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.     

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.     

Transfusion-transmitted virus infection in China: Prevalence in blood donors and in patients with liver diseases

BACKGROUND: Prevalence of transfusion-transmitted virus (TTV) infection among blood donors and in patients with liver diseases in China was studied. METHODS: DNA was extracted from serum and amplified by seminested polymerase chain reaction with reported primer sets from a conserved region of the TTV genome. RESULTS: TT Virus DNA was detected in 55 of 196 blood donors (28%); 31% (40 of 127) in the north and 22% (15 of 69) in the south. TT Virus DNA was also detected in 14 of 31 patients (45%) with non-A-non-G fulminant hepatitis and in eight of 25 patients (32%) with non-A-non-G chronic hepatitis. The rate of TTV viraemia in these patients with liver disease was comparable to that in blood donors. TT Virus DNA sequencing of 12 isolates showed that the prevalence of genotype 2 was significantly higher than that reported in Japan (66.7 vs 2.6%, P < 0.001). Furthermore, genotyping assays based on restriction fragment length polymorphism were carried out on all 88 TTV DNA-positive samples. It was found that 42 isolates (47.7%) belonged to genotype 1 and 40 (45.5%) to genotype 2. It was of particular interest that the prevalence of genotype 1 in patients with non-A-non-G fulminant hepatitis was significantly higher than that in blood donors (10/14 vs 22/55, P < 0.05). CONCLUSIONS: The data indicate that TTV infection is common in China and that the pathogenic potential of TTV toward the liver (if any) may differ between genotypes.     

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.     

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.     

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.     

Virologic analysis of non-B, non-C hepatocellular carcinoma in Japan: frequent involvement of hepatitis B virus

Serum and liver tissues from hepatitis B surface antigen-negative/anti-hepatitis C virus (HCV)-negative (non-B, non-C) hepatocellular carcinoma (HCC) patients in Japan were examined for the presence of hepatitis B virus (HBV), HCV, and TT virus (TTV) by polymerase chain reaction. The studies evaluated the contribution of these viruses to pathogenesis of HCC. HBV DNA was detected in the sera of 20 (47.6%) of 42 non-B, non-C HCC patients, which was significantly higher than in age-matched controls without liver disease (P<.001). In 8 of 12 patients with liver tissues available, HBV DNA was detected in cancerous and adjacent noncancerous liver tissues. No HCV RNA was detected. The positivity for TTV DNA was not significantly different between HCC patients and controls. These results indicate that HBV is associated with a substantial proportion of non-B, non-C HCC cases in Japan. The role of HBV in hepatocarcinogenesis in such patients needs to be clarified.     

Prevalence of TT virus infection in US blood donors and populations at risk for acquiring parenterally transmitted viruses

Two overlapping sets of TT virus (TTV)-specific polymerase chain reaction primers were used to test for presence of TTV, which was found in approximately 10% of US volunteer blood donors, 13% of commercial blood donors, and 17% of intravenous drug abusers. The rate of TTV infection among US non-A, non-B, non-C, non-D, non-E hepatitis patients was only 2%. Among commercial blood donors and intravenous drug abusers, only 1%-3% of the TTV-positive individuals were coinfected with GB virus C (GBV-C), a parenterally transmitted virus. This suggests that GBV-C and TTV may have different routes of transmission. Comparison of the sensitivities of 2 TTV polymerase chain reaction (PCR) primer sets showed that the majority of samples were detected with only 1 of the 2 sets. Therefore, previous studies in which only a single PCR primer pair was used may have significantly underestimated the true prevalence of TTV.     

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.     

