Understanding drug-induced liver injury from the perspective of traditional Chinese medicine theory—Huohou theory of traditional Chinese medicine

Drug-induced liver injury (DILI) is one of the primary forms of adverse drug reactions, potentially leading to acute liver failure or even mortality. Currently, there remains a paucity of objective and specific diagnostic methods for DILI in clinical settings, and the complexity introduced by polypharmacy and underlying chronic liver diseases complicates the identification of the causative factors. Furthermore, therapeutic options for DILI are limited. Recent research has highlighted the potential of plant-derived bioactive compounds in the prevention and treatment of DILI, despite this area being also marked by controversy due to the overreporting of herb-induced liver injury (HILI). The challenges in diagnosing, treating, and predicting the prognosis of DILI have garnered global attention. Applying huohou theory of traditional Chinese medicine (TCM) to clinical practice may offer promising solutions to these issues.

The term “huohou” originates from Taoism and is a term used in the alchemy of Taoism. It comprehensively means the control of fire, the critical moment, and extend to the degree of cultivation of skill, learning, and morality. It stresses on changing with time and potential, to achieve the precise control of “du (balanced point)”. For alchemy and the cultivation of Neidan (Taoist term), the precise control of “huohou” remains the key to success. The concept of “huohou” enriches the development of huohou theory of TCM.

Huohou theory of TCM explores the rules of disease occurrence, progress and change, thereby guides clinical differentiation and treatment, which is deeply rooted in the Chinese civilization, reflecting the profound heritage of Chinese traditional culture. The theory is based on ancient Chinese philosophy, following the development laws of TCM, and guided by TCM holistic concept and treatment based on syndrome-pattern differentiation, combining the universality and particularity of contradiction. It stresses on understanding the human body and diseases by the methodology of TCM and guiding the whole process of disease prevention, diagnosis, treatment and rehabilitation.

TCM focus on preventive medicine

Huohou theory of TCM emphasizes the comprehensive understanding of the dynamic changes of human physiology, disease and natural environment as the basis. Guided by the holistic view and treatment based on syndrome differentiation, the theory stresses on a blockage or reversion of the disease in its advancing process. It values the state of qi, blood, yin and yang in the human body, and aims to restore their physiological state through various therapeutic methods, away from the pathological state of qi and blood loss, and yin and yang in balance—qi, blood, yin and yang run freely without obstruction and all in harmony, the focus of ensuring health and disease prevention. The key point of TCM preventive medicine is not to prevent from advancing to the next stage after the onset of the disease, but to intervene “qi and blood disharmony” when it appears in the human body, to regulate qi and blood before the disease occurs. In the prevention of DILI, attention should also be paid to the patient’s qi and blood state.

Precise identification of diseases

To get the precise huohou of diagnosis, it is essential to seize the timing and depth, combine comprehensiveness and focus, balance both commonality and individuality, fully consider the condition, avoid supposition, and concern individual differences and disease features to ensure the accuracy, validity, and comprehensiveness of the diagnosis. The excessive reporting of HILI has not only brought negative impacts on the development of TCM but also hindered patients from receiving effective treatment. It is crucial to conduct a comprehensive analysis of the drug sources of DILI patients, concomitant medications, alcohol consumption, and the use of health supplements. At the same time, special attention should be paid to patients with multiple underlying conditions. Avoiding misdiagnosis is very important.

Promoting self-healing power

Self-healing power, also known as self-repair ability or natural healing ability, refers to the ability of a life body to repair and recover from an injury or disease by relying on its own physiological, biochemical and immune mechanisms. This ability is a self-protective mechanism formed during the evolution of life and is essential for maintaining the health and survival of living organisms. The human body has its own ability to resolve pathogenic factors, known as “Zhengqi” or “vital qi”, which is guided by the Xin-shen (heart spirit) and is manifested by the functional activities of the viscera based on the foundation of qi and blood, also referred to as “spiritual qi”. All therapeutic methods aim to enhance this vital qi and restore “spiritual qi” to play a role in supporting vital qi and dispelling pathogenic factors, as well as in coordinating Yin and Yang, in order to achieve the ideal state of “When Yin and Yang are balanced, the spirit is at peace”. In TCM acupuncture, the concept of Qi arrival (Deqi) is stressed. Its mechanism is to invigorate the body’s meridian qi, fully mobilize the body’s self-healing power, and utilize the body’s own self-healing ability to prevent and treat diseases, thereby avoiding excessive medical intervention.

