Traditional Chinese Medicine (TCM) and Herbal Hepatotoxicity: RUCAM and the Role of Novel Diagnostic Biomarkers Such as MicroRNAs

Abstract

Background: Traditional Chinese Medicine (TCM) with its focus on herbal use is popular and appreciated worldwide with increased tendency, although its therapeutic efficacy is poorly established for most herbal TCM products. Treatment was perceived as fairly safe but discussions emerged more recently as to whether herb induced liver injury (HILI) from herbal TCM is a major issue; Methods: To analyze clinical and case characteristics of HILI caused by herbal TCM, we undertook a selective literature search in the PubMed database with the search items Traditional Chinese Medicine, TCM, alone and combined with the terms herbal hepatotoxicity or herb induced liver injury; Results: HILI caused by herbal TCM is rare and similarly to drugs can be caused by an unpredictable idiosyncratic or a predictable intrinsic reaction. Clinical features of liver injury from herbal TCM products are variable, and specific diagnostic biomarkers such as microsomal epoxide hydrolase, pyrrole-protein adducts, metabolomics, and microRNAs are available for only a few TCM herbs. The diagnosis is ascertained if alternative causes are validly excluded and causality levels of probable or highly probable are achieved applying the liver specific RUCAM (Roussel Uclaf Causality Assessment Method) as the most commonly used diagnostic tool worldwide. Case evaluation may be confounded by inappropriate or lacking causality assessment, poor herbal product quality, insufficiently documented cases, and failing to exclude alternative causes such as infections by hepatotropic viruses including hepatitis E virus infections; Conclusion: Suspected cases of liver injury from herbal TCM represent major challenges that deserve special clinical and regulatory attention to improve the quality of case evaluations and ascertain patients’ safety and benefit.

Drug induced liver injury with analysis of alternative causes as confounding variables

“…The list of differential diagnoses, which should be excluded or verified, is a kind reminder for the physician caring for the patient (Figure ). Several listed diagnostic parameters are also key items of RUCAM , which is also used in suspected herb‐induced liver injury by herbal medicines, traditional Chinese medicine and dietary supplements . However, RUCAM cannot compensate for incorrect case data transfer by physicians from clinical charts to the RUCAM scale, conditions which must be avoided .…”

“…Transparent documentation of complete case data is mandatory for publication, at least as supplementary files if space is restricted. However, among the published reports on liver injury cases, many journals allow long tables of case narratives and RUCAM based details of scored key items . For instance, a recent report presented among other tables specifically two tables for all 26 patients, one for case narratives and the other one for RUCAM based details .…”

Drug Induced Liver Injury: Can Biomarkers Assist RUCAM in Causality Assessment?

“…Other diagnostic biomarkers such as serum pyrrole-protein adducts are available for HILI due to the herbal TCM San Chi ( Gynura segetum ), which contains unsaturated PAs causing hepatic sinusoidal obstruction syndrome (HSOS) [34,35,40]. …”

Hepatotoxizität in der chinesischen Arzneitherapie – Fiktion und Fakten

“…Ein Beispiel für untaugliche Fallberichte ist eine Fallserie aus Honkong [16], die gleichwohl in einigen Publikationen als alleiniger Beleg für die Hepatotoxizität von gleich 7 Arzneidrogen angeführt wird [11], [17], [18]. Es handelt sich bei der Publikation um 7 Fälle von Patienten mit einer chronischen Hepatitis B, drei davon mit Leberzirrhose, einer an sich schon problematischen Population.…”