S3171 Statin-Related Autoimmune Hepatitis: A Case Study of a Rare Entity and Review of Current Knowledge

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