Echinacea Induced Acute Hepatitis Transitioning to Autoimmune Hepatitis Varun Kesar M.B.B.S1, Joseph A.Odin M.D, Ph.D1, Jawad Ahmad MD1, M. Isabel Fiel MD 1, Vivek Kesar M.B.B.S2 1Division of Liver Diseases – Icahn School of Medicine at Mount Sinai New York, New York. 2Department of Medicine – Lenox Hill Hospital. New York, New York. Would need biopsy slides – I have emailed Dr. Fiel couple of times, I would need your help Dr. Odin Should we add picture of Echinacea bottle – I just google and copied from internet ABSTRACT CASE IMAGES Introduction: The use of herbal and dietary supplements (HDS) in the United States is increasing and there is growing evidence of HDS associated hepatotoxicity. Echinacea purpurea is a very widely used herbal supplement recommended as a common cold remedy. Echinacea has only once been associated with hepatotoxicity (1). We report a second case of Echinacea associated acute hepatotoxicity. Case: A 58 year old Caucasian woman with a history of hypertension presented with abdominal pain, jaundice, and dark urine for 2 days and fatigue for 3 weeks. She denied fever, nausea, vomiting, chills, change in bowel habits, rash, joint pains, muscle aches, abdominal swelling, or confusion. She denied alcohol or drug abuse, recent travel, and any new medications. She was only taking enalapril for hypertension for 18 years. On examination, she was icteric, alert, and had no stigmata of chronic liver disease. On presentation, liver labs were: total bilirubin 12.7 mg/dL, aspartate aminotransferase (AST) 1466 U/L, alanine aminotransferase (ALT) 1486 U/L, Alkaline phosphatase (ALP) 303 U/L. Serologies for viral hepatitis were negative. Her ANA was 1:160, but her IgG level was only 1.61 g/dL. Abdominal imaging was negative for any biliary abnormalities. Careful history revealed that she had taken Echinacea for approximately 10 days for common cold type symptoms during the month before presentation. A liver biopsy showed active hepatitis with eosinophils, many ceroid filled macrophages, and only rare plasma cells consistent with drug induced liver injury. She stopped all HDS and her liver biochemistries initially improved. Her liver biochemistries started to rise again 4 months after presentation (Table). A repeat liver biopsy showed few ceroid filled macrophages and sheets of plasma cells with severe interface hepatitis consistent with autoimmune hepatitis. Prednisone was started with gradual improvement in liver biochemistries after two months. Discussion: This appears to be a rare case of Echinacea induced liver injury. Both cases resulted in autoimmune hepatitis. This case highlights the need to consider all HDS as a potential cause of liver injury. 58 year old female presented with abdominal pain, jaundice and dark urine for 2 days and fatigue for 3 weeks. She denied fever, melena, confusion, recent travel and excessive alcohol or acetaminophen intake. Patient admits to taking an OTC herbal supplement (Echinacea drops) for URI symptoms. On examination, she was A+OX3, icteric, and had a diffusely tender abdomen. Lab Parameters (normal range) *Day 0 (date of presentation) Day 10 Day 77 Day 136 Day 203 AST(1-50 U/L) 1466 889 469 602 151 ALT(1-53 U/L) 1486 866 466 557 228 ALP (30-110 U/L) 303 244 325 357 235 Total Bilirubin (0.1 – 1.2 mg/dL) 12.7 10.9 2.8 1.0 ANA titer N/A 1:160 1:320 Image 1 Image 2 Biopsy: Image 1- Acute hepatitis (on presentation) Biopsy: Image 2-Autoimmune hepatitis (repeat biopsy on Day 159) *Hepatitis A, B, C, CMV, EBV, autoimmune hepatitis, Wilson disease, alpha-1 AT deficiency, PBC, PSC, acetaminophen overdose and hemochromatosis were ruled out with appropriate testing. MRCP, CT scan, and abdominal ultrasound were negative for biliary obstruction. Background Liver biopsy #1 (image 1) was consistent with drug induced liver injury. She was managed symptomatically, lab parameters improved initially, but later (Day 136) her liver enzyme levels started rising again. A repeat liver biopsy (image 2) showed evidence of autoimmune hepatitis, which was slowly responsive to prednisone. Echinacea flower Echinacea drops Echinacea purpurea, a group of perennial prairie wildflowers native to the central grasslands of North America belonging to family Asteraceae. Echinacea preparations are widely used as an immuno-modulator and for the prevention and treatment of common cold symptoms. We report a case of Echinacea induced acute hepatitis transitioning to autoimmune hepatitis. Discussion High Index of suspicion is required for diagnosis of drug Induced liver injury. LIVERTOX (NIDDK) is a freely available website that provides up-to-date, comprehensive and unbiased information about drug induced liver injury caused by prescription and nonprescription drugs, herbals and dietary supplements. http://livertox.nih.gov/index.html BIBLIOGRAPHY Kocaman O, Hulagu S, Senturk O. Echinacea-induced severe acute hepatitis with features of cholestatic autoimmune hepatitis. Eur J Intern Med. 2008 Mar;19(2):148