Prevalence and persistence of a novel DNA TT virus (TTV) infection in Japanese haemophiliacs

To clarify the clinical implication of a newly discovered 'TT virus (TTV)', we assayed TTV DNA in sera from 50 haemophiliacs by a seminested-PCR. TTV DNA was detected in 75% (35/50), which was a much higher prevalence than for HBV (HBc-Ab), HCV RNA, or HGV RNA. In particular, TTV DNA was found in 44.4% (4/8) of patients who had been treated only with virally inactivated factor VIII concentrates. Elevated ALT levels were observed in patients with HCV RNA and TTV DNA; however, the elevation in TTV DNA was obtained from patients co-infected with HCV RNA (62.9%, 22/35). There was no significant difference in ALT levels between TTV DNA-positive and DNA-negative in patients without HCV RNA. 85.3% (35/41) of TTV DNA-positive sera in 1990 were again positive for TTV DNA in 1995. These findings suggest that many haemophiliacs have been infected with TTV. Although TTV infection was not associated with serum ALT elevation, persistent TTV infection may contribute to cryptogenic hepatic failure in haemophiliacs.     

Effects of HAART on hepatitis C, hepatitis G, and TT virus in multiply coinfected HIV-positive patients with haemophilia

In multiply coinfected human immunodeficiency virus (HIV)-positive patients, we investigated the effects of high-activity antiretroviral therapy (HAART) using HIV protease inhibitors on three other viruses: hepatitis C virus (HCV), hepatitis G virus (HGV), and TT virus (TTV). Viral concentrations were measured serially by polymerase chain reaction methods in five patients with quadruple infection (HIV, HCV, HGV, and TTV) and in two patients with triple infection (HIV, HCV, and HGV) before and during HAART. In addition, CD4+ cell counts and serum alanine aminotransferase (ALT) levels were measured serially. Generally we observed no difference in serum HCV RNA, HGV RNA, or TTV DNA concentrations between samples obtained before and after initiation of HAART, whereas HIV RNA concentration decreased and CD4 counts increased in most patients. However, two patients had markedly decreased concentrations of HCV RNA and HGV RNA, respectively, more than 12 months after beginning HAART. Normalization of serum ALT levels was observed in a patient with decline of HCV RNA concentrations. No interactions were observed among these four viruses. HAART had no apparent direct effects on HCV, HGV, or TTV. Further studies will be required to elucidate whether the restoration of immune status through suppression of HIV replication by HAART may affect HCV or HGV RNA concentrations.     

The epidemiology of TT virus (TTV) infection in a hepatitis C and B virus hyperendemic area of southern Taiwan

TT virus (TTV) is a newly isolated DNA virus from the serum of a patient with posttransfusion hepatitis of unknown etiology in 1997. To evaluate the clinical and molecular characteristics of TT virus (TTV) in a hepatitis C virus (HCV) and B (HBV) hyperendemic area (Masago), 200 residents were enrolled in the study. The sera were tested for alanine aminotransferase (ALT), HCV RNA and GB virus C/Hepatitis G virus (HGV) RNA, TTV DNA, HBsAg, anti-HCV and antibodies to HGV E2-protein (anti-E2). TTV DNA was positive in 99 of the 200 sera with a prevalence rate of 49.5%. The prevalence of HBsAg, anti-HCV, HCV RNA, HGV RNA, anti-E2 and HGV exposure (defined as positive for serum HGV RNA and/or anti-E2) was 38.9%, 69.5%, 64.5%, 17.0%, 25.5% and 39.5%, respectively. Neither clinical nor virological factors were associated with TTV viremia. The rate of ALT abnormality was significantly elevated in HCV RNA-positive (34.9%) than -negative (7.0%) residents (p < 0.001). HCV viremia was the only factor significantly associated with ALT elevation by multiple logistic regression (odds ratio: 6.96; 95% C.I.: 2.60-18.7). We concluded that in this HCV/HBV hyperendemic area, the prevalence of TTV DNA was high. No significant clinical factor was observed to be associated with TTV infection. TTV infection is not related to abnormal ALT levels and ALT abnormality was mainly attributable to HCV but not TTV, HBV or HGV infection.     

