Drug-induced severe liver injury due to Sterculia versicolor: a case report with causality assessment from possible to probable

Sterculia gum,the dry exudate of Sterculia versicolor and other members of the same genus,is used as a thickener and emulsifier in foods.It is generally considered safe as a food or drug,and its adverse reactions,such as Sterculia-induced liver injury,have never been reported.A 46-year-old woman was admitted to hospital with fatigue,nausea,abdominal distension,jaundice and a>16-fold increase in transaminase and bilirubin level.The patient had used Sterculia gum prior to the onset of her symptoms.Her symptoms and clinical indicators improved after treatment.The possibility of acute viral hepatitis,autoimmune hepatitis,and metabolic liver disease was excluded.After discharge from hospital,the patient had a severe liver injury again when re-exposed to Sterculia gum.And the Roussel Uclaf Causality Assessment Method score was updated from 5 to 7,which was consistent with probable drug-induced liver injury.This is the first report of Sterculia-induced liver injury.Clinicians need to be aware of the potential hepatotoxicity of Sterculia.

Drug-and Herb-Induced Liver Injury in Clinical and Translational Hepatology:Causality Assessment Methods, Quo Vadis?

Drug-induced liver injury (DILI) and herb-induced liver injury (HILI) are typical diseases of clinical and translational hepatology. Their diagnosis is complex and requires an experienced clinician to translate basic science into clinical judgment and identify a valid causality algorithm. To pro-spectively assess causality starting on the day DILI or HILI is suspected, the best approach for physicians is to use the Council for International Organizations of Medical Sciences (CIOMS) scale in its original or preferably its updated version. The CIOMS scale is validated, liver-specific, structured, and quantitative, providing final causality grades based on scores of specific items for individual patients. These items include latency period, decline in liver values after treatment cessa-tion, risk factors, co-medication, alternative diagnoses, hepatotoxicity track record of the suspected product, and unintentional re-exposure. Provided causality is established as probable or highly probable, data of the CIOMS scale with all individual items, a short clinical report, and complete raw data should be transmitted to the regulatory agencies, manufacturers, expert panels, and possibly to the scientific community for further refinement of the causality evaluation in a setting of retrospective expert opinion. Good-quality case data combined with thorough CIOMS-based assessment as a standardized approach should avert subsequent necessity for other complex causality assessment methods that may have inter-rater problems because of poor-quality data. In the future, the CIOMS scale will continue to be the preferred tool to assess causality of DILI and HILI cases and should be used consistently, both prospectively by physicians, and retrospectively for subsequent expert opinion if needed. For comparability and international harmonization, all parties assessing causality in DILI and HILI cases should attempt this standardized approach using the updated CIOMS scale.

Herb induced liver injury by Xianling Gubao Tablets: A case assessed for causality using updated RUCAM and integrated evidence chain

Objective:A typical case of Xianling Gubao(XLGB)Tablets-induced liver injury was systematically studied in the clinic and the laboratory.Methods:A patient with herb-induced liver injury(HILI)and a history of taking XLGB Tablets before disease onset was engaged as the study subject,and the case was diagnosed according to the updated Roussel Uclaf Causality Assessment Method(RUCAM)and the integrated evidence chain(iEC)method recommended by the Guidelines for Diagnosis and Treatment of Herb-induced Liver Injury(HILI Guidelines).Results:Clinical history,biochemical indexes and imaging tests were used to exclude the influence of fundamental diseases and confusing liver diseases such as viral,alcoholic and autoimmune liver diseases on the diagnosis.Based on an investigation of the patient’s medication history,she was suspected to have HILI caused by XLGB Tablets,as the patient was only taking an oral preparation of XLGB Tablets,and the influence of other drugs on the diagnosis was excluded.This patient with alanine aminotransferase(ALT)3 upper limit of normal(ULN)and a calculated R of 6 was diagnosed with possible acute drug-induced hepatocellular injury.The relationship was considered“highly probable”(score of 9)using the updated RUCAM of 2016.Moreover,the fingerprint similarity between the preparation taken by the patient and a commercially available preparation was 0.99,suggesting that the patient was consuming XLGB Tablets rather than another drug.LC-MS technology and the Agilent Fake TCM-Drugs database were used to investigate the drug,and no chemical additions were found.Examination of the drug for pesticide residues,heavy metals,aflatoxins and other exogenous substances indicated compliance with the content limits of the Chinese Pharmacopoeia.Conclusion:In summary,the final diagnosis of XLGB-induced liver injury reached the clinical diagnosis of HILI and was acute severe hepatocellular injury type by the updated RUCAM and iEC.Therefore,this study provides scientific evidence regarding the causality evaluation of compound preparations of traditional Chinese medicines-induced liver injury.

