 37 patients with chronic viral hepatitis (CVH), 31 patients with cirrhosis of liver and 32 patients with fulminant hepatic failure (FHF), were analyzed both for TTV-DNA and hepatitis A-E viral markers. Presence of hepatitis B virus (HBV), hepatitis C virus (HCV) and hepatitis E virus (HEV) infections was detected in different proportions in different groups. Moreover, TTV-DNA was simultaneously tested in 100 healthy blood donors also. RESULTS: None of the patients had hepatitis A virus (HAV) and hepatitis D virus (HDV) infections. Overall prevalence of TTV-DNA was detected in 27.1% cases with AVH, 18.9% cases with CVH, 48.4% cases with cirrhosis and 9.4% cases with FHF. TTV-DNA simultaneously tested in 100 healthy blood donors showed 27% positivity. On establishing a relation between TTV infection with other hepatitis viral infections, TTV demonstrated co-infection with HBV, HCV and HEV in these disease groups. Correlation of TTV with ALT level in sera did not demonstrate high ALT level in TTV-infected patients, suggesting that TTV does not cause severe liver damage. CONCLUSION: TTV infection is prevalent both in patients and healthy individuals in India. However, it does not have any significant correlation with other hepatitis viral infections, nor does it produce an evidence of severe liver damage in patients with liver diseases.     

TT virus infection among blood donors and patients with non-B, non-C liver diseases in Korea

BACKGROUND/AIMS: A novel virus, designated the TT virus (TTV), was isolated from the serum of a patient with posttransfusion hepatitis of unknown etiology, in Japan. Subsequently, TTV was suggested to be a causative agent in a proportion of cases with cryptogenic hepatitis in Japan. This study aimed to elucidate the significance of TTV infection in cases with cryptogenic liver disease in Korea, a neighbor of Japan. METHODS: The prevalence of TTV infection was studied in 120 patients with liver diseases, including 85 patients diagnosed as having non-B, non-C liver diseases. As controls, 220 blood donors were also examined. TTV DNA was detected by polymerase chain reaction, and the sequence was analyzed by phylogenetic analysis. RESULTS: Fourteen (14.0%) of 100 accepted blood donors, 23 (19.2%) of 120 rejected blood donors, and 15 (17.6%) of 85 patients with non-B, non-C liver diseases were positive for TTV DNA. The prevalences of TTV infection among these groups were not significantly different. Phylogenetic analysis suggested the existence of four major genotypes of TTV The proportions of each genotype among patients with non-B, non-C liver diseases were not different from those among accepted blood donors. CONCLUSIONS: TTV exists in Korea, but the prevalence among patients with non-B, non-C liver diseases was almost the same as that among blood donors. TTV may not be the main causative agent of cryptogenic liver disease in Korea. The relationship between non-B, non-C liver diseases and TTV genotype remains unclear, although TTV can be classified into four genotypes.     

TT virus infection among Egyptian patients with hepatocellular carcinoma

Hepatitis B and C viruses (HBV and HCV) have been associated with hepatocellular carcinoma (HCC). Recently, a novel DNA virus was isolated from a patient with posttransfusion hepatitis of unknown etiology and designated TT virus (TTV). To examine whether this virus is associated with HCC, we investigated sera from 82 Egyptian patients with histopathologically-diagnosed HCC. All subjects underwent serological investigations for detection of hepatitis B surface antigen (HbsAg), hepatitis B core antibody (HbcAb) and anti-HCV. Detection of TTV-DNA was performed by semi-nested polymerase chain reaction (PCR) using TTV-specific primers. TTV-DNA was detected in 28% of the patients. Age, gender, risk factors and biochemical liver functions did not significantly differ between TTV-DNA positive and negative patients. TTV was detected in 27.1% of patients with HCV-HCC, 25% of HBV-HCC, 66.7% of dual HCV and HBV infection and 40% of those with non-B, non-C-HCC (NBNC-HCC). It is concluded that, in this the cohort of Egyptian patients with HCC, TTV infection is common and is not associated with HCV, HBV, NBNC-HCC, history of schistosomiasis or blood transfusion.     

