LONDON – Herbal medicines and other home remedies or supplements are a significant cause of hepatotoxicity experts warned recently during a symposium at the International Liver Congress, which unintentionally coincided with World Homeopathy Awareness Week.
Although they are not at the very top of the list when it comes to drug-induced liver injury (DILI) – that accolade being reserved for antimicrobial agents used to treat tuberculosis – the use of homeopathy-based approaches are potentially on the increase in the western world and the use of such substances are often not reported to physicians.
Dr. Dominique Larrey
"Herbal medicines represent a significant cause of liver injury," Dr. Dominique Larrey (Central University Hospital, Montpellier, France), said at the meeting that was sponsored by the European Association for the Study of the Liver. "Herbs can cause almost the whole spectrum of hepatic and biliary lesions, acute hepatitis being the most frequent one," he added.
The rise of herbal medicine
Dr. Larrey, who works in the liver and transplantation department of Saint Eloi Hospital, also in Montpellier, noted that the use of herbs in traditional medicine was very important in many parts of the world, notably in Asia, Africa, and Central and South America. They are used for both traditional and cultural reasons, he added, are often easy to access and are low cost in comparison to regulated medicines.
Their use is probably on the increase in western countries for a variety of reasons, Dr. Larrey suggested, such as the migration of people from cultures in which the use of traditional medicines is high, to the thinking that "what is natural can only be good" and "herbal medicines are considered completely innocuous in contrast to classical drugs." Furthermore, the lack of satisfactory treatments for some severe diseases – cancer, multiple sclerosis, AIDS, and hepatitis C virus infection to name a few – mean that people often are willing to try out complementary or alternative medicines (CAM).
In the United States, the total sale of herbal remedies in 2010 was an estimated $5.2 billion per year, having increased around 3% a year over the past decade, Dr. Larrey pointed out.
The problem is that patients do not often tell their doctors about their use of CAM. A staggering 90% of patients taking the anticoagulant drug warfarin – which is renowned for having a very narrow therapeutic window and careful monitoring is required – were taking herbal medicines in one study, he said.
Prospective studies on the use of herbal medicines in western countries are scarce but those that have been conducted specifically in patients with liver disease suggest that as many as one-fifth (Hepatology 2008;47:605-12) to one-third (Gastroenterology 2001;120[Suppl 1]:A228) might be taking herbal remedies unbeknownst to their doctor.
The problem of assessment
There are limited data on how frequently herbal medicines cause liver damage, but estimates range from 2% to 16%, Dr. Larrey observed, adding that reported cases could be just the tip of the iceberg.
"Herbal medicine hepatoxicity is clearly underestimated for many reasons," he suggested. First, their intake is hard to analyze. Second, the mechanism of liver damage is often uncertain, and third, it is hard to confirm causality. Indeed, herbal medicines do not have to undergo the rigorous testing or regulation in the same way that prescribed medicines do, and sales via the Internet make them easily available to all.
There is then the uncertainty of what is really in the preparations, if they contain the right plant at all or the wrong part of it, and then whether or not they have been stored correctly, or if they have been contaminated with other liver-damaging agents or microorganisms.
Advice for physicians
DILI from prescription and nonprescription medicines is an important but rare event in the westernized world, Dr. Robert Fontana of the University of Michigan in Ann Arbor said in an interview. However, because it can bring about very bad and unpredictable liver injury, it is of great importance for hepatologists and general family physicians alike.
Dr. Robert Fontana
"In the United States and I think worldwide, the frequency in use of [herbal treatments] is increasing and as we start to see registry data I think we will start to see more and more cases [of hepatoxicity]," Dr. Fontana said.
Dr. Fontana is part of the National Institutes of Health–funded Drug-Induced Liver Injury Network (DILIN), a multicenter, prospective registry looking at the etiologies, risk factors, and outcomes of DILI in the United States (Drug Saf. 2009;32:55-68). Data from the registry show the prevalence of herbal and dietary supplements is around 9% (n = 300) in confirmed DILI cases.