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

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.

To describe the epidemiology, clinical and biochemical features at presentation, differential diagnoses, pathophysiology, imaging, histological characteristics and management associated with SSC.

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).

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.

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.