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.

[Interpretation on Consensus on drug-induced liver injury by CIOMS Working Group:liver injury attributed to herbal and dietary supplements].

With the increase in the medical level, the improvement of adverse drug reaction(ADR) monitoring systems, and the enhancement of public awareness of safe medication, drug safety incidents have been frequently reported. Drug-induced liver injury(DILI), especially liver injury attributed to herbal and dietary supplements(HDS), has globally attracted high attention, bringing great threats and severe challenges to the people for drug safety management such as clinical medication and medical supervision. Consensus on drug-induced liver injury had been published by the Council for International Organizations of Medical Sciences(CIOMS) in 2020. In this consensus, liver injury attributed to HDS was included in a special chapter for the first time. The hot topics, including the definition of HDS-induced liver injury, epidemiological history, potential risk factors, collection of related risk signals, causality assessment, risk prevention, control and management were discussed from a global perspective. Based on the previous works, some experts from China were invited by CIOMS to undertake the compilation of this chapter. Meanwhile, a new causality assessment in DILI based on the integrated evidence chain(iEC) method was widely recognized by experts in China and abroad, and was recommended by this consensus. This paper briefly introduced the main contents, background, and characteristics of the Consensus on drug-induced liver injury. Significantly, a brief interpretation was illustrated to analyze the special highlights of Chapter 8, "Liver injury attributed to HDS", so as to provide practical references for the medical staff and the researchers who worked on either Chinese or Western medicine in China.

[Re-evaluation of liver injury associated with Buguzhi Preparations based on passive monitoring data and hospital cases].

In this paper,the case reports on rug-induced liver injury( ADR cases) related to Gukang Capsules containing Psoralea corylifolia( Buguzhi,BGZ) were collected from the adverse reaction monitoring database from January 1,2012 to December 31,2016,and the in-patients cases with drug-induced liver injury admitted to a tertiary Class A liver disease hospital from January 1,2010 to December 31,2016 were also collected. These collected cases were re-evaluated and analyzed. 110 cases with liver injury related to this preparation were collected from adverse reaction monitoring database,and 55 cases of them received the preparation alone,mainly for fracture treatment( 52. 74%). Ninty one cases( 82. 72%) met the standard of the biochemical diagnostic criteria for drug-induced liver injury. 89. 01% of patients were over the age of 41 and women accounted for 60. 9%. The time from administration to liver injury was 1-208 days,with the median of 29 d. The dose of the preparation was 2. 4-4. 8 g per day,with a cumulative dose ranging from 3. 6-699. 6 g. The recovery and improvement rate reached 96. 70% after positive treatment. Seven inpatient cases related to the preparation were collected in a tertiary Class A liver disease hospital,6 females and 1 male. All of them were over 40 years old. Two cases reached the " suspicious diagnosis" standard and 5 cases reached the " clinical diagnosis" standard in Guidelines for the diagnosis and treatment of herb-induced liver injury. Six patients had a good prognosis effect,but another one had liver failure. This preparation is commonly used in fracture,osteoarthritis and other diseases,with remarkable curative effect. However,ADR cases and hospital cases all indicated the risk of liver injury. There was no significant correlation between the time and dose of drug use and the occurrence of liver injury.The induced-liver injury may have immunological heterogeneity,thus regular monitoring of liver function should be taken during clinical use.

[Dictamni Cortex powder-induced liver injury based on integrated evidence chain].

A typical clinical case of taking Dictamni Cortex(Baixianpi) powder was analyzed to study liver damage caused by Dictamni Cortex. Liver damage was diagnosed according to the integrated evidence chain method recommended by the Guideline for Diagnosis and Treatment of Herb-Induced Liver Injury. By analyzing clinical history and biochemistry and imaging examinations, underlying diseases, such as viral hepatitis, autoimmune liver disease and alcoholic liver disease, were excluded. Through the investigation of medication history, we made it clear that the patient only took Dictamni Cortex powder during the period, and thus suspected that the liver injury was induced by Dictamni Cortex. Furthermore, the quality of the drug was tested, and the results showed it was consistent with the quality standard of Chinese Pharmacopoeia. DNA barcoding showed that the drug was 100% similar with Dictamnus dasycarpus. Moreover, exogenous harmful substances and chemical drug additions were tested, and the results showed that the content of heavy metal, pesticide residues and microbial toxin were consistent with the required standards, and no chemical drug additions were found in Agilent Fake TCM-Drugs database. In summary, we confirmed that the clinical case of drug-induced liver injury was induced by D. dasycarpus with the dose of 15 g•d⁻¹, which exceeded the prescribed amount of Chinese Pharmacopoeia. According to the Guideline for Diagnosis and Treatment of Herb-Induced Liver Injury, the case of drug-induced liver injury induced by D. dasycarpus was confirmed, which provided a direct and reliable evidence for the study of risk of liver injury induced by D. dasycarpus and its relevant preparations.