Epidemiology of Drug- and Herb-Induced Liver Injury Assessed for Causality Using the Updated RUCAM in Two Hospitals from China

Abstract

Drug- and herb-induced liver injury (DILI and HILI) is an increasingly common and serious condition. Here, data for DILI and HILI patients from two large tertiary hospitals were retrospectively analyzed. Patient characteristics, causes and severity of DILI and HILI, the correlation between expression of p62 and the severity of DILI and HILI, treatment of DILI and HILI, and the prognostic factors of DILI and HILI were studied. A total of 82 patients with DILI and HILI were recruited for the study. Most patients presented with hepatocellular injury, followed by cholestatic injury and mixed injury. Our results indicate that traditional Chinese medicine or herbal and dietary supplements were the prevalent causal agents of HILI, which was characterized by higher frequencies of hepatocellular injury. Expression of p62 in the liver correlated with the severity of DILI and HILI. Improvements in the results of the liver enzymatic tests correlated with alanine transaminase (ALT) levels upon the first diagnosis of DILI and HILI and with the hepatocellular type of DILI and HILI. In conclusion, we provide an epidemiological assessment of DILI and HILI based on causality using the updated RUCAM on patients from two hospitals in China. ALT levels at first diagnosis and the hepatocellular type of injury may be prognostic factors of DILI and HILI.

Treatment of Drug-Induced Liver Injury

“…The top drugs causing RUCAM-based DILI worldwide have been assessed as to whether they were metabolized through CYP isoforms [62]. Literature provided highquality data on clinical features of DILI [1][2][3][4][5][6][7][8][9][10][16][17][18][19][20][21][22][23][24][25][26][27][28]39,64]. However, although most of the clinical features are well established, a variety of mechanistic steps remain unresolved in this complex disease.…”

“…Cessation of all non-essential drugs is mandatory as soon as the idiosyncratic DILI is suspected [13,28,29,90,91]. This alone has a positive effect on LTs as shown in many reports on DILI with verified diagnosis based on the RUCAM [1][2][3][4][5][6][7][8][9]. In most cases, a complete resolution of the liver injury is achieved, while in a few others, a protracted course of LTs is observed.…”

“…Drug-induced liver injury (DILI) remains an important concern among scientists, physicians, regulators, and experts in the field, with a focus on general aspects [1][2][3][4][5][6] or more specifically on drugs such as multiple antidepressants [7], teriflunomide [8], tigecyc-line [9], or potassium para-aminobenzoate [10]. The last three decades have witnessed substantial efforts on the question of how best to ensure the diagnosis of DILI in patients with abnormal liver tests (LTs) under treatment with drugs.…”

Molecular Idiosyncratic Toxicology of Drugs in the Human Liver Compared with Animals: Basic Considerations

“…The potential risk of liver injury by the use of conventional drugs [ 1 , 2 , 3 ] is shared by a variety of other toxicants such as phytochemicals found in regulatory approved herbal drugs or non-approved herbal medicines like Traditional Chinese Medicines (TCM) [ 4 , 5 ]. Humans may also experience liver injury due to aluminum, arsenic, beryllium, cadmium, chromium, cobalt, copper, iron, lead, mercury, molybdenum, nickel, platinum, thallium, titanium, vanadium, zinc, carbon tetrachloride and herbicides [ 6 , 7 ] as well as pesticides [ 8 ] amanitin of Amanita phalloides [ 9 ], aflatoxins [ 10 ], plants containing 1,2-unsaturated pyrrolizidine alkaloids (PAs), contaminating food or drinking water [ 11 , 12 ], and alcoholic beverages [ 13 , 14 , 15 , 16 , 17 , 18 ].…”

Multi-Omics Integration to Reveal the Mechanism of Hepatotoxicity Induced by Dictamnine

“…In clinical practice, the prevention and diagnosis of HILI are extremely difficult owing to the lack of test criteria for an accurate diagnosis and the limited understanding of HILI mechanisms. The Roussel Uclaf causality assessment method (RUCAM) is commonly used to assess the association between liver injury and the medications implicated to cause the injury ( Rochon et al, 2008 ; Danan and Teschke, 2018 ; Chen et al, 2021 ). Reliable HILI diagnostic methods were recently established based on the integrated evidence from the chain-based identification of Chinese herbal medicines ( Wang et al, 2015 , 2018 ).…”