E0549 - Statin-Related Autoimmune Hepatitis: A Case Study of a Rare Entity and Review of Current Knowledge

Tuesday, October 25, 2022

3:00 PM – 5:00 PM ET

Location: Crown Ballroom

Has Audio

Presenting Author(s)

Antonio Pizuorno Machado, MD

University of Texas Health Science Center
Houston, TX

Antonio Pizuorno Machado, MD¹, Dongfeng Tan, MD², Rafaela Horrillo, PA-C², Hao Chi Zhang, MD³
¹University of Texas Health Science Center, Houston, TX; ²MD Anderson Cancer Center, Houston, TX; ³UT MD Anderson Cancer Center, Houston, TX

Introduction: Statins are the most commonly prescribed drugs for the prevention and management of dyslipidemia globally. Although statins provide therapeutic benefits, they are associated with potential clinically-significant adverse effects involving muscle and the liver. While non-life-threatening statin-related drug-induced liver injury (DILI) can occur, a rare subset of cases comprise of a phenotype resembling autoimmune hepatitis (AIH). We report a case of DILI related to atorvastatin resembling AIH, which naturally resolved with cessation of the statin and without need for immunosuppressive therapy.

Case Description/Methods: A 74-year-old woman with a history of hypertension, hyperlipidemia, diabetes mellitus type II, and endometrial carcinoma presented for evaluation after being referred her oncologist for elevated liver enzymes. The patient had taken atorvastatin 40 mg/d for many years. The liver enzymes exhibited a hepatocellular pattern (Figure 1). Lab studies revealed positive ANA, ASMA, and AMA (Table 1). An ultrasound and CT of the abdomen were performed which reported no discrete hepatic changes. After the patient discontinued atorvastatin, the liver enzymes exhibited subsequent decrease (Figure 1). Liver biopsy was performed which reported liver parenchyma with portal and interface chronic inflammation, patchy minimal steatosis, and single cell necrosis of hepatocytes. The patient was diagnosed with AIH-like DILI induced by atorvastatin which was then permanently discontinued. Thirty-one days after discontinuation of statin therapy, liver enzymes improved without steroids.

Discussion: Statins are generally considered safe. The risk of severe statin-induced hepatotoxicity is reported as being 0.001%. True idiopathic AIH can be difficult to distinguish from drug-induced AIH due to overlap of clinical, laboratory, and histologic features. In the event of autoimmune-like DILI, liver enzymes normalize after the discontinuation of the offending agent. Our case shares similarities with only two other cases in the literature. In clinical practice, a case-by-case decision about statin re-challenge should be formulated in a multidisciplinary fashion to ensure the safety of prescribing a statin.

Figure: Figure 1. (A): Timeline of liver enzyme trends from July 2020 through March 2022. Atorvastatin was discontinued on October 29, 2021. The delayed onset of transaminase elevations while on statin therapy may in retrospect represent also an idiosyncratic form of drug-induced liver injury. Liver enzymes naturally improved after discontinuation of statin medication, without the need for systemic corticosteroid therapy. (B): Liver biopsy histology (H&E, 400x) - Moderately portal chronic inflammation consisting of mainly lymphocytes, admixed with eosinophils and occasional plasma cells (arrow: a plasma cell). (C): Liver biopsy histology (H&E, 400x) - Minimal steatosis and single cell necrosis (Councilman body) of hepatocytes (arrow: Councilman body). Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; ALP, alkaline phosphatase; GGT, gamma-glutamyl transferase.

Variable	Reference Range, Adults*	Result
White blood cell count (per μL)	4,000–11,000	6.6
Hemoglobin (g/dL)	14.0–18.0	13.2
Mean corpuscular volume (fL)	82–98	92
Platelet count (per μL)	140,000–440,000	214
Sodium (mEq/L)	136–145	135
Blood urea nitrogen (mg/dL)	8–20	9
Creatinine (mg/dL)	0.70–1.30	0.81
Lactate dehydrogenase (U/L)	135–225	172
Total IgG (mg/dL)	610–1,616	1811
Total IgA (mg/dL)	61–356	Not obtained
Hepatitis A IgG antibody	Negative	Positive
Hepatitis B surface antigen	Non-reactive	Non-reactive
Hepatitis B surface antibody (mIU/mL)	< 5.0 (Negative)	21.6
Hepatitis B total core antibody	Non-reactive	Negative
Hepatitis C antibody	Non-reactive	Negative
Hepatitis E IgG antibody	Negative	Negative
Anti-nuclear antibody titer	< 1:80 (Negative)	1:640
Anti-smooth muscle antibody	Negative	63.4
Anti-liver/kidney microsomal-1 antibody	Negative	Negative
Anti-mitochondrial antibody	< 0.1 (Negative)	105
Ceruloplasmin (mg/dL)	19.0–31.0	27
Ferritin (ng/mL)	30–400	284
Iron (μg/dL)	59–158	90
Total iron binding capacity (μg/dL)	250–450	342
HFE gene mutation analysis	—	Not obtained
Alpha-1 antitrypsin antibody (serum)	***	176
Triglycerides (mg/dL)	< 150	185
Total cholesterol (mg/dL)	< 200	152
LDL-cholesterol (mg/dL)	< 100	89
Anti-tissue transglutaminase IgA antibody (U/mL)	< 4.0	1.2
Anti-tissue transglutaminase IgG antibody (U/mL)	< 6.0	Not obtained
Celiac HLA DQ alleles	—	Negative

Table: Table 1. Laboratory results for patient within timeframe from 10/29/2021-3/24/2022

Disclosures:

Antonio Pizuorno Machado indicated no relevant financial relationships.

Dongfeng Tan indicated no relevant financial relationships.

Rafaela Horrillo indicated no relevant financial relationships.

Hao Chi Zhang indicated no relevant financial relationships.

Antonio Pizuorno Machado, MD¹, Dongfeng Tan, MD², Rafaela Horrillo, PA-C², Hao Chi Zhang, MD³. E0549 - Statin-Related Autoimmune Hepatitis: A Case Study of a Rare Entity and Review of Current Knowledge, ACG 2022 Annual Scientific Meeting Abstracts. Charlotte, NC: American College of Gastroenterology.