3 Discussion
Lipid-lowering therapy is the current standard treatment for patients
with hyperlipidemia or coronary heart disease.
Currently, statins are the first-line lipid-lowering therapies for
reducing the risk of cardiovascular events in patients. Niacin and its
analogs are useful alternatives for patients who are intolerant to
statins or who experience an unsatisfactory curative effect.
Niacin, a broad-spectrum lipid-regulating agent, has been demonstrated
to exert multiple favorable effects on cholesterol metabolism, including
reductions of total cholesterol, triglyceride, very low-density
lipoprotein, low-density lipoprotein cholesterol and lipoprotein levels
and an augmentation of high-density lipoprotein cholesterol levels
(6,7).
Compared with several other commonly used lipid-altering drugs,
including gemfibrozil, fenofibrate, simvastatin and atorvastatin, niacin
is associated with lower rates of serious adverse events (defined as
events resulting in hospitalization or death) and hepatotoxicity (8,9).
Unlike niacin, acipimox has not been reported to induce liver injury in
clinical application (5).
In the traditional diagnostic approach for suspected drug-induced liver
injury (DILI), which involves clinical, biochemical, and histological
evaluations, attempts are made to establish the latency between the
start of drug therapy and the onset of injury, clinical signatures, the
exclusion of alternate etiologies and evidence of improvement of liver
injury upon drug withdrawal (dechallenge). In fact, although the
assessment of liver pathology through liver biopsy following treatment
with the suspected cause is an important component of
diagnostic criteria, this is
often unethical to perform in practice.
Several diagnostic methods are applied clinically, such as expert
opinion by experienced clinicians, RUCAM, the Maria and Victorino scale
and the Naranjo scale. The opinions of clinicians can be problematic
because of the inherently subjective nature of this approach. Meanwhile,
the Naranjo scale was designed to assess all forms of adverse drug
reactions.
In this case, RUCAM has proven most accurate for diagnosing
hepatotoxicity (10,11).
Liver biopsy was not performed because of his rapid clinical and
biochemical recovery, this procedure would have resulted in discomfort
for our patient.
Our patient was retreated with acipimox in light of acipimox- or
fluvastatin-induced liver injury was suspected, the patient’s score of 9
of 14 on the RUCAM scale established a probable diagnostic relationship
between acipimox exposure and hepatocellular injury.
Over the past several years, N-acetylcysteine has been used as a
potential therapeutic approach for DILI (12,13). It was proposed that
N-acetylcysteine could improve microcirculatory dysfunction and oxygen
delivery in peripheral tissue beds by inducing an antioxidant effect and
ameliorating the ‘cytokine storm’ (14). N-acetylcysteine was in short
supply because of the COVID-19 outbreak in China in March 2020.
Clinicians and clinical pharmacists adopted MgIg instead of
N-acetylcysteine even though it was not mentioned in guidelines (13).
Experiments revealed that MgIg was effective and safe in patients with
acute DILI, possibly by reducing oxidant stress and modulating
cyclooxygenase and 5-lipoxygenase pathways (16-18). Although
MgIg was successfully used to treat DILI, large randomized controlled
trials are needed to confirm its efficacy and safety. One limitation of
this report is that liver biopsy was not performed before diagnostic
procedures or after the administration of MgIg.
We encountered a case of hepatocellular injury induced by acipimox that
was successfully treated with MgIg. Clinical features are important for
determining the type of hepatitis, in addition to the results of
rechallenge (e.g., considerable elevation of AST and ALT levels compared
with the findings for biliary tract enzymes such as ALP and total
bilirubin, which indicate liver cell injury). Excellent therapeutic
results were obtained in our patient by discontinuing the suspected
causative agent and applying MgIg. Our patient recovered during the
follow-up period.