Outcomes of high-grade immune checkpoint inhibitor hepatitis in hospitalized and non-hospitalized patients

Abstract:

Background and 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 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 (IPTW) was applied to perform Cox regression. A sensitivity analysis was performed excluding patients with grade 4 hepatitis.

Results

166 patients (56.5%) were hospitalized for a median of 6 [IQR 3-11] days. On IPTW Cox regression, hospitalization was not associated with time to ALT normalization (HR 1.11, 95% CI 0.86-1.43, p=0.436) or time to ALT≤100 U/L (HR 1.11, 95% CI 0.86-1.43, p=0.420). 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=0.474) or time to ALT ≤100 U/L (HR 1.19, 95% CI 0.90-1.58, p=0.225). 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=0.798). Notably, despite their CTCAE classification of high-grade hepatitis, 94% of patients had "mild" liver injury based on International DILI criteria.

Conclusion

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 CTCAE criteria may overestimate severity of liver injury.