Hiroyuki Isayama, Toshio Fujisawa, Taito Fukuma, Muneo Ikemura, Ko Tomishima, Nobuhiro Nakamoto, Shuichiro Umetsu, Shintaro Yagi, Itaru Naitoh, Suguru Mizuno, Katsuhiro Sano, Kenji Notohara, Yoshihiro Hirata, Atsushi Tanaka
Primary sclerosing cholangitis (PSC) is a chronic, progressive cholangiopathy characterized by inflammation and fibrosis of intrahepatic and/or extrahepatic bile ducts. Its pathogenesis remains incompletely understood, and liver transplantation is currently the only curative treatment available. The diagnosis remains challenging, and no disease-specific biomarkers have been established. Recently, anti-integrin αvβ6 antibodies have emerged as promising serological biomarkers with high specificity for PSC. Advances in imaging modalities, including magnetic resonance cholangiopancreatography and peroral cholangioscopy, have improved diagnostic accuracy for PSC. Although various therapeutic approaches have been investigated, no treatment has been shown to improve the long-term outcomes. Microbiota-targeted therapies represent a promising emerging strategy. The clinical course of PSC, particularly in its early stages, is poorly defined. We propose a definition of early stage PSC consisting of two subtypes: small-duct PSC without liver fibrosis and large-duct PSC without cholestatic enzyme elevation or biliary strictures. Early intervention at this stage may improve the prognosis, thus highlighting the need for further validation.