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.