Fact-check: The link between paracetamol and liver toxicity

Fact-check: The link between paracetamol and liver toxicity

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Excess acetaminophen intake is the leading cause of drug-induced liver injury, one of the most common causes of liver failure. 

Does paracetamol, a painkiller commonly used to mitigate fever and treat mild to moderate pain, cause liver toxicity? That’s the recurring question many readers have asked over the last couple of weeks. Based on the available scientific evidence and expert opinion, here’s what First Check recommends: Prolonged use of paracetamol aka acetaminophen, even in low doses, can be injurious to the liver. The key is to avoid self-medication and consult with a qualified doctor before taking any pills, including over-the-counter (OTC) drugs. 

Pharmacies sell paracetamol/acetaminophen under different brand names such as Tylenol in North America and Panadol and Calpol in Asian, European, and African markets. Despite its household prevalence, the OTC drug’s mechanism at the molecular level is not quite clear. What scientists do know is that paracetamol works by suppressing prostaglandin (PG) activity to mitigate fever and pain. Prostaglandins are hormone-like substances that affect several bodily functions, including inflammation and pain. 

Researchers find that paracetamol is one of the most widely used substances in overdose in many parts of the world, and the leading cause of acute liver injury. The drug gets metabolised in the liver as N-acetyl-p-benzoquinone imine (NAPQI), a nitrogenous compound, which in turn gets eliminated in urine. However, in case of an overdose, the NAPQI is not excreted in urine and thereby leads to hepatotoxicity (liver damage) and could result in liver failure. The damage could occur by harming the vital connections between adjacent liver cells called tight junctions. Further, long-term usage of acetaminophen can aggravate health conditions such as high blood pressure (hypertension).

Scientists who studied the impact of paracetamol consumption on liver cells in humans and on mice liver tissue found that even at low doses paracetamol carries liver-damaging potential. Incidentally, excess acetaminophen intake is the leading cause of drug-induced liver injury (DILI), one of the most common causes of liver failure.

“Paracetamol poisoning is usually accidental, particularly in children. The toxic dose is 200mg/kg/day or more. In adults, the toxic dose is over 10gms/day. Even so, in cases of chronic pain, such as arthritic pain, it is considered to be a safe option,” says Dr Aditya Gautam, an endocrinologist and diabetologist based in Guwahati, India. 

A 2017 article in the Lancet shares similar views. In most cases of hepatotoxicity pertaining to excess consumption of paracetamol, the quantum of drug consumed is insufficient to result in liver failure or warrant treatment with antidote acetylcysteine, it notes. 

However, it’s prudent to take the medication only on doctor’s advice. Long-term paracetamol consumption could be injurious to health. 

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