Secondary Sclerosing Cholangitis due to Drugs With a Special Emphasis on Checkpoint Inhibitors

Abstract

Background: Secondary sclerosing cholangitis (SSC), is one of the phenotypes of DILI first described in the 1980s. Check point inhibitors (CPIs) are currently the most frequent cause of SCC. Aims: To describe the epidemiology, clinical and biochemical features at presentation, differential diagnoses, pathophysiology, imaging, histological characteristics and management associated with SSC. Materials and Methods: A language and date-unrestricted Medline literature search was conducted to identify case reports and clinical series on SSC with special emphasis on CPIs (2007-2023). Results: We identified 19 different drugs that have been shown to induce SSC. A total of 64 cases with SSC due to CPIs are presented. This was mostly seen in patients treated with anti-Programmed cell death (PD)-1/PD-L1 inhibitors. The most frequent presenting signs and symptoms were abdominal pain and jaundice. Large-duct cholangitis induced by CPIs is a very rare condition while small-duct cholangitis is more common. Nivolumab and pembrolizumab were the most commonly implicated agents. Biopsies have revealed predominant CD8+ T cell infiltration in biliary strictures. Corticosteroids is linked to a low frequency of success and is the only agent recommended to begin the treatment. Conclusions: CPIs-induced SSC seems to affect the entire biliary system. Clinicians should consider and suspect SSC when a probable CPIs-induced hepatitis does not respond to corticosteroids. Additionally, further randomized, controlled trials should prospectively investigate alternative therapies for treatment.