Herbal Traditional Chinese Medicine and suspected liver injury: A prospective study

AIM To analyze liver tests before and following treatment with herbal Traditional Chinese Medicine(TCM) in order to evaluate the frequency of newly detected liver injury.METHODS Patients with normal values of alanine aminotransferase(ALT) as a diagnostic marker for ruling out pre-existing liver disease were enrolled in a prospective study of a safety program carried out at the First German Hospital of TCM from 1994 to 2015. All patients received herbal products, and their ALT values were reassessed 1-3 d prior to discharge. To verify or exclude causality for suspected TCM herbs, the Roussel Uclaf Causality Assessment Method(RUCAM) was used.RESULTS This report presents for the first time liver injury data derived from a prospective, hospital-based and largescale study of 21470 patients who had no liver disease prior to treatment with herbal TCM. Among these, ALT ranged from 1 × to < 5 × upper limit normal(ULN) in 844 patients(3.93%) and suggested mild or moderate liver adaptive abnormalities. However, 26 patients(0.12%) experienced higher ALT values of ≥ 5 × ULN(300.0 ± 172.9 U/L, mean ± SD). Causality for TCM herbs was RUCAM-based probable in 8/26 patients, possible in 16/26, and excluded in 2/26 cases. Bupleuri radix and Scutellariae radix were the two TCM herbs most commonly implicated. CONCLUSION In 26(0.12%) of 21470 patients treated with herbal TCM, liver injury with ALT values of ≥ 5 × ULN was found, which normalized shortly following treatment cessation, also substantiating causality.

Ayurvedic drug induced liver injury

Drug induced liver injury is responsible for 50% of acute liver failure in developed countries. Ayurvedic and homeopathic medicine have been linked to liver injury. This case describes the first documented case of Punarnava mandur and Kanchnar guggulu causing drug induced liver injury. Drug induced liver injury may be difficult to diagnosis, but use of multi-modalities tools including the ACG algorithms, causative assessment scales, histological findings, and imaging, is recommended. Advanced imaging, such as magnetic resonance cholangiopancreatography, may possibly have a greater role than previously reported in literature.

Herbal and dietary supplement induced liver injury:Highlights from the recent literature

Herbal-induced liver injury(HILI)is an important and increasingly concerning cause of liver toxicity,and this study presents recent updates to the literature.An extensive literature review was conducted encompassing September 2019 through March 2021.Studies with clinically significant findings were analyzed and included in this review.We emphasized those studies that provided a causality assessment methodology,such as Roussel Uclaf Causality Assessment Method scores.Our review includes reports of individual herbals,including Garcinia cambogia,green tea extract,kratom as well as classes such as performance enhancing supplements,Traditional Chinese medicine,Ayurvedic medicine and herbal contamination.Newly described herbals include ashwagandha,boldo,skyfruit,and‘Thermo gun’.Several studies discussing data from national registries,including the United States Drug-Induced Liver Injury(DILI)Network,Spanish DILI Registry,and Latin American DILI Network were incorporated.There has also been a continued interest in hepatoprotection,with promising use of herbals to counter hepatotoxicity from anti-tubercular medications.We also elucidated the current legal conversation surrounding use of herbals by presenting updates from the Federal Drug Administration.The highlights of the literature over the past year indicate interest in HILI that will continue as the supplement industry in the United States grows.