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。     

Transfusion-transmitted virus (TTV) in Brazil. Preliminary report

TTV is a recently discovered DNA virus, isolated from a patient with post-transfusion hepatitis of unknown etiology by Japanese researchers. In the present study, we evaluated the presence of TTV among chronic liver diseases patients in S?o Paulo and Pará states, representing two geographically distinct Brazilian regions. TTV DNA was found in 21/105 (20%) and 9/20 (45%) cases from S?o Paulo and Pará States, respectively. DNA sequence data confirmed the presence of TTV genotypes 1a and 2a, as well as other genotypes not yet described. In conclusion, TTV is present in chronic liver diseases cases from Southeast and North Brazil. However, further studies involving healthy populations are necessary before establishing any causal relationship among TTV and human hepatitis.     

TT virus infection in hemodialysis patients

OBJECTIVE: Recently, TT virus (TTV), associated with posttransfusion hepatitis, was discovered. Prevalence of TTV infection in maintenance hemodialysis (HD) units and its pathogenicity to liver was investigated. METHODS: A total of 115 patients on HD were assessed for presence of serum TTV. DNA was purified from sera, and nested polymerase chain reaction was done for the detection of TTV DNA. RESULTS: TTV was detected in 59 patients on HD (51.3%), as compared with healthy blood donors (15 of 91 [16.5%], p < 0.0001). Serum HCV RNA and HBs antigen were positive in 16 and three patients, respectively. The prevalence rate of TTV was already 58.3% in the patients on HD for only 1 yr, and did not change according to the duration of HD until 15 yr on HD. TTV was positive in 51.2% (43 of 84) of the patients with history of blood transfusion, and in 51.6% (16 of 31) of those without it. In HCV-negative patients, alanine aminotransferase (ALT) levels of TTV-positive patients were similar to those of TTV-negative patients. Contrarily, in HCV-positive patients, ALT levels were more frequently > or =15 IU/L in TTV-positive patients (14 of 18) than in TTV-negative patients (five of 15) (p < 0.05). CONCLUSIONS: TTV infection is remarkably prevalent in patients on HD and in healthy blood donors. It is suggested that TTV generally does not cause liver disease by itself, but there remains the possibility that TTV may aggravate liver disease caused by HCV.     

TT virus and hepatitis G virus infections in Korean blood donors and patients with chronic liver disease

AIM: To determine the prevalences of TTV and HGV infections among blood donors and patients with chronic liver disease in Korea, to investigate the association of TTV and HGV infections with blood transfusion, and to assess the correlation between TTV and HGV viremia and hepatic damage. METHODS: A total of 391 serum samples were examined in this study. Samples were obtained from healthy blood donors (n=110), hepatitis B surface antigen (HBsAg)-positive donors (n=112), anti-hepatitis C virus (anti-HCV)-positive donors (n=69), patients with type B chronic liver disease (n=81), and patients with type C chronic liver disease (n=19). TTV DNA was detected using the hemi-nested PCR. HGV RNA was tested using RT-PCR. A history of blood transfusion and serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were also determined. RESULTS: TTV DNA was detected in 8.2 % of healthy blood donors, 16.1 % of HBsAg-positive donors, 20.3 % of anti-HCV-positive donors, 21.0 % of patients with type B chronic liver disease, and 21.1 % of patients with type C chronic liver disease. HGV RNA was detected in 1.8 % of healthy blood donors, 1.8 % of HBsAg-positive donors, 17.4 % of anti-HCV-positive donors, 13.6 % of patients with type B chronic liver disease, and 10.5 % of patients with type C chronic liver disease. The prevalence of TTV and HGV infections in HBV- or HCV-positive donors and patients was significantly higher than in healthy blood donors (P<0.05), except for the detection rate of HGV in HBsAg-positive donors which was the same as for healthy donors. There was a history of transfusion in 66.7 % of TTV DNA-positive patients and 76.9 % of HGV RNA-positive patients (P<0.05). No significant increase in serum ALT and AST was detected in the TTV- or HGV-positive donors and patients. CONCLUSION: TTV and HGV infections are more frequently found in donors and patients infected with HBV or HCV than in healthy blood donors. However, there is no significant association between TTV or HGV infections and liver injury.     

