Defibrotide improved the outcome of monocrotaline induced rat hepatic sinusoidal obstruction syndrome

Liu, Zhenli; Liang, Shan; Wei, Xinhuan; Du, Xiaofei; Zhang, Jing

doi:10.1186/s12876-022-02523-3

Cited by 3 publications

(2 citation statements)

References 31 publications

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“…Anticoagulants are the medicines of choice to treat patients with HSOS (Table 3), whether it is caused by drugs such as sirolimus, gemtuzumab, cyclophosphamide, or oxaliplatin, leading to drug-induced liver vascular injury [42,118,119], due to hematopoietic cell transplantation (HCT) [120][121][122], or following use of plants containing 1,2-unsaturated PAs [68,123,124]. HSOS is characterized among many other features by platelet aggravation and adhesion, damage of the endothelial cells, and the risk of occlusion of the hepatic sinusoids [68,118].…”

Section: Anticoagulantsmentioning

confidence: 99%

“…HSOS is characterized among many other features by platelet aggravation and adhesion, damage of the endothelial cells, and the risk of occlusion of the hepatic sinusoids [68,118]. Approved by the FDA to treat HSOS caused by HCT, defibrotide is under discussion for use in HSOS by other causatives as this drug is a plasminogen inhibitor and thereby protects from blood clotting [121,122,124].…”

Section: Anticoagulantsmentioning

confidence: 99%

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Treatment of Drug-Induced Liver Injury

Teschke

2022

Biomedicines

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Current pharmacotherapy options of drug-induced liver injury (DILI) remain under discussion and are now evaluated in this analysis. Needless to say, the use of the offending drug must be stopped as soon as DILI is suspected. Normal dosed drugs may cause idiosyncratic DILI, and drugs taken in overdose commonly lead to intrinsic DILI. Empirically used but not substantiated regarding efficiency by randomized controlled trials (RCTs) is the intravenous antidote treatment with N-acetylcysteine (NAC) in patients with intrinsic DILI by N-acetyl-p-aminophenol (APAP) overdose. Good data recommending pharmacotherapy in idiosyncratic DILI caused by hundreds of different drugs are lacking. Indeed, a recent analysis revealed that just eight RCTs have been published, and in only two out of eight trials were DILI cases evaluated for causality by the worldwide used Roussel Uclaf Causality Assessment Method (RUCAM), representing overall a significant methodology flaw, as results of DILI RCTs lacking RUCAM are misleading since many DILI cases are known to be attributable erroneously to nondrug alternative causes. In line with these major shortcomings and mostly based on anecdotal reports, glucocorticoids (GCs) and other immuno-suppressants may be given empirically in carefully selected patients with idiosyncratic DILI exhibiting autoimmune features or caused by immune checkpoint inhibitors (ICIs), while some patients with cholestatic DILI may benefit from ursodeoxycholic acid use; in other patients with drug-induced hepatic sinusoidal obstruction syndrome (HSOS) and coagulopathy risks, the indication for anticoagulants should be considered. In view of many other mechanistic factors such as the hepatic microsomal cytochrome P450 with a generation of reactive oxygen species (ROS), ferroptosis with toxicity of intracellular iron, and modification of the gut microbiome, additional therapy options may be available in the future. In summation, stopping the offending drug is still the first line of therapy for most instances of acute DILI, while various therapies are applied empirically and not based on good data from RCTs awaiting further trials using the updated RUCAM that asks for strict exclusion and inclusion details like liver injury criteria and provides valid causality rankings of probable and highly probable grades.

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