Drug Induced Autoimmune Hepatitis by Amoxicillin-Clavulanate

Drug induced liver injury (DILI) is a disease caused by xenobiotics (drugs, herbal or diet products) and diagnosed by exclusion of other causes. Some drugs that cause DILI can also cause drug induced autoimmune hepatitis (DI-AIH) by triggering the immune response against liver proteins (1, 2). A 24-yr old male patient in 2015, was admitted to Turkiye Yuksek Ihtisas Hospital, gastroenterology clinic with complaints of 3 days of vomiting, weakness joint pain and jaundice. In his laboratory analysis the results were as followes: alanine ami-notransferase: 3388 U/L (<33), aspartate transam-inase: 3319 U/L (<32), alkaline phosphatase: 176 U/L (33-105), total bilirubin: 19.5 mg/dL (<1.2), direct bilirubin: 11.3 mg/dL (<0.3), albumin: 4.4 mg/dL (3.5-5.2), INR 1.4, immunoglobulin-G (Ig-G): 18.4g /L (6-16) respectively and complete blood count was within normal limits. Viral sero-logical tests for hepatitis A, hepatitis B and hepatitis C were negative. Screening for other diseases such as Wilson and hemacromotosis diseases that can cause liver failure were also negative. Written informed consent was obtained from the patient. The patient was hospitalized due to fulminant hepatitis. Amoxicillin-clavulanate had been prescribed because of tooth abscess 15 days ago. In his previous history there was not any disease, alcohol consumption or smoking. Patient's score for Council for International Organization of Medical Science was 7 (probable), and hepatocellular type damage pattern was present (3). Antinuclear antibody (ANA) was positive by 1/1000 ratio (immunoflu-orescence assay). At the seventh day of hospitalization , liver biopsy was performed. In histopatho-logic examination of liver biopsy revealed interface hepatitis, lymphoplasmacytic cell infiltration in portal area, emperipolesis and hepatic rosette formation which supporting autoimmune hepatitis. Confluent necrosis in lobular area and eosinophilic infiltration were seen (Fig. 1). One mg kg/d prednisone therapy was started with the diagnosis of amoxicillin-clavulanate induced autoimmune hepatitis by using simplified autoim-mune hepatitis scoring system (6 points: probable autoimmune hepatitis) (4). Patient whose transam-inases and bilirubin levels declined rapidly after steroid treatment was discharged with maintenance treatment. DILI accounts for 5-10% of patients with new jaundice and 25-50% of patients with acute liver failure. Damage can be due to dose dependent (intrinsic) or idiosyncratic reaction (5). The most common agent causing idiosyncratic DILI are an-timicrobial agents, especially amoxicillin-clavula-nate. There are publications about agents such as