Autoimmune Hepatitis with Drug Induced Liver Injury From Methimazole in Patient with Graves Disease

Summary: Background: Autoimmune Hepatitis is a rare inflammatory condition marked by elevated liver function enzymes, serum antibody detection (ANA, Anti-SMA, Anti-LKM1) and characteristic liver biopsy findings. Treatment with immunosuppressive agents and avoidance of hepatotoxic agents is important in preventing progression of disease. Case Description: 21-year old female with Graves Disease on daily Methimazole presented to the hospital after experiencing several days of scleral icterus, jaundice, diffuse itching and abdominal pain. She denied any history of alcohol use, illicit drug use or Acetaminophen use, which was confirmed by a toxicology lab panel. Patient was born in Papua New Guinea and was adopted therefore was unaware of her family history. Initial work up revealed signs of acute hepatitis given severely elevated bilirubin and liver function enzymes. Infectious hepatitis panel was negative and Initial Imaging including RUQ US and CT Abdomen and Pelvis revealed abnormal gallbladder wall thickening with mild periportal edema. Patients home medication Methimazole for treatment of Graves Disease was held on arrival due to its known hepatotoxicity. Throughout the hospital course patient liver enzymes and total bilirubin continued to increase. Further work up including MRCP showed nonspecific concentric gallbladder wall thickening, without intra or extrahepatic biliary ductal dilatation, choledocholithiasis or obstructing mass. Further labs showed positive ANA, Anti-SMA, Anti-SSB, Anti-dsDNA, and Anti-Histone Antibody. Patient was started on oral Prednisone 40mg daily given concern for autoimmune process. Methimazole continued to be held and she was started on propranolol for symptom management of Graves Disease. Liver biopsy was obtained which revealed hepatic parenchyma with lobular disarray, patchy hepatocyte ballooning, hepatocyte rosetting, many acidophilic bodies, pericentral necrosis, and marked lobular inflammation comprised of lymphocytes, neutrophils, few plasma cells and rare eosinophils. The portal tracts had severe inflammatory infiltrates composed predominantly of lymphocytes, and few plasma cells. Based on histology results and clinical features, the patient was diagnosed with Acute Hepatitis secondary to Autoimmune Hepatitis and Drug-Induced Liver Injury with Autoimmune features. Patients' symptoms and liver function enzymes began to slowly improve with continuation of high dose oral Prednisone and discontinuation of Methimazole however, patients hyperthyroid state continued to worsen with increased T3 and T4 levels. It was determined that thyroidectomy would be the best course of action in management of the patients Graves Disease as she was no longer able to tolerate Methimazole given its hepatotoxicity and her underlying Autoimmune Hepatitis. She was educated on importance of close medical follow up given possibility of developing further autoimmune disease Discussion: This young female’s presentation displays the discovery of a rare case of multifactorial acute hepatitis secondary to Drug Induced Liver Injury from Methimazole use (for treatment of Graves Disease) and newly diagnosed Autoimmune Hepatitis. Autoimmune hepatitis is a rare progressive disease mainly affecting women and is characterized by increased IgG levels, autoimmune antibody positivity (ANA, Anti-SMA etc.), clinical acute or chronic hepatitis, liver histology of portal mononuclear cell infiltrate (generally lymphoplasmacytic, with occasional eosinophils) around the peri-portal triad with rosettes of hepatocytes, bridging necrosis, and multinucleated giant cells. Patients generally respond well to corticosteroids and/or azathioprine. In patients with Autoimmune Hepatitis, it is important to receive close follow-up, receive Hepatitis A and B vaccinations and avoid hepatotoxic agents including various medications (Methimazole in this case) and alcohol. Conclusion: We are reminded that treatment for Graves Disease may cause further liver injury in those with underlying Autoimmune Hepatitis. As in this case, thyroidectomy should be considered as the preferred treatment of Graves Disease in those with Autoimmune Hepatitis as medical treatment of the disease with Methimazole can cause further liver injury. This case serves as a reminder that having one autoimmune disease is often associated with other various autoimmune diseases. Early detection and screening for autoimmune disease can help guide management and lead to better outcomes.