Case Report
This was a 66-year-old female who was initially admitted to a different hospital for balloon angioplasty of a partially thrombosed internal carotid artery. Following the procedure, she developedStaphylococcus hominis bacteremia and was prescribed six weeks of cloxacillin. Three weeks after completing her antibiotic course, she presented to our hospital with a two weeks history of generalized weakness and jaundice. Her past medical history additionally included gastroesophageal reflux disease, for which she was on pantoprazole twice daily, and hypopituitarism for which she was on levothyroxine and hydrocortisone. She had no personal or family history of liver disease, alcohol overconsumption, or IV drug use. She had allergies to codeine and penicillin. Jaundice and scleral icterus were noted on physical examination.
On admission, her liver enzymes were markedly elevated with a mixed pattern: aspartate aminotransferase (AST) 822 U/L (5-34 U/L), alanine aminotransferase (ALT) 877 U/L (5-55U/L), and alkaline phosphatase (ALP) 4279 U/L (40-150 U/L). Her total bilirubin level was also high, 752 umol/L (3.4-20.5 umol/L) and predominantly conjugated, 588.3 umol/L (1.6-8.6 umol/L). A blood routine test showed leukocytosis, 12.6 x 109/L (4.0-11.0 x 109/L) with eosinophilia, 1.2 x109/L (0.0-0.1 x109/L), as well as microcytic anemia: hemoglobin 95 g/L (115-155 g/L) and mean corpuscular volume 78.5 fL (82-97 fL). Workup for hemolysis as well as other causes of acute transaminitis was unremarkable. During her admission, she displayed signs of hepatic encephalopathy and she became hypotensive necessitating ICU admission. It was unclear whether this was related to acute liver failure or adrenal insufficiency. Abdominal ultrasound and CT scan showed no hepatosplenomegaly or ascites and were otherwise unremarkable. She was started empirically on oral prednisone (40mg daily) for presumed hepatotoxicity and underwent a liver needle biopsy on post-admission day 15.
The biopsy specimen was adequate for histopathologic evaluation, containing 19 portal tracts. In the lobules, there was severe zone 3 and focal zone 2 cholestasis in hepatocytes and dilated canaliculi (Figure 1A), patchy hepatocyte feathering degeneration, and scattered lymphocytes and neutrophils. The portal tracts revealed mild or no inflammation. However, 13 portal tracts had no interlobular bile ducts nor ductular reaction (Figure 1B), which was further confirmed by CK7 immunostain (Figure 1B inset). The remaining bile ducts showed features of epithelial degeneration characterized by cytoplasmic eosinophilia, nuclear pleomorphism, uneven spacing of nuclei, pyknotic nuclei, and cytoplasmic vacuoles (Figures 1C and 1D). There was no cholate stasis nor interface hepatitis. Copper stain (Rhodanine) was negative. Given the clinical history of recent cloxacillin use, the biopsy findings were compatible with acute cholestatic liver injury with bile duct injury and loss secondary to cloxacillin. The differential also included ischemic cholangiopathy secondary to her hypotensive episode, however the lack of ischemic changes at zone 3 hepatocytes makes this less likely.
After spending more than two months in hospital, the patient was discharged. In addition to her admission medications, she was discharged on ursodiol (250mg three times per day for cholestasis), lactulose (30ml three times per day for hepatic encephalopathy), N-acetylcysteine (600mg daily), and Slow-K (1200mg daily). Her hydrocortisone was tapered down from stress dose to total 15mg daily because her adrenal insufficiency was stable. During follow-up, her liver enzymes, particularly ALP level, remained elevated and an outpatient MRCP revealed beaded appearance of the common bile duct and the left intrahepatic bile duct. She was assessed by a liver transplantation center for potential LT. Unfortunately, about two months after discharge, this patient had a fall and developed multiple fractures. She passed away after two more months hospital stay. The final cause of death was drug-induced liver failure. No autopsy was performed.