NSAID-associated drug-induced liver injury prior to and following liver transplantation.

Case Report A 43-year-old male patient was admitted to the outpatient clinic for nausea, jaundice, and dark-colored urine in July 2019. He has been taking dexketoprofen/diclofenac sodium twice a week for headaches. He consumed 25 packs of cigarettes per year and 60–70 g of alcohol per week for 2 years. On his physical examination, he was icteric and had mild epigastric tenderness. At that time, his serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were 897 U/L (0–50) and 1799 U/L (0–50), respectively. His serum alkaline phosphatase (ALP) level was 141 U/L (40–130), gammaglutamyl transferase (GGT) 158 U/L (10–71), total bilirubin 7.4 mg/dL (0.1–1.2), direct bilirubin 4.3 mg/dL, and albumin 2.7 g/dL (3.5–5.2). INR was 1.32. Serological studies for viral hepatitis, autoimmune panel, and metabolic panel were all normal. We diagnosed NSAID-induced toxic hepatitis. After the drug was discontinued, his laboratory values returned to the normal range. He was discharged with normal liver tests. The patient was admitted to our clinic with jaundice 45 days after he was discharged. He was on intermittent NSAIDs. His serum AST and ALT levels were 1391 U/L and 1680 U/L, respectively. His serum ALP level was 113 U/L, GGT 104 U/L, total bilirubin 18.2 mg/dL, and direct bilirubin 14.2 mg/dL. His INR was 3.1. Medical supportive treatment was initiated. Hepatic encephalopathy was developed on the seventh day of hospitalization, and INR was 5.0. Plasmapheresis was started. His clinical status and encephalopathy worsened. Living donor liver transplantation was performed on the 16th day of admission. Explant liver pathology was revealed with submassive necrosis characterized by severe liver parenchyma loss accompanied by a marked ductular reaction and regenerative nodule (Fig. 1a, b). He was discharged from the hospital in Oct 2019. During the posttransplant follow-up period, liver test abnormality was detected. His serum AST, ALT, ALP, and GGT levels were 407 U/L, 729 U/L, 250 U/L, and GGT 280 U/L, respectively. His total bilirubin level was 2.1 mg/dL. He was on flurbiprofen 2–3 times a month for headaches. Liver biopsy was performed. Liver biopsy revealed mild portal and lobular inflammatory lesion combined with a cholestatic reaction was remarkable biopsy findings were primarily compatible with drug-induced injury (Fig. 2). Methylprednisolone was started with a dose of 1 mg/kg per day. His aminotransferase levels were decreased, but cholestatic parameters were stable. Magnetic resonance cholangiopancreatography revealed biliary stenosis on the anastomotic site. A plastic biliary stent was placed during endoscopic retrograde cholangiopancreatography. The patient is currently very well with normal liver tests. Dear Editor,