Hepatotoxicity of Agents Used in the Management of Inflammatory Bowel Disease

Abstract

Patients with inflammatory bowel disease (IBD) are at risk for hepatobiliary disease and toxicity, and the diagnosis of drug-induced liver disease in patients being treated for IBD can represent a clinical challenge. There are a number of disease states associated with IBD, which are primary sclerosing cholangitis, cholangiocarcinoma and autoimmune hepatitis. There is a wide spectrum of hepatic injury that can occur from the agents used to treat IBD, such as acute or chronic hepatic injury directly attributable to the drugs used to treat IBD (e.g. sulfasalazine, mesalamine, thiopurines, methotrexate, TNF antagonists, quinolone antibiotics); liver toxicity from drugs used to treat complications of immunomodulators and TNF antagonists (e.g. isoniazid for treatment of reactivation tuberculosis), and exacerbation of underlying chronic viral hepatitis with infliximab and other TNF antagonists. Thiopurines are also associated with the development of hepatic vascular lesions, such as nodular regenerative hyperplasia and peliosis hepatic. In addition, biologics can be associated with the reactivation of underlying chronic viral hepatitis, mandating universal screening prior to initiation of TNF-alpha antagonist therapy.

Infliximab-Induced Autoimmune Hepatitis with Successful Switch to Adalimumab in a Patient with Crohn’s disease: The Index Case

“…In combination with the liver biopsy findings, the pattern of LFT elevation, the absence of a viral process and the positive autoimmune hepatitis serologies supported the diagnosis of drug-induced autoimmune hepatitis, an unusual type of drug-induced liver injury (DILI) [2]. This uncommon hepatic response to infliximab has been reported in patients with psoriasis and rheumatoid arthritis, and appears related to autoimmune hepatitis type I-immune mechanisms as also described in other rare cases [1,3,4].…”

Autoimmune hepatitis

“…The authors speculated that AIH developed as a result of a breakdown of immune tolerance induced by methotrexate. Other reviews have focused on evidence of hepatotoxicity of methotrexate in patients treated for inflammatory bowel disease [199]. Overall, there are no compelling data to justify methotrexate as an alternative treatment when better agents are available.…”

Liver dysfunction and immunosuppressive therapy

“…2 Patients with IBD are at risk for hepatobiliary disease and organ toxicity along with reactivation of hepatitis B or C. 3 In 2009, a prospective Spanish study reported the prevalence of HBV or HCV in patients with IBD at 9.7%, similar to that of their general reference population and lower than in previously published series. 1 This has been confirmed on follow-up studies.…”