TIMING AND SEVERITY OF INITIAL HEPATITIS-C RECURRENCE AS PREDICTORS OF LONG-TERM LIVER ALLOGRAFT INJURY

Background. The majority of patients infected with hepatitis C virus ( HCV) undergoing liver transplantation develop evidence of histologic r ecurrence, and multiple mechanisms are likely poised to affect long-te rm allograft injury, The purpose of this analysis was to study the hyp othesis that histologic and biochemical features at the onset of HCV r ecurrence predict the long-term evolution of allograft hepatitis. Meth ods. We studied 34 consecutive liver transplant recipients with eviden ce of histologic HCV recurrence and with a minimal histologic follow-u p 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 in flammation, and hepatic fibrosis, The presence of hepatocyte balloonin g degeneration and cholestasis was also assessed. Results, Although th ere was no significant difference with regard to initial hepatic activ ity index scores between patients who ultimately developed allograft c irrhosis (group 1; n=8) versus those with milder hepatitis (group 2; n =26), the finding of ballooning degeneration/cholestasis was more freq uent in the former group (P=0.04), The distribution of HCV genotypes, the mean follow-up after orthotopic liver transplantation, the mean nu mber of allograft biopsy specimens per patient, basal immunosuppressio n, 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 pea k total bilirubin (pT.Bili, the highest value in the ensuing month). A ctuarial rates of moderate-to-severe allograft hepatitis were signific antly greater in patients with pT.Bili greater than or equal to 3.5 mg /dl (p=0.004). Multiple regression analysis identified pT.Bili as the only independent predictor of allograft cirrhosis. Conclusions. Featur es at the onset of histologic HCV recurrence predict the natural histo ry of allograft injury; specifically, marked, transient hyperbilirubin emia is associ ated with the subsequent development of allograft cirrh osis.