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      Epidemiology and Clinical Significance of Chronic Hepatitis-Related Viruses Infection in Hemodialysis Patients from Taiwan


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          Background/Aims: A novel DNA virus which was designated TT virus (TTV) in 1997 was considered a possible hepatitis-related virus, like hepatitis C (HCV), hepatitis B (HBV) and GB virus C/hepatitis G viruses (GBV-C/HGV). In the present study, the molecular epidemiology and clinical significance of TTV, GBV-C/HGV and HCV infection in hemodialysis patients from Taiwan are investigated. Methods: Sera of 85 patients on maintenance hemodialysis were tested for alanine aminotransferase (ALT), hepatitis B surface antigen (HBsAg), second-generation HCV antibody (anti-HCV), anti-envelope protein 2 antibody (anti-E2) and RNA of GBV-C/HGV, HCV RNA and TTV DNA. Sera of patients with positive TTV DNA, GBV-C/HGV RNA or HCV RNA were tested for viruses 2 years later. Results: Seven (8.2%) 29 (34.1%), 21 (24.7%), 12 (14.1%) and 9 (10.6%) hemodialysis patients were positive for HBsAg, Anti-HCV, HCV RNA, GBV-C/HGV RNA and anti-E2, respectively. TTV DNA was positive in 46 (54.1%) patients. Neither clinical nor virological factors were associated with TTV viremia. The ALT level was significantly elevated in HCV RNA-positive individuals than –negative ones (34.5 vs. 12.5%, p < 0.05). TTV DNA, GBV-C/HGV RNA and HCV RNA remained detectable in sera of 31 (86.1%), 6 (50%) and 21 (100%) patients collected 2 years after first diagnosis of viremia. Conclusion: Among Taiwanese hemodialysis patients, TTV infection is highly prevalent. No clinical or virological factor was observed to be significantly associated with TTV infection. The ALT abnormality was mainly attributable to HCV but not TTV infection in Taiwanese hemodialysis patients.

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          Most cited references14

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          A novel DNA virus (TTV) associated with elevated transaminase levels in posttransfusion hepatitis of unknown etiology.

          By means of representational difference analysis, a viral clone (N22) of 500 nucleotides was isolated from serum of a patient (TT) with posttransfusion hepatitis of unknown etiology. The N22 clone showed a poor homology to any reported sequences. Oligonucleotide primers were deduced from the N22 sequence for detecting it by polymerase chain reaction. N22 sequence in serum banded at a sucrose density of 1.26 g/cm3, indicating its association with a viral particle which was designated TT virus (TTV). Since nucleic acids of TTV were sensitive to DNase I, it would be a DNA virus. TTV DNA was detected in sera from three of the five patients with posttransfusion non-A to G hepatitis, including the index case (TT). TTV DNA titers closely correlated with aminotransferase levels in the three patients. These results indicate that TTV would be a novel DNA virus with a possible capacity to induce posttransfusion non-A to G hepatitis. Copyright 1997 Academic Press.
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            Molecular and biophysical characterization of TT virus: evidence for a new virus family infecting humans.

            The recent isolation of a novel DNA virus from the serum of a Japanese patient (T.T.) has provided the latest possible candidate virus associated with cryptogenic hepatitis. In the present study, we report the complete nucleotide sequence of this virus (TTV) isolated from the serum of a West African. Based on PCR studies designed to amplify overlapping regions of the viral genome and sensitivity to digestion with mung bean nuclease, the viral genome is circular and negative stranded, and comprises 3,852 nt, which is 113 nt longer than the prototype isolate from Japan. Cesium chloride density gradient centrifugation demonstrated banding of the virus at 1.31-1.34 g/ml; filtration studies indicated that TTV had a particle size of 30-50 nm. These results suggest that the virus is similar to the Circoviridae, viruses known to infect plants and vertebrates (e. g., birds and swine); however, sequence similarity searches of available databases did not reveal identity between TTV and other viruses. Phylogenetic analyses of a 260-nt region from 151 globally distributed isolates demonstrated the existence of three major TTV genotypes. Several individuals at high risk for infection with parenterally transmitted viruses were infected with more than one genotype. There was no correlation between genotype and geographic origin. Finally, intravenous inoculation of TTV-positive human serum into chimpanzees demonstrated that TTV can be transmitted to primates; no biochemical or histological evidence for hepatitis was obtained. The distinct biophysical and molecular characteristics of TTV suggest that it is a member of a new family of viruses, which we have tentatively named the Circinoviridae.
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              Molecular cloning and characterization of a novel DNA virus (TTV) associated with posttransfusion hepatitis of unknown etiology

              H Okamoto (1998)

                Author and article information

                S. Karger AG
                February 2002
                30 January 2002
                : 90
                : 2
                : 148-153
                aHepatobiliary Division, Department of Internal Medicine, College of Medicine, Kaohsiung Medical University, and bHemodialysis Unit, Chann-Ann Clinic, Kaohsiung City, Taiwan/ROC
                49035 Nephron 2002;90:148–153
                © 2002 S. Karger AG, Basel

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                Page count
                Tables: 2, References: 40, Pages: 6
                Self URI (application/pdf): https://www.karger.com/Article/Pdf/49035
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                Self URI (journal page): https://www.karger.com/SubjectArea/Nephrology
                Original Paper

                Cardiovascular Medicine,Nephrology
                HCV,Hemodialysis,TT virus,GBV-C/HGV
                Cardiovascular Medicine, Nephrology
                HCV, Hemodialysis, TT virus, GBV-C/HGV


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