Molecular epidemiology and clinical implications of TT virus (TTV) infection in Indian subjects

GOALS: This study was aimed at obtaining data on the epidemiology and clinical course of TT virus (TTV) infections among Indian subjects. BACKGROUND: The TTV is a nonenveloped DNA virus, first identified in the peripheral blood of individuals with posttransfusion hepatitis of unknown etiology. There has been much conjecture regarding the disease association of this virus. STUDY: A total of 494 serum specimens from various groups of high-risk and control subjects were screened for TTV DNA by a semi-nested PCR, using the ORF1-derived N22 primers. The sera were also screened for the HBsAg surface antigen by an ELISA, HCV RNA by a 5' NCR-based RT-PCR and GBV-C/HGV RNA by a 5' UTR-based RT-PCR. The clinical and hepatic profiles of the various subjects were also studied. Seventy-one randomly picked TTV isolates were directly sequenced and their phylogeny was studied. RESULTS: TTV showed an overall positivity rate of 45.34% with a significant higher prevalence of 52.9% among the high-risk subjects as against a prevalence of 28% among healthy control subjects (P < 0.001). Abnormal liver function profiles were frequent among TTV viremic individuals and among the acute hepatitis cases studied a higher mortality rate correlated with a superimposed TTV infection. The 71 TTV isolates sequenced were found to belong to genotype 1a being closely homologous to TTV prototype TA278. CONCLUSION: The TT virus shows a significant prevalence in the Indian population, particularly among subjects at risk for acquiring parenterally transmitted infections. Our study corroborates a putative role of the virus in the etiology of liver disease, particularly in coinfection with other agents.     

Detection and viral nucleotide sequence analysis of transfusion-transmitted virus infection in acute fulminant and non-fulminant hepatitis

The impact of transfusion-transmitted virus (TTV) infection on acute fulminant and non-fulminant hepatitis is unclear. In this study, serum samples from 164 patients with acute hepatitis of various aetiologies, from 34 asymptomatic hepatitis B virus carriers and from 202 healthy adults were tested for TTV DNA by the semiconserved nested polymerase chain reaction. TTV viraemia was prevalent in patients with acute hepatitis C, in patients with acute hepatitis D virus superinfection and in patients with non-A–E hepatitis (27–30%) but the incidence was not significantly different from that of healthy controls (31 of 202, 15.3%). There were no significant differences in gender, age, presence of hepatitis G virus, the occurrence of fulminant hepatitis, or in serum albumin, bilirubin or alanine aminotransferase levels (9/30 vs 35/134) between patients with or without TTV viraemia. Seven of the nine TTV-positive patients with fulminant hepatitis were co-infected with hepatitis C, D or E. TTV clones from 18 subjects, with or without fulminant hepatitis, were sequenced and analysed phylogenetically. Eleven (61.1%) belonged to TTV group 1, six (33.3%) to TTV group 2 and one to TTV group 3. No particular strain of TTV was associated with fulminant hepatitis. In summary, in Taiwan, TTV is prevalent in the general population as well as in patients with liver diseases. TTV plays an insignificant role in acute fulminant and non-fulminant hepatitis. Its influence on outcome requires a longitudinal study.     

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.     