Transmission of and liver injury by TT virus in patients on maintenance hemodialysis

To study the prevalence and clinical significance of TT virus (TTV) infection in hemodialysis patients, we tested for TTV DNA in serum, using the nested polymerase chain reaction. The prevalence of TTV DNA in 352 hemodialysis patients was 32%, significantly higher than that in 50 healthy blood donors (12%). The prevalence increased with age (P = 0.0098); it was 20% (22/110) in patients aged less than 49 years, 37% (69/188) in those aged 50–69 years, and 41% (22/54) in those aged over 70 years. Other clinical features and the prevalence of other hepatitis viral markers tested did not differ between patients with TTV DNA and those without it. The detection rate of hepatitis C virus (HCV) and hepatitis G virus (HGV) viremias increased with duration of hemodialysis and with the number of blood transfusion units, but the prevalence of TTV viremia did not. Twenty-nine of 91 patients followed for 5 years were initially positive for TTV DNA. Of these 29 patients, 17 (59%) carried this viremia for at least 5 years. Fourteen of the 62 patients (23%) who were initially negative for TTV DNA acquired TTV viremia. Serum alanine aminotransferase (ALT) levels were elevated in patients with HCV viremia but not in patients with HGV or TTV viremia. However, the mean ALT level in patients with all three viremias (HCV, HGV, and TTV) was significantly higher than that in patients with one or two of the viremias. More than 30% of the hemodialysis patients had TTV viremia and the carrier state was maintained for years. The hemodialysis procedures, including blood transfusion, did not seem to be crucial for the transmission of TTV. The pathogenic effects of TTV on hepatitis appear to be limited. (Received July 21, 1998; accepted Sept. 25, 1998)     

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.     

TT viral infection through blood transfusion: retrospective investigation on patients in a prospective study of post-transfusion hepatitis

AIM To investigate the role of blood transfusion in TT viral infection (TTV).METHODS We retrospectively studied serum samples from 192 transfusion recipients who underwent cardiovascular surgery and blood transfusion between July 1991 and June 1992. All patients had a follow-up every other week for at least 6 months after transfusion. Eighty recipients recipents blood before screening donors for hepatitis C antibody (anti-HCV), and 112 recipients reveiver screened blood.Recipients with alanine aminotransferase level ＞ 2.5 times the upper normal limit were tested for serological markers for viral hepatitis A, B,C, G, Epstein-Barr virus and cytomegalovirus.TTV infection was defined by the positivity for serum TTV DNA using the polymerase chain reaction method. RESULTS Eleven and three patients, who reveiver anti-HCV unscreened and screened blood, respectively, had serum ALT levels ＞90 IU/L. Five patients (HCV and TTV: 1; HCV,HGV, and TTV: 1; TTV: 2; and CMV and TTV: 1 )were positive for TTV DNA, and four of them had sero-conversion of TTV DNA. CONCLUSION TTV can be transmitted via blood transfusion. Two recipients infected by TTV alone may be associated with the hepatitis.However, whether TTV was the causal agent remains unsettled, and further studies are necessary to define the role of TTV infection in chronic hepatitis.     

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.     

维持性血透患者六种肝炎病毒感染的调查研究

目的：了解维持性血液透析患者六种肝炎病毒感染情况,探讨其与输血、透析时间、肝功能的关系。方法：对１６７例维持性血液透析患者进行调查,采用第二代酶联免疫法（ＥＬＩＳＡ）检测ＨＡＶ、ＨＢＶ、ＨＥＶ、ＨＧ,用套式ＰＣＲ法检测经输血传播的肝炎病毒（ＴＴＶ）ＤＮＡ,并按血透时间、输血次数等分组进行对比分析。结果：ＨＡＶ、ＨＢＶ、ＨＣＶ、ＨＨＥＶ、ＨＧＶ、ＴＴＶ感染率分别为０％、２０．４％、５５．７％、０％、     

Natural history of the TT virus infection through follow-up of TTV DNA-positive multiple-transfused patients

