ICIs target immune checkpoint receptors, such as CTLA-4 and PD-1, as well as the PD-1 ligand expressed on T cells. By inhibiting these pathways, ICIs enhance the immune response against tumors. However, this mechanism can also activate T cells that respond not only to tumor antigens but also to non-tumor (self-antigen) antigens, leading to irAEs [1].

Liver injury due to ICIs, particularly PD-1 inhibitors, has been reported in approximately

4-10% of cases and is more frequent with combination therapies involving PD-1 inhibitors and CTLA-4 inhibitors. Symptoms of irAE hepatitis may include fever, jaundice, and abdominal pain; however, the condition is often asymptomatic and detected only through elevated liver enzyme levels in blood tests. Imaging abnormalities in irAE hepatitis are uncommon; however, severe cases may show hepatomegaly, heterogeneous enhancement of the liver parenchyma, periportal edema, and portal lymphadenopathy on CT or MRI [5, 8].

Recently, irAE cholangitis, a form of liver injury primarily involving the bile duct, has been reported [6]. Previously, cases of liver injury caused by ICIs, including cholangitis, were classified as irAE hepatitis. While 98% of irAE hepatitis cases resolve with or without steroid therapy, irAE cholangitis has a steroid response rate of only 11.5%, making its differentiation clinically significant [9, 10]. IrAE cholangitis occurs in up to 3% of cases and exhibits imaging features resembling sclerosing cholangitis, such as nonobstructive bile duct dilation and diffuse thickening of the extrahepatic bile duct wall [6]. Takinami et al. examined the clinical differences between irAE hepatitis and irAE cholangitis. They found that hepatitis was more common in patients treated with CTLA-4 inhibitors, whereas all cases of cholangitis occurred in those treated with PD-1 inhibitors. The median time from immunotherapy initiation to grade 2 or higher liver enzyme elevation was 55.5 d for irAE hepatitis and 257 d for irAE cholangitis. Additionally, irAE cholangitis is associated with elevated cholestatic enzyme levels, such as increased ALP levels [11]. Our case aligns with these findings, as the patient was treated with a PD-1 inhibitor and presented with cholestatic liver enzyme elevation approximately 7 months after the first dose. Reports also suggest that 13.3% of irAE cholangitis cases are accompanied by irAE hepatitis [9].

The incidence of pancreatitis following ICI therapy is approximately 2%. Similar to hepatitis, pancreatitis is often asymptomatic and is diagnosed based on elevated pancreatic enzyme levels in laboratory tests. Although there are no reports on differences in incidence rates among drug classes, combination therapy with PD-1 and CTLA-4 inhibitors increases the incidence of pancreatitis as an irAE [7]. Imaging findings on contrast-enhanced CT or MRI may include diffuse or localized pancreatic enlargement and peripancreatic edema. Patients receiving monotherapy frequently develop localized pancreatitis, whereas those undergoing combination therapy are more likely to develop diffuse pancreatitis [12]. However, pancreatic necrosis and pseudocyst formation are rare. Approximately 16% of irAE pancreatitis cases exhibit imaging findings consistent with autoimmune pancreatitis, including focal or diffuse parenchymal enlargement [12]. However, the absence of a capsule-like rim, a characteristic imaging feature of autoimmune pancreatitis, along with normal serum IgG4 levels, can aid in differentiation. Clinical information on ICI use is crucial. After treatment, 44% of patients with irAE pancreatitis develop pancreatic atrophy, and 36% develop exocrine or endocrine pancreatic insufficiency, necessitating diabetes monitoring. Moderate to severe irAE pancreatitis responds well to steroid therapy, highlighting the importance of early diagnosis and intervention [12].