Non‐alcoholic fatty liver disease is a potential risk factor for liver injury caused by immune checkpoint inhibitor

Abstract

Background and Aim Because of their survival benefits, immune checkpoint inhibitors (ICIs) are widely administered to patients with various advanced‐stage malignancies. During ICI treatment, drug‐induced liver injury (DILI) occasionally occurs. In particular, hepatic immune‐related adverse events (irAEs) are rare but serious and fatal. In patients with hepatic irAEs, immediate steroid treatment is generally recommended; however, the risk factors for ICI‐associated DILI remain unknown. In the present study, we identified a risk factor for ICI‐associated DILI. Methods We retrospectively analyzed 135 patients treated with anti‐programmed cell death‐1 (PD‐1) antibodies, such as nivolumab and pembrolizumab, at Asahikawa Medical University Hospital. We investigated grade ≥ 2 hepatotoxic AEs during anti‐PD‐1 therapy, and PD‐1 inhibitor‐associated DILI was then diagnosed according to the Digestive Disease Week Japan (DDW‐J) 2004 scale. The risk factors for PD‐1 inhibitor‐associated DILI were identified by Cox hazard analysis. Results Thirty‐six patients developed grade ≥ 2 hepatic AEs during anti‐PD‐1 therapy. Among them, eight patients were diagnosed with PD‐1 inhibitor‐associated DILI based on the DDW‐J 2004 scale. Cox hazard analysis revealed that non‐alcoholic fatty liver disease (NAFLD) was a risk factor for PD‐1 inhibitor‐associated DILI. In addition, we revealed that the outcomes of patients with the DDW‐J 2004 score = 3 were improved without steroid treatment. Conclusions NAFLD is a potential risk factor for PD‐1 inhibitor‐associated DILI based on the DDW‐J 2004 scale. The DDW‐J 2004 scale might be useful for determining whether steroid treatment is required in patients with PD‐1 inhibitor‐associated DILI.

Prevalence, clinical course, and predictive factors of immune checkpoint inhibitor monotherapy‐associated hepatitis in Japan

“…However, quite recently, Sawada et al . reported that the DDW‐J 2004 scale might be useful for diagnosing and determining whether steroid treatment is required in patients with PD‐1 inhibitor‐associated drug‐induced liver injury 19 . Thus, the DDW‐J 2004 may be utilized for diagnosis of irAE hepatitis; however, further investigation is required.…”

High Serum Estradiol Reduces Acute Hepatotoxicity Risk Induced by Epirubicin Plus Cyclophosphamide Chemotherapy in Premenopausal Women with Breast Cancer

“…This may be related to the exclusion criteria of the current study. Hepatitis B virus carriers, cholelithiasis, and fatty liver identified as underlying liver diseases may increase the susceptibility to DILI ( Lewis et al, 2007 ; Massart et al, 2017 ; Sawada et al, 2019 ).…”

Immunotherapy and Gene Therapy: New Challenges in the Diagnosis and Management of Drug-Induced Liver Injury

“…Based on clinical trials and observational studies, several factors have been shown to influence the risk of ICI-induced liver injury development or to impact liver toxicity pattern such as the type of ICIs, the dose, or the use of a combination therapy. An underlying liver disease such as non-alcoholic fatty liver disease, a preexisting autoimmune profile, or the type of cancer, such as hepatocellular carcinoma, for which the immunotherapy is prescribed is another important factor ( Brown et al, 2017 ; European Association for the Study of the Liver, 2019 ; Sawada et al, 2020 ). Moreover, patients with prior irAEs due to ICIs are considered to be at risk for new irAEs (hepatic or extra-hepatic) even from a different class of ICIs ( Peeraphatdit et al, 2020 ; Regev et al, 2020 ).…”