S5579 Checkpoint and Checkmate: Concurrent Immune-Mediated Hepatitis and HBV Reactivation in a Cancer Patient

Introduction: With the expanding use of immune checkpoint inhibitors (ICI), there has been a notable rise in immune-related adverse events, including ICI hepatitis, a potentially severe and under-recognized etiology of liver injury. Furthermore, hepatitis B reactivation is a rare but potentially life-threatening complication that can emerge unexpectedly in patients receiving ICI therapy. We present a unique case of a patient with acute liver injury due to both reactivated hepatitis B and ICI hepatitis. Case Description/Methods: A 42-year-old Kenyan woman with metastatic renal cell carcinoma (RCC) presented to the hospital with worsening abdominal pain. She was receiving pembrolizumab and Lenvatinib for her RCC. Labs revealed elevated aspartate aminotransferase 800, alanine aminotransferase 312, alkaline phosphatase 237, and international normalized ratio 1.5. Physical exam was pertinent for diffusely tender abdomen. Serologies showed a positive hepatitis B core antibody, hepatitis B surface antigen, and PCR >10 million. She was started on treatment for hepatitis B reactivation with tenofovir and N-Acetylcysteine (NAC). The patient’s liver function tests (LFTs) continued to rise despite treatment and hence underwent endoscopic ultrasound-guided liver biopsy. Pathology revealed injury from both ICI therapy and HBV. After a multidisciplinary discussion, she was initiated on Solumedrol 1 g/kg in addition to continuing her Tenofovir. Thereafter, the patient’s LFTs and international normalized ratio rapidly improved, and she was transitioned to oral prednisone taper. Labs 3 months later showed normalization of her LFTs, and labs 6 months later showed her HBV DNA was undetectable. Discussion: The diagnosis of ICI-induced hepatitis is a diagnosis of exclusion and while histopathology is not required, liver biopsy is essential in cases of diagnostic uncertainty or treatment of refractory hepatitis. When diagnosed, treatment for ICI-induced hepatitis includes holding therapy for grade 2 and above injury and initiation of corticosteroids for persistent or severe cases. The challenge in this case was that the patient needed steroids to manage the immune-mediated liver damage caused by ICI therapy, but using steroids also risked enhancing viral replication and potentially leading to additional liver injury. Patients with undiagnosed hepatitis B are at increased risk of developing fulminant liver failure. Therefore, it is imperative to check hepatitis B serologies before immunosuppression and initiate antiviral prophylaxis when indicated. Unfortunately, our patient did not have her serologies checked before starting treatment.