Early Liver Specialist Consultation is Associated With Faster Biochemical Resolution of Severe Immune Checkpoint Inhibitor–Induced Hepatitis

Abstract

BACKGROUND: We evaluated the impact of gastroenterology/hepatology consultation, as recommended by guidelines, on the management of severe immune checkpoint inhibitor (ICI)-induced hepatitis. METHODS: We conducted a multicenter, retrospective cohort study of 294 patients who developed grade ≥3 (alanine aminotransferase [ALT] >200 U/L) ICI-induced hepatitis, with early gastroenterology/hepatology consultation defined as occurring within 7 days of diagnosis. The primary outcome was time to ALT normalization (≤40 U/L), and the secondary outcome was time to ALT improvement to ≤100 U/L. RESULTS: A total of 117 patients received early consultation. In the 213 patients with steroid-responsive hepatitis, early consultation was not associated with faster ALT normalization (hazard ratio [HR], 1.12; 95% CI, 0.83-1.51; P=.453). A total of 81 patients developed steroid-refractory hepatitis, with 44 (54.3%) receiving early consultation. In contrast to the patients whose hepatitis responded to steroid treatment, early consultation in those with steroid-refractory disease was associated with faster ALT normalization (HR, 1.89; 95% CI, 1.12-3.19; P=.017) and ALT improvement to ≤100 U/L (HR, 1.72; 95% CI, 1.04-2.84; P=.034). Notably, additional immunosuppressive therapy for steroid-refractory disease was initiated sooner after diagnosis in the early consult group (median 7.5 vs 13.0 days; log-rank P=.001). When time to additional immunosuppression was added as a covariate to the Cox model in mediation analysis, early consultation was no longer associated with time to ALT normalization (HR, 1.39; 95% CI, 0.82-2.38; P=.226) or with time to ALT improvement to ≤100 U/L (HR, 1.25; 95% CI, 0.74-2.11; P=.404). Time to additional immunosuppression remained associated with faster ALT normalization and faster ALT improvement to ≤100 U/L in the model, suggesting that the faster hepatitis resolution in the early consultation group was primarily attributable to earlier initiation of additional immunosuppression. CONCLUSIONS: Early gastroenterology/hepatology consultation is associated with faster resolution of biochemical abnormalities in patients with steroid-refractory hepatitis. This beneficial effect appears to be mediated by earlier initiation of additional immunosuppressive therapy in those receiving early consultation.

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