Abstract
The 3Ks (kava, kratom and khat) are herbals that can potentially induce liver injuries. On the one hand, growing controversial data have been reported about the hepatotoxicity of kratom, while, on the other hand, even though kava and khat hepatotoxicity has been investigated, the hepatotoxic effects are still not clear. Chronic recreational use of kratom has been associated with rare instances of acute liver injury. Several studies and case reports have suggested that khat is hepatotoxic, leading to deranged liver enzymes and also histopathological evidence of acute hepatocellular degeneration. Numerous reports of severe hepatotoxicity potentially induced by kava have also been highlighted, both in the USA and Europe. The aim of this review is to focus on the different patterns and the mechanisms of hepatotoxicity induced by “the 3Ks”, while trying to clarify the numerous aspects that still need to be addressed.
Highlights
Liver damage caused by herbal medicines, called herb induced liver injury (HILI), is a rare event that occurs in a small number of susceptible individuals [1,2,3]
The assessment of causality according to Teschke et al [2] should be performed using the Council for International Organizations of Medical Sciences Scale (CIOMS), known as RUCAM (Roussel Uclaf Causality Assessment Method) [4], which is specific for the liver and validated for hepatotoxicity
In all the rats of the treated group, the histological analysis revealed a severe hepatotoxicity, with a major number of Kupffer cells, hemorrhagic hepatocytes, sinusoids congestion, steatosis and centrilobular necrosis. These studies show that the sub-chronic dosages (1–10 mg/kg) of mitragynine in rats, which in humans corresponds to a dose of 0.1 to 1.7 mg/kg, seems to be quite safe when compared to those consumed by kratom users: the content of kratom juice regularly consumed in the northern regions of the Malaysia Peninsular, is equal to approximately 0.3 to 5.1 mg/kg per day and users do not show any side effects related to the chronic use of this substance, as reported by Vicknasingam et al [41,52]
Summary
Liver damage caused by herbal medicines, called herb induced liver injury (HILI), is a rare event that occurs in a small number of susceptible individuals [1,2,3]. In HILI and DILI cases, injury is related to idiosyncratic reaction that occurs at recommended doses [4]. The ad hoc approach and the World Health Organization (WHO) method are not equal to the CIOMS scale in the evaluation of HILI causality. If HILI is caused by herb intake, caution is mandatory and the compound must be avoided, even when lacking causality assessment. The most suitable criterion for HILI causality assessment has been defined by some authors [5] to be a positive re-exposure reaction, if evaluated by established test criteria.
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