B0546 - A Rare Case of Refractory Drug Induced Liver Injury Following Ocrelizumab Use for Multiple Sclerosis

Monday, October 24, 2022

10:00 AM – 12:00 PM ET

Location: Crown Ballroom

Has Audio

Presenting Author(s)

Ahmed M. Ibrahim, MD

Henry Ford Hospital
Bloomfield Hills, Michigan

Award: Presidential Poster Award

Ahmed M. Ibrahim, MD¹, Syed-Mohammed Jafri, MD²
¹Henry Ford Hospital, Bloomfield Hills, MI; ²Henry Ford Health System, Detroit, MI

Introduction: Ocrelizumab, a humanized anti-CD20 monoclonal antibody, has been recently approved for use in Multiple Sclerosis (MS). Thus far, it has not been associated with liver enzyme elevations during therapy or idiosyncratic liver injury, but has been linked to cases of reactivation of Hepatitis B in susceptible patients. We present a case of severe liver injury in a patient with relapsing-remitting MS who received Ocrelizumab.

Case Description/Methods: A 34-year-old Hispanic woman with newly diagnosed MS was planned to start treatment with Ocrelizumab. Pre-treatment acute and chronic Hepatitis B labs were negative. During the first infusion session, the patient developed an infusion reaction with rash and pruritis, which resolved spontaneously. Three weeks later, she presented to the ED with abdominal pain, nausea, fatigue, diminished appetite, and dark urine. Labwork revealed ALT 2209 U/L, AST 2261 U/L, Tbili 10.6 mg/dL, ALP 232 U/L (LFTs two months prior were all within normal limits). INR was elevated to 1.5, but she had no signs of hepatic encephalopathy. Viral and toxic etiologies of acute hepatitis were thoroughly ruled out. Autoimmune markers, including those specific for autoimmune hepatitis, were negative. Abdominal US and MRCP revealed no abnormalities other than a surgically absent gallbladder. As LFTs continued to rise despite drug withdrawal, she was started on IV steroids. INR further rose to 1.8, and inpatient liver transplant evaluation was initiated. Liver biopsy revealed acute hepatitis with hepatocyte trabecular disarray and parenchymal collapse, perivenular zone 3 confluent necrosis, and mixed inflammatory infiltrate with no lymphocytes/plasma cells identified, suggestive of drug-induced liver injury (DILI). Considering the above workup and timeline of symptoms and lab abnormalities in relation to initiation of Ocrelizumab, DILI secondary to Ocrelizumab was favored as the culprit. The patient’s symptoms resolved and LFTs steadily improved with IV steroids. She was discharged on PO steroids with close follow-up and monitoring.

Discussion: We report what is, to our knowledge, the first case of DILI (4+ on DILI Network severity scale) related to Ocrelizumab. As it is a high-efficacy disease-modifying therapy now approved for various subtypes of MS, its use will continue to increase. Therefore, characterizing, monitoring, and reporting Ocrelizumab-related hepatotoxicity is important. However, further studies are needed to shed light on the mechanisms underlying DILI from Ocrelizumab.

		Total		Advanced Adenoma		Non-Advanced Adenoma		p value
		N=148		n=31		n=117

# Polyps	median(IQR)	2	1-2	2	1-4	1	1-2	< 0.001
Largest polyp size	mean(SD)	7.0	4.8	14.1	5.1	5.1	2.2	< 0.001
Polyp Location(s)	n(%)
Terminal Ileum		1	0.3%	0	0.0%	1	0.3%	0.608
Cecum		35	9.5%	8	25.8%	27	8.0%	0.752
Ascending Colon		38	10.3%	10	32.3%	28	8.3%	0.349
Hepatic Flexure		3	0.8%	2	6.5%	1	0.3%	0.050
Transverse Colon		32	8.6%	13	41.9%	19	5.6%	0.002
Splenic Flexure		1	0.3%	0	0.0%	1	0.3%	0.608
Descending Colon		17	4.6%	2	6.5%	15	4.4%	0.326
Sigmoid		44	11.9%	9	29.0%	35	10.3%	0.925
Rectum		26	7.0%	3	9.7%	23	6.8%	0.197
Anal Verge		0	0.0%	0	0.0%	0	0.0%
Surgery	n(%)	3	0.8%	3	9.7%	0	0.0%	< 0.001
Mortality	n(%)	11	3.0%	2	6.5%	9	2.7%	0.235

Table: Characteristics of polyps in patients with advanced adenoma (n=31) as compared to all other sub-types (n=117)

Disclosures:

Ahmed Ibrahim indicated no relevant financial relationships.

Syed-Mohammed Jafri indicated no relevant financial relationships.

Ahmed M. Ibrahim, MD¹, Syed-Mohammed Jafri, MD². B0546 - A Rare Case of Refractory Drug Induced Liver Injury Following Ocrelizumab Use for Multiple Sclerosis, ACG 2022 Annual Scientific Meeting Abstracts. Charlotte, NC: American College of Gastroenterology.