Analyzing Abnormal Liver Enzymes in a Patient With Renal Cell Carcinoma

Abstract

Introduction: Targeted agents have greatly improved the prognosis of patients with advanced-stage renal cell carcinoma (RCC). However, tyrosine kinase inhibitors (TKI) may induce liver injury, which may present a challenge in diagnostic evaluation. Case Description: A 75-year-old male patient with metastatic RCC presented with new-onset nausea, decreased appetite, and jaundice, in association with abnormal liver profile testing. Metastatic sites included the ribs, thoracic vertebrae, and pancreas. He started treatment with pazopanib six weeks prior, during which liver enzymes and synthetic function tests were normal. Acetaminophen use was not significant; the patient denied the use of herbal supplements. On physical examination, he was jaundiced, and the abdomen was soft, non-tender, non-distended, without ascites or hepatosplenomegaly. He exhibited no stigmata of advanced liver disease. Labs showed ALT 484 U/L, AST 277 U/L, alkaline phosphatase 562 U/L, total bilirubin 7.9 mg/dL, direct bilirubin 6.2 mg/dL, albumin 3.3 g/dL, and INR 1.02. Abdominal ultrasound did not reveal hepatobiliary abnormalities. Abdominal MRI/MRCP did not show intrahepatic or extrahepatic biliary ductal dilatation. Laboratory testing for ANA, anti-smooth muscle antibody, anti-LKM-1 antibody, anti-mitochondrial antibody, serum ceruloplasmin, ferritin/iron profile, and viral hepatitides (A, B, and C) were unrevealing. Serum IL-6 levels were elevated. After nine days, the ALT and AST improved to 183 U/L and 186 U/L, respectively, although the total bilirubin continued to gradually increase from 7.9 g/dL to 16.1 g/dL. The patient did not develop signs or symptoms of acute liver failure. Liver biopsy showed moderate inflammatory infiltrate in portal tracts, with predominance of lymphocytes, admixed with eosinophils and neutrophils, as well as cholestasis without cirrhosis. The patient was diagnosed with pazopanib-induced hepatotoxicity, and supportive care was offered. Discussion: Pazopanib is a VEGF-receptor TKI approved for use in patients with advanced RCC. In clinical trials, incidence of hepatotoxicity was as high as 53%. Patients with a diagnosis of RCC may encounter scenarios that would require clinician interpretation of abnormal liver tests, whether as a result of therapy such as pazopanib, or a paraneoplastic syndrome of cholestasis, namely Stauffer's syndrome. Careful analysis of history and exclusion of other causes of hepatitis may allow for a more confident diagnosis.Figure: Liver biopsy: Cholestatic hepatitis with portal and lobular mixed lymphocytic and neutrophilic inflammation (H&E stain, 100X).Figure: Liver biopsy: Expansion of portal tract with inflammatory infiltrate (H&E stain, 200X).Figure: Liver biopsy: Cholestasis, mild steatosis, and inflammatory infiltrate involving the lobule (H&E stain, 200X).Table: Table. Liver enzymes and hepatic function laboratory results relative to day of pazopanib administration