title: Timing and severity of initial hepatitis C recurrence as predictors of long-term liver allograft injury.
abstract: BACKGROUND
  The majority of patients infected with hepatitis C virus (HCV) undergoing liver transplantation develop evidence of histologic recurrence, and multiple mechanisms are likely poised to affect long-term allograft injury. The purpose of this analysis was to study the hypothesis that histologic and biochemical features at the onset of HCV recurrence predict the long-term evolution of allograft hepatitis.
  
  
  METHODS
  We studied 34 consecutive liver transplant recipients with evidence of histologic HCV recurrence and with a minimal histologic follow-up of 1 year (up to 6.2 years; mean: 696+/-83.2 days). Two-hundred and seventy-eight serial allograft biopsies (mean: 6.85+/-0.62 per patient, range: 4-21) were analyzed. The hepatic activity index was utilized to quantitate piecemeal necrosis, intralobular degeneration, portal inflammation, and hepatic fibrosis. The presence of hepatocyte ballooning degeneration and cholestasis was also assessed.
  
  
  RESULTS
  Although there was no significant difference with regard to initial hepatic activity index scores between patients who ultimately developed allograft cirrhosis (group 1; n=8) versus those with milder hepatitis (group 2; n=26), the finding of ballooning degeneration/cholestasis was more frequent in the former group (P=0.04). The distribution of HCV genotypes, the mean follow-up after orthotopic liver transplantation, the mean number of allograft biopsy specimens per patient, basal immunosuppression, and incidence of rejection were comparable in both groups. Patients who ultimately developed allograft cirrhosis had significantly higher initial total bilirubin at the onset of histologic recurrence and peak total bilirubin (pT. Bili, the highest value in the ensuing month). Actuarial rates of moderate-to-severe allograft hepatitis were significantly greater in patients with pT. Bili > or = 3.5 mg/dl (P=0.004). Multiple regression analysis identified pT. Bili as the only independent predictor of allograft cirrhosis.
  
  
  CONCLUSIONS
  Features at the onset of histologic HCV recurrence predict the natural history of allograft injury; specifically, marked, transient hyperbilirubinemia is associated with the subsequent development of allograft cirrhosis.
authors.affiliation: Department of Medicine, Oregon Health Sciences University and Portland Veterans Affairs Medical Center, 97207, USA.
authors.forename: H R
authors.initials: HR
authors.lastname: Rosen
authors.forename: D R
authors.initials: DR
authors.lastname: Gretch
authors.forename: M
authors.initials: M
authors.lastname: Oehlke
authors.forename: K D
authors.initials: KD
authors.lastname: Flora
authors.forename: K G
authors.initials: KG
authors.lastname: Benner
authors.forename: J M
authors.initials: JM
authors.lastname: Rabkin
authors.forename: C L
authors.initials: CL
authors.lastname: Corless
mesh_terms: D001706:Biopsy; D005500:Follow-Up Studies; D006526:Hepatitis C / Q000473:pathology / Q000503:physiopathology* / Q000601:surgery*; D006801:Humans; D006932:Hyperbilirubinemia / Q000209:etiology; D008099:Liver / Q000473:pathology*; D008103:Liver Cirrhosis / Q000209:etiology; D016031:Liver Transplantation; D011183:Postoperative Complications; D011379:Prognosis; D012008:Recurrence; D012720:Severity of Illness Index; D013997:Time Factors