Clinical and pathological features of immune checkpoint inhibitor-induced drug-induced liver injury

Abstract

Abstract: Objective To investigate the clinical and pathological features of drug-induced liver injury (DILI) induced by immune checkpoint inhibitors (ICIs). Methods A total of 85 cancer patients treated with ICIs were selected, including 38 cases of non-small cell lung cancer, 21 cases of renal cell carcinoma, 14 cases of urothelial carcinoma, and 12 cases of malignant melanoma. DILI occurring after ICIs treatment was classified into hepatocellular injury type, cholestatic type, and mixed type. Clinical data were compared between DILI and non-DILI patients, as well as among different clinical subtypes of DILI. Liver biopsies were analyzed to compare pathological manifestations across subtypes. Results In the DILI group, the prevalence of hyperlipidemia, duration of ICI treatment, and levels of ALT, AST, ALP, and TBil were 9 cases (16.7%), 120 (80, 140) d, 162 (78, 204) U/L, 155 (70, 195) U/L, 208 (122, 310) U/L, and 78.6 (55.0, 93.8) μmol/L, respectively, which were significantly higher than those in the non-DILI group [1 case (3.2%), 85 (62, 114) d, 54 (38, 68) U/L, 55 (35, 63) U/L, 120 (86, 160) U/L, and 24.5 (17.0, 42.6) μmol/L, respectively; P<0.05].. Conversely, the disease control rate was significantly lower in DILI patients compared to non-DILI patients: 40.7% vs. 64.5% (P<0.05). After hepatoprotective treatment, blood biochemical indicators improved in all DILI subtypes: hepatocellular injury type showed more significant ALT and AST improvements, while cholestatic and mixed types demonstrated greater ALP and TBil improvements. Liver biopsies in some DILI patients revealed statistically significant differences in pathological features such as centrilobular necrosis, spotty necrosis, interface hepatitis, portal inflammation, and ductular reaction among subtypes (P<0.05). Hepatocellular injury type predominantly presented with central necrosis and spotty necrosis, whereas cholestatic and mixed types were characterized by interface hepatitis, portal inflammation, and bile duct reactions. Conclusion Hepatocellular injury type dominates among cases of ICI-induced DILI, but cholestatic and mixed types exhibit distinct biochemical and histological patterns.

Key words: Immune checkpoint inhibitors, Drug-induced liver injury, Hepatocellular injury type

Li Zhaoqiang, Liu Dongmei, Du Junying. Clinical and pathological features of immune checkpoint inhibitor-induced drug-induced liver injury[J]. Chinese Hepatolgy, 2026, 31(8): 1174-1177.

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