NAFLD may be a risk
factor for DILI; drugs can cause NAFLD
Nonalcoholic
fatty liver disease (NAFLD) is one of the most common causes of chronic liver
disease globally. It is characterized by the presence of hepatic steatosis
(fatty liver), when no other causes for secondary hepatic fat accumulation
(heavy alcohol consumption) are present. Left untreated, it may progress to
cirrhosis and is likely an important cause of cryptogenic cirrhosis.
The
prevalence of this condition is higher among obese and diabetic patients.
Recently
NAFLD has also been recognized as risk factor for drug-induced liver injury
(DILI).
A
study published in the November 2018 issue of the journal Alimentary
Pharmacology and Therapeutics has shown a reciprocal association between
NAFLD and DILI, which means that drugs can cause NAFLD by acting as steatogenic
factors, and pre‐existing NAFLD could be a predisposing condition for certain drugs to cause
DILI - intrinsic DILI (induced by acetaminophen, methotrexate and volatile
anesthetics) more than idiosyncratic DILI.
Although
the cause for this increased susceptibility is likely to be multifactorial,
usually it is due to the triggering by the drug of similar steatogenic,
inflammatory and/or fibrotic pathomechanisms that characterize NAFLD or changes
in drug detoxification systems.
“Drugs
can induce macrovesicular steatosis by mimicking NAFLD pathogenic factors,
including insulin resistance and imbalance between fat gain and loss. Other
forms of hepatic fat accumulation exist, such as microvesicular steatosis and
phospholipidosis, and are mostly associated with acute mitochondrial
dysfunction and defective lipophagy, respectively. Drug‐induced
mitochondrial dysfunction is also commonly involved in drug-induced
steatohepatitis.”
The
prevalence of NALFD is higher in obese patients. Polypharmacy is common in this
patient group as they take multiple drugs to manage their weight or coexisting
chronic conditions. Hence, they are more vulnerable to hepatotoxicity, whether
or not they have an intrinsic higher susceptibility to DILI due to their liver
disease.
The
study cautions clinicians to restrict the number of prescribed medications in
these patients, whenever possible and initiate pharmacotherapy in a stepwise
manner. They should be closely monitored. Also, patients should be advised
against OTC self-medication.
(Source:
Bessone F, Dirchwolf M, Rodil MA, et al. Review article: drug-induced liver
injury in the context of nonalcoholic fatty liver disease - a
physiopathological and clinical integrated view. Aliment Pharmacol Ther. 2018
Nov;48(9):892-913).
Dr KK Aggarwal
Padma Shri
Awardee
President Elect Confederation of Medical
Associations in Asia and Oceania
(CMAAO)
Group
Editor-in-Chief IJCP Publications
President
Heart Care Foundation of India
Immediate Past National President IMA
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