Outcomes of High-Grade Immune Checkpoint Inhibitor Hepatitis in Hospitalized and Nonhospitalized Patients

Background & Aims: Guidelines recommend hospitalization for severe immune checkpoint inhibitor (ICI) hepatitis. We compared patient outcomes in the inpatient versus outpatient settings. Methods: We conducted a multicenter, retrospective cohort study of 294 ICI-treated patients who developed grade 3-4 ICI hepatitis. The primary outcome was time to alanine aminotransferase (ALT) normalization (≤40); secondary outcomes included time to ALT ≤100 U/L and time to death. To account for confounding by indication, inverse probability of treatment weighting was applied to perform Cox regression. A sensitivity analysis was performed excluding patients with grade 4 hepatitis. Results: One hundred and sixty-six patients (56.5%) were hospitalized for a median of 6 (interquartile range, 3–11) days. On inverse probability of treatment weighting Cox regression, hospitalization was not associated with time to ALT normalization (hazard ratio [HR], 1.11; 95% confidence interval [CI], 0.86–1.43; P = .436) or time to ALT ≤100 U/L (HR, 1.11; 95% CI, 0.86–1.43; P = .420). In the sensitivity analysis limited to patients with grade 3 hepatitis, hospitalization was also not associated with time to ALT normalization (HR, 1.11; 95% CI, 0.83–1.50; P = .474) or time to ALT ≤100 U/L (HR, 1.19; 95% CI, 0.90–1.58; P = .225). In a subgroup analysis of 152 patients with melanoma, hospitalization was not associated with reduced risk of all-cause death (HR, 0.93; 95% CI, 0.53–1.64; P = .798). Notably, despite their Common Terminology Criteria for Adverse Events classification of high-grade hepatitis, 94% of patients had “mild” liver injury based on International Drug-Induced Liver Injury Criteria. Conclusions: Hospitalization of patients with high-grade ICI hepatitis was not associated with faster hepatitis resolution and did not affect mortality. Routine hospitalization may not be necessary in all patients with high-grade ICI hepatitis and Common Terminology Criteria for Adverse Events criteria may overestimate severity of liver injury.