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Figure 1. Endoscopic view of the 2 cm bile duct wall defect via a percutaneous approach (Left) vs the repaired defect with endoclips (Right).

Figure 1. A. superior dominant of subcapsular periherpatic biloma B. collection in the gallbladder fossa C. coronal view of the biloma.

Immune checkpoint inhibitors (ICPI) are monoclonal antibodies that interrupt co-inhibitory signaling pathways and promote immune-mediated eradication of cell tumors. ICPI has emerged in recent years as an efficacious treatment for advanced malignancies. Hepatotoxicity is an established adverse event associated with ICPI. The aim of this study is to determine the predictors of hepatotoxicity in patients receiving ICPI. Methods: We reviewed data from a large database (Explorys IBM) that aggregates health records from 26 large healthcare systems. We identified adults who received ICPI from 2011-2021. We excluded patients diagnosed with alcoholism, viral hepatitis, other drug induced liver injury & biliary disease. Of this cohort, we collected data on hepatocellular injury after the initiation of ICPI. Demographic information & data on potential risk factors were collected including malnutrition, chronic kidney disease (CKD), metabolic syndrome, non-alcoholic fatty liver disease (NAFLD), smoking, concomitant use of cytochrome P450-CYP2E1 inducers & use of ICPI combination. Univariable & multivariable logistic regression analyses were performed. Results: Out of 69 million adults in the database, 21060 received ICPI (0.03%) of whom 1780 had ICPI-induced hepatotoxicity (8.4%). Men received more ICPI than women (57.4% vs 42.5%). The majority who received ICPI were . 65 yr old (63.7%). Table summarizes the characteristics of patients received ICPI. In multivariable model, NAFLD & the use of ICPI combination were most associated with hepatotoxicity ] & ), respectively. These factors were closely followed by metabolic syndrome & malnutrition ) & (OR 3.07 [95% CI: 2.97-3.16]), respectively. Moreover, ICPI-induced hepatotoxicity was significantly associated with CKD (OR 2.46 [95% CI: 2.39-2.52]), smoking ), concomitant CYP2E1 inducers ), and to a lesser extent, with age .65 ). No significant association with gender was noted (OR 1.00 [95% CI: 0.93-1.07]), Figure . Conclusion: This large study shows that the highest predictors of ICPI-induced hepatotoxicity were underlying NAFLD & the use of ICPI combination. Other significant factors were age .65, metabolic syndrome, malnutrition, CKD, smoking, & concomitant use of CYP2E1 inducers. Further studies are needed to evaluate pathophysiology and molecular aspects of these relationships.

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