2 RESULTS – CASE PRESENTATION
A 40-year-old man was admitted to our hospital with complaints of nausea and lack of appetite. The patient was previously healthy, and he had no history of liver disease and no known drug allergies. He also denied alcohol use, smoking, or any illicit drug use. Regarding lipid levels, the patient’s total cholesterol and triglyceride levels were 5.7 (normal, <5.2 mmol/L) and 8.5 mmol/L (normal, <1.7 mmol/L), respectively. Computed tomography revealed fatty liver, resulting in a diagnosis of hyperlipidemia caused by abnormal triglyceride levels. The patient started treatment with fluvastatin (40 mg, quaque nocte, po). Several days later, his serum lipid levels were reexamined, but no major difference in total cholesterol and triglyceride levels was noted. Because of a lack of efficacy, the doctor switched his treatment to acipimox capsules (250 mg, three times/day, po) as replacement therapy.
Three days later, he presented with fever and progressive fatigue. The patient’s laboratory findings were as follows: aspartate aminotransferase (AST), 93 U/L (normal, 0–40 U/L); alanine transaminase (ALT), 336 U/L (normal, 0–50 U/L); alkaline phosphatase (ALP), 112 U/L (normal, 45–125U/L); and total bilirubin, 14.5 mg/dL (including a direct bilirubin level of 2.4 mg/dL). In response to the findings of elevated liver marker levels, acipimox treatment was discontinued.
Over the next 2 days, his liver enzyme levels decreased as follows: AST, 35 U/L; ALT, 96 U/L; ALP, 91 U/L and total bilirubin, 15.2 μmol/L.
Abdominal ultrasonography performed on day 9 of hospitalization revealed no abnormalities or stones in the gallbladder or common bile duct. The patient had experienced no recent changes in his medication, excluding fluvastatin.
Because the patient’s condition was stable and acipimox- or fluvastatin-induced liver injury was suspected, acipimox 100 mg/day was reintroduced on day 13. His liver enzyme levels then increased rapidly, peaking as follows: AST, 55 U/L; ALT, 240 U/L; ALP, 59 U/L and total bilirubin, 11.5 μmol/L. Repeat abdominal Doppler ultrasonography was performed, revealing no evidence of stones and patent portal, splenic, and hepatic veins. Serologic inspections for acute viral hepatitis A, B, and C; infectious mononucleosis antinuclear antibody; and anti-smooth muscle actin antibody were negative. The results for tumor markers such as alpha-fetoprotein, carcinoembryonic antigen, and cancer antigen 19-9 were also negative.
In the absence of any mechanical obstruction in the common bile duct or other obvious causes of hepatic injury, acipimox-induced hepatocellular injury was suspected.
The patient subsequently did not undergo diagnostic liver biopsy because the invasive procedure would have resulted in discomfort. Acipimox was discontinued on day 14. The patient was treated with magnesium isoglycyrrhizinate (MgIg) 0.1 g daily after the Roussel-Uclaf Causality Assessment Method (RUCAM) was implemented. Subsequently, both his ALT and AST levels were improved. Three days later, his liver biochemistry profile started to improve gradually, including the following findings: AST 27 U/L; ALT 72 U/L; and total bilirubin 13.4 μmol/L (day 17). Figure 1 presents the patient’s liver enzyme levels throughout hospitalization (days 1–17) and during follow-up. The final diagnosis was acipimox-induced hepatocellular injury. On day 18, the patient was released from hospital. The results of follow-up liver function tests conducted 1 week after discharge were normal.