Management of Drug-Induced Liver Injury with Persian Medicine: Case Report

Abstract

Complications of chemotherapy including liver injury have always been an issue in the management of cancerous patients. A 5-year-old girl, known case of acute lymphocytic leukemia, presented with rise of liver enzymes diagnosed as chemotherapy drug-induced liver injury grade 1. A juice from soaked fruits (consisted of tamarind, prune, manna of Hedysarum, and brown sugar) followed by chicory distilled water with oxymel was used concomitant with chemotherapy; it resulted in a significant decrease in liver enzymes. Such natural products recommended by Persian Medicine for the management of liver injury (liver dystemperament in this viewpoint) should be further evaluated in experimental studies.

Introduction

Chemotherapy-induced liver injury is a frequent medical problem that is not adequately preventable by current treatments. ¹ In recent decades, many studies have intended to evaluate the effectiveness of medicinal herbs or traditional medical formulas as adjuvant therapy in controlling the side effects of chemotherapy.^2–5

Persian Medicine (PM), as a type of complementary and alternative medicine, is a comprehensive medical school that its history goes back to the thousands of years ago. This Hikmat (philosophy)-based medicine has originated from the humoral medicine that considers the balance between the quadruple qualities (hotness, coldness, wetness, and dryness) according to the theory of Mizaj (temperament).^6,7 Natural simple remedies that have been recommended in its remained written sources from famous physicians such as Rhazes (865–925 AD), ⁸ Avicenna (980–1037 AD), ⁹ and Aghili Shirazi (1670–1747 AD) ¹⁰ could help in controlling the diseases and complications of the treatments. ¹¹

In recent decades, following World Health Organization strategy in promoting universal health by integrating traditional medicine knowledge into current health care services, academic education of PM and specialized integrative clinics have been initiated in Iran to deliver scientific and safe services to those people who are interested in benefiting from traditional medicine. ¹² This context has led to the design of several novel researches to investigate the efficacy of some PM therapeutic recommendations in controlling chemoradiotherapy adverse effects.^11,13,14 In this study, we present a case of chemotherapy-induced liver injury referred to the PM clinic, due to increased liver enzymes.

Case Presentation

A 5-year-old girl was referred to the PM clinic of Shiraz University of Medical Sciences by the pediatric oncologist due to elevated liver enzymes after chemotherapy. She was a known case of acute lymphocytic leukemia (ALL) treated with vincristine and methotrexate for 6 months. In her follow-up, increased liver enzymes were found in laboratory tests (SGOT = 189, SGPT = 384) without any significant clinical symptoms. According to her mother, the girl's body temperature was always felt high without an obvious fever. She also had constant thirst that had made her drink cold milk in the mornings.

Stool passing was reported to be once a day with a slight solid consistency, but there were no specific abnormal changes in patient's condition. Physical examination was unremarkable; her abdomen was soft without any tenderness or organomegaly. However, sonography of the abdomen revealed the upper limit of normal liver size with mild increase in echogenicity and mildly enlarged size of both kidneys.

The asymptomatic hepatotoxicity secondary to chemotherapy had been diagnosed for the patient by the pediatric oncologist (S.Z.). It was categorized as grade 1 (mild) liver injury according to the National Institute of Health drug-induced liver injury (DILI) network. ¹

Considering the diagnosis of liver hot dystemperament from the Persian Medicine viewpoint, one glass of Nogho-e-Favakeh (soaked fruits) juice in two divided doses (morning and evening) per day was prescribed for 15 days as an adjuvant treatment to chemotherapy with liver functions test follow-up. It is prepared in this order: a combination of 150 g tamarind, 250 g prune, 100 g Persian manna, and 100 g brown sugar is soaked in seven glasses of boiled water for 12 h. ¹⁵ Then, the juice is kept in a refrigerator after filtering. This method was repeated again to provide the required amount of juice for the duration of 15 days (one glass per day).

A dramatic decrease of liver enzymes was observed after 15 days (SGOT = 44, SGPT = 109). In the next phase (second visit), drinking a cup of Araq-e-Kasni (chicory distilled water) with two spoons of Sekanjebin (oxymel) in the mornings was prescribed for 1 month according to the PM approach for the management of liver hot dystemperament. One month later, liver enzymes reached almost normal levels (SGOT = 77, SGPT = 40). The last liver functions test that was repeated 3 months later revealed totally normal results (SGOT = 49, SGPT = 29).

Discussion

For the patients with DILI, discontinuation of the causal agents and supportive care is recommended as the only effective treatments of DILI. ¹ According to PM, liver injury is divided into two main categories of either hot or cold imbalances of nature (dystemperament) that are relatively representative of acute and chronic organ malfunction, respectively. In liver hot dystemperament, patients do not necessarily present with typical signs and symptoms of acute liver inflammation; they may only have increased body temperature, thirst, and constipation. ¹⁵

One of the repetitive prescribed herbal formulas in this condition is a juice from a combination of tamarind (Tamarindus indica), prune (Prunus domestica), manna of Hedysarum (Taranjebin or Persian manna), and brown sugar (Saccharum officinarum), which is called Nogho-e-Favakeh (or quadruple syrup) in the PM literature. ¹⁵ In addition, chicory and oxymel are also recommended for liver hot dystemperament. All of these components have been known to contain antioxidant, anti-inflammatory, and hepatoprotective effects.

Although the exact mechanism of chemotherapy-induced liver injury is unknown, it seems that it is a consequence of oxidative damages. ¹ The recommended formulas in PM textbooks for managing liver hot dystemperament are simple edible sources of phytochemicals for ameliorating the hepatic toxicities. Antioxidant and hepatoprotective properties of P. domestica,^16–18 S. officinarum,^19,20 manna of Hedysarum,^21,22 and T. indica^23–25 have been shown in previous studies.

Moreover, various studies have revealed the protective effects of chicory (Chichorium intybus L.) against oxidative stress and liver injuries.^26–28 Also, Sekanjebin (oxymel) possesses beneficial effects on the hepatobiliary system. It is one of the important medicinal drinks/syrups in PM with a wide variety of formulations basically made of vinegar and honey/sugar. ²⁹ A recent animal study on thyme oxymel by Nimrouzi et al. showed improvement of oxidative stress, inflammation, and dyslipidemia. ³⁰

This is the first report of treating drug-induced hepatotoxicity using PM recommendations in a patient with ALL. It seems that Nogho-e-Favakeh (soaked fruits) and chicory distilled water with oxymel have the potential for the protection of hepatocytes during chemotherapy. However, further basic and clinical investigations are needed to confirm such an effect. Confirming the safety and efficacy of such natural products could provide a useful adjuvant treatment option for patients with DILI during chemotherapy.

Conclusion

In summary, this leukemic patient who had presented with chemotherapy-induced liver injury improved using PM prescriptions. This case report, in turn, demonstrates the importance of interdisciplinary cooperation in the realm of integrative pediatric oncology. The therapeutic effect of the proposed PM combinations in this patient expresses the possible effectiveness of these natural recipes in controlling DILI; however, future controlled trials are needed to vigorously verify this assumption.