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.     

Clinical characteristics and distribution of genotypes of TT virus infection in a hepatitis C virus-hyperendemic township of a hepatitis B virus-endemic country (Taiwan)

BACKGROUND: The prevalence of TT virus (TTV) viremia, without definite clinical significance, has been reported to be higher among chronic hepatitis C patients. The status and clinical characteristics of TT virus (TTV) infection and distribution of TTV genotypes in a hepatitis C virus (HCV) hyperendemic township (Masago community) in a hepatitis B virus (HBV) endemic country (Taiwan) were investigated. METHODS: Sera from 100 Masago residents were tested for alanine aminotransferase (ALT) and markers of HBV, HCV and GB virus C/hepatitis G virus (GBV-C/HGV) and TTV-DNA. Sera of 250 blood donors as a control group were tested for TTV-DNA. Sera of Masago residents and blood donors with positive TTV-DNA were directly sequenced, and phylogenetic analyses were performed subsequently. RESULTS: The prevalences of TTV viremia in different age groups among individuals from Masago were significantly higher than that among blood donors. In regard to the subtypes of TTV, 23, seven, two, eight, one, six and one isolate were related to the genotypes 1a, 1b, 2a, 2b, 3, 4 and 5, respectively, from Masago and 21, 14, one, nine and three isolates were related to the genotypes 1a, 1b, 2a, 2b, and 4, respectively, from donors. No clinical or virological factor was associated with TTV viremia or TTV genotypes. CONCLUSIONS: TT Virus prevalence was higher among HCV hyperendemic township residents than blood donors with similar genotype distributions (genotype 1 was the most prevalent) in Taiwan. Neither TTV viremia nor a particular genotype was associated with HBV, HCV or GBV-C/HGV infection and abnormal ALT levels.     

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.     

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.     

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 and genotype distribution in blood donors and a group of patients from Turkey

Background: TT virus (TTV) DNA has been found in a large proportion of patients with different forms of non-A-G hepatitis, however the clinical importance is unclear. We aimed to determine the genotypes of TTV isolates foung in blood donors and different patient groups from the western part of Turkey. Materials and Methods: TT DNA was investigated in serum samples of 91 volunteer blood donors (BD), 105 thalassemia (TH) patients, ten patients with fulminant hepatitis (FH) and 16 hemodialysis (HD) patients by heminested PCR using primers NG059, NG061 and NG063 from the ORF1 region. 39 isolates were genotyped by analyzing the partial sequence of ORF1. Results: TTV DNA was found in 75% of HD, 80% of FH, 61% of TH patients and in 51.6% of BD. Among the sequenced isolates, 14 (35.9%) belonged to genotype 1 (G1) and 25 (64.1%) belonged to genotype 2 (G2). Among the G2 sequences, 22 were grouped as G2c. Conclusion: TTV infection was common in the population studied, even with moderately sensitive primers. G2 was the major genotype of the studied population without any significant differences in distribution between various patient groups and BD. Received: December 27, 2001 · Revision accepted: April 4, 2002 S. Erensoy (corresponding author)     

Prevalence of TT virus in patients with fulminant hepatic failure in Japan

A novel virus (TT virus) was isolated from patients with posttransfusion hepatitis of unknown etiology. We studied the prevalence of TT virus in 26 patients with fulminant hepatic failure without risk factors, including blood transfusion, and also examined 106 healthy blood donors as controls. We assayed serum TT virus DNA by seminested polymerase chain reactions and also examined the genotypes of this virus. Serum was obtained at admission from patients with fulminant hepatic failure. Serum samples at admission from seven (27%) of the 26 patients were positive for TT virus DNA. There were no differences in clinical findings, duration from onset to coma, or results of laboratory tests in patients with and without TT virus DNA. However, all 7 patients with TT virus died, whereas 9 of the 19 patients without TT virus died. The outcome for patients with fulminant hepatic failure and TT virus was significantly worse than for patients without the virus (P = 0.0227). TT virus was also detected in 29 (27%) of the 106 healthy blood donors. The genotype of the TT virus was mainly 1a in both groups. There were no differences in the rate of positivity and the genotypes of TT virus between patients with fulminant hepatic failure and healthy blood donors. TT virus infection may not cause severe hepatitis, such as fulminant hepatic failure, but it may indicate a poor outcome in such patients. Received: September 14, 1998 / Accepted: May 28, 1999     

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.     

