Causes, Features, and Outcomes of Drug-Induced Liver Injury in 69 Children from China

Zhu, Yichao; Li, Yonggang; Wang, Jia bo; Liu, Shu Hong; Wang, Li Fu; Zhao, Yan; Bai, Yun Feng; Wang, Zhong Xia; Li, Jian Yu; Xiao, Xiao He

doi:10.5009/gnl14184

Cited by 39 publications

(31 citation statements)

References 33 publications

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“…Drug therapy varies across both age and gender and it is difficult to collect enough cases of a particular drug injury to probe the effects of age and gender directly. In children, similar histological patterns of liver injury have been observed as are seen in adults, but specific differences that might be related to pubertal status are poorly understood. At the other end of the age spectrum, older patients may be at greater risk of DILI mainly because they take more medications and the histological implications have yet to be studied in detail .…”

Section: Histological Changes Related To Age and Gendermentioning

confidence: 82%

Histopathological challenges in suspected drug‐induced liver injury

Kleiner

2017

Liver International

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When a patient with suspected drug-induced liver injury (DILI) undergoes liver biopsy, the pathologist is confronted with two major challenges. The first and most important is to establish the pattern(s) of injury which are present. Patterns of injury represent stereotypical responses of an organ to injury and relate to specific aetiologies of liver damage. The pattern of injury and the histological details of that injury can then be analysed with respect to the patient's intercurrent diseases and medication history.The specific expertise of the pathologist can be used to weigh the prospect of DILI against the likelihood of other explanations of injury. The second challenge is to characterize specific types of injury and the severity of injury, both of which may have importance for clinical decision-making and prognosis. The pathologist's report should convey both an accurate description of the pathology as well its interpretation. K E Y W O R D Sacute hepatitis, autoimmune hepatitis, cholestasis, hepatic necrosis, hepatotoxicity

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Section: Histological Changes Related To Age and Gendermentioning

confidence: 82%

Histopathological challenges in suspected drug‐induced liver injury

Kleiner

2017

Liver International

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“…Additional data may be derived from review articles and other publications, which partially covered also large cohorts [181,182,184,185,186,187,188,189,190]. …”

Section: Tcm Herbs With Published Claims Of Hepatotoxic Potentialmentioning

confidence: 99%

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

et al. 2016

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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.

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“…The sale of Ephedra containing supplements was banned in 2004 due to cardiotoxicity [239]. Currently accumulating clinical cases also show that ephedrine has potential hepatotoxicity [240, 241], with mitochondria playing a key role in ephedrine-induced caused liver damage. Ephedrine can increase intracellular ROS production in hepatic stellate cells, which may induce the loss of mitochondrial membrane potential, causing accumulation of PINK1 on outer membranes of damaged mitochondria and activating mitophagy [236].…”

Section: Herbal Hepatotoxicitymentioning

confidence: 99%

Mitochondrial dysfunction as a mechanism of drug-induced hepatotoxicity: current understanding and future perspectives

et al. 2018

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Mitochondria are critical cellular organelles for energy generation and are now also recognized as playing important roles in cellular signaling. Their central role in energy metabolism, as well as their high abundance in hepatocytes, make them important targets for drug-induced hepatotoxicity. This review summarizes the current mechanistic understanding of the role of mitochondria in drug-induced hepatotoxicity caused by acetaminophen, diclofenac, anti-tuberculosis drugs such as rifampin and isoniazid, anti-epileptic drugs such as valproic acid and constituents of herbal supplements such as pyrrolizidine alkaloids. The utilization of circulating mitochondrial-specific biomarkers in understanding mechanisms of toxicity in humans will also be examined. In summary, it is well-established that mitochondria are central to acetaminophen-induced cell death. However, the most promising areas for clinically useful therapeutic interventions after acetaminophen toxicity may involve the promotion of adaptive responses and repair processes including mitophagy and mitochondrial biogenesis, In contrast, the limited understanding of the role of mitochondria in various aspects of hepatotoxicity by most other drugs and herbs requires more detailed mechanistic investigations in both animals and humans. Development of clinically relevant animal models and more translational studies using mechanistic biomarkers are critical for progress in this area.

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Causes, Features, and Outcomes of Drug-Induced Liver Injury in 69 Children from China

Cited by 39 publications

References 33 publications

Histopathological challenges in suspected drug‐induced liver injury

Histopathological challenges in suspected drug‐induced liver injury

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

Mitochondrial dysfunction as a mechanism of drug-induced hepatotoxicity: current understanding and future perspectives

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