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(A) Liver: canalicular cholestasis surrounding the central veins with associated bile duct injury. (B) Liver: zone 3 cholestasis and bile duct injury with patchy hepatocyte necrosis. Hematoxylin and eosin stain. (C) Sigmoid colon: surface epithelium with reactive changes, eosinophilic cytoplasm, and disorganized epithelial cell placement. Rare neutrophils are seen with the underlying lamina propria devoid of the normal glandular elements. (D) Sigmoid colon: ulcerated mucosa replaced with granulation tissue (hematoxylin and eosin stain).
Source publication
Consumption of herbal supplements has been linked to multiorgan toxicities. Kratom is an herbal extract that has gained popularity for its analgesic and psychotropic properties. Several cases of kratom-induced liver injury have been reported, but data on multiorgan involvement remain scarce. We present the case of a 37-year-old woman who developed...
Contexts in source publication
Context 1
... screening was negative for metals, cannabinoids, opioids, amphetamines, and benzodiazepines. She underwent a transjugular liver biopsy; histology revealed centrizonal cholestasis and bile duct loss, most consistent with drug-induced liver injury (Figure 1). Her cholestasis was treated with ursodiol. ...
Context 2
... from the sigmoid colon revealed ulceration with granulation tissue. Immunohistochemical staining was negative for Epstein-Barr virus, cytomegalovirus, and adenovirus (Figure 1). Her corticosteroids were tapered in the absence of meaningful improvement in diarrhea. ...
Context 3
... screening was negative for metals, cannabinoids, opioids, amphetamines, and benzodiazepines. She underwent a transjugular liver biopsy; histology revealed centrizonal cholestasis and bile duct loss, most consistent with drug-induced liver injury (Figure 1). Her cholestasis was treated with ursodiol. ...
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Citations
... There could be several reasons for the increased risk of MODS in critically ill children who take traditional herbal medicines. Firstly, herbal medicines may interact with other medications or treatments that the child is receiving, leading to adverse reactions and potentially increasing the risk of MODS [37,39]. Secondly, children who take herbal medicines may have underlying health conditions that are not adequately treated with conventional medicine, which increases their risk of developing MODS [34,[40][41][42]. ...
Background
Traditional herbal medicine (THM) is frequently used in pediatric populations in many low-income countries as a form of healthcare and has been associated with a range of adverse events, including liver toxicity, renal failure, and allergic reactions. Despite these concerns, its impact on multi-organ dysfunction syndrome (MODS) risk has not been thoroughly investigated.
Objective
This study aimed to investigate the incidence and predictors of MODS in a pediatric intensive care unit (PICU) in Ethiopia, with a focus on the association between THM use and the risk of MODS.
Methods
This was a single-center prospective cohort study conducted at a PICU in the university of Gondar Comprehensive Specialized hospital, Northwest Ethiopia. The study enrolled eligible patients aged one month to 18 years admitted to the PICU during the study period. Data on demographic characteristics, medical history, clinical and laboratory data, and outcome measures using standard case record forms, physical examination, and patient document reviews. The predictors of MODS were assessed using Cox proportional hazards models, with a focus on the association between traditional herbal medicine use and the risk of MODS.
Results
A total of 310 patients were included in the final analysis, with a median age of 48 months and a male-to-female ratio of 1.5:1. The proportion and incidence of MODS were 30.96% (95% CI:25.8, 36.6) and 7.71(95% CI: 6.10, 9.40) per 100-person-day observation respectively. Renal failure (17.74%), neurologic failure (15.16%), and heart failure (14.52%) were the leading organ failures identified. Nearly one-third of patients (32.9%) died in the PICU, of which 59.8% had MODS. The rate of mortality was higher in patients with MODS than in those without. The Cox proportional hazards model identified renal disease (AHR = 6.32 (95%CI: 3.17,12.61)), intake of traditional herbal medication (AHR = 2.45, 95% CI:1.29,4.65), modified Pediatric Index of Mortality 2 (mPIM 2) score (AHR = 1.54 (95% CI: 1.38,1.71), and critical illness diagnoses (AHR = 2.68 (95% CI: 1.77,4.07)) as predictors of MODS.
Conclusion
The incidence of MODS was high. Renal disease, THM use, mPIM 2 scores, and critical illness diagnoses were independent predictors of MODS. A more than twofold increase in the risk of MODS was seen in patients who used TMH. Healthcare providers should be aware of risks associated with THM, and educate caregivers about the potential harms of these products. Future studies with larger sample sizes and more comprehensive outcome measures are needed.
... Kratom, or Mitragyna speciosa, has been increasingly described as a cause of HILI and acts on serotonin and opioid receptors [44]. It is derived from the leaves of a native tree found in Southeast Asia and is composed of alkaloids [45]. ...
