Liver and Bile

J Hepatol. 2024;80(3):431–42

Celsa C, Cabibbo G, Fulgenzi CAM, Scheiner B, D'Alessio A, Manfredi GF, Nishida N, Ang C, Marron TU, Saeed A, Wietharn B, Pinter M, Cheon J, Huang YH, Lee PC, Phen S, Gampa A, Pillai A, Vivaldi C, Salani F, Masi G, Roehlen N, Thimme R, Vogel A, Schönlein M, von Felden J, Schulze K, Wege H, Galle PR, Kudo M, Rimassa L, Singal AG, El Tomb P, Ulahannan S, Parisi A, Chon HJ, Hsu WF, Stefanini B, Verzoni E, Giusti R, Veccia A, Catino A, Aprile G, Guglielmini PF, Di Napoli M, Ermacora P, Antonuzzo L, Rossi E, Verderame F, Zustovich F, Ficorella C, Di Pietro FR, Battelli N, Negrini G, Grossi F, Bordonaro R, Pipitone S, Banzi M, Ricciardi S, Laera L, Russo A, De Giorgi U, Cavanna L, Sorarù M, Montesarchio V, Bordi P, Brunetti L, Pinto C, Bersanelli M, Cammà C, Cortellini A, Pinato DJ

Characteristics and outcomes of immunotherapy-related liver injury in patients with hepatocellular carcinoma versus other advanced solid tumors

Background and aims: Immune-related liver injury (irLI) is commonly observed in patients with cancer treated with immune checkpoint inhibitors (ICIs). The aim of this study was to compare the incidence, clinical characteristics, and outcomes of irLI between patients receiving ICIs for hepatocellular carcinoma (HCC) versus other solid tumors.
Methods: Two separate cohorts were included: 375 patients with advanced/unresectable HCC, Child-Pugh A class treated with first-line atezolizumab + bevacizumab from the AB-real study, and a non-HCC cohort including 459 patients treated with first-line ICI therapy from the INVIDIa-2 multicenter study. IrLI was defined as a treatment-related increase of aminotransferase levels after exclusion of alternative etiologies of liver injury. The incidence of irLI was adjusted for the duration of treatment exposure.
Results: In patients with HCC, the incidence of any grade irLI was 11.4% over a median treatment exposure of 4.4 months (95% confidence interval [CI]: 3.7–5.2) vs. 2.6% in the INVIDIa-2 cohort over a median treatment exposure of 12.4 months (95% CI: 11.1–14.0). Exposure-adjusted-incidence of any grade irLI was 22.1 per 100-patient-years in patients with HCC and 2.1 per 100-patient-years in patients with other solid tumors (p < 0.001), with median time-to-irLI of 1.4 and 4.7 months, respectively. Among patients who developed irLI, systemic corticosteroids were administered in 16.3% of patients with HCC and 75.0% of those without HCC (p < 0.001), and irLI resolution was observed in 72.1% and 58.3%, respectively (p = 0.362). In patients with HCC, rates of hepatic decompensation and treatment discontinuation due to irLI were 7%. Grade 1–2 irLI was associated with improved overall survival only in patients with HCC (hazard ratio = 0.53, 95% CI: 0.29–0.96).

Conclusions: Despite higher incidence and earlier onset, immune-related liver injury (irLI) in patients with hepatocellular carcinoma is characterized by higher rates of remission and lower requirement for corticosteroid therapy (vs. irLI in other solid tumors), low risk of hepatic decompensation and treatment discontinuation, not negatively affecting oncological outcomes.

DOI: 10.1016/j.jhep.2023.10.040