Liver Failure Associated with Ibuprofen

Abstract

Purpose: Purpose: To report extremely rare cause of hepatic failure. Methods: 43 years old male prisoner admitted with 10 days history of fatigue and jaundice. His medical history was positive for hypertension, dyslipidemia and chronic back pain which were being treated with lisinopril, clonidine, simvastatin, ibuprofen 400 mg every 8 hr PRN. He denied any active alcohol abuse or IVDU. Physical exam was notable for icterus, ascites, hepatomegaly and pedal edema. Investigations showed ALT 89 IU/l, AST 190 IU/l, ALP 532 IU/l, Total bilirubin 5.2 mg/dl, GGT 300 U/l, albumin 1.5mg/dl, BUN 106 mg/dl, Creatinine 7.5 mg/dl with nephrotic range proteinuria and normal coagulation profile. No biliary obstruction noted on imaging studies. The patient had normal complete metabolic panel in the prison 3 months ago. Markers for hepatitides (A, B, C, EBV, CMV), ANA, Anti mitochondrial antibodies, cANCA, pANCA, HIV, AFP tumor marker were negative. Septic work up including ascitic fluid culture and TEE were negative. Liver biposy showed granulomatous hepatitis most likely due to drug induced liver injury. Renal biopsy showed minimal change disease and severe Acute Tubular Necrosis likely secondary to NSAID use. Ibuprofen was held. The patient's clinical condition and serum chemistry improved over the next 2 weeks and was discharged back to prison. Results: About 15% of adult population use short course of NSAIDS at least once a year. The frequency of liver injury with NSAIDS is 5 per 100,000 persons per year. Immunologic and metabolic idiosyncrasy are suggested mechanisms. The risk factors are concomitant use of hepatotoxic drugs, autoimmune disease, female sex, age >50 years, chronic liver disease like Hepatitis C and heavy alcohol abuse. Hepatotoxicity pattern including self limiting hepatitis, cholestasis, acute hepatic failure, hepatic granulomas, ductopenia can occur at any time after drug administration, commonly within 6-12 weeks of initiation of therapy. Abnormalities of transaminases normalise within 4-6 weeks of stopping the offending drug. Ibuprofen is one of the most commonly used NSAIDS. The incidence of liver damage is 1.6 in 100,000 users, presenting as cholestasis to mild transaminitis. Our case is the first case which illustrates hepatic failure with granulomatous hepatitis, which occurred concurrently with acute renal failure and nephrotic syndrome associated with Ibuprofen. Conclusion: Hepatotoxicity is an uncommon adverse effect of NSAIDS. Increased awareness and reporting of these events will lead to a better understanding of the risk factors and NSAIDS related hepatotoxicity. Physicians should inform their patients about hepatotoxic potential while prescribing.