Cholestasis as a Diagnostic Challenge

Abstract

Cholestasis results from an impairment in the excretion of bile acids and is caused by numerous disorders. Most of the time, the etiology can be predicted with a good history, physical examination and rational diagnostic testing. The most common causes of cholestasis include biliary obstruction, acute hepatitis, advanced cirrhosis, drug-induced liver injury (DILI), sepsis and malignancy. Even when the cause of cholestasis is apparent, additional mechanisms can contribute to or aggravate underlying liver pathology that manifests with prolonged hyperbilirubinemia. Here we report a patient with severe cholestasis who underwent extensive evaluation for unresolved jaundice. A 75-year-old lady presented to the hospital with worsening jaundice, diffuse pruritus, dark urine, pale colored stools, weight loss, palpitations and thinning of hair. Ultrasound revealed common bile duct stones and an Endoscopic retrograde cholangiopancreatography (ERCP) was done to remove the stones. As her elevated bilirubin levels did not improve after ERCP, liver biopsy was performed which showed stage 3 fibrosis and marked cholestasis consistent with congestion and outflow obstruction leading to congestive hepatopathy.Thyroid function tests were done to evaluate as part of the evaluation for abnormal liver function tests and were consistent with hyperthyroidism. An ultrasound of the neck revealed two nodules without calcification and irregular margins. A thyroid uptake scan revealed a pattern of Graves' disease. Echocardiogram showed severe tricuspid regurgitation. Her bilirubin dropped to 24 mg/dl and she was discharged with metoprolol, methimazole and ursodiol. The patient returned to the hospital after 15 days with worsening jaundice and labs showed bilirubin of 26.7 mg/dl (table 1). Ultrasound imaging showed no evidence of biliary obstruction. During her second hospitalization, her bilirubin started trending down to 13 mg/dl with subsequent improvement of symptoms. In this case, we postulate that hyperthyroidism might have worsened her heart failure, which contributed to the severity of congestive hepatopathy. Patient's condition improved despite the use of methimazole, which rules out DILI. Hence, prolonged cholestasis after ERCP can be a diagnostic dilemma. One should consider other etiologies, especially intrahepatic causes of cholestasis such as congestive hepatopathy,hyperthyroidism,DILI and sepsis when cholestasis fails to improve after biliary decompression.2264 Figure 1. Laboratory trends in bilirubin during hospital course