Clinicopathological Features of He Shou Wu-induced Liver Injury

This Ancient Anti-aging Therapy Is Not Liver-friendly

Yan Wang; Lan Wang; Romil Saxena; Aileen Wee; Ruiyuan Yang; Qiuju Tian; Jiping Zhang; Xinyan Zhao; Jidong Jia

Disclosures

Liver International. 2019;39(2):389-400. 

In This Article

Abstract and Introduction

Abstract

Background & Aims: Polygonum Multiflorum Thumb (PMT), an ancient anti-aging Chinese herb known traditionally as He Shou Wu, has side effects of liver toxicity. To determine the main clinical and pathological characteristics of liver toxicity induced by PMT and the clinical course after its cessation.

Methods: Data of patients, diagnosed as drug-induced liver injury and hospitalised in Beijing Friendship Hospital from August 2005 to August 2017, were retrospectively reviewed. Clinical, pathological data and outcome after cessation of He Shou Wu were obtained and analysed. Kruskal-Wallis and Chi-square (χ 2) tests were performed.

Results: Twenty-nine patients with He Shou Wu-induced liver injury were enrolled. The median age was 53 years (range 15–74) and 75.9% (22/29) were women. The most common symptom was jaundice (79.3%, 23/29). Of nine patients with liver biopsies, six showed acute cholestatic hepatitis, two acute, and one chronic hepatocellular injury pattern. The latency, liver chemistries and outcomes were comparable between pure He Shou Wu (5 patients) and its compounds (24 patients). Twenty-five of 29 patients (86.2%) had normal serum alanine aminotransferase levels after 45 days (range: 10–138 days) and total bilirubin of 46 days (range: 0–551 days). One patient was rechallenged with He Shou Wu and two developed autoimmune features. One patient died of liver failure and three had chronic persistent liver injury.

Conclusions: The main clinicopathological injury pattern of He Shou Wu-induced liver injury is moderate to severe hepatitis with or without cholestasis. Most patients recover completely; however, chronic disease and death do occur.

Introduction

Herbal products have been trusted and widely used since antiquity in Northeast Asia, resulting in a high incidence of herbal-induced liver injury (HILI) in these countries. HILI accounts for up to 50% of all cases of drug induced liver injury (DILI) in mainland China[1] and 20% of cases in South Korea.[2] Herbs and nutritional supplements which may contain undeclared/unrecognised herbal constituents are now being increasingly consumed in Western countries[3] due to the widespread accessibility and availability over the internet and in local Chinatowns. As reported, the amount of money spent in consumption of herbal and dietary supplements had increased from $4 billion to $5.6 billion from 1999 to 2012 in America.[3] Not surprisingly, the incidence of herbal and dietary supplement-induced liver injury has increased notably in tandem with widespread usage in countries such as United States[4] and Spain.[5] The massive Chinese/Asian diaspora has also created a global impact for this health issue. Furthermore, the prognosis of HILI is worse than that of liver injury caused by well-characterised modern drugs because of the complex ingredients of herbal compounds, possible and undefined interactions between different components, and the longer durations of herb consumption due to widespread belief of lay persons that herbs are "natural" harmless compounds that can be taken long term without regular monitoring for adverse effects.[6] Hence, there is an urgent need for greater awareness and further research of HILI.

However, attributing liver injury to the umbrella term "herb" does not result in timely diagnosis, treatment, prevention, or exploration of the underlying mechanisms of HILI. As is available for modern drug(s) from hepatology textbooks,[7] recent publications[8,9] and the LiverTox website,[10] it is time to summarise the chief clinical and histological characteristics of herbal hepatic toxicity and its natural history for specific herbs. Such data would improve hepatologists' understanding of the characteristics of hepatotoxic effects of a given herb, which in turn would contribute to early recognition of disease, provision of optimal care, and establishment of a comprehensive database to facilitate study of the underlying mechanisms of such toxicity.

He Shou Wu is one of the most common herbs that can cause liver injury as reported. It is believed to have anti-aging properties and can enhance general health, Thus, it has been used as a tonic for various conditions, including premature greying of hair, insomnia, backache, dizziness, hyperlipidemia, coronary heart disease, diabetes, and many others.[11] This drug is fairly easily available in various herbal forms, such as Ban Tu Wan, Shou Wu Pian, Shen Min, Yangxueshengfa granules and Qibaomeiran tablets;[12] and can be procured online in western countries too, notably, as fo-ti. However, its safety is questionable due to the fact that reports of He Shou Wu-induced liver toxicities have increased worldwide in the past several years. Up until 2016, 612 patients with liver injury induced by He Shou Wu had been reported (Pubmed and www.cnki.net, both in Chinese and English literature).[11,13] Of these patients, four had cirrhosis,[13,14] five had liver failure, four had undergone liver transplantation,[15–17] and seven had died.[13,15,16,18,19] However, most of these studies were case reports or reports of small series of patients, and lacked data on causality assessment, latency, histological features, and long term follow-up after cessation of the herb. Furthermore, the dominant clinicopathological pattern of liver injury induced by He Shou Wu and the clinical course after its cessation had not been thoroughly elucidated.

In the study, we treated the herb He Shou Wu as a single medication and hypothesised that it has a dominant liver injury pattern. Our objective was to elucidate the main clinical and histological characteristics and clinical outcome of He Shou Wu-induced liver injury.

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