Plasma cell hepatitis (PCH) is characterized by plasma cell infiltration seen in allografts of patients who underwent liver transplantation (LT) for conditions other than autoimmune hepatitis. We identified 40 PCH patients who underwent LT for hepatitis C virus (HCV) by searching our pathology database (1994-2006) for the keywords liver allograft, lymphoplasmacytic, and plasma cell(s). We selected 2 control patients who received LT for HCV for each PCH case. The control patients were matched according to date of LT and availability of biopsy material at the time interval to development of PCH in PCH patients. Explant and post-LT biopsy slides were blindly reviewed by 2 liver pathologists and the severity of the plasma cell infiltrate was scored. A score of 3 (plasma cells composing >30% of the infiltrate) defined PCH in allograft biopsies. Five random areas of dense inflammation were also examined in explant livers and the highest score was used. Poor outcome was defined as death or advanced fibrosis (stage >or= 4 of 6). We found that PCH patients were more likely to have worse outcomes than control patients (65% versus 40%, P < 0.01), including increased mortality (50% versus 30%, P < 0.05). Kaplan-Meier survival analysis showed significantly worse survival for PCH patients from 4 to 10 years post-LT (P < 0.05). Explants from 40% of PCH patients had a score of 3 compared to 18% of control patients (P < 0.01). We found that the development of PCH is associated with poor outcome in patients undergoing LT for HCV. The association of significant plasma cell infiltrates in native livers of HCV patients developing PCH suggests that some patients may have a predisposition to developing PCH.