Autoimmune Hepatitis Induced by Immune Checkpoint Inhibitors in Adults: A Systematic Review.

Background/Objectives: Immune checkpoint inhibitors (ICIs) have changed the treatment landscape for several advanced malignancies, but their use is accompanied by immune-related adverse events, including liver injury. Some cases resemble autoimmune hepatitis (AIH), although many are more accurately described as AIH-like immune-mediated hepatitis rather than classical AIH. This distinction matters, as diagnosis is often based on exclusion and management must balance hepatic recovery against interruption of potentially life-prolonging cancer therapy. This systematic review summarised the clinical phenotype, diagnostic assessment, treatment strategies, treatment response, ICI discontinuation, and rechallenge outcomes in patients with ICI-associated AIH-like liver injury. Methods: A systematic PubMed search was performed for English-language human studies reporting autoimmune hepatitis, AIH-like liver injury, or immune-mediated hepatitis following exposure to ICIs. Eligible studies included case reports, case series, retrospective cohorts, prospective cohorts, and pharmacovigilance-type studies with extractable clinical, treatment, or outcome data. Reviews, guidelines, non-original articles, animal studies, non-English publications, and reports without usable liver injury data were excluded. The review followed PRISMA principles. Risk of bias was assessed using Joanna Briggs Institute tools and summarised with ROBVIS. Given the heterogeneity of study design, diagnostic criteria, treatment definitions, and outcome reporting, formal meta-analysis was not appropriate; results were therefore synthesised descriptively. Results: Twenty-two studies were included, comprising 195 patients with ICI-associated AIH-like or immune-mediated hepatitis. Of these, 140 patients received active treatment, and 133/140 achieved clinical or biochemical recovery with varying therapies. Corticosteroids were the most frequently used first-line therapy, with recovery reported in 102/105 patients treated with corticosteroids alone. Mycophenolate mofetil was the main second-line agent for steroid-refractory disease, with response reported in 9/10 treated patients. Other therapies, including tacrolimus, azathioprine, ursodeoxycholic acid, bezafibrate, tocilizumab, basiliximab, infliximab, budesonide, and double plasma molecular adsorption system with or without plasma exchange, were described only in small numbers or isolated cases. Spontaneous recovery without pharmacological treatment was reported in 19 patients. ICI interruption or discontinuation occurred in 141 patients, and rechallenge was reported in 55 patients after recovery, with no recurrent hepatic toxicity documented in the extracted dataset. Conclusions: ICI-associated AIH-like liver injury is an important immune-related toxicity, but the available literature remains fragmented and methodologically heterogeneous. Most reported patients recovered, particularly with corticosteroids, and MMF appears to be the most consistently used escalation therapy in steroid-refractory cases. However, the strength of evidence is limited by uncontrolled designs, variable terminology, inconsistent diagnostic work-up, and non-standardised outcome definitions. Future studies should separate classical AIH from AIH-like immune-mediated hepatitis, use uniform criteria for severity and response, and report treatment denominators clearly, especially for rechallenge and steroid-refractory disease.