Time to use the right classification to predict the severity of checkpoint inhibitor-induced liver injury, as assessed for causality using the updated RUCAM.

BACKGROUND AND AIMS: While immune checkpoint inhibitors (ICIs) are revolutionising cancer therapy, checkpoint inhibitor-induced liver injury is a significant immune-related side effect of this immunotherapy. This study focuses on the severity classifications and characteristics of patients with checkpoint inhibitor-induced hepatitis. METHODS: A retrospective analysis of patients with severe Checkpoint Inhibitor-induced hepatitis grade 3 and 4 according to the recommended Common Terminology Criteria for Adverse Events (CTCAE) classification was conducted. Data on clinicobiological characteristics, treatment and outcomes were collected from 3 university hospitals, and causality was assessed by using the updated Roussel Uclaf Causality Assessment Method. The severity of hepatitis was assessed using the Model for End-stage Liver Disease score, the Drug-Induced Liver Injury Network, and the Drug-Induced Liver Injury International Expert Working Group classifications. RESULTS: We retrospectively included 100 patients presenting various hepatitis patterns with a median time to onset of 20 days after checkpoint inhibitors. Severity grading varied significantly among the classifications used. A lower incidence of severe cases was observed when using the Drug-Induced Liver Injury classifications instead of the recommended CCTCAE classification, and this was correlated with outcomes. CONCLUSIONS: This retrospective study challenges the efficacy of the CTCAE classification in defining the severity of Checkpoint Inhibitor-induced hepatitis and suggests that the traditional hepatology-focused scores may be more relevant. The CTCAE classification is inconsistent and gives equal weight to jaundice and elevated transaminases, which leads to steroid overtreatment and limits the rechallenge of ICIs.

Cholangitis Induced by Immune Checkpoint Inhibitors: Analysis of Pharmacovigilance Data.

Immune checkpoint inhibitors (ICIs) are remarkable anticancer therapies that have revolutionized the oncological prognosis of many cancers.1 The considerable efficacy of ICIs is associated with the onset of more- or less-serious, immune-related adverse effects (irAEs) affecting several organs, which can concern up to 70% of patients, owing to a loss of self-tolerance during the restoration of antitumor immunity.2 Checkpoint inhibitor-induced liver injury (CHILI), which may occur in up to 25% of patients, is treated with steroids as first-line treatment, and immunosuppressive drugs as second-line treatment.3 Recently, ICI-induced cholangitis was described as an emerging irAE. Hence, Pi et al4 reviewed all 53 published cases of ICI-induced cholangitis and compared the different types of bile duct involvement. We recently described CHILI according to the biological profile: cholestatic, hepatocellular, or mixed.5 Cholestatic profiles were associated with macroscopic and/or microscopic bile duct damage, and time to resolution was significantly longer. More recently, Onoyama et al6 and Parlati et al7 described a poorer response to steroids in cases of biliary histologic damage or ICI-induced sclerosing cholangitis. The latest European Society for Medical Oncology guidelines include the management of cholangitis, which is succinct and still poorly documented.3 The aim of this study therefore was to analyze the cases of ICI-induced cholangitis reported in the French pharmacovigilance system to describe their clinical characteristics, evolution, and outcome.

Transjugular Intrahepatic Portosystemic Shunt is effective to treat portal hypertension due to sinusoidal obstructive syndrome.

Transjugular Intrahepatic Portosystemic Shunt (TIPS) is an established procedure for the complications of portal hypertension, such as variceal bleeding, refractory ascites and hepatic hydrothorax. We report an original case of a renal transplant patient successfully treated with TIPS for portal hypertension due to sinusoidal obstructive syndrome (SOS) induced by azathioprine (AZA). By reporting this case, we wish to draw the attention of healthcare professionals managing organ transplant patients, especially nephrologists, to the possible occurrence of liver toxicity due to AZA, and to emphasize the role of TIPS as an effective therapeutic option for portal hypertension-related complications.

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

Background & Aims: Immune checkpoint inhibitors (ICIs) have changed the landscape of cancer therapy. Liver toxicity occurs in up to 25% of patients treated with ICIs. The aim of our study was to describe the different clinical patterns of ICI-induced hepatitis and to assess their outcome. Methods: We conducted a retrospective observational study of patients with checkpoint inhibitor-induced liver injury (CHILI) discussed in multidisciplinary meetings between December 2018 and March 2022 in three French centres specialised in ICI toxicity management (Montpellier, Toulouse, Lyon). The hepatitis clinical pattern was analysed by the ratio of serum alanine aminotransferase (ALT) and alkaline phosphatase (ALP) (R value = (ALT/ULN)/(ALP/ULN)) for characterisation as cholestatic (R ≤2), hepatocellular (R ≥5), or mixed (2