Interferon graft dysfunction: a final chapter for interferon and hepatitis C

Alpha-interferon (IFN) has been the backbone of treatments for the hepatitis C virus (HCV) for a quarter of a century. HCV universally recurs after liver transplantation (LT), and there is more rapid progression of fibrosis, estimated to be twice that of pre-LT HCV. The chance of developing cirrhosis at 5 years has been reported to range from 15 to 50 %, depending on the reference. Mortality in patients transplanted for HCV is the worst among the various disease indications for LT. Because of increased morbidity and mortality in this population, there has been a logical push to improve outcomes by attempting to aggressively treat post-LT HCV. However, sustained virological response (SVR) rates with IFN-based post-LT treatment have been relatively poor, and there have been, heretofore, no other effective treatments for HCV. Moreover, there are risks associated with post-LT IFN-based HCV treatment. In this issue of Hepatology International, Ikegami and colleagues from Kyushu University describe interferoninduced graft dysfunction (IGD) in a series of 80 patients who received pegylated-IFN (Peg-IFN) after living donor LT [1]. Their goal was to identify common characteristics and management strategies for this potentially morbid condition. Patients were treated for HCV if they had recurrent HCV with abnormal liver tests and histologic evidence of hepatitis. Most patients had treatment initiated at 6 months post-LT. These authors chose Peg-IFNa-2b with ribavirin for 48 weeks as primary treatment but switched patients to Peg-IFNa-2a if HCV RNA levels did not decrease satisfactorily. Their reasoning for this conversion was based on the longer half-life of Peg-IFNa-2a and other studies suggesting that this strategy may increase the chance for SVR [2]. They defined IGD as ‘‘graft dysfunction during or after interferon treatment for HCV. The pathological diagnoses included plasma cell hepatitis (PCH), acute cellular rejection (ACR), or chronic rejection (CR), or a combination of these findings.’’ They did not discuss or compare pathological or laboratory abnormalities in their LT patients who did not receive interferon, with or without HCV. They defined ACR as mixed lymphocytic aggregates with bile duct damage and vascular endotheliitis, a standard definition. PCH was identified by the presence of plasma cell aggregates without bile duct damage or endotheliitis. Plasma cell aggregates along with bile duct damage or endotheliitis was considered PCH ? ACR. CR was defined as having bile duct loss, Glissonean or central venous fibrosis progression without cellularity, portal venous peliosis and foamy hepatic arterial cells. Eight patients experienced IGD: one with ACR, two with PCH, three with PCH ? ACR and two with CR (initially diagnosed as ACR and with PCH ? ACR). Six of these patients were treated with Peg-IFNa 2a, and four of them developed IGD after the switch from 2b to 2a. When IGD was identified, IFN treatment was stopped and immunosuppression increased. The patients who manifested CR experienced graft loss. Of those without CR, five of them achieved SVR. Treatment with Peg-IFNa 2a was the only factor found to significantly contribute to IGD. Patients with IGD had lower 5-year graft survival compared to those without (71 vs. 93 %). While the number of patients studied was small, this study reminds us of the controversial classification of the J. A. Thompson J. R. Lake (&) University of Minnesota, Minneapolis, MN, USA e-mail: lakex009@tc.umn.edu