TTV与其它肝炎病混合感染及其基因型的研究

研究TTV与其它肝炎病混合感染对肝脏病变的影响及本地区TTVDNA的基因型。选TTV ORF1的保守序列作内外引物,采用微板核酸杂交－ELISA方法检测患者血清TTVDNA并对检测结果和临床资料进行统计学分析。选取异源性大于50％的序列作显色探针Ⅰ和显色探针Ⅱ,进行分型研究。学生、非甲－非戊型肝炎、慢性乙型肝炎和肝硬化患者血清TTV阳性率分别为3．3％、14．3％、12％、16％。TTV阳性和TTV阴性的慢性乙型肝炎及肝硬化患者,在年龄、性别、ALT和TBil之间无显著差异（P＞0．05）。本地区流行的TTV可分为两个主要的基因型,即I型（66．75）、Ⅱ型（25％）,部分存在混合感染（8．3％）。TTV可能与HBV、HCV有类似的传播途径,故常重叠感染。TTV与乙型肝炎及肝硬化混合感染后不影响两者的肝脏病变。TTV不是本地区非甲－非戊型肝炎的主要病因。     

Seroprevalence of hepatitis C virus nucleocapsid antibodies in patients with cryptogenic chronic liver disease.

The serological responses to two different hepatitis C virus antigens were studied by enzyme-linked immunosorbent assay in a variety of chronic liver diseases and in healthy blood donors. The study population comprised 97 cases of cryptogenic chronic liver disease (40% with a history suggestive of parenterally transmitted non-A, non-B hepatitis and 60% without such a history), 87 cases of other well-characterized chronic liver diseases and 96 voluntary blood donors. The commercially available C100-3 assay and a new assay utilizing a 22 kD recombinant protein (c22) from the nucleocapsid region of the virus were used for antibody detection. Overall in the non-A, non-B hepatitis group, 77% were positive for anti-c22, 55% were positive for anti-C100-3 and 24% were negative by both tests. In the parenterally transmitted chronic liver disease group, 82% were positive for anti-C100-3 and 90% were positive for anti-c22 (not significant). In the cryptogenic chronic liver disease cases 36% were positive for anti-C100-3 and 67% were positive for anti-c22 (p less than 0.001). Only in one case (a patient with hepatitis B virus infection) was anti-C100-3 detected without concomitant anti-c22. None of the voluntary blood donors had detectable hepatitis C virus antibodies. The new enzyme-linked immunosorbent assay test for anti-c22 would appear to be a more sensitive indicator of chronic hepatitis C virus infection than the existing commercial test, suggesting a useful diagnostic role in both cases of cryptogenic chronic non-A, non-B hepatitis liver disease and for the screening of blood products for prevention of hepatitis after transfusion.     

Role of hepatitis C virus in non-B chronic liver disease.

To assess the contribution of the recently identified hepatitis C virus to chronic liver diseases of unknown cause and chronic hepatitis attributed by exclusion to non-A, non-B hepatitis, we tested for antibody to hepatitis C in hepatitis B surface antigen-negative patients with a spectrum of chronic liver diseases. Antibody to hepatitis C virus, a marker of hepatitis C infection, was detected with a first-generation radioimmunoassay at the following frequencies in the following patient groups: 69% of transfusion-associated non-A, non-B hepatitis; 53% of non-transfusion-associated non-A, non-B hepatitis; 26% of hepatitis B surface antigen-negative hepatocellular carcinoma; 8% of cryptogenic cirrhosis; 5% to 7% of autoimmune chronic liver diseases; 19% of patients with miscellaneous types of chronic liver disease; and 0.67% of healthy controls. Among non-transfusion-associated cases, 81% with a history of intravenous drug use but only 18% with occupational exposure as health workers had antibody to hepatitis C virus. Among cases of hepatocellular carcinoma, 63% of Japanese patients but only 11% of American patients had evidence of hepatitis C infection. Comparison in a subgroup of 79 serum samples of a second-generation radioimmunoassay with the first-generation assay demonstrated a 12% increase in antibody frequency from 30% to 42%. We conclude that hepatitis C plays a substantial role in transfusion-associated and non-transfusion-associated non-A, non-B hepatitis as well as in hepatocellular carcinoma, especially in Japan, a limited role in cryptogenic cirrhosis, and essentially no role in autoimmune chronic liver diseases. Application of more sensitive immunoassays will increase the frequency of antibody seropositivity in all subgroups, but relative distinctions among risk groups are likely to remain.     

