De novo autoimmune hepatitis has been described in both pediatric and adult liver transplantation (LT) recipients. Studies of small numbers of patients have proposed it to be an alloimmune hepatitis or form of chronic rejection. We have recently noted an increasing number of patients with post-LT recurrent hepatitis C virus (HCV) developing this, with an apparent negative impact on outcome and survival. We term this entity posttransplant plasma cell hepatitis (PCH). A search of our institution's pathology database was performed with the terms "plasma cell(s)," "lymphoplasmacytic infiltrate," and "liver allograft." A histological scoring system was devised to more reliably diagnose PCH in the setting of recurrent HCV. Thirty-eight patients were identified, and their clinical data were analyzed. Sixty percent had a negative outcome as defined by the development of cirrhosis, need for retransplantation, or death. Eighty-two percent had recent lowering of immunosuppression or subtherapeutic calcineurin inhibitor levels; 58% developed PCH within 2 years post-LT. Histologic resolution of PCH was associated with good outcome (P Ͻ 0.001). Patients not receiving treatment had a negative outcome (P ϭ 0.007) as did patients receiving corticosteroids as therapy (P ϭ 0.02). Persistence (P ϭ 0.007) or recurrence of PCH was associated with negative outcome. In conclusion, PCH is a histologic variant of rejection. On liver biopsy, PCH can at times be difficult to diagnose, and the use of a standardized scoring system is recommended to differentiate it from other forms of allograft dysfunction. Treatment by optimization of immunosuppression without the use of corticosteroids appears effective. The development of PCH in the setting of recurrent HCV is a negative prognostic factor for patient outcome and allograft failure.

A 55-year-old Caucasian male developed a well characterized autoimmune hepatitis after completing treatment with pegylated interferon and ribavirin for recurrent hepatitis C. We hypothesize that pegylated interferon triggered a severe form of immune-mediated hepatitis.Received September 7, 2005; accepted December 21, 2005.Recurrent hepatitis C viral infection (HCV) is universal post-liver transplantation (LT) and may result in considerable graft dysfunction and mortality. The most effective current therapy for recurrent HCV infection post-LT is pegylated interferon (peg-IFN) in combination with ribavirin (RBV).Interferon (IFN) and RBV exert a variety of immunomodulatory effects. Antiviral therapy may confer a potential increased risk of inducing or unmasking underlying autoimmune diseases. Prolonged exposure to exogenous IFN has been implicated in the induction of organ-specific autoimmune diseases such as autoimmune thyroiditis and rheumatoid arthritis. 1,2 Furthermore, IFN has been demonstrated to trigger and exacerbate autoimmune hepatitis when used to treat chronic HCV infection in the nontransplant setting. [3][4][5][6] Lastly, HCV itself is independently associated with a high incidence of autoimmune diseases, such as thyroiditis. 7 We describe a patient who developed an aggressive plasma-cell-predominant hepatitis post-LT for HCV-related cirrhosis and hepatocellular carcinoma. This condition occurred in the absence of a prior history of autoimmune hepatitis, while the patient was being treated with peg-IFN and had undetectable HCV RNA. We hypothesize that peg-IFN was the likely trigger for a severe form of immune mediated hepatitis. PATIENT AND METHODSA 55-year-old Caucasian male underwent LT for HCVrelated cirrhosis and early-stage hepatocellular carcinoma in September 2002. He had not received IFN antiviral therapy for HCV prior to LT and had no manifestations of autoimmunity. His immediate postoperative course was unremarkable. Induction immunosuppression consisted of daclizumab and prednisolone with tacrolimus titrated to maintain trough levels of 8-12 g/L during the first 2 months, then 6-10 g/L thereafter. Corticosteroids were rapidly tapered and discontinued by 1 month post-LT with the patient maintained on tacrolimus monotherapy.Five months later, a rise in liver enzymes was noted: alanine aminotransferase (ALT), 931 IU/mL (normal, Ͻ40 IU/mL); aspartate aminotransferase, 495 IU/mL (normal, Ͻ35 IU/mL); alkaline phosphatase, 212 IU/mL (normal, Ͻ120 IU/mL); bilirubin, 0.7 mg/dL (normal, Ͻ1.0 mg/dL). In addition, the tacrolimus level was 6.8 g/dL, HCV genotype was 1, and quantitative HCV RNA viral load was 476,000 copies/mL (Roche Cobas Amplicor, Roche, Rotkreuz, Switerland). Liver biopsy revealed panlobular hepatitis and a lymphoid follicle in 1 of the portal tracts, consistent with severe recurrent hepatitis C infection (Fig. 1).Antiviral therapy was commenced with an escalating regimen of peg-IFN (Pegasys, Roche, Nutley, NJ) and

No abstract