S3029 Hydralazine-Induced Liver Injury With Autoimmune Features: A Case Report and Literature Review

Abstract

Introduction: Autoimmune drug induced liver injury (AI-DILI) is a syndrome characterized by liver injury accompanied by laboratory evidence of autoimmunity due to the ingestion of a drug or herbal product. DILI accounts for approximately 15% of the cases of acute liver failure. Many drugs have been associated with DILI such as Amoxicillin-clavulanate, Diclofenac, Azathioprine, Infliximab. However, very rare cases have been reported on hydralazine-induced DILI. A response to treatment with steroids supports the diagnosis. Case Description/Methods: We present a case of a 59 year old female with no reported past history of liver disease. Patient was admitted for workup of jaundice, fatigue, and abdominal dissension of one month duration. Labs were significant for liver enzymes elevation with a cholestatic pattern. ERCP and EUS were done and results came back unremarkable. An extensive infectious and autoimmune workup was also negative. On further clarification of medication history, patient appeared to have had started hydralazine roughly 3 months prior to presentation. A liver biopsy was done and showed cholestatic injury and granulomatous inflammation (Figures A&B). Hydralazine was presumed the cause of patient’s liver injury, it was immediately stopped and patient was started on oral prednisone with significant improvement in symptoms and liver function test. Discussion: Autoimmune features and autoantibody reactivity in such cases of DILI vary according to liver injury severity and disease progression. The presentation of AI-DILI is classically indistinguishable from idiopathic autoimmune hepatitis (I-AIH). The presence of autoimmune features of liver injury due to hydralazine is not associated with the typical HLA alleles found in I-AIH such as HLA-DRB1*03:01 and DRB1*04:01 alleles. Histologically, AI-DILI shows changes that cannot be definitively distinguished from I-AIH without clinical correlation. Features on liver biopsy favoring DILI with autoimmunity include portal inflammation, fibrosis, portal neutrophils and plasma cells, and intracellular cholestasis. Liver biopsy is not performed in many cases of DILI, but may be useful if the liver injury is prolonged and does not promptly resolve with discontinuation of the drug and to also decide on need for treatment with steroids. In the attached table we present a review of the body of research on hydralazine-induced DILI with autoimmune features.Figure 1.: A- H&E stained section of the liver demonstrates moderate cholestasis (arrows) with surrounding inflammation.​ B- H&E stained section of the liver demonstrating a portal triad with mixed inflammation composed of predominately lymphocytes with rare neutrophils and plasma cells and mild interface activity. Moderate bile duct injury is seen (arrow). Table 1. - Literature review for hydralazine-induced DILI with autoimmune features Author Number of cases Average age Signs/Symptoms Sex Type Average LFTs Markers Course Outcome Our case (2022) 1 59 Jaundice, ascites, abdominal distension F Cholestatic ALT 100sAST 200sBili 17 ANA-ASMA-AMA - Moderate Resolved de Boer (2016) 7 60 (42-76) Jaundice, itching, rash, fever, eosinophilia 5 F2 M Hepatocellular (3)Mixed (2)Cholestatic (2) ALT 500sAST 1000sALP 200sBili 2 - Mild (2)Moderate (3)Severe (2) Liver transplant (1)Death (0) deLemos et al. (2014) 1 42 Flu-like symptoms, jaundice, ascites M ALT 1000sAST 1000sALP 200sINR 2 ANA+ASMA-AMA- Very severe Liver transplant Donald Rice, MD (1983) 1 51 Nausea, vomiting, malaise, fever, dark urine F Granulomatous hepatitis AST 500sALP 200sBili 5 Lupus - mild Resolved Abbreviations: F:female, M:male, LFT: liver function test, ANA:anti-nuclear antibody, ASMA:anti-smooth muscle antibody, AMA:anti-mitochondrial antibody.