... The two major ingredients are mitragynine and 7-hydroxymytragynine. It is found to be primarily metabolized in the liver and can be tested via a mitragynine urine test [44,45]. Hepatic injury has been reported to have an average latency period of 21 days but has a wide range of onset from the time of ingestion [44]. ...
... It is found to be primarily metabolized in the liver and can be tested via a mitragynine urine test [44,45]. Hepatic injury has been reported to have an average latency period of 21 days but has a wide range of onset from the time of ingestion [44]. Kratom is also commonly used for pain management, improving fatigue, and utilized for mood disorders while inducing euphoria. ...
Herbal-induced liver injury (HILI) continues to increase in prevalence each year due to the ongoing popularity of herbal supplements and complementary and alternative medicines. A detailed literature review of case reports and clinical studies published from March 2021 to March 2023 was performed. We discuss the epidemiology and diagnosis of HILI as well as the current and proposed laws and regulations. The 2021 ACG guidelines and 2022 AASLD practice guidelines for the diagnosis and management of drug and herbal-induced liver injury are discussed. We describe updates to previously reported etiologies of HILI such as ayurveda, ashwagandha, turmeric, kratom, green tea extract, and garcinia cambogia. Newly described supplements resulting in HILI, such as tinospora cordifolia, horse chestnut, alkaline water, and more, are described. We discuss newly and previously identified hepatoprotective herbal supplements as they have been reported in the study of animal models and human liver cells. This review suggests the need for ongoing research on the causes and mechanisms of HILI to ensure its proper diagnosis, prevention, and treatment in the future. The goal of this review is to provide novice and expert readers with knowledge regarding the possible etiologies of HILI and a general overview.
... Based on the title of the case report or case series, kratom use was directly implicated as being responsible for the morbidities observed in 28 studies (through language such as "Kratom Induced Hepatotoxicity" [24]; "Recurrent Seizures from Chronic Kratom Use" [25]; or "A Popular Supplement Leads to Acute Liver Injury" [26]). Kratom use was described as being associated with or related to the morbidities observed in the titles of 9 studies (e.g., "Kratom-Associated Ventricular Fibrillation" [27]; or "Multiorgan Dysfunction Related to Kratom Ingestion" [28]). In the remaining 15 studies, the title described the morbidity as occurring after kratom use or in a person who used kratom (e.g., "Seizure and Coma Following Kratom" [29]; "Posterior Reversible Leukoencephalopathy Syndrome after Kratom Ingestion" [30]; or "Intrahepatic Cholestasis Following Abuse of Powdered Kratom (Mitragyna speciosa)" [31]). ...
Purpose of review
In this systematic review, we examined case reports of patients who use kratom and evaluated their rigor based on reporting of clinically relevant information.
Recent findings
Millions of people use kratom in the USA each year. Despite its prevalence, there is little peer-reviewed clinical literature available on kratom, and clinicians must predominantly rely on case reports for guidance in the assessment, diagnosis, and treatment of patients who use kratom.
Summary
We found considerable variation in reported information and in the thoroughness of the case reports. Reports tended to be inadequate in full assessment of the patient’s kratom use. As kratom use continues to increase in the USA, consistent and detailed reporting, usage of biospecimen testing and kratom product assays, consultation of experts to aid with patient workup, usage of causality assessment tools, and acknowledgement of limitations will improve the quality of case reports.
... Only 2 case reports of fulminant hepatic failure requiring liver transplantation have been documented due to kratom ingestion. 23,24 Recently, Thailand decriminalized the possession and sale of kratom, which led many people to explore this as new income avenue in time of high unemployment rate due to Covid-19. This situation is reminiscent of liberal cannabis policies in the United States which increased the prevalence of cannabis-related disorders. ...
Introduction:
Mitragyna speciosa (commonly known as kratom) has both opioid and stimulant-like effects. Recently, Thailand decriminalized the possession and sale of kratom which led people in many areas to seek income from the sale of kratom at a time of widespread unemployment due to COVID-19. Here, we report a patient with post-COVID syndrome who developed a mixed cholestatic-hepatocellular liver injury secondary to kratom.
Case presentation:
A 23-year-old Thai man was seen for an evaluation of fatigue and nausea which was soon followed by pruritus, dark urine and jaundice. The patient had no known underlying disease but had been treated with mild COVID-19 pneumonia in the past 2 months. He reported taking kratom recreationally for 2 weeks as a treatment for his post-COVID insomnia. Kratom was purchased from a friend and used in a homemade iced cocktail called "4 × 100" consisting of Coca-Cola, tea made from boiled kratom leaves, and diphenhydramine-containing cough syrup which has been popular in Southernmost provinces of Thailand. His lab workup showed his total bilirubin to be 10.6 mg/dL, aspartate aminotransferase was 642 U/L, and alanine aminotransferase was 1635 U/L. Extensive workups including viral etiologies was negative. Abdominal ultrasound revealed normal liver and no cirrhosis. The case was managed conservatively for 5 days in the hospital by giving intravenous fluid and stopping all medications. Urine toxicology screening confirmed the presence of mitragynine and diphenhydramine. He was in a stable condition with normalized liver function tests at 3 months after discharge.
