Late-Onset Rosiglitazone-Associated Acute Liver Failure in a Patient with Hodgkin's Lymphoma

Objective: To report a case of rosiglilazone-associated hepatotoxicity in a patient with Hodgkin's lymphoma. Case Summary: A 52-year-old man presented with low-grade fever and fatigue that had been present for 4 months. He had been receiving insulin for 5 years and rosiglitazone 4 mg/day for 11 months for control of type 2 diabetes; he was receiving no other drug therapy. During hospitalization, hepatotoxicity was shown, with abnormal liver function test results including alanine aminotransferase 488 U/L, aspartate aminotransferase 344 U/L, alkaline phosphatase B32 U/L, total bilirubin 4.61 mg/dL, and direct bilirubin 3.63 mg/dL. Rosiglitazone was discontinued after further elevation of bilirubin (total 14.67 mg/dL, direct 12.10 mg/dL) occurred. Other causes for hepatotoxicity were ruled out, Hodgkin's lymphoma was diagnosed during the workup; however, liver imaging and biopsy also excluded this as the direct cause of acute liver failure. Despite discontinuation of rosiglitazone, the bilirubin level continued to increase to 49.29 mg/dL (direct >20 mg/dL). The patient died 3 months after admission. Discussion: Rosiglitazone maleate is a thiazolidinedione approved for treatment of type 2 diabetes mellitus. The first member of this drug class, troglitazone, was withdrawn from the market due to reports of acute liver failure. Rosiglitazone has been shown to be much safer than troglitazone, despite some reported cases of early-onset nonfatal hepatotoxicity. Use of the Naranjo probability scale indicated that rosiglitazone was the probable cause of acute liver failure in our patient. Conclusions: We conclude that rosiglitazone may be associated with late-onset acute liver failure. Clinicians should be aware of such a complication and monitor liver function in patients receiving the drug.