Little is known about the natural history and the pathogenicity of the TT virus (TTV). We present our findings of a cross-sectional study based on the TTV DNA screening of 173 multiple-transfused patients and a longitudinal study based on the follow-up of TTV DNA-positive patients. Overall, 48 patients (27.7%) tested positive for TTV DNA. The influence of the number of blood donor exposures on the prevalence of blood-borne viral infection indicates that TTV, hepatitis C virus (HCV), and an RNA virus known as GB virus C/hepatitis G virus (GBV-C/HGV) share a parenteral transmission, but that TTV, in contrast to the 2 other viruses, is also transmitted by at least another efficient means. The patients having a well-defined date of TTV infection were positive for TTV DNA during a mean period of 3.1 years. A chronic infection was observed in 31 cases (86%). TTV carriage appeared clinically benign in all patients. No clinical evidence of a disease potentially linked to the TTV infection was observed in patients with TTV DNA carriage over several years. The majority of TTV carriers had no biochemical evidence of liver disease. The prevalence of elevated serum alanine aminotransferase (ALT) level was higher in the TTV DNA-positive group, even in the absence of HCV infection, but the observed peaks of ALT level were most often transient and very mild. The prevalence of TTV DNA observed in blood recipients is consistent with that of TTV infection observed in blood donors. TTV infection frequently tends to persist. (Blood. 2000;95:347-351)     

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。     

A survey of current liver biopsy practice patterns

GOALS: To study transfusion-transmitted virus (TTV) infection in 75 patients on hemodialysis and examine its relationship with age, sex, duration of dialysis, history of transfusion, and chronic elevation of alanine aminotransferase (ALT) levels. STUDY: Serum TTV was analyzed by polymerase chain reaction (PCR), TTV genotypes by restriction fragment length polymorphism, and hepatitis C virus (HCV) RNA by PCR. RESULTS: Transfusion-transmitted virus was detected in 32 patients (42.7%). Transfusion-transmitted virus genotypes were as follows: G1 in 16 patients; G2, 3; G3, 1; G4, 2; G2-G5, 6; and unclassified, 4. Mean duration of dialysis was 37 +/- 32 months for TTV-positive patients and 43 +/- 37 months for TTV-negative patients (not significant). Twenty-seven (84%) TTV-positive patients and 27 (63%) TTV-negative patients had a history of transfusions ( p = 0.04). Chronic ALT elevation was observed in 9 patients; 5 of them were TTV-positive (16%) and 4 were TTV-negative (9%) (not significant). Four (40%) HCV RNA-positive patients and 5 (8%) HCV RNA-negative patients had chronic ALT elevation ( p = 0.003). Three TTV-positive patients with chronic ALT elevation were also infected with HCV. The two patients with isolated TTV infection did not have another clinical feature to explain their ALT elevation. CONCLUSIONS: Transfusion-transmitted virus had a high prevalence in the patients on hemodialysis; genotype G1 accounts for half of the cases. Transfusion-transmitted virus infection depends on the transfusional antecedent but not on the duration of dialysis. Chronic ALT elevation is significantly associated with HCV infection but not TTV infection. However, TTV could be a causative agent of chronic ALT elevation in some patients.     

Effect of TT virus co‐infection on interferon response in chronic hepatitis C patients

Abstract: Aim: TT virus (TTV) is a single stranded DNA virus found in serum of patients with post‐transfusion non‐A to ‐G hepatitis. TTV‐DNA has been investigated in sera of patients with various liver diseases. This study aimed at finding whether co‐infection with TTV in HCV patients, may influence the effect of interferon (IFN) in complete elimination of HCV, and analysed the correlation between HCV and TTV by semi‐quantification of both HCV RNAs and TTV DNA. Methods: In 28 chronic hepatitis C (CH‐C) patients with TTV co‐infection, the presence of TTV DNA was checked in sera six months before and after the end of IFN therapy. Result: Five out of 28 patients became negative for both HCV‐RNA and TTV‐DNA following IFN therapy. But 10 out of 28 patients persistently remained positive for both. Among the remaining 13 patients, 5 tested negative for HCV‐RNA but positive for TTV‐DNA. Post IFN therapy changes in serum alanine aminotransferase (ALT) levels did not appear to be influenced by the presence of TTV co‐infection. HCV‐RNA was found to be the most important predictor of IFN response in CH‐C patients with TTV co‐infection. TTV DNA level in sera had no correlation with IFN response. In addition, there was no relationship between HCV RNA and TTV DNA. Conclusion: Based on these results, it can be concluded that the effectiveness of IFN in eliminating HCV does not seem to be influenced by co‐infection.     