Conclusion:
The COVID-19 pandemic has posed unprecedented challenges to health consequences and this case highlights the importance of kratom as potential cause of acute liver injury. Future studies should accumulate further case series and identify kratom-user subgroups or the polydrug patterns of kratom use that are at heightened risk of severe liver injury.
Purpose of review:
This work aims to provide an up-to-date review of the preclinical and clinical scientific literature on the therapeutic value of kratom to better understand the underlying mechanisms related to its use and inform future therapeutic applications.
Recent findings:
A growing number of studies, mainly of cross-sectional nature, describe the widespread use of kratom by individuals to self-treat pain, psychiatric symptoms, and substance use disorders (SUD) outside a controlled clinical setting. Preclinical evidence suggests kratom is effective as an analgesic agent and might decrease the self-administration of other drugs. A randomized controlled trial has further supported kratom's therapeutic value as an analgesic. Investigations in nonclinical samples of long-term kratom users also indicate its therapeutic benefit in managing SUD symptoms (e.g., craving) and long-term or acute symptoms (e.g., withdrawal) for alcohol, opioids, and other illicit drugs. However, episodes of kratom-related intoxications have also been reported, often due to the adulteration and the contamination of kratom products mainly sold online or mixed toxicities when consumed outside clinical and traditional settings.
Summary:
Evidence on the clinical implications of kratom use is still limited and uncertain, with kratom research constantly evolving. Therefore, further randomized trials are needed.
Kratom, also known as herbal speed, is the powdered leaves of the Asian kratom tree (Mitragyna speciosa Korth.). The consumption of kratom powder or kratom tea for diarrhea, inflammation, fever, and pain, but also for anxiety and depression is based on traditional experiences from East Asian herbal medicine.
Pharmacologically, kratom is an intoxicant or narcotic. In low doses, the leaves have a stimulating effect, in high doses, they are depressant and psychoactive like opioids. There is a steadily increasing popularity of the herbal drug kratom and its psychoactive compounds mitragynine and 7-hydroxymitragynine around the world. To date, no randomized controlled human intervention study has evaluated the safety and efficacy of kratom ingestion. In addition, there are increasing reports of kratom-associated adverse effects including herb-induced liver toxicity and nephrotoxicity, cardiovascular and neurological symptoms, and withdrawal syndrome.
The still unsatisfactory lack of regulatory control and easy availability via internet providers will continue to increase kratom use in many countries. Clinicians should be aware that kratom use can be addictive and have potentially serious side effects. It is important to determine the consumption of dietary and herbal supplements when taking the patient's medical history.
Kratom (Mitragyna speciosa) consists of over 40 alkaloids with two of them, mitragynine (MG) and 7‐OH‐mitragynine (7‐OH‐MG) being the main psychoactive compounds. MG and 7‐OH‐MG each target opioid receptors and have been referred to as atypical opioids. They exert their pharmacologic effects on the μ, δ, and κ opioid receptors. In addition, they affect adrenergic, serotonergic, and dopaminergic pathways. Kratom has been touted as an inexpensive, legal alternative to standard opioid replacement therapy such as methadone and buprenorphine. Other uses for kratom include chronic pain, attaining a “legal high,” and numerous CNS disorders including anxiety depression and post‐traumatic stress disorder (PTSD). Kratom induces analgesia and mild euphoria with a lower risk of respiratory depression or adverse central nervous system effects compared to traditional opioid medications. Nonetheless, kratom has been associated with both physical and psychological dependence with some individuals experiencing classic opioid withdrawal symptoms upon abrupt cessation. Kratom use has been linked to serious adverse effects including liver toxicity, seizures, and death. These risks are often compounded by poly‐substance abuse. Further, kratom may potentiate the toxicity of coadministered medications through modulation of cytochrome P450, P‐glycoprotein, and uridine diphosphate glucuronosyltransferase enzymes (UGDT). In 2016 the U.S. Drug Enforcement Administration (DEA) took steps to classify kratom as a federal schedule 1 medication; however, due to public resistance, this plan was set aside. Until studies are conducted that define kratom's role in treating opioid withdrawal and/or other CNS conditions, kratom will likely remain available as a dietary supplement for the foreseeable future. This article is protected by copyright. All rights reserved