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.     

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。     

The prevalence of transfusion transmitted virus infection in blood donors

INTRODUCTION A newly discovered DNA virus,transfusion transmitted virus (TTV), was reported as a cause of post-transfusion hepatitis of unknown etiology in Japan[1]. In order to investigate TTV prevalence in southern China, a study was carried out among blood donors, patients with liver diseases and hemodialysis to determine the epidemiological charateristics.     

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.     

Prevalence and genomic variability of transfusion transmitted virus in Italian cryptogenic chronic liver disease and healthy blood donors

BACKGROUND: Infection with transfusion transmitted virus, a new member of the Parvoviridae family, has been found in patients both with chronic and fulminant post-transfusion cryptogenic hepatitis. AIM: To evaluate the prevalence and clinical impact of transfusion transmitted virus infection in Italy. PATIENTS AND METHODS: Studies were carried out on 256 patients and control subjects from three centres from Northern, Central and Southern Italy (92 nonA-nonC chronic hepatitis, 10 acute non fulminant cryptogenic hepatitis, 41 hepatitis C virus-related chronic hepatitis and 113 blood donors). Serum transfusion transmitted virus was detected by nested polymerase chain reaction using two overlapping sets of primers. RESULTS: A total of 52 of the 92 patients (54.3%) with chronic cryptogenic liver disease and 17 of the 41 hepatitis C virus chronic hepatitis patients (41.4%) were transfusion transmitted virus-DNA positive. Transfusion transmitted virus co-infection in hepatitis C virus patients was not associated with either a higher severity of liver histology or higher alanine transaminase levels or signs of cholestasis, transfusion transmitted virus was found in 48 out of 113 (42.4%) blood donors. In the majority of samples, transfusion transmitted virus DNA was detected with only one of the two sets of primers used. Genotyping and phylogenetic analysis performed on 21 randomly selected viral isolates showed the presence of both type 1 and type 2 transfusion transmitted virus and allowed identification of two isolates with high homology to genotype 6, described, so far, mostly in Japan. CONCLUSIONS: Transfusion transmitted virus type 1 and 2 infection is common among blood donors and patients with liver disease in Italy. The pathogenic potential of transfusion transmitted virus type 1 and 2 in nonA-nonC hepatitis patients is unlikely but further studies are needed to evaluate the epidemiological and clinical impact of other transfusion transmitted virus subtypes.     

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.     

病原不明肝炎患者肝组织中TTV正链的检测及其与病变的关系

目的探讨 ＴＴＶ与病原不明肝炎的关系及 ＴＴＶ能否在肝组织中复制。方法用巢式 ＰＣＲ法对３１例某职校流行的病原不明肝炎患者的血清进行３．２ｋｂＴＴＶ ＤＮＡ扩增, ３０例同地区志愿献血员为对照组,结合肝炎患者的病理改变进行分析;同时用核酸酶保护法对其中７例肝炎患者的肝组织做ＴＴＶ正链的检测。结果在病原不明肝炎患者中,ＴＴＶ的检出率为９６．９％,在志愿献血员中检出率为６０％,两组间ＴＴＶ的检出率差异有显著性。在ＴＴＶ ＤＮＡ阳性的３０例肝炎患者中,尽管大多数肝脏损害轻微,但仍有６．６％有慢性肝炎改变。在７例病原不明肝炎患者的肝组织中用核酸酶保护法均检出ＴＴＶ ＤＮＡ的正链。结论 ＴＴＶ感染可能与该病原不明肝炎的流行有关,ＴＴＶ可以在人肝组织中复制,ＴＴＶ可能导致的肝脏损害轻微,但仍有少数有慢性肝炎发生。     

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.