P1866 - Did the Drug Do It? A Hepatic Conundrum: Vedolizumab-Related Liver Injury

Preeyanka Sundar, MD, MPH¹, Suma Harsha Kosuru, MBBS², Matthew Hillam, DO¹, Sara Ancello, DO^3
1Midwestern University, Mountain Vista Medical Center, Mesa, AZ; ²Mountain Vista Medical Center, Aldie, VA; ³Central Arizona Medical Associates, Mesa, AZ

Introduction: Vedolizumab (VDZ) is a gut-selective humanized monoclonal IgG1 antibody to α4β7 integrin. VDZ was approved since 2014 for induction and maintenance of ulcerative colitis and moderate to severe refractory Crohn's disease. Generally well tolerated, VDZ’s serious adverse events (SAEs) have been reported in 7–12% of patients in the pre-marketing phase III trials, but this range is like that of the SAEs experienced by the placebo groups (4–9%). To our knowledge, biopsy-proven liver injury was only reported with VDZ in one Portuguese report by Saraiva et al. We report the second case of biopsy proven VDZ causing Drug Induced Liver Injury (DILI).

Case Description/Methods: A 36-year-old female with Crohn's disease on Mesalamine presented with fever and abdominal pain. Labs showed AST 270, ALT 455, AP 125, TB 0.2. Liver biopsy was consistent with HSV hepatitis with positive HSV immunohistochemical stain (Figure 1, A-B). Valacyclovir was initiated and mesalamine continued. One year later she had worsening diarrhea and abdominal pain. Colonoscopy revealed pancolitis. Immunomodulators, steroids and TNF inhibitors were relatively contraindicated to prevent reactivation of HSV. Due to the failure of conventional treatment, VDZ was chosen for its gut selectivity. Six days after the first infusion, she developed nausea, vomiting, diarrhea and fevers of 102F. Serum transaminases (AST: 662, ALT: 569, ALP: 205) and HSV IgM 1 and 2 were elevated, HSV PCR negative. Liver biopsy revealed active chronic hepatitis with mild portal fibrosis (Figure 1, C: grade 1, stage 1) and RUCAM Score of 8. After discontinuing VDZ, there was a clinical and serological improvement with complete recovery in 20 days. This was most consistent with DILI, secondary to VDZ.

Discussion: In phase III trials, out of 3,326 patients, less than 2% had ALT five times above the upper limit which is like placebo patients. 3 reported DILI cases were resolved with drug discontinuation and/or administration of corticosteroids. However, cholestatic liver injury persisted despite discontinuation leading to the diagnosis of chronic DILI.
We report this case to illustrate the importance of hepatotoxic virus screening prior to VDZ initiation, in addition to tuberculosis screening. Complete etiologic workup in patients with a history of hepatic injury and abnormal LFTs is key to ensuring prompt diagnosis and early consideration of drug discontinuation.


Figure: A. Patchy areas of hepatocyte necrosis with associated hemorrhage and scant inflammatory response. B. Characteristic pattern for HSV hepatitis. HSV immunohistochemical stain positive. C. Nonspecific findings. Architecture intact. Moderate inflammation within the portal vessels, interface zone, lobules, eosinophils noted. HSV 1/2 immunohistochemical stain negative. Mildly active chronic hepatitis with mild portal fobrosis (grade 1, stage 1)


Disclosures:
Preeyanka Sundar indicated no relevant financial relationships.
Suma Harsha Kosuru indicated no relevant financial relationships.
Matthew Hillam indicated no relevant financial relationships.
Sara Ancello indicated no relevant financial relationships.


Preeyanka Sundar, MD, MPH¹, Suma Harsha Kosuru, MBBS², Matthew Hillam, DO¹, Sara Ancello, DO³. P1866 - Did the Drug Do It? A Hepatic Conundrum: Vedolizumab-Related Liver Injury, ACG 2021 Annual Scientific Meeting Abstracts. Las Vegas, Nevada: American College of Gastroenterology.