Allopurinol-Induced Granulomatous Hepatitis

Abstract

Introduction: Liver enzyme elevation is a common reason for referral to the Gastroenterologist. Drugs are one of the most common reasons for asymptomatic elevation of liver enzymes. We present here a case of granulomatous hepatitis (GH) secondary to long-term use of allopurinol.Figure: A low power showing the expanded portal tracts.Figure: a higher power showing the mixed nature of the inflammation (including lymphocytes, plasma cells, neutrophils and eosinophils).Case: An 83-year old male with a history of chronic gout and hypertension was evaluated for elevation of liver enzymes. He denies any complaints of abdominal pain, nausea, fever, chills, weight loss, night sweats or yellowness of skin. He denies any use of herbal medications. He was a heavy drinker in the past but now cut down his drinking to 2 beers a week. He was on Losartan, statins and allopurinol for years. No new medications reported. Physical examination was unremarkable. Labs showed AST 101 U/L, ALT 81 U/L, and ALP 645 U/L. Hepatitis panel, ANA and anti-smooth muscle antibody unremarkable. Ultrasound of the abdomen showed coarse liver texture concerning for parenchymal disease. Liver biopsy was done which showed mixed GH (Figure 1, 2 and 3). Given negative autoimmune and viral serologies, allopurinol-induced GH was suspected. His liver chemistries improved after stopping the allopurinol (Table 1).Figure: Well-formed epithelioid granuloma seen.Discussion: Hepatic Granulomas are associated with many systemic conditions including systemic infections, malignancy and autoimmune disorders. Many drugs have been associated with GH including allopurinol, diltiazem, amiodarone, and penicillin. The clinical manifestation of GH is variable. Fever is common in infectious causes like AIDS. Weight loss and night sweats are also common. Similar to our patient, some present with asymptomatic elevation of liver enzymes. Removal of the offending drug is the beneficial treatment. Corticosteroids are not generally recommended for drug-induced liver injury and the use is limited to severe cholestatic jaundice with no improvement after removal of drug or concomitant extrahepatic manifestation secondary to hypersensitivity to the drug. Serial follow-up of liver chemistries should be done to evaluate for improvement. Patients with signs and symptoms of hepatic failure should be referred to transplant center. Bilirubin levels > 2 times along with ALT > 3 times the upper normal limit following initiation of a drug is the indicator of a poor outcome and should be evaluated by a hepatologist. Prevention is the key and can be done by patient education, appropriate dosing and checking liver chemistries if liver dysfunction is suspected.