Molecular Research on Drug Induced Liver Injury

Teschke, Rolf; Danan, Gaby

doi:10.3390/ijms19010216

Cited by 7 publications

(13 citation statements)

References 10 publications

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“…Under the influence of many factors, such as unreasonable drug use and the interactions among drugs, drug-induced liver and kidney injuries, as the most important adverse drug reactions, have attracted increasing attention from clinicians. e ability to diagnose these conditions is also continually improving [8,9]. Drug-induced liver and kidney injuries are easily missed due to the lack of specific clinical manifestations and biochemical and pathological changes.…”

Section: Discussionmentioning

confidence: 99%

Clinical Characteristics of 162 Patients with Drug-Induced Liver and/or Kidney Injury

Wang

Chen

2020

BioMed Research International

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Context. Drug-induced liver and kidney injuries are the most common adverse drug reactions in the clinic, and they have similar pathogeneses. Aims. To analyze the clinical characteristics of patients with drug-induced liver and/or kidney injury. Settings and Design. This was a retrospective study. Methods and Materials. We analyzed data from 162 patients with drug-induced liver and/or kidney injury from 2008 to 2018 at the Chinese Rocket Force Characteristic Medical Center. Univariate and multivariate logistic analyses were performed on the drugs used, sex, age, weight, complications, and laboratory test results. Statistical analysis was performed using SPSS 25.0 statistical software. Results. (1) The most common drugs causing organ injury in this study were antineoplastic drugs, antibiotics, traditional Chinese medicine, lipid-lowering drugs, and nonsteroidal anti-inflammatory drugs. (2) Among 22 patients with drug-induced liver and kidney injuries, 68.18% had a hepatocellular pattern, 13.64% had a mixed pattern, and 18.18% had a cholestatic pattern. Among the three groups, the P value for creatinine was 0.002. (3) The P value for urinary protein between the isolated kidney injury group and the liver and kidney injury group was 0.028. (4) Multivariate analysis showed that, among the drug-induced renal injury patients and all injury patients, those with a higher neutrophil percentage had a lower risk of liver injury (OR = 0.574, 95% CI: 0.390–0.846; OR = 0.545, 95% CI: 0.396–0.749). Conclusions. (1) The serum creatinine level was higher in liver injury patients with the cholestatic pattern than in those with the hepatocellular or mixed pattern. (2) There was a significant difference in urinary protein between the isolated kidney and the liver and kidney injury groups. (3) Among patients with drug-induced organ injury, those with a higher neutrophils percentage had a lower risk of liver injury.

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Section: Discussionmentioning

confidence: 99%

Clinical Characteristics of 162 Patients with Drug-Induced Liver and/or Kidney Injury

Wang

Chen

2020

BioMed Research International

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“…Oxidative stress is an important cause of liver injury, and the metabolites of CCl 4 , CCl3- and CCl3OO-, both of which can cause oxidative stress in hepatocytes and consequently hepatocellular injury [ 38 ]. Flavonoids improve oxidative stress by activating the Nrf2/HO-1 pathway, and Nrf2 is a key transcription factor that upregulates the antioxidant gene HO-1 [ 39 ].…”

Section: Discussionmentioning

confidence: 99%

Shibi Tea (Adinandra nitida) and Camellianin A Alleviate CCl4-Induced Liver Injury in C57BL-6J Mice by Attenuation of Oxidative Stress, Inflammation, and Apoptosis

