Drug-Induced Liver Injury Used in the Treatment of Inflammatory Bowel Disease

Abstract

Therapeutic options for the management of inflammatory bowel disease (IBD) have been expanding in recent decades. New biological and small molecule therapies have been incorporated into the pharmacological arsenal, allowing a more personalized management, seeking increasingly strict remission goals. However, the fear of developing adverse events represents one of the most important limitations in deciding its use by patients and a multidisciplinary team. Despite the risk of hepatotoxicity of thiopurines and methotrexate, these drugs are still used either as monotherapy or as combined therapy with anti-TNF biologic agents. Although drug-induced liver injury (DILI) appears to be less frequent with anti-TNF agents, newer biologics and small molecules, monitoring liver tests should be considered in the follow-up of these patients, especially if in the future raises the option of combined therapy of biologics or these drugs with small molecules. The objective of this review is to show data on the risk of developing DILI in patients with IBD who are undergoing treatment with traditional therapy or new drugs, whether biological or small molecules.

Causal effects from inflammatory bowel disease on liver function and disease: a two-sample Mendelian randomization study

“…PSC and bone metabolic disorders are well-documented extraintestinal manifestations of IBD ( 2 ). Meanwhile, individuals with IBD undergoing treatment with thiopurines, methotrexate, and biologics are at risk of developing DILI ( 27 ). The decreased levels of ALB caused by UC in the present study may be related to malnutrition induced by chronic inflammatory conditions or reduced albumin synthesis due to poor liver function.…”

Inflammatory Bowel Disease Therapies and Acute Liver Injury

“…Additionally, patients treated with 6MP had higher dose reduction rates than those treated with AZA, although discontinuation rates were similar in the two groups [30]. Thiopurine-associated liver damage has been related to the activity of thiopurine S-methyltransferase (TPMT), an enzyme involved in the metabolism of both 6-MP and azathioprine [3,22]. In fact, the presence of genetic polymorphisms can decrease the activity level of this enzyme resulting in variable levels of thiopurine metabolites influencing the degree of hepatotoxicity [31].…”

“…In patients with IBD, anomalies in the biohumoral parameters of liver function can be found in percentages ranging from 3% to 50% of cases. The liver diseases that can develop in these cases include hepatic steatosis, primary sclerosing cholangitis (PSC), cholelithiasis, autoimmune hepatitis, cirrhosis, cholangiocarcinoma, and drug induced liver injury (DILI) [2,3].…”

Inflammatory Bowel Disease Therapies and Acute Liver Injury

“…In patients with IBD, anomalies in the biochemical parameters of liver function can be found in percentages ranging from 3% to 50% of cases. The liver diseases that can develop in these cases include hepatic steatosis, primary sclerosing cholangitis (PSC), cholelithiasis, autoimmune hepatitis, cirrhosis, cholangiocarcinoma and drug-induced liver injury (DILI) [ 2 , 3 ].…”