Clinical implications of TT virus superinfection in patients with chronic hepatitis C

OBJECTIVE: TT virus (TTV) has been identified as a candidate agent of non-A-E hepatitis virus. We investigated superinfection of TTV in patients with chronic hepatitis C and studied the susceptibility to interferon (IFN) treatment and its association with liver disease caused by hepatitis C virus (HCV). METHODS: TTV DNA was examined using the seminested polymerase chain reaction (PCR), and its virus level was measured by the real-time fluorometric PCR. RESULTS: TTV DNA was detected in 20 of 102 (19.6%) patients examined. There was no significant difference in the alanine aminotransferase (ALT) level between patients with or without TTV DNA. Quantitative analysis of HCV RNA and TTV DNA revealed no correlation between virus levels in HCV/TTV-coinfected patients. Both TTV and HCV were sensitive to IFN therapy. Complete response to IFN with a sustained loss of viremia for 24 wk after completion of IFN treatment was found in 11 of 20 (55%) patients with respect to TTV DNA and in five of 20 (25%) patients with respect to HCV RNA. The mean pretreatment HCV RNA level was significantly lower in the complete-response cases than in the no-response cases, but there was no significant difference in the pretreatment TTV DNA levels between them. ALT normalization resulting from IFN therapy was not attributable to the eradication of TTV DNA but was attributable to that of HCV RNA. Superinfection by TTV did not influence the effect of IFN against HCV. No specific TTV genotype correlating with IFN sensitivity was found. CONCLUSIONS: These results suggest that TTV infection stands independent of HCV infection, with no influence on liver injury as a result of HCV infection.     

Infection with TT virus, a novel transfusion-transmissible DNA virus, in haemophiliacs and in blood products

We evaluated the characteristics and rate of infection with TT virus (TTV), a novel DNA virus, in Japanese haemophiliacs. TTV DNA was measured in 60 haemophiliacs by semi-nested polymerase chain reaction. Co-infection with hepatitis C virus (HCV), hepatitis G virus (HGV) and human immunodeficiency virus (HIV) was also evaluated. In addition, the rate of detection of TTV DNA in blood products was evaluated. TTV DNA was detected in 35/60 haemophiliacs (58.3%). There were no differences in the backgrounds or characteristics between haemophiliacs with and without TTV infection, except for higher levels of IgG and IgM in patients with TTV infection. In patients infected with TTV of types other than type 1, which are rarely detected in Japan, the rate of co-infection with HCV of imported types was high; TTV of types other than type 1 in Japanese haemophiliacs were probably transmitted by imported blood products. TTV DNA was detected in over half of the blood products tested, but TTV DNA concentrations in these products were lower than in the serum of haemophiliacs.     

血液透析患者丙型和庚型肝炎病毒感染的研究

为了解血液透析患者中丙型肝炎病毒(HCV)和庚型肝炎病毒(HGV)的感染情况,并探讨相对危险因素,对48例在302医院和武警总医院进行维持性血液透析的患者用逆转录聚合酶链(PCR)反应和酶联免疫法检测了血清中HCV RNA、HGV RNA及其抗体水平。结果显示,抗-HCV和HCV RNA阳     

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。     

Hepatitis G virus infection in patients with hepatitis C virus infection undergoing liver transplantation

BACKGROUND & AIMS: Hepatitis G virus (HGV) is transmissible by blood transfusion, but its role in chronic liver disease is unknown. The aim of this study was to determine the prevalence of HGV infection in patients infected with hepatitis C virus (HCV) undergoing transplantation and evaluate the effects of HGV coinfection on the course of posttransplantation HCV infection. METHODS: One hundred twenty-four patients infected with HCV undergoing liver transplantation were studied. Serum samples were tested for HCV and HGV RNA; HCV RNA was quantitated by branched DNA assay, and HCV genotype was determined. RESULTS: The prevalence of pretransplantation and posttransplantation HGV infection was 24% and 28%, respectively. Pre-transplantation HGV infection was positively correlated with posttransplantation HGV infection (P < 0.001). Pretransplantation clinical features were not different in patients infected with HCV with and without HGV infection. Posttransplantation HCV RNA levels were not significantly different in patients with and without HGV coinfection, but HCV genotype 1b was more frequent in patients with HGV coinfection. There were no differences in the histological severity of posttransplantation liver disease, graft, and patient survival between patients with and without HGV infection. CONCLUSIONS: Although HGV coinfection is frequent in patients with end- stage HCV disease undergoing liver transplantation, there is no association between the presence of HGV coinfection and the severity of liver disease post-transplantation, graft, or patient survival. (Gastroenterology 1996 Dec;111(6):1569-75)     

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.     

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.