Immunosuppressant mycophenolate mofetil for patients with steroid-refractory immune-related hepatitis induced by checkpoint inhibitors in oncology

Background: Immune-checkpoint inhibitor (ICI) hepatitis, which does not improve with steroids and requires additional immunosuppressant, is defined as steroid-refractory ICI hepatitis. The outcome of patients with steroid-refractory ICI hepatitis remains poorly determined. Herein, we investigated the incidence, clinical features, and outcome of patients treated with second-line immunosuppressant for steroid-refractory ICI hepatitis. Methods: This is a retrospective analysis of patients who presented ICI hepatitis from 1st June 2016 to 30th September 2022. Steroid-refractory ICI hepatitis was defined as no clinical and biological improvement after systemic steroid therapy ≥1 mg/kg/d. Main objectives were to assess the frequency and risk factors associated with steroid-refractory ICI hepatitis and to evaluate the efficacy of second-line immunosuppressants. Results: In total, 130 patients with grade ≥3 ICI hepatitis were screened, of them 60 (46.2%) were treated with systemic steroids. In total, 11/130 (8.5%) had steroid-refractory hepatitis. Statistically significant factors associated with steroid-refractory hepatitis included previous liver comorbidities (54.5% versus 11.6%; p < 0.01), hyperbilirubinemia (p < 0.001), and general symptoms (fever, jaundice, ascites, and/or encephalopathy) associated with hepatitis (72.7% versus 30.8%; p = 0.015). The 11 patients with steroid-refractory hepatitis were treated with mycophenolate mofetil. In total, resolution or return to grade ≤1 for hepatitis was observed in 81.8% (9/11) of patients. Conclusions: Steroid-refractory ICI hepatitis accounted for 8.5% of patients with grade ≥3 immune-related hepatitis and was statistically associated with previous liver comorbidities, hyperbilirubinemia, and general symptoms. Mycophenolate mofetil was a suitable option of therapy for steroid-refractory ICI hepatitis.