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A Case of Hepatocellular Carcinoma (HCC) Immunotherapy Inducing Liver Transplant Rejection

2018; Lippincott Williams & Wilkins; Volume: 113; Issue: Supplement Linguagem: Inglês

10.14309/00000434-201810001-02415

1572-0241

Paul Gomez, Alan Naim, Kelly Zucker, Mark Wong,

Hepatocellular Carcinoma Treatment and Prognosis

Hepatocellular carcinoma (HCC) is a leading cause of cancer globally. Nivolumab is a new immunotherapy option to treat HCC. It is a monoclonal antibody that targets programmed cell death protein 1 (PD-1), therefore blocking immune checkpoint signaling and ultimately helping to restore T cell activity. However, the use of this novel agent in liver transplant recipients has not been well studied. 61-year-old male with history of cirrhosis from hepatitis C virus, complicated by hepatocellular carcinoma (HCC), had an uneventful liver transplant. Two years later he developed HCC recurrence, treatment was started with Sorafenib but he did not tolerate the adverse effects. His Oncologist started him on Nivolumab and after the second dose his laboratory tests showed AST 502 IU/L, ALT 480 IU/L, total bilirubin 7.2 mg/dL, INR 1.3, platelet 71 K/MM3, and albumin 3.4 g/dL. Patient had no complaints and his physical exam was normal. A liver biopsy showed findings consistent with severe acute cellular rejection. Due to Nivolumab's extended half-life, the patient was treated for rejection with a prolonged course of high dose intravenous cortico- steroids. Biopsy was repeated 13 days later and showed signs of treated acute cellular rejection. Liver chemistry tests improved and he was discharged home on 60 mg of oral prednisone with plan for close follow up. Prior to discharge the AST and ALT were 75 IU/L and 301 IU/L respectively. The increasing prevalence of HCC brought a need for new and more effective therapies. Nivolumab was granted accelerated clearance by the FDA on 9/22/17 for patients who did not respond to Sorafenib. However, there are currently no guidelines for the use of Nivolumab in recipients of liver transplant, and there are a few reports of rejection following its use in the post-transplant setting. The main mechanism by which Nivolumab induces rejection is the blockage of PD-1, which helps restore T-cell antitumor function, acting as a type of immune reconstitution. Given the long half- life of Nivolumab, a high dose of immunosuppression (IS) is needed for a prolonged time in face of an episode of rejection. This in turn increases the risk of complications associated with high dose of IS. There is strong evidence to support the use target immunotherapy, such as Nivolumab, for the treatment of HCC. However, given the risk of rejection in the post-transplant setting, caution must be used prior to its utilization in this patient population.