Jason J. John, BS1, Elizabeth S. John, MD2, Mangesh Pagadala, MD2
1Virginia Commonwealth University School of Medicine, Richmond, VA; 2Methodist Dallas Medical Center, Dallas, TX
Dapagliflozin, a sodium-glucose co-transporter 2 (SGLT-2) inhibitor, is an oral hypoglycemic agent that was released in 2011. FDA approval was initially delayed due to concerns of hepatotoxicity. We present a case of drug induced liver injury (DILI) from dapagliflozin in a patient with newly diagnosed non-alcoholic fatty liver disease (NAFLD).
A 54-year-old Caucasian female with a history of obesity, diabetes mellitus, hyperlipidemia, and macular edema presented to the emergency room with new onset jaundice and intermittent episodes of confusion. She denied history of liver disease, recent travel, new or unusual foods, tattoos, incarcerations, previous blood transfusions, alcohol abuse, illicit substance use, or intake of herbal preparations. She started dapagliflozin one month prior for her diabetes. Her physical exam revealed scleral icterus and jaundice. Laboratory workup revealed total bilirubin 20.5, direct bilirubin 18.8, AST 228, ALT 222, alkaline phosphatase 1,145. She had a normal CBC, INR, ferritin, negative viral hepatitis panel, ASMA, AMA, and ANA. MRCP was unremarkable. Liver biopsy revealed a
free hepatic venous pressure of 11 and wedged hepatic venous pressure of 14, and gradient was 3 mm Hg. Histology revealed cholestasis, several missing bile ducts, bile duct proliferation, portal edema from neutrophil related inflammation, and 35% steatosis with ballooning cells and stage 3-4 fibrosis.
Dapagliflozin was stopped, and the patient's bilirubin and LFTs normalized over the next few months.
With the incidence of type 2 diabetes mellitus projected to rise, novel medications are being introduced to treat patients. Obesity, metabolic syndrome, and diabetes are all risk factors for NAFLD, and currently the prevalence of NAFLD in this group is estimated at 75%. As patients with chronic liver disease have less hepatic reserve, physicians must identify signs of NAFLD or other chronic liver diseases prior to starting potentially hepatotoxic medications. Dapagliflozin is 1,200 times more specific for SGLT-2, but also has some inhibitory effects on SGLT-1, a cotransporter responsible for reabsorption of glucose from bile.
SGLT-1 inhibition causes increased glucose saturation of bile, which can result in hepatocyte injury. It is pivotal to screen diabetics beforehand for NAFLD when considering hypoglycemic agents like dapagliflozin that may be hepatotoxic given the potential for acute liver failure as was seen in our patient.
Citation: Jason J. John, BS; Elizabeth S. John, MD; Mangesh Pagadala, MD. P1599 - DAPAGLIFLOZIN, DIABETES, LIVER DISEASE: WITH NEW MEDICATIONS COME NEW RESPONSIBILITIES. Program No. P1599. ACG 2019 Annual Scientific Meeting Abstracts. San Antonio, Texas: American College of Gastroenterology.