Superinfection of TT virus and hepatitis C virus among chronic haemodialysis patients

BACKGROUND: The TT virus (TTV), a new DNA virus found in Japan from a patient with post-transfusion hepatitis non-A-non-G, is frequently positive in the sera of patients with liver disease. It is not established whether this virus causes liver damage. We studied the frequency of superinfection of this virus and hepatitis C virus (HCV) known to be endemic among haemodialysis patients, and the possible deleterious effect of TTV on HCV-induced chronic liver disease. METHODS: We used primers from a conservative region in the TTV genome (Okamoto, 1998) to detect TTV. Sera from 163 dialysis patients positive for anti-HCV and 77 dialysis patients negative for anti-HCV (control) were tested. RESULTS: TT Virus positivity was 35% among HCV antibody (anti-HCV)-positive patients and 45.4% among anti-HCV-negative patients. TT Virus positivity was unrelated to the length of haemodialysis or amounts of blood the patients had received in the past. More anti-HCV-positive patients had a history of transfusion, but TTV positivity was not as closely associated with transfusion as anti-HCV positivity. The severity of chronic liver disease was estimated from peak serum alanine aminotransferase levels in the preceding 6 months. Among anti-HCV positives, TTV-positive patients tended to have less active disease; at least there was no indication that TTV superinfection aggravated chronic hepatitic C in long-term dialysis patients. Four of 35 anti-HCV-negative, TTV-positive patients had chronic active liver disease, while none of the anti-HCV-negative and TTV-negative patients did. CONCLUSIONS: TT Virus infection is prevalent among haemodialysis patients. Its transmission occurs not only by blood transfusion, but also by non-parenteral infection. Superinfection of TTV does not exert deleterious effects on the liver disease induced by HCV. However, it may cause chronic hepatitis in a limited number of patients, but remains dormant most of the time. Triple infection, HCV and TTV plus HBV or HGV (one case each), did not cause severe liver disease.     

High prevalance of TT virus infection in Japanese patients with liver diseases and in blood donors.

BACKGROUND/AIMS: Although a novel DNA virus, TT virus (TTV), has been isolated from a patient with cryptogenic post-transfusion hepatitis, its pathogenic role remains unclear. To elucidate its prevalence and clinical impact in patients with liver diseases, the presence of TTV DNA was assessed in patients with liver diseases and blood donors (BDs) in Japan using two primer sets, one conventional and the other new and highly sensitive. METHODS: We studied 261 samples, 72 with chronic hepatitis associated hepatitis C virus (HCV-CH), 57 with hepatocellular carcinoma associated HCV (HCV-HCC), 12 with HCC without either HCV or hepatitis B virus (NBNC-HCC), and 120 of BDs. RESULTS: Using two primer sets, TTV DNA was detected in 68 (94.4%), 53 (93.0%), 12 (100%), and 98 (81.7%) HCV-CH, HCV-HCC, NBNC-HCC, and BDs, respectively. The prevalence was not significantly different between HCV-CH and HCV-HCC, or between HCV-HCC and NBNC-HCC. Comparison between patients with and without TTV revealed no significant differences in backgrounds or biochemical findings. Histopathological findings in patients with HCV-CH, and number, maximum diameter, and histological differentiation of HCC also did not demonstrate any relation to TTV infection. TTV strains can be divided into five groups using phylogenetic analysis, but no disease-specific group appears to exist. CONCLUSIONS: Our data suggest that: 1) TTV is very prevalent among patients with liver diseases and even among BDs in Japan, 2) TTV infection does not impact on liver damage with HCV infection, and 3) TTV infection also does not affect the development or progression of HCC.     

肝组织中TTV DNA原位检测及临床病理分析

目的：探讨非甲－非庚型急慢性病毒性肝炎患者肝细胞中ＴＴＶ（ｔｒａｎｓｆｕｓｉｏｎ－ｔｒａｎｓ－ｍｉｔｔｅｄ ｖｉｒｕｓ，ＴＴＶ）ＤＮＡ表达与临床病理的关系．方法：采用地高辛素标记ＴＴＶ ＤＮＡ探针以原位杂交技术对１９例血清学病毒标记非甲－非戊型、免疫组化检测肝细胞中ＨＧＶ ＮＳ５阴性的病毒性肝炎患者石蜡炎患者石蜡包埋肝组织进行了检测，并对其中７例相应血清进行了ＰＣＲ检测。结果：急慢性病毒性肝炎肝组     

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.