S2455 Delayed-Onset Immunotherapy-Related Hepatitis Instigated by the Stress of Surgery

Abstract

INTRODUCTION: Immune checkpoint inhibitors are prone to elicit immune-related adverse events that can affect many different organ systems. Specifically, hepatitis is relatively infrequent and may only present with elevated LFT’s and fever. We report a rare case of delayed immunotherapy-related hepatitis provoked by the acute immunologic stress of surgery. CASE DESCRIPTION/METHODS: Presenting a 63-year-old male with Stage 3A SCC of the lung who completed four cycles of neoadjuvant carboplatin, paclitaxel, and pembrolizumab followed by a recent left upper lobe lobectomy with mediastinal lymph node dissection. His initial post-operative course was uneventful; however, he presented two weeks later with intermittent fevers and vague abdominal complaints consisting of discomfort, distension, and early satiety. Labs showed a normal WBC, total bilirubin, and INR, but newly elevated labs with AST 66, ALT 111, and ALP 197. He was started on piperacillin-tazobactam, but continued to fever to a maximum temperature of 102°F. CT abdomen showed a normal liver and gallbladder with enlarged hepatoduodenal ligament lymph nodes. Infectious workup including blood and urine cultures, HSV, CMV, EBV, HIV, a hepatitis panel, and a respiratory viral panel was negative. Other labs included an elevated IgA, normal IgG and IgM, negative anti-nuclear antibody, and an anti-smooth muscle antibody positive at 1:40. The patient’s AST and ALT continued to gradually increase to a peak of 187 and 246 IU/L, respectively. Given the negative infectious workup and previous treatment with pembrolizumab, the patient was started on prednisone for presumed immunotherapy-related hepatitis resulting in complete resolution of his symptoms and elevated liver enzymes twelve days after beginning treatment (Figure 1). His prednisone was slowly tapered over an eight-week course. DISCUSSION: Immunotherapy-related hepatitis occurs in a very small percentage of patients on immune checkpoint inhibitors. Hepatitis typically occurs within a week to a few months of starting therapy, but can occur months after discontinuation of therapy as well. Given the extended half-life of anti-PD-1 therapy with a high percentage of sustained T-cell occupancy, our patient’s delayed immune reaction was thought to be instigated by the stress of his recent surgery. Since immunotherapy-related hepatitis has a vague and varying onset, it is important to keep this as a differential to allow for early initiation of steroids to prevent progression to liver failure.Figure 1.: Timeline of Altered LFT's.