AASLD practice guidance on drug,herbal,and dietary supplement-induced liver injury:also useful for hepatobiliary surgeons

Drug-induced liver injury(DILI)is a term used to describe an unexpected liver reaction to drugs,but also to herbal products and dietary supplements(HDS).In the current therapeutic armamentarium,only a small number of available drugs are still capable of causing liver damage in overdose.These include,in addition to paracetamol-the prototypical example of this group-niacin(now rarely used to treat hypercholesterolaemia),intravenous methotrexate and probably ketamine(an intravenous hypnotic used in critically ill patients for rapid sequence induction)(1).

Traditional Chinese Medicine and Herb-induced Liver Injury: Comparison with Drug-induced Liver Injury

Cases of suspected herb-induced liver injury(HILI)caused by herbal Traditional Chinese Medicines(TCMs)and of druginduced liver injury(DILI)are commonly published in the scientific literature worldwide.As opposed to the multiplicity of botanical chemicals in herbal TCM products,which are often mixtures of several herbs,conventional Western drugs contain only a single synthetic chemical.It is therefore of interest to study how HILI by TCM and DILI compare with each other,and to what extent results from each liver injury type can be transferred to the other.China is among the few countries with a large population using synthetic Western drugs as well as herbal TCM.Therefore,China is well suited to studies of liver injury comparing drugs with TCM herbs.Despite some concordance,recent analyses of liver injury cases with verified causality,using the Roussel Uclaf Causality Assessment Method,revealed major differences in HILI caused by TCMs as compared to DILI with respect to the following features:HILI cases are less frequently observed as compared to DILI,have a smaller proportion of females and less unintentional rechallenge events,and present a higher rate of hepatocellular injury features.Since many results were obtained among Chinese residents who had access to and had used Western drugs and TCM herbs,such ethnic homogeneity supports the contention that the observed differences of HILI and DILI in the assessed population are well founded.

Recent advance of fluorescent probes for detection of drug-induced liver injury markers

Drug-induced liver injury(DILI)is a common and serious adverse drug reaction.At present,DILI is perfectly diagnozed in clinical settings using Roussel Uclaf causality assessment method(RUCAM)in its original version published 1993 and its updated version published 2016,well established worldwide as a diagnostic algorithm with a high sensitivity and specificity.Nevertheless,the search for additional detection methods supporting RUCAM continues.In recent years,with the development of optical imaging technology,fluorescent probes have gradually shown great advantages in the detection and diagnosis of DILI markers such as high sensitivity,anti-interference,real-time monitoring and non-invasive measurement.In this review,the recent advances of fluorescent probes for evaluation of DILI in experimental studies were summarized according to various markers of DILI.We believe that learning about the design and practical application of these probes will contribute to the further development of detection sensors for DILI markers.

Progress in the Clinical Features and Pathogenesis of Abnormal Liver Enzymes in Coronavirus Disease 2019

With the rapid development of research on coronavirus disease 2019(COVID-19),more and more attention has been drawn to its damage to extrapulmonary organs.There are increasing lines of evidence showing that liver injury is closely related to the severity of COVID-19,which may have an adverse impact on the progression and prognosis of the patients.What is more,severe acute respiratory syndrome coronavirus-2 infection,cytokine storm,ischemia/hypoxia reperfusion injury,aggravation of the primary liver disease and drug-induced liver injury may all contribute to the hepatic damage in COVID-19 patients;although,the drug-induced liver injury,especially idiosyncratic drug-induced liver injury,requires further causality confirmation by the updated Roussel Uclaf Causality Assessment Method published in 2016.Up to now,there is no specific regimen for COVID-19,and COVID-19-related liver injury is mainly controlled by symptomatic and supportive treatment.Here,we review the clinical features of abnormal liver enzymes in COVID-19 and pathogenesis of COVID-19-related liver injury based on the current evidence,which may provide help for clinicians and researchers in exploring the pathogenesis and developing treatment strategies.