Clinical Updates in IgG4-Related Pancreatic and Hepatobiliary Disease

Immunoglobulin G4-related disease (IgG4-RD) is a systemic fibro-inflammatory immune-mediated condition. The Pancreato-Hepato-Biliary subtype is the most frequent phenotype. The subtype encompasses immunoglobulin G4 (IgG4)-related pancreatitis (autoimmune pancreatitis type 1), IgG4-related cholangitis, IgG4-related hepatopathy and IgG4-related cholecystitis. The condition is characterised by multi-organ involvement and unpredictable recurrent disease flares, which lead to organ damage and failure in the absence of early recognition and adequate treatment. It is associated with a 2-fold increase in mortality and higher incidences of malignancies, such as solid-organ tumours and lymphoma. Diagnostic delays result from the lack of awareness and the absence of a single diagnostic test, leading to multiple generalist and specialist visits prior to the initiation of therapy. There have been major advances in the management of IgG4-RD to include a move to more targeted therapies. This includes the novel cluster of differentiation 19 (CD19)-depletion therapy inebilizumab, which has been approved in the United States, Europe and Japan for the treatment of IgG4-RD. This review highlights crucial diagnostic clues and emerging therapeutic advances in the evolving field of the Pancreato-Hepato-Biliary subtype of IgG4-RD.