title: Fibrosis in chronic hepatitis C acquired in infancy: is it only a matter of time?
abstract: OBJECTIVE
  The natural history of chronic hepatitis C acquired in infancy is not well understood. The progression of fibrosis was analyzed in untreated children with chronic hepatitis C virus infection and no other hepatotoxic cofactors.
  
  
  METHODS
  A total of 112 pediatric patients (13 with paired liver biopsies) were considered. Fibrosis was assessed by METAVIR score (i.e., stage F1 to F4). The ratio between the stage of fibrosis (METAVIR units) and the presumed duration of infection represented the "estimated" rate of fibrosis progression per year. In patients with paired biopsies, the "observed" rate of fibrosis progression was defined as the difference between the stage of fibrosis in the two biopsies divided by the time interval between them.
  
  
  RESULTS
  Both age of patients at biopsy and duration of infection correlated with stage of fibrosis (p < 0.002 and p < 0.0005, respectively). Stage of fibrosis differed significantly between patients with infection lasting less or more than 10 yr (p < 0.0006). Sex, hepatitis C virus genotype, and route of infection did not correlate with stage of fibrosis. Among the 13 patients with paired biopsies, stage of fibrosis increased in seven and did not change in six; the median rate of estimated fibrosis progression per year was 0.142. The difference between estimated and observed fibrosis progression rates was significant (coefficient of determination, r(2) = 0.031), which demonstrated that the prediction of the fibrosis progression was unreliable in 97% of patients.
  
  
  CONCLUSIONS
  Chronic hepatitis C acquired in childhood is a progressive, slow-moving, fibrotic disease. Fibrosis progression inferred on the basis of linear mathematical models should be critically evaluated in the clinical practice.
authors.affiliation: Dipartimento di Scienze Oncologiche and Chirurgiche, Università degli Studi di Padova, Azienda Ospedale Padova, Padova, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Guido
authors.forename: Flavia
authors.initials: F
authors.lastname: Bortolotti
authors.forename: Gioacchino
authors.initials: G
authors.lastname: Leandro
authors.forename: Paloma
authors.initials: P
authors.lastname: Jara
authors.forename: Loreto
authors.initials: L
authors.lastname: Hierro
authors.forename: Javier
authors.initials: J
authors.lastname: Larrauri
authors.forename: Cristiana
authors.initials: C
authors.lastname: Barbera
authors.forename: Raffaella
authors.initials: R
authors.lastname: Giacchino
authors.forename: Lucia
authors.initials: L
authors.lastname: Zancan
authors.forename: Fiorella
authors.initials: F
authors.lastname: Balli
authors.forename: Carlo
authors.initials: C
authors.lastname: Crivellaro
authors.forename: Emilio
authors.initials: E
authors.lastname: Cristina
authors.forename: Angela
authors.initials: A
authors.lastname: Pucci
authors.forename: Massimo
authors.initials: M
authors.lastname: Rugge
mesh_terms: D000293:Adolescent; D000328:Adult; D001706:Biopsy; D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000635:transmission; D006801:Humans; D007223:Infant; D008103:Liver Cirrhosis / Q000201:enzymology / Q000473:pathology / Q000821:virology*; D008297:Male; D012189:Retrospective Studies; D012307:Risk Factors; D012720:Severity of Illness Index; D013997:Time Factors