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 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.     

Transfusion-transmissible virus and hepatocellular carcinoma: a case-control study

Although transfusion-transmissible virus (TTV) is often present in the serum of patients with acute and chronic non-A–C liver diseases, its hepatotropism, pathogenicity to the liver and hepatocarcinogenicity have not been proven. We used a case-control format to compare the prevalence of TTV infection among 148 southern African Blacks with hepatocellular carcinoma and 148 matched hospital-based controls, and to test for possible interactive effects between this virus and hepatitis B virus (HBV) and hepatitis C virus (HCV) in the development of the tumour. We also determined the prevalence of TTV in 988 blood donors in Gauteng province of South Africa. The presence of TTV DNA in serum samples was detected by using the polymerase chain reaction, Southern hybridization and nucleotide sequencing. Individuals infected with TTV did not have an increased risk of developing hepatocellular carcinoma (relative risk 1.1; 95% confidence limits 0.5–2.4). Moreover, co-infection with TTV did not further increase the risk of tumour development in patients chronically infected with HBV and/or HCV. TTV was present in the serum of 2.2% of blood donors: 4.0% in Black and 1.5% in White donors. We conclude that TTV is unrelated to the development of hepatocellular carcinoma in Black Africans.     

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。     

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。     

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.     

Role of transfusion-transmitted virus in acute viral hepatitis and fulminant hepatic failure of unknown etiology

BACKGROUND AND AIM: The role of the newly described transfusion-transmitted virus (TTV), a circular single-stranded DNA virus, has been investigated in acute liver disease, comprising 36 patients with acute viral hepatitis (AVH) and 25 with fulminant hepatic failure (FHF), including 50 volunteer blood donors as controls. METHODS: Detection of TTV DNA sequences was carried out by polymerase chain reaction (PCR) using primers derived from the UTR(A) region of the TTV genome. The clinical course and biochemical profile when infected with TTV alone or coinfected with other classical hepatotropic viruses were analyzed. All patients were first evaluated for liver function profile and for the presence of various hepatotropic viruses using serological tests and PCR in serologically negative patients. RESULTS: Transfusion-transmitted virus DNA was detected in 80.6% (29/36) of the AVH cases and in 76% (19/25) of the FHF cases, which were significantly higher levels (P < 0.05) than the 52% (26/50) observed in volunteer blood donors. No significant difference in symptoms, clinical course, liver function and risk factor profile between TTV-positive and TTV-negative patients could be observed in both AVH and FHF patients. TTV was found to coexist with both parenterally and non-parenterally transmitted hepatotropic viruses in similar frequency in both AVH and FHF patients. Further, there was no significant difference in the mortality rates between TTV-positive and TTV-negative FHF patients. Also, there was no difference between patients coinfected by TTV and other hepatotropic viruses and those with TTV infection alone. CONCLUSION: Thus, it appears that TTV, although it exists in a very high frequency in the Indian population, appears to have no significant etiological role in AVH and FHF.     

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.     

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 Italy: prevalence and genotypes in healthy subjects, viral liver diseases and asymptomatic infections by parenterally transmitted viruses

