Comparison of clinical features between immune-related sclerosing cholangitis and hepatitis

Abstract

SummaryBackground Immune-related hepatotoxicity is often regarded as immune-related hepatitis (irHepatitis) despite including immune-related sclerosing cholangitis (irSC). This study examined the clinical differences between irSC and irHepatitis. Methods A single-center retrospective study of 530 consecutive patients who received immunotherapy between August 2014 and April 2020 was performed. IrSC and irHepatitis were respectively defined as the radiological presence and absence of bile duct dilation and wall thickness. Results Forty-one patients (7.7%) developed immune-related hepatotoxicity. A CT scan was performed on 12 patients, including 11 of 12 with ≥ grade 3 aminotransferase elevations. IrSC and irHepatitis were diagnosed in 4 (0.8%) and 8 (1.5%) patients, respectively. All the irSC patients had been treated with anti-PD-1. IrHepatitis was more common among patients receiving anti-CTLA-4 than among those receiving anti-PD-1/PD-L1 inhibitors (14%, 7/50 vs. 0.2%, 1/480, P < 0.001). A ≥ grade 2 alkaline phosphatase (ALP) elevation resulting in a cholestatic pattern was seen in all 4 irSC patients. Among the irSC patients, 3 (3/4, 75%) developed ≥ grade 3 aminotransferases elevation. The median duration from the start of immunotherapy until ≥ grade 2 liver enzymes elevation was 257 and 55.5 days in irSC and irHepatitis patients. The median times for progression from grade 2 to 3 liver enzyme elevation were 17.5 and 0 days, respectively. Conclusions IrSC and irHepatitis have different characteristics in the class of immune checkpoint inhibitor and onset pattern. Radiological examination for the diagnosis of irSC should be considered for patients with ≥ grade 2 ALP elevation resulting in a cholestatic pattern. (Registration number J2020-36, Date of registration June 3, 2020)

Clinical pattern of checkpoint inhibitor-induced liver injury in a multicentre cohort

“…These forms of secondary sclerosing cholangitis have already been reported in the literature. [24] , [25] , [26] In our study, all the patients with macroscopic biliary injury had the cholestatic pattern. These results support the idea that radiological assessment is relevant for evaluating macroscopic bile duct injury, especially in patients with cholestatic CHILI.…”

“…All patients with bile duct injury had been treated with anti PD(L)-1-containing regimen alone, and not with anti-CTL-4 alone as reported by Takinami et al. 24 in their case series study. Previously, Stein et al.…”

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

“…In contrast to the DILI clinical practice guidelines ( European Association for the Study of the Liver, 2019 ), the recommendations of the oncology societies ( Haanen et al, 2017 ; Puzanov et al, 2017 ) do not take into account the phenotype of hepatitis (cholestatic, hepatocellular, or mixed). Several clinical cases and case series have reported cholestatic forms with or without secondary sclerosing cholangitis for which corticosteroids alone have not been effective ( Onishi et al, 2020 ; Sato et al, 2020 ; Takinami et al, 2021 ). In these cases, ursodeoxycholic acid (UDCA) improved liver tests.…”

Drug-induced bile duct injury: new agents, new mechanisms

“…Hepatotoxicity is one of the growing concerns in the use of immunotherapy [35,36 ▪▪ ,37]. Bile duct injury is much rarer than hepatocellular injury, with which it is usually associated but in some cases, may raise difficult clinical and therapeutic challenges [37,38 ▪▪ ,39,40].…”