Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Dec 27, 2021; 13(12): 1828-1849
Published online Dec 27, 2021. doi: 10.4254/wjh.v13.i12.1828
Liver-side of inflammatory bowel diseases: Hepatobiliary and drug-induced disorders
Stefano Mazza, Sara Soro, Maria Chiara Verga, Biagio Elvo, Francesca Ferretti, Fabrizio Cereatti, Andrea Drago, Roberto Grassia
Stefano Mazza, Sara Soro, Maria Chiara Verga, Biagio Elvo, Fabrizio Cereatti, Andrea Drago, Roberto Grassia, Gastroenterology and Digestive Endoscopy Unit, ASST Cremona, Cremona 26100, Italy
Francesca Ferretti, Gastroenterology Unit, ASST Fatebenefratelli-Sacco, Department of Biomedical and Clinical Sciences (DIBIC), Università degli Studi di Milano, Milan 20157, Italy
Author contributions: All authors contributed to literature search and data collect; Mazza S, Soro S and Elvo B wrote the paper; Verga MC, Ferretti F, Cereatti F, Drago A and Grassia R critically revised the paper and contributed to the final version of the manuscript.
Conflict-of-interest statement: Authors declare no conflict of interests for this article.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Stefano Mazza, MD, Doctor, Gastroenterology and Digestive Endoscopy Unit, ASST Cremona, Viale Concordia 1, Cremona 26100, Italy.
Received: March 1, 2021
Peer-review started: March 1, 2021
First decision: July 6, 2021
Revised: July 16, 2021
Accepted: November 13, 2021
Article in press: November 13, 2021
Published online: December 27, 2021

Hepatobiliary disorders are among the most common extraintestinal manifestations in inflammatory bowel diseases (IBD), both in Crohn’s disease and ulcerative colitis (UC), and therefore represent a diagnostic challenge. Immune-mediated conditions include primary sclerosing cholangitis (PSC) as the main form, variant forms of PSC (namely small-duct PSC, PSC-autoimmune hepatitis overlap syndrome and IgG4-related sclerosing cholangitis) and granulomatous hepatitis. PSC is by far the most common, presenting in up to 8% of IBD patients, more frequently in UC. Several genetic foci have been identified, but environmental factors are preponderant on disease pathogenesis. The course of the two diseases is typically independent. PSC diagnosis is based mostly on typical radiological findings and exclusion of secondary cholangiopathies. Risk of cholangiocarcinoma is significantly increased in PSC, as well as the risk of colorectal cancer in patients with PSC and IBD-related colitis. No disease-modifying drugs are approved to date. Thus, PSC management is directed against symptoms and complications and includes medical therapies for pruritus, endoscopic treatment of biliary stenosis and liver transplant for end-stage liver disease. Other non-immune-mediated hepatobiliary disorders are gallstone disease, whose incidence is higher in IBD and reported in up to one third of IBD patients, non-alcoholic fatty liver disease, pyogenic liver abscess and portal vein thrombosis. Drug-induced liver injury (DILI) is an important issue in IBD, since most IBD therapies may cause liver toxicity; however, the incidence of serious adverse events is low. Thiopurines and methotrexate are the most associated with DILI, while the risk related to anti-tumor necrosis factor-α and anti-integrins is low. Data on hepatotoxicity of newer drugs approved for IBD, like anti-interleukin 12/23 and tofacitinib, are still scarce, but the evidence from other rheumatic diseases is reassuring. Hepatitis B reactivation during immunosuppressive therapy is a major concern in IBD, and adequate screening and vaccination is warranted. On the other hand, hepatitis C reactivation does not seem to be a real risk, and hepatitis C antiviral treatment does not influence IBD natural history. The approach to an IBD patient with abnormal liver function tests is complex due to the wide range of differential diagnosis, but it is of paramount importance to make a quick and accurate diagnosis, as it may influence the therapeutic management.

Keywords: Inflammatory bowel diseases, Hepatobiliary disorders, Primary sclerosing cholangitis, Drug-induced liver injury, Biological drugs, Viral hepatitis

Core Tip: Hepatobiliary disorders are commonly associated with inflammatory bowel diseases (IBD) and represent a management challenge. They include (1) Immune-mediated diseases that can coexist with IBD, mainly primary sclerosing cholangitis; (2) Other non-immune-mediated disorders like gallstone disease; (3) Liver injury induced by drugs used in IBD; and (4) Risks related to concomitant viral hepatitis B and C. All these conditions are summarized in this review, according to the latest literature evidence and the current clinical practice guidelines.