title: Clinicopathological study on TTV infection in hepatitis of unknown etiology.
abstract: OBJECTIVE
  To investigate the state of infection, replication site, pathogenicity and clinical significance of transfusion transmitted virus (TTV) in patients with hepatitis, especially in patients of unknown etiology.
  
  
  METHODS
  Liver tissues taken from 136 cases of non-A non-G hepatitis were tested for TT virus antigen and nucleic acid by in situ hybridization (ISH) and nested-polymerase chain reaction (PCR). Among them, TT virus genome and its complemental strand were also detected in 24 cases of autopsy liver and extrahepatic tissues with ISH. Meanwhile, TTV DNA was detected in the sera of 187 hepatitis patients by nested-PCR. The pathological and clinical data of the cases infected with TTV only were analyzed.
  
  
  RESULTS
  In liver, the total positive rate of TTV DNA was 32.4% and the positive signals were located in the nuclei of hepatocytes. In serus, TTV DNA was detected in 21.4% cases of hepatitis A-G, 34.4% of non-A non-G hepatitis and 15% of healthy donors. The correspondence rate of TTV DNA detection between liver tissue with ISH and sera with PCR was 63.2% and 89.3% in the same liver tissues by ISH and by PCR, respectively. Using double-strand probes and single-strand probes designed to detect TTV genome, the correspondence rate of TTV DNA detected in liver and extrahepatic tissues was 85.7%. Using single-strand probes, TTV genome could be detected in liver and extrahepatic tissues by PCR, but its complemental strands (replication strands) could be observed only in livers. The liver function of most cases infected with TTV alone was abnormal and the liver tissues had different pathological damage such as ballooning, acidophilia degeneration, formation of apoptosis bodies and focus of necrosis, but the inflammation in the lobule and portal area was mild.
  
  
  CONCLUSIONS
  The positive rate of TTV DNA among cases of hepatitis was higher than that of donors, especially in patients with non-A non-G hepatitis, but most of them were coinfected with other hepatitis viruses. TTV can infect not only hepatocytes, but also extrahepatic tissues. However, the chief replication place may be liver. The infection of TTV may have some pathogenicity. Although the pathogenicity is comparatively weak, it can still damage the liver tissues. The lesions in acute hepatitis (AH) and chronic hepatitis (CH) are mild, but in severe hepatitis (SH), it can be very serious and cause liver function failure, therefore, we should pay more attention to TTV when studying the possible pathogens of so-called "liver hepatitis of unknown etiology".
authors.affiliation: Department of Pathology, Beijing You'an Hospital, 8 You'an Men Wai, Beijing 100054, China. huzhong-jie@263.net
authors.forename: Zhong-Jie
authors.initials: ZJ
authors.lastname: Hu
authors.forename: Zhen-Wei
authors.initials: ZW
authors.lastname: Lang
authors.forename: Yu-Sen
authors.initials: YS
authors.lastname: Zhou
authors.forename: Hui-Ping
authors.initials: HP
authors.lastname: Yan
authors.forename: De-Zhuang
authors.initials: DZ
authors.lastname: Huang
authors.forename: Wan-Rong
authors.initials: WR
authors.lastname: Chen
authors.forename: Zhao-Xia
authors.initials: ZX
authors.lastname: Luo
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D004266:DNA Virus Infections / Q000821:virology*; D005260:Female; D006525:Hepatitis, Viral, Human / Q000209:etiology / Q000821:virology*; D006801:Humans; D017403:In Situ Hybridization; D008099:Liver / Q000473:pathology / Q000821:virology; D008297:Male; D008875:Middle Aged; D022783:Torque teno virus / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*