A 68-year-old woman admitted for community-acquired pneumonia 4 days ago is evaluated in the hospital for new-onset jaundice. During morning rounds today, it is noted that she has yellowish discoloration of both eyes. The patient has no abdominal pain, nausea, or prior history of liver disease, but she has a history of hypertension. She does not use tobacco, alcohol, or illicit drugs. Her current medications include azithromycin, ceftriaxone, lisinopril, and acetaminophen as needed.
Her temperature is 36.7 C (98 F), blood pressure is 120/70 mm Hg, and pulse is 72 /min. The patient's pulse oximetry shows 96% on 2 liters oxygen. Examination reveals scleral icterus, rales in the right lower lobe, and normal heart sounds without murmurs. The abdomen is soft and nontender with no organomegaly.
Laboratory results are as follows:

Acute viral hepatitis serologies are negative. Abdominal ultrasound reveals normal liver size and echotexture, a thin-walled nondistended gallbladder, no gallstones or biliary sludge, and a normal common bile duct.
Which of the following is the best next step in management of this patient?

Question

A 68-year-old woman admitted for community-acquired pneumonia 4 days ago is evaluated in the hospital for new-onset jaundice.  During morning rounds today, it is noted that she has yellowish discoloration of both eyes.  The patient has no abdominal pain, nausea, or prior history of liver disease, but she has a history of hypertension.  She does not use tobacco, alcohol, or illicit drugs.  Her current medications include azithromycin, ceftriaxone, lisinopril, and acetaminophen as needed.
Her temperature is 36.7 C (98 F), blood pressure is 120/70 mm Hg, and pulse is 72 /min.  The patient's pulse oximetry shows 96% on 2 liters oxygen.  Examination reveals scleral icterus, rales in the right lower lobe, and normal heart sounds without murmurs.  The abdomen is soft and nontender with no organomegaly.
Laboratory results are as follows:

Acute viral hepatitis serologies are negative.  Abdominal ultrasound reveals normal liver size and echotexture, a thin-walled nondistended gallbladder, no gallstones or biliary sludge, and a normal common bile duct.
Which of the following is the best next step in management of this patient?

Quizplus · Accepted Answer

This patient's disproportionately elevated alkaline phosphatase with direct hyperbilirubinemia is consistent with cholestasis. Cholestasis may be extrahepatic (eg, choledocholithiasis, primary sclerosing cholangitis, malignant biliary obstruction) or intrahepatic (eg, primary biliary cirrhosis, drug toxicity, pregnancy, postoperative, infectious hepatitis [rare]). The initial evaluation should include a liver ultrasound to evaluate for biliary obstruction. If obstruction is absent, intrahepatic cholestasis should be suspected. Although antimitochondrial antibodies can be obtained, primary biliary cirrhosis is unlikely given this patient's acute presentation in the hospital setting. initial evaluation This patient's recent therapy with antibiotics (eg, azithromycin, ceftriaxone) raises suspicion for drug-induced cholestasis. Antibiotics are one of the most common causes of drug-induced liver injury (DILI) in the United States. Clinical features supportive of DILI include the development of liver injury after initiating a known offending medication, the absence of underlying liver disease, and improvement in liver function after drug cessation. Removal of the offending agent will lead to recovery in most patients. (Choice A) Acetaminophen toxicity typically results in a hepatocellular pattern of liver injury with serum transaminases in the thousands, as opposed to this patient's cholestatic pattern. (Choice C) Cholescintigraphy (HIDA scan) can assess patency of the common bile duct and may confirm acute cholecystitis if the diagnosis is uncertain after abdominal ultrasound. However, this patient's normal ultrasound and absence of abdominal pain/tenderness make common bile duct obstruction and acute cholecystitis unlikely. (Choice D) Liver biopsy is typically performed in the setting of unexplained liver function abnormalities and may be considered if this patient's liver function does not improve after discontinuing the offending drug. (Choice E) MR cholangiopancreatography (MRCP) is an option if primary sclerosing cholangitis is suspected or if the initial workup of intrahepatic cholestasis is unrevealing. This patient should have her antibiotics changed before considering MRCP. Educational objective: Intrahepatic cholestasis is suspected in patients with a cholestatic pattern of liver injury and absence of biliary obstruction on abdominal ultrasound. Drug toxicity is an important cause of intrahepatic cholestasis and often occurs with antibiotic use. Removal of the offending agent will lead to recovery in most patients. __________ References: Drug-induced cholestasis. (http://www.ncbi.nlm.nih.gov/pubmed/21480339) Drug-induced cholestasis. (http://www.ncbi.nlm.nih.gov/pubmed/24099015)

A 68-Year-Old Woman Admitted for Community-Acquired Pneumonia 4 Days Ago