et al. 2022

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Liver injury is a significant public health issue nowadays. Shibi tea is a non-Camellia tea prepared from the dried leaves of Adinandra nitida, one of the plants with the greatest flavonoid concentration, with Camellianin A (CA) being the major flavonoid. Shibi tea is extensively used in food and medicine and has been found to provide a variety of health advantages. The benefits of Shibi tea and CA in preventing liver injury have not yet been investigated. The aim of this study was to investigate the hepatoprotective effects of extract of Shibi tea (EST) and CA in mice with carbon tetrachloride (CCl4)-induced acute liver injury. Two different concentrations of EST and CA were given to model mice by gavage for 3 days. Treatment with two concentrations of EST and CA reduced the CCl4-induced elevation of the liver index, liver histopathological injury score, alanine aminotransferase (ALT), and aspartate aminotransferase (AST). Western blotting and immunohistochemical analysis demonstrated that EST and CA regulated the oxidative stress signaling pathway protein levels of nuclear factor E2-related factor 2 (Nrf2)/heme-oxygenase-1 (HO-1), the expression of inflammatory cytokines, the phosphorylated nuclear factor-kappaB p65 (p-NF-κB)/nuclear factor-kappaB p65 (NF-κB) ratio, the phospho-p44/42 mitogen-activated protein kinase (p-MAPK), and the apoptosis-related protein levels of BCL2-associated X (Bax)/B cell leukemia/lymphoma 2 (Bcl2) in the liver. Taken together, EST and CA can protect against CCl4-induced liver injury by exerting antioxidative stress, anti-inflammation, and anti-apoptosis.

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“…Apart from the eight reports ( Table 1 ), several cases of COVID-19 patients with drug treatment and documented increased LTs were published but were not assessed for DILI by using the RUCAM and were not evaluated for non-drug causes [ 57 , 58 ]. Among the eight publications presenting RUCAM-based DILI cases ( Table 1 ) [ 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 ], one of these [ 49 ] used the original RUCAM of 1993 [ 5 ] whereas the applied RUCAM version was not disclosed in two other reports [ 52 , 53 ].…”

Section: Rucam In Dili Of Covid-19 Patientsmentioning

confidence: 99%

Advances in Idiosyncratic Drug-Induced Liver Injury Issues: New Clinical and Mechanistic Analysis Due to Roussel Uclaf Causality Assessment Method Use

Teschke

Danan²

2023

IJMS

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Clinical and mechanistic considerations in idiosyncratic drug-induced liver injury (iDILI) remain challenging topics when they are derived from mere case narratives or iDILI cases without valid diagnosis. To overcome these issues, attempts should be made on pathogenetic aspects based on published clinical iDILI cases firmly diagnosed by the original RUCAM (Roussel Uclaf Causality Assessment Method) or the RUCAM version updated in 2016. Analysis of RUCAM-based iDILI cases allowed for evaluating immune and genetic data obtained from the serum and the liver of affected patients. For instance, strong evidence for immune reactions in the liver of patients with RUCAM-based iDILI was provided by the detection of serum anti-CYP 2E1 due to drugs like volatile anesthetics sevoflurane and desflurane, partially associated with the formation of trifluoroacetyl (TFA) halide as toxic intermediates that form protein adducts and may generate reactive oxygen species (ROS). This is accompanied by production of anti-TFA antibodies detected in the serum of these patients. Other RUCAM-based studies on serum ANA (anti-nuclear antibodies) and SMA (anti-smooth muscle antibodies) associated with AIDILI (autoimmune DILI) syn DIAIH (drug-induced autoimmune hepatitis) provide additional evidence of immunological reactions with monocytes as one of several promoting immune cells. In addition, in the blood plasma of patients, mediators like the cytokines IL-22, IL-22 binding protein (IL-22BP), IL-6, IL-10, IL 12p70, IL-17A, IL-23, IP-10, or chemokines such as CD206 and sCD163 were found in DILI due to anti-tuberculosis drugs as ascertained by the prospective updated RUCAM, which scored a high causality. RUCAM-based analysis also provided compelling evidence of genetic factors such as HLA (human leucocyte antigen) alleles contributing to initiate iDILI by a few drugs. In conclusion, analysis of published RUCAM-based iDILI cases provided firm evidence of immune and genetic processes involved in iDILI caused by specific drugs.

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Molecular Research on Drug Induced Liver Injury

Cited by 7 publications

References 10 publications

Clinical Characteristics of 162 Patients with Drug-Induced Liver and/or Kidney Injury

Clinical Characteristics of 162 Patients with Drug-Induced Liver and/or Kidney Injury

Shibi Tea (Adinandra nitida) and Camellianin A Alleviate CCl4-Induced Liver Injury in C57BL-6J Mice by Attenuation of Oxidative Stress, Inflammation, and Apoptosis

Advances in Idiosyncratic Drug-Induced Liver Injury Issues: New Clinical and Mechanistic Analysis Due to Roussel Uclaf Causality Assessment Method Use

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