An Update on Treatment of Drug-Induced Liver Injury

Giordano, Christin; Rivas, John; Zervos, Xaralambos

doi:10.14218/jcth.2014.00005

Cited by 14 publications

(11 citation statements)

References 31 publications

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“…As such, diagnosis often does not require the use of these scales for confirmation. In general, a clear temporal relationship between drug administration and liver injury, as well as exclusion of other causes, is the key finding to diagnose DILI [12]. Resolution following cessation of the drug further supports the conclusion.…”

Section: Discussionmentioning

confidence: 68%

“…Diagnosis of DILI is often difficult to confirm and may therefore be a diagnosis of exclusion, ruling out other causes such as liver metastases, viral infection, autoimmune disease, and ischemia [11]. Multiple assessment tools have been developed and validated in previous studies, but there is no consensus regarding their use in diagnosis of DILI [12]. As such, diagnosis often does not require the use of these scales for confirmation.…”

Section: Discussionmentioning

confidence: 99%

“…Regarding DILI management, the cornerstones of treatment are withdrawal of the offending agent and supportive care [12]. Close monitoring of AST, ALT, alkaline phosphatase, gamma-glutamyl transferase, total bilirubin, and PT/INR is necessary to monitor response.…”

Section: Discussionmentioning

confidence: 99%

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Severe Drug-Induced Liver Injury from Combination Encorafenib/Binimetinib

Gravbrot

Sundararajan

2019

Case Reports in Oncological Medicine

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Encorafenib/binimetinib is a new combination BRAF/MEK inhibitor used in the treatment of advanced or metastatic BRAFV600-mutant melanoma. Though generally tolerated well, mild to moderate aminotransferase elevations are common. However, significant liver injury has not been demonstrated in the literature. Here, we report the first case of severe hepatic injury associated with encorafenib/binimetinib in a 58-year-old gentleman requiring admission and extensive workup. He was successfully treated by withdrawing the combination therapy, and liver function returned to normal range.

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Section: Discussionmentioning

confidence: 68%

Section: Discussionmentioning

confidence: 99%

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Severe Drug-Induced Liver Injury from Combination Encorafenib/Binimetinib

Gravbrot

Sundararajan

2019

Case Reports in Oncological Medicine

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“…Hepatic injury caused by the long-term administration of particular drugs, including acetaminophen, amoxicillin-clavulanate and antiepileptic drugs are common clinical phenomenons ( 29 , 30 ). The degree of hepatocyte damage depends on the accumulation of toxicity and the protection afforded by physical or exogenous factors ( 31 , 32 ).…”

Section: Discussionmentioning

confidence: 99%

Effect of autophagy‑associated proteins on the arecoline‑induced liver injury in mice

Wang

Song

et al. 2018

Exp Ther Med

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Arecoline can be used to treat diseases including glaucoma and tapeworm infection, however, long-term administration can cause severe adverse effects, including oral submucosal fibrosis, oral cancer, hepatic injury and liver cancer. Autophagy serves a role in these injuries. The present study established a mouse model of arecoline-induced hepatic injury and investigated the role of autophagy-associated proteins in this injury. The results indicated that the expression levels of the autophagy marker protein microtubule associated protein 1 light chain 3 B (MAP1LC3B) and autophagy-promoting protein beclin 1 were elevated in the injured hepatic cells, while the expression levels of a well-known negative regulator of autophagy, mammalian target of rapamycin (mTOR), were reduced. Following treatment of the hepatic injury with glutathione, the liver function improved and liver damage was reduced effectively. Compared with the control group, the expression levels of both MAP1LC3B and beclin 1 were significantly upregulated in the glutathione-treated mice, but the expression of mTOR was significantly downregulated. It may be concluded that in the process of protecting against arecoline-induced hepatic injury, glutathione cooperates with mTOR and beclin 1 to accelerate autophagy, maintaining stable cell morphology and cellular functions.

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“…Acetaminophen ( N -acetyl- p -aminophenol, APAP), also known as paracetamol, is the main medication associated with drug-induced liver injury (DILI) and acute liver failure in the United States [ 1 , 2 ]. APAP-related adverse events are still considered a public health burden, accounting for an approximate annual average of 112,000 calls to poison centers, 59,000 emergency department visits, and 38,000 hospitalizations, with an in-hospital mortality rate of 1.2% [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

Aedes aegypti mosquito saliva ameliorates acetaminophen-induced liver injury in mice

et al. 2021

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Acetaminophen (N-acetyl-p-aminophenol, APAP) overdose is the most common cause of drug-induced liver injury (DILI). Although the primary hepatic damage is induced by APAP-derived toxic intermediates resulting from cytochrome P450 metabolism, immune components also play an important role in DILI pathophysiology. Aedes aegypti saliva is a source of bioactive molecules with in vitro anti-inflammatory and immunomodulatory activities. However, evidences on the therapeutic use of Ae. aegypti salivary preparations in animal models of relevant clinical conditions are still scarce. Thus, the present study was designed to evaluate the protective role of Ae. aegypti saliva in a murine model of APAP-induced DILI. C57BL/6 mice were exposed to Ae. aegypti bites 2 hours after APAP overdose. Biochemical and immunological parameters were evaluated in blood and liver samples at different time points after APAP administration. Exposure to Ae. aegypti saliva attenuated liver damage, as demonstrated by reduced hepatic necrosis and serum levels of alanine aminotransferase in APAP-overdosed mice. The levels of hepatic CYP2E1, the major enzyme responsible for the bioactivation of APAP, were not changed in Ae. aegypti exposed animals, suggesting no effects in the generation of hepatotoxic metabolites. On the other hand, mice treated with Ae. aegypti saliva following APAP overdose presented lower serum concentration of TNF-α, IL-6, IL-1β and IL-10, as well as reduced frequency of inflammatory cell populations in the liver, such as NKT cells, macrophages and dendritic cells. These findings show that Ae. aegypti saliva has bioactive molecules with therapeutic properties and may represent a prospective source of new compounds in the management of DILI-associated inflammatory disorders and, perhaps, many other inflammatory/autoimmune diseases.

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An Update on Treatment of Drug-Induced Liver Injury

Cited by 14 publications

References 31 publications

Severe Drug-Induced Liver Injury from Combination Encorafenib/Binimetinib

Severe Drug-Induced Liver Injury from Combination Encorafenib/Binimetinib

Effect of autophagy‑associated proteins on the arecoline‑induced liver injury in mice

Aedes aegypti mosquito saliva ameliorates acetaminophen-induced liver injury in mice

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