Drug-Induced Liver Injury With Warzone: A War Against Drug Supplements?

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Drug induced liver injury (DILI) is an important cause of hepatic injury and is a growing challenge given the increasing number of drugs. We describe a rare case of severe liver injury after the use of Warzone and Protex. A 29-year-old man with a history of depression and GERD presented with 2 weeks of progressive jaundice, pruritus and nausea after 3 weeks of initiating a body building supplement - Warzone (Trenavar, DMZ, Carbopol, Methystem, and Halodrol). Upon becoming jaundiced, Protex (milk thistle, n-acetyl cysteine, alpha lipoic acid and selenium) was self-initiated to support hepatic function. No family history of liver disease, recent travel or sick contacts. No alcohol use, illicit drug use, body piercing or tattoos. On exam, he was afebrile, hemodynamically stable, well appearing but icteric. No hepatosplenomegaly, encephalopathy or asterixis noted. Laboratory studies showed AST 183 U/L, ALT 524 U/L, total bilirubin 8.8 mg/dL (peaking at 52 mg/dL 4 weeks later), alkaline phosphatase 73 U/L and INR of 0.94. Hemogram, renal function, tests for autoimmune hepatitis, viral hepatitis, Wilson's disease, alpha 1 antitrypsin deficiency and hemochromatosis were unremarkable. Abdominal US and CT showed unremarkable liver and bile ducts, without stones or sludge. Liver biopsy showed marked cholestasis, moderate chronic inflammation with hepatocellular dropout consistent with DILI without any massive hepatocellular necrosis, interface hepatitis, macrovesicular steatosis, lymphoid aggregate, features of cholangitis or fibrosis. He was counseled to avoid supplements. Cholestyramine and ursodiol were initiated, with prednisolone 40 mg daily added 1 month later, as he continued to show cholestatic injury with rising bilirubin. With a 4 week taper of prednisolone, LFTs improved (AST 44 U/L, ALT 27 U/L, total bilirubin 38 mg/dL, and alkaline phosphatase 178 U/L). DILI is the leading cause of drug withdrawal from the United States market. The severity of liver injury due to androgenic or anabolic steroids ranges from minor transient serum enzyme elevations to profound prolonged cholestasis. Early recognition allows for prompt discontinuation of the inciting agent and treatment allowing for a successful recovery. Merely decreasing the dose of the offending agent or switching to another formulation is not appropriate and should be discouraged. Healthcare providers should be aware of the potential for liver injury due to supplements.