This study was aimed to evaluate TT virus prevalence in subjects with hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV) infections in patients affected by hepatitis of unknown origin (non-A–non-E hepatitis) and in healthy subjects who had not been exposed to HBV, HCV and HIV. A total of 317 subjects were tested; 40 were HBsAg asymptomatic carriers, 57 subjects were anti-HCV positive (45 without chronic hepatitis and 12 with HCV-related chronic hepatitis), and 27 had chronic non-A–non-E hepatitis. Fifty-seven subjects were intravenous drug users (IVDUs) (52 with HCV or/and HIV infections), seven patients underwent a liver transplant for fulminant hepatitis and 137 were healthy subjects from the general population. Overall, TTV-DNA was detected in 62 subjects (19.6%): in 17.9% of the HBsAg carriers, in 14% of the anti-HCV-positive patients (in 8.3% and in 15.5% of patients with and without chronic hepatitis, respectively), in 22.2% of non-A–non-E hepatitis patients, in 22.8% of IVDUs, in 57.1% of fulminant hepatitis patients. TTV-DNA was also found in 20.4% healthy subjects. The prevalence in the different subgroups was not statistically different. The genotypes were identified in 40 of the 62 (64.5%) TTV-DNA positive samples: genotype 1a in 17.5%, 1b in 27.5%, genotype 2 in 27.5%, genotype 3 in 15.0%, genotype 4 in 5.0% and genotype 5 in 7.5%; the genotype distribution in the subsets of patients was not significantly different. In conclusion, this study showed that TTV infection is common in Italy; it is widespread throughout the entire population and five genotypes are present in Sardinia. Our results further dismiss the role of TTV as cofactor in influencing the clinical course of infections with other hepatitis viruses as well as the role of HIV in enhancing TTV transmission and replication.     

Clinical significance of TT virus in chronic hepatitis C

BACKGROUND AND AIMS: Much is still unknown about the clinical significance of TT virus (TTV), which has been reported as a candidate for non A-G hepatitis virus. The aim of this study was to clarify the clinical significance of TTV in patients coinfected with TTV and hepatitis C virus (HCV). METHODS: The 95 subjects studied had chronic hepatitis C (CHC), and underwent interferon (IFN) therapy. TT Virus DNA was detected by using polymerase chain reaction. The nucleotide sequences were determined by using a dideoxy chain termination method. A phylogenetic tree was drawn up by using the neighbor-joining method. RESULTS: TT Virus DNA was detected in 37.9% of patients with the use of an open reading frame 1 (ORF1) primer, and in 88.4% of patients by using a 5' untranslated region (5' UTR) primer. Using both sets of primers, no differences were found between TTV-DNA-positive and -negative subjects with CHC in the clinical findings. Serum TTV DNA was eradicated in 30.6% of patients with the ORF1 primer, and in 19.1% of patients with the 5' UTR primer at 6 months after the cessation of IFN therapy. The levels of TTV DNA before IFN therapy were significantly lower in the viral eradication group than in non-eradication group. The changes in alanine aminotransferase (ALT) concentrations were significantly correlated with changes in HCV-RNA in CHC patients with TTV. Moreover, there was no correlation between the changes in TTV DNA and the course of ALT. CONCLUSION: Hepatocellular injury in patients with chronic hepatitis who are coinfected with HCV and TTV appears to primarily be caused by HCV and is less attributable to TTV.     

Prevalence of TT viral DNA in italian blood donors with and without elevated serum ALT levels: molecular characterization of viral DNA isolates

BACKGROUND AND OBJECTIVE: A novel non-enveloped DNA virus, called TT virus (TTV), has been reported to be associated with post-transfusion hepatitis of unknown etiology. Although its clinical role still remains obscure, its presence in blood donations might cause problems. It, therefore, appeared of interest to investigate TTV prevalence in voluntary blood donors. DESIGN AND METHODS: A total of 595 Italian blood donors with and without elevated serum alanine aminotransferase (ALT) levels were tested by polymerase chain reaction using two sets of semi-nested primers that amplify the well-known region in the N22 clone. The amplified products were then sequenced to assess the genotype by phylogenetic and restriction fragment length polymorphism analyses. RESULTS: The prevalence of TTV in blood donors was 5+/-1.9% (25 out of 500) with a 95% confidence limit. A similar prevalence was found in 95 selected blood donors with increased ALT levels. A viral load of 10(3)-10(4) viral DNA molecules/mL was found, thus indicating a rather narrow range of variability. A phylogenetic tree built up on the basis of 210 base sequences of ORF1 allowed isolates to be classified into 2 groups corresponding, at least, to two of the putatives TTV genotypes, group 1 and group 2 of Okamoto's classification. A similar classification was also obtained by site restriction enzyme analysis. INTERPRETATION AND CONCLUSIONS: The results show that TTV infection is present among Italian blood donors. No significant difference in prevalence of TTV infection was found between patients with normal and increased ALT, making the association between TTV infection and human hepatitis questionable.