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• W2912334225 abstract "See Article on Page 389 Liver toxicities related to the use of herbs and dietary supplements (HDS) are a growing health concern although this rising burden is less well acknowledged than the risk posed by conventional drugs.1 In the current issue of Liver International, Wang et al2 from China present their long-term experience with the hepatotoxicity induced by He Shou Wu (Polygonum multiflorum Thunb), an ancient anti-ageing Chinese herb claimed to have benefits on a number of conditions such alopecia and greying of hair, cancer, diabetes, atherosclerosis, sleep disorders and neurodegenerative diseases. The potential of this herb to cause liver injury is well known. Indeed, Polygonum multiflorum was the major implicated Chinese herbal medicine in the largest series of drug-induced liver injury cases published to date from China, either as a single agent or as a preparation containing this compound.3 However, this and other studies did not go into details when reporting the hepatotoxicity of this herb. Thus, the study by Wang et al2 have the merit to compile consistent clinical and pathological data on 29 patients from a single centre over a 13-year period providing detailed information of the clinical presentation and outcome of liver injury induced by He Shou Wu. Hence, clinicians facing a new potential case will find this data very valuable. The majority of the patients (75%) were of female gender. The phenotype was consistently (100% of the cases) hepatocellular at presentation with markedly elevated levels of transaminases and total bilirubin. In addition, one patient was rechallenged with the product, one patient died of liver failure, and three had a chronic outcome. This characteristic presentation and outcome of Polygonum multiflorum-induced liver injury seem to be a specific signature of the hepatotoxicity caused by herbs in general when compared with those of prescription drugs as was highlighted in the retrospective analysis of DILI and Chinese herbal medicine cases from a single centre in China3 and confirmed in cases attributed to herbs that were included in the Drug-induced Liver Injury Network and the Spanish DILI Registry. Polygonum multiflorum-induced liver injury predominantly affects young women, with hepatocellular pattern of injury at presentation, no concomitant medical conditions, higher transaminase and bilirubin levels values than DILI cases induced by conventional drugs and with a greater frequency of inadvertent rechallenge.4, 5 This phenotype is of particular concern because hepatocellular jaundice heralds the development of acute liver failure, death and requirement for liver transplantation in no less than a 10% of the cases in DILI Registries, with female sex6 and Asian Race7 identified as independent risk factors that predict fulminant liver failure and death within 6 months after DILI onset respectively. Of note, the relative contribution of herbs and dietary supplements to the cases of toxic acute liver failure in the Acute Liver Failure study group experience has increased in the past decade from 12% to 20%.8 Most importantly, herbal and dietary supplement-induced acute liver failure has been shown to have a poorest prognosis than that of prescription medicines with higher transplantation rates (56% vs 32%) and only 17% spontaneous survival vs 34% of recovery in cases attributed to conventional drugs.9 Because herbal consumption is often overlooked, clinician's awareness of this specific HILI phenotype is important to enquire about consumption of herbal and dietary supplements and could help refine causality assessment methods. Indeed, the widely used RUCAM scale yielded lower scores when it was used to assess suspected herbal hepatotoxicity as compared to prescription medicines3 in part because RUCAM was developed specifically for drugs and one of the domains (information in the summary of product characteristics) does not apply to herbs.1 The diagnostic approach for HILI is actually similar to that of DILI although more potential pitfalls need to be taken into account when herbs are suspected causes of liver injury (Figure 1). The study by Wang et al2 also highlights the issue of distinguishing herbal (or drug)-induced liver injury from true autoimmune hepatitis (AIH); 26% of cases had high titres of antinuclear antibodies (ANA), and one patient required steroids to induce remission of the laboratory abnormalities. The differential diagnosis between true (idiopathic) AIH and drug-induced AIH or “AIH-like” drug-induced liver injury remains an open unresolved question. In support of “drug-induced” AIH is the absence of significant fibrosis in the liver biopsy and the lack of recurrence of transaminases flares once steroid therapy is stopped.10 Liver biopsy is in any case mandatory when AIH is a potential diagnosis and can also assist in the differential diagnosis between DILI and AIH, two liver diseases with non-specific features whose diagnosis is often one of exclusion. In an international collaboration, the histological findings of 35 adjudicated DILI cases and 28 cases of AIH were assessed in a blinded fashion for three expert pathologists; they concluded that hepatocellular cholestasis and portal neutrophils were consistent with the diagnosis of DILI while the presence of fibrosis suggested AIH.11 The hepatotoxic compound responsible for Polygonum multiflorum-induced liver injury is unclear. Constituent analysis has suggested that toxicity of this herb may be associated with tetrahydroxystilbene-O-(galloyl)-hex and emodin-O-hex-sulphate (an anthraquinone derivative).12 The issue of herb use and acceptance as alternative medicines in the West and the East strikingly differs. In Western countries, the lack of clinical trials supporting the efficacy of herbs to treat diseases has precluded its integration in clinical guidelines and evidence-based recommendations. However, taking herbs and dietary supplements is increasingly popular in modern Western societies; a cohort study survey in a multiethnic North American representative sample reported a high use of supplements in absence of chronic disease, which tended to increase with age, education and a healthier style of life.13 Indeed, in another recent survey supplement users were more likely to report very good or excellent health and the most commonly reported reasons for using supplements were to improve (45%) or maintain (33%) overall health.14 In European countries (Finland, Germany, Romania, Italy, Spain and the United Kingdom), a recent survey reported an 18.8% rate of usage of plant food supplements, with the highest figures in Italy (22.7%) and the lowest in Finland (9.6%).15 In contrast, in the East, in particular in Asian countries where traditional medicine incorporates these remedies since millennia, there is a market for herbal plants as a main source of primary healthcare delivery and traditional medicines are often integrated into their healthcare system even in countries with high socioeconomic status such as Singapore or Korea.16 The true incidence of HILI is unknown, but it is probably underestimated a main reason being the low frequency with which patients report their use. The calculation of HILI incidence using in the denominator sales figures as a surrogate for exposed subjects is even more unreliable than that of DILI because accurate estimates based on sales figures are hindered by the many places (health food stores, street markets and the Internet) where one can buy these products. Two recent population-based studies estimated the annual incidence of herbal and dietary supplement hepatotoxicity to be 1.2 and 3 cases per 100 000 inhabitants in the State of Delaware (USA) and Iceland respectively.17, 18 In Asia, where no population-based studies have been published so far the proportion of HILI cases from the whole of hepatotoxicity cases is quite high albeit substantially different across countries, with 28.4% (and an additional 27.8% considering the combination of western and chines traditional medicine) in China,3 71% in Singapore19 and 72.7% in Korea,20 probably in agreement with the generalized use of herbs as therapeutic agents in all these countries. The issue of herbal-induced liver injury is multilayered as encompasses economic and cultural considerations, in addition to botanical, toxicological, regulatory and pathophysiological aspects requiring multiple concerted actions and efforts at several levels. Nevertheless, physicians prescribing herbs otherwise potentially harmful such as Polygonum multiflorum should keep in mind that a correct benefit/risk assessment would require a proof of efficacy based in well-designed and well-conducted clinical trials. Only this might justify a price to pay (hepatotoxicity) for a healthier life. The authors do not have any disclosures to report." @default.
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• W2912334225 date "2019-01-29" @default.
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• W2912334225 title "Herbal-induced liver injury: The price to pay for a healthier life?" @default.
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