P064 Drug-Induced Liver Injury (DILI) Associated With Anti-tumor Necrosis Factor Alpha (Anti-TNFα) Agent
Authors: Paniagua Carmen , Garg Shashank 
Published: December 2019

BACKGROUND:

Anti-TNFα therapy has become the mainstay in the treatment of Crohn's disease (CD), improving the rates of response and remission in patients. Significant considerations are needed when treating patients with anti-TNFα therapy including immunogenicity, duration of treatment, and safety profile. Anti-TNFα agents have been associated with drug-induced liver injury (DILI). This case presents a highly suspected association between Renflexis and DILI.

CASE REPORT:

20 year old with ileocolonic CD started on Renflexis 5 mg/kg infusions to be given at 0, 2, and 6 weeks, followed by every 8 weeks. Before receiving Renflexis, tested negative for viral hepatitis with normal liver function tests. Infusions were followed by improvement in clinical symptoms and inflammatory markers. After the fourth infusion, serum liver aminotransferases were slightly elevated and rose higher several weeks after therefore, infusions were discontinued. Extensive serological work up did not find a definite cause (viral hepatitis and autoimmune antibodies) except for a weakly positive ASMA. Liver biopsy performed that showed a pattern of chronic hepatitis, no fibrosis highly suggestive of DILI. The patient remained asymptomatic, anicteric without rash, fever, or signs of hepatic disease. She was monitored on no IBD therapy and liver aminotransferase tests started to normalized and fell to normal within 12 weeks after infusion discontinuation and budesonide 9 mgs daily. This led to a prompt clinical response and serum liver transaminases remained normal during the subsequent following weeks of treatment with budesonide taper dose.

DISCUSSION:

Renflexis is an anti-TNFα antagonist that is biosimilar to Remicade (infliximab) for the treatment of moderate to severe active Cronh's disease. The mechanism of action is highly similar to the originator biologic. Infliximab is a monoclonal antibody genetically engineered chimeric immunoglobulin G1 anti human tumor necrosis factor agent. It has the ability to fix complement and lyse cells expressing membrane-bound TNF-alpha and induce downregulation of the inflammatory mechanisms in the entire mucosal layer. Two liver injury issues had been associated with infliximab; reactivation of underlying chronic hepatitis B and direct hepatotoxicity with different phenotypes including acute hepatitis (hepatocellular), cholestatic, autoimmune-liked injury, and acute liver failure. The hepatocellular pattern is marked by isolated or predominant elevation of serum transaminases. Cholestatic have elevation in serum alkaline phosphatase with normal or mild elevation in serum transaminases and markedly elevated bilirubin level. An autoimmune mechanism can present with a hepatocellular pattern if the hepatocytes are involved (autoimmune hepatitis) or cholestatic or if the immune mechanism targets the biliary ducts. In this case, the pattern was hepatocellular with elevation of aminotransferase, which generally arise after 2 to 5 infusions. Elevation of transaminases are usually transient and asymptomatic.

CONCLUSION:

This case described an association between Renflexis and DILI. Acute liver injury caused by anti-TNFα antagonist may be a class effect since several agents in this category have been implicated. In this case, the most common presentation occurred as an autoimmune phenotype with marked hepatocellular injury. A possible dual mechanism of immune deregulation with an inflammatory response and dysfunction of liver repair may be the etiology of hepatic injury associated with infliximab use.