Proton Pump Inhibitor-Induced Liver Injury

Abstract

Proton Pump Inhibitors (PPIs) are one of the most widely prescribed medications in the world and for a long time they were regarded as one of the safest medications. Recent studies have linked them with numerous adverse effects like dementia, interstitial nephritis, bone fractures, clostridium difficile infection, pneumonia etc. however, acute liver injury is not one of them. A 65-year-old female with no known liver disease presented with jaundice, dark urine and light stool 3 days after starting esomeprazole for heartburn which prompted her to stop the medication and seek medical attention. Outpatient laboratory studies were significant for total bilirubin of 12.4 mg/dl, AST 374 U/L, ALT 678 U/L, ALP 114 U/L and INR of 2. The patient was promptly sent to emergency department by her primary physician for further evaluation. Her mental status remained intact. Inpatient studies showed consistent elevation of liver test as well as positive ANA (antinuclear antibody) of 1:320 and AMA (antimitochondrial antibody) of 1:20. Due to concern for drug induced liver injury and possible autoimmune liver disease given positive autoimmune markers, liver biopsy was performed which showed acute cholestatic hepatitis compatible with drug induced liver injury (DILI). The patient's serum aminotransferase levels improved to AST 113 U/L, ALT 278 U/L respectively and total bilirubin of 10 upon discharge. At outpatient visit 6 week later, her labs were back to normal. DILI is one of the most common causes of acute hepatitis in the United States. Majority of the studies have not documented association of PPIs with liver injury. However, a few cases of PPI induced liver injury with minor elevation of liver enzymes which normalized after discontinuation of PPI have been documented. Omeprazole and pantoprazole are the main culprits among the PPIs but there are a few cases associated with esomeprazole as well. To our knowledge this is the first case of biopsy proven acute liver injury caused by esomeprazole. DILI may cause serious liver failure which warrants early diagnosis and treatment including referral to liver transplantation. Our case provides a convincing evidence that esomeprazole linked to acute liver injury. Once thought the safest and the most prescribed group of medications, is it time to add one more adverse effect on their extensive list of adverse effects?2422_A Figure 1. The normal architecture of the liver is preserved without scarring. There is marked portal and lobular inflammatory infiltrates and mild steatosis.2422_B Figure 2. Portal tracts contain a mild mixed inflammatory infiltrate including eosinophils (thin arrow). Lobular hepatitis is evidenced by collections of pigment laden macrophages (angled arrow), focal mixed inflammatory infiltrates and scattered acidophil bodies (thick arrow)2422_C Figure 3. Cholestatic features are evidenced by prominent bilirubinostasis in zone 3 hepatocytes (thin arrow), focal canalicular bile plugs (thick arrow), and bile pigment in macrophages (angled arrow).