title: Gastrointestinal and Hepatic Complications of Immune Checkpoint Inhibitors.
abstract: OBJECTIVE
  Gastrointestinal complications are very common in patients undergoing cancer treatment. Some of these complications can be life threatening and require prompt and appropriate diagnosis and treatment. The purpose of this review is to address luminal gastrointestinal and hepatic complications associated with a new class of anticancer drugs, immune checkpoint inhibitors (CPIs), and focuses on the identification, evaluation, and management of the complications associated with this class of drugs.
  
  
  RESULTS
  It is now recognized that immune checkpoint inhibitors are frequently associated with luminal GI side effects such as diarrhea and enterocolitis and hepatic complications such as hepatitis. While colitis associated with CPIs, to some extent, mimics that found in idiopathic inflammatory bowel disease, the complex interplay of genes, the environment, the immune system, and the microbiome make it difficult to fully differentiate these conditions clinically. CPI-induced hepatitis is most often associated with a pattern of hepatocellular injury with panlobular hepatitis. A variety of biomarkers have been proposed to predict an adverse response to CPIs and are under investigation. It has been proposed that alterations in the microbiome may impact the risk of developing colitis, and these studies are reviewed. In contrast to idiopathic chronic inflammatory bowel disease, CPI-induced colitis is often reversible if rapidly treated in accordance with the immune-mediated adverse reaction management guidelines. Treatment algorithms have been suggested but are, to some extent, empiric and based on algorithms for the treatment of idiopathic inflammatory bowel disorders. CPIs may be associated with significant GI complications which impact their successful use in the treatment of neoplastic diseases. Much of what we currently know about the mechanisms and treatment of these complications is empiric and extrapolated from experience with idiopathic inflammatory bowel disease and other immune disorders. Current research focuses on understanding genetic predisposition and the role of the microbiome and identifying predictive risk markers for developing complications.
authors.affiliation: Department of Gastroenterology, Hepatology and Nutrition, The University of Texas MD Anderson Cancer Center, 1515 Holocombe Boulevard, Unit 1466, Houston, TX, 77030, USA.
authors.forename: Peyton
authors.initials: P
authors.lastname: Cramer
authors.affiliation: Department of Gastroenterology, Hepatology and Nutrition, The University of Texas MD Anderson Cancer Center, 1515 Holocombe Boulevard, Unit 1466, Houston, TX, 77030, USA. rbresali@mdanderson.org.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Bresalier
mesh_terms: D000911:Antibodies, Monoclonal / Q000009:adverse effects*; D000970:Antineoplastic Agents / Q000009:adverse effects*; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology*; D003092:Colitis / Q000139:chemically induced / Q000175:diagnosis; D003937:Diagnosis, Differential; D005767:Gastrointestinal Diseases / Q000139:chemically induced* / Q000175:diagnosis; D000069196:Gastrointestinal Microbiome; D006801:Humans; D007167:Immunotherapy / Q000009:adverse effects; D015212:Inflammatory Bowel Diseases / Q000175:diagnosis; D009369:Neoplasms / Q000188:drug therapy / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents
keywords: CTLA-4; Checkpoint inhibitors; Colitis; Hepatitis; Immune modulation; Ipilimumab; Microbiome; PD-1; Toxicity