The prevalence and natural history of untreated isolated central perivenulitis in adult allograft livers

Central perivenulitis (CP) in the allograft liver can be associated with portal-based acute cellular rejection and autoimmune hepatitis or can occur in isolation (isolated CP). Although several studies have demonstrated the significance of CP, the prevalence and natural history of untreated isolated CP have not been well studied. We examined 100 adult allograft liver recipients who had long-term follow-up, had routine protocol biopsies, and received no treatment for isolated CP. Isolated CP was identified in 28 (28%) patients. It occurred late at a mean of 658 days. Interestingly, patients with late isolated CP (defined as >3 months posttransplant) usually manifested only mildly to modestly elevated liver function tests. However, late isolated CP was associated with prior and subsequent allograft complications. Nearly all (94%) cases of late isolated CP occurred in patients who had early episodes of CP and/or acute cellular rejection. Of 13 patients who developed adverse outcomes in their allografts (zone 3 fibrosis in 10, de novo autoimmune hepatitis in 3, and ductopenia in 3), all experienced episodes of prior CP, and 12 (92%) had late CP; 1 patient required retransplant for chronic rejection, but all were alive within the last year. In summary, "transplant-associated" isolated CP occurs in 28% of adult patients, early CP is predictive of late CP, and late CP (often present as isolated CP) is associated with long-term liver injury in some patients.