title: TT virus infection in patients with primary hypogammaglobulinaemia: natural history and relationship to liver disease in the immunocompromised host.
abstract: BACKGROUND
  TT virus (TTV) is a recently discovered human DNA virus with worldwide distribution, but with no clear disease association. The possibility of an enhanced TTV virulence in patients with immunodeficiencies has not yet been investigated but is of particular interest because other viruses have been demonstrated to cause severe and rapid liver disease in such patients. Here we analysed the characteristics of TTV infection in a large cohort of patients with primary hypogammaglobulinaemia (PHG) and whether TTV has a role in the frequently observed cryptogenic liver disease in these patients.
  
  
  METHODS
  83 Norwegian patients with PHG (serum immunoglobulin G < 2 g/L), receiving substitution treatment with immunoglobulins, were followed regularly for median 10.2 years (range 2-30). TTV DNA was sought in serum samples and three immunoglobulin preparations by polymerase chain reaction; TTV DNA quantitation, DNA sequencing and phylogenetic analysis were performed in selected samples.
  
  
  RESULTS
  TTV DNA was detected in 27 of 83 (32.5%) patients and was not associated with a particular type of PHG. The prevalence of TTV infection was dependent on intravenous immunoglobulin administration, duration of therapy and patient's age. TTV DNA was found in two of three currently used immunoglobulin preparations. In the longitudinal study, whether TTV was cleared or newly acquired had no impact on liver function tests and no particular TTV strain was found in patients with more severe liver disease.
  
  
  CONCLUSIONS
  TTV infection is common in patients with PHG. Treatment with immunoglobulins has a role in the transmission of TTV in these patients. However, we found no evidence of TTV-induced liver disease in this group of immunocompromised patients.
authors.affiliation: Dept. of Medicine, National Hospital, Oslo, Norway. kristian.bjoro@labmed.uio.no
authors.forename: K
authors.initials: K
authors.lastname: Bjøro
authors.forename: E P
authors.initials: EP
authors.lastname: Petrova
authors.forename: M G
authors.initials: MG
authors.lastname: Thomas
authors.forename: S S
authors.initials: SS
authors.lastname: Frøland
authors.forename: R
authors.initials: R
authors.lastname: Williams
authors.forename: N V
authors.initials: NV
authors.lastname: Naoumov
mesh_terms: D000328:Adult; D000361:Agammaglobulinemia / Q000276:immunology / Q000821:virology*; D015331:Cohort Studies; D004266:DNA Virus Infections / Q000453:epidemiology / Q000276:immunology* / Q000635:transmission; D004279:DNA, Viral / Q000302:isolation & purification; D005260:Female; D005500:Follow-Up Studies; D006525:Hepatitis, Viral, Human / Q000276:immunology / Q000821:virology*; D006801:Humans; D016867:Immunocompromised Host; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use; D008297:Male; D015995:Prevalence; D013997:Time Factors; D022783:Torque teno virus / Q000302:isolation & purification
chemical_list: D004279:DNA, Viral; D016756:Immunoglobulins, Intravenous