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.