Correctly understanding and using TCM herbs

TCM treatment adheres to the profound wisdom of syndrome differentiation and treatment. As a kind of natural essence, herbal medicine serves as a vital carrier of TCM’s therapeutic effects, embodying the rich connotations and unique charm of TCM concepts, including huohou theory of TCM. Among them, toxic TCM herbs hold a particularly special position. Some of TCM’s achievements in treating complex and intractable diseases are attributed to the use of toxic TCM herbs. However, in recent years, with the global rise of various natural therapies, the contradiction between the confirmed efficacy of herbal medicine and the occurrence of HILI has become a global hotspot and point of contention.

Mastering and understanding huohou theory of TCM is the key to the safe and effective use of Chinese herbal medicine. For example, the hepatotoxicity of Polygonum multiflorum (Heshouwu) should not be controlled merely by dosage and duration of use. The preparation of Heshouwu requires a process of nine times of steaming and sun-drying, which should be done with black soybeans for steaming and should avoid the use of iron utensils. Arsenic (As₂O₃), though toxic, plays an important role in the treatment of acute promyelocytic leukemia. To get its huohou, it is necessary to master the processing method and dosage administration.

In addition, we should fully utilize the bidirectional regulatory effect of TCM herbs. Based on the principles of holistic concept and syndrome differentiation, we can use the bias of medicinal properties to correct the imbalance of yin and yang in the human body. Through these measures, we can avoid the abuse and misuse of drugs. Dual-directional regulation shows in multiple levels:

• Single herb (or prescription) with dual-directional effect: Radix notoginseng (Sanqi) can not only disperse blood stasis and stop bleeding, but also replenish blood and invigorate blood circulation. The volatile oil and ferulic acid in Angelica sinensis (Danggui) have an inhibitory effect on uterine smooth muscle, while its non-volatile components have an excitatory effect on uterine smooth muscle. Rhubarb (Dahuang) contains both anthraquinone components that have a laxative effect and tannins that have an astringent and anti-diarrheal effect. Golden Cabinets Kidney’s Qi Pill can be used to treat frequent urination caused by diabetes or diabetes insipidus, as well as urinary retention associated with nephritis or nephrotic syndrome.
• Different dosages of a medicine (or prescription) with dual-directional effect: low dosage of brucine in Nux Vomica (Maqianzi) has excitatory effects on the central nervous system, while high dosage has sedative effects. Low dosage of Astragalus (Huangqi) can increase blood pressure, while high dosage will reduce blood pressure.
• Different processing methods yielding dual-directional effect: when Rhubarb (Dahuang) is used raw or boiled for a short time, its purgative effect is strong. Prolonged boiling can weaken the purgative effect or even lead to constipation, while stir-frying it can enhance its hemostatic properties.
• Different medicinal parts with dual-directional effect: Ephedra (Mahuang) with its herbaceous stem relieves exterior syndrome by diaphoresis, while ephedra root has the effect of exterior-strengthening and sweat-reducing.
• Dual-directional pharmacological activities vary according to the functional state of the human body. For low immunity condition, Ginseng (Renshen) can enhance the body’s immunity, promote the production of antibodies, and improve the phagocytic ability of white blood cells. While for hyperimmune condition, such as patients with autoimmune diseases, ginseng can play a role of immune regulation and reduce the excessive reaction of the immune system.

Huohou should also be mattered in herbal combination and use of herbs guiding to meridians, such as when treating headache: for occipital pain, add Notopterygium root (Qianghuo) and Fructus viticis (Manjingzi); for forehead pain, add Pueraria lobata (Gegen) and Angelica dahurica (Baizhi); for temporal pain, add Bupleurum chinense (Chaihu) and Radix Scutellariae (Huangqin); for vertex pain, add Fructus Evodiae (Wuzhuyu) and Radix ligustici sinensis (Gaoben). In clinical practice, every link embodies the wisdom of huohou, from the timing of herb collection, processing techniques, decoction skills, administration and medicine combination.

Huohou theory of TCM, with a global perspective and adapting to the needs of times, elaborates a series of medical issues on life, health, disease and healing, rooting in the Chinese philosophical quintessence of vital essence theory, yin and yang theory, and five phases theory. A deep understanding of it, with its application through all stages of disease diagnosis and treatment, is of great significance for providing new ideas and perspectives for solving difficult problems in the current medical field, giving full play to the unique advantages and characteristics of TCM, cultivating clinical talents, inheriting and innovating TCM theories, promoting the sustainable development of TCM and the mutual promotion and mutual progress of TCM and Western medicine.

Acknowledgments

Funding: None.

Footnote

Provenance and Peer Review: This article was commissioned by the editorial office, HepatoBiliary Surgery and Nutrition. The article did not undergo external peer review.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://hbsn.amegroups.com/article/view/10.21037/hbsn-2024-669/coif). The authors have no conflicts of interest to declare.

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