Discontinuation of the nonbiologic disease-modifying antirheumatic drug leflunomide is appropriate for this patient with rheumatoid arthritis who has developed abdominal pain and tenderness with acute hepatitis. The most likely diagnosis is leflunomide-induced hepatitis. Leflunomide-induced elevation of liver chemistries can occur in up to 20% of patients taking the medication, and a threefold elevation of serum aminotransferase levels has been noted in up to 13% of patients treated with leflunomide. She is at a slight increased risk for it due to concomitant NSAID use. Mild elevations less than three times the upper limit of normal are usually reversible with dose reduction or drug discontinuation. Hence, temporary or permanent discontinuation of leflunomide is indicated in this patient. In patients with more severe elevations (> three times), additional therapy with cholestyramine to quickly decrease the drug levels would also be indicated because leflunomide undergoes significant enterohepatic circulation. The current American College of Rheumatology treatment guidelines recommend periodic monitoring of liver chemistry tests (every 8-12 weeks) in patients being treated with leflunomide.

Etanercept is a receptor fusion protein, which blocks tumor factor necrosis α. Etanercept-induced liver disease is extremely rare and should not be considered the likely diagnosis.

The usual presentation of biliary colic is episodic, with severe abdominal pain typically in the epigastrium and/or right upper quadrant. The pain rapidly intensifies over a 15-minute interval to a steady plateau that lasts as long as 3 hours and resolves slowly. The pain is often associated with nausea or vomiting, and there is no jaundice. This patient's symptoms are not suggestive of biliary colic; therefore, cholecystectomy is not indicated.

Liver biopsy may be needed to evaluate the cause of liver disease, but it is an invasive process and is only recommended if repeat testing and discontinuation of a known offending agent do not lead to resolution, if the cause of liver disease is uncertain, or if there is evidence of chronic liver disease.