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.