A prospective study of acute drug‐induced liver injury in patients suffering from non‐alcoholic fatty liver disease

Tarantino, Giovanni; Conca, Paolo; Basile, Vincenzo S.; Gentile, Antonio; Capone, Domênico; Polichetti, Giuliano; Leo, Emilio

doi:10.1111/j.1872-034x.2007.00072.x

Cited by 142 publications

(100 citation statements)

References 29 publications

(25 reference statements)

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“…Several experimental and clinical investigations reported that NAFLD could sensitize to drug-induced acute liver injury (Tarantino et al, 2007;Begriche et al, 2011). However, the present study indicates that fatty liver per se and preexistent hepatic cytolysis are not systematically involved in this sensitization.…”

Section: Discussioncontrasting

confidence: 45%

“…Moreover, there is increasing evidence that obesity and NAFLD can increase the risk and the severity of liver injury induced by several drugs. Indeed, in addition to APAP, this is suspected for halothane, tamoxifen, irinotecan, methotrexate, and some antibiotics (Tarantino et al, 2007;Aubert et al, 2011;Begriche et al, 2011). Obesity and NAFLD also favor hepatotoxicity of toxic compounds such as ethanol, carbon tetrachloride, and thioacetamide (Robin et al, 2005a;Donthamsetty et al, 2007;Kučera et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

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Differences in Early Acetaminophen Hepatotoxicity between Obeseob/obanddb/dbMice

Aubert

Begriche

Delannoy

et al. 2012

J Pharmacol Exp Ther

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Clinical investigations suggest that hepatotoxicity after acetaminophen (APAP) overdose could be more severe in the context of obesity and nonalcoholic fatty liver disease. The preexistence of fat accumulation and CYP2E1 induction could be major mechanisms accounting for such hepatic susceptibility. To explore this issue, experiments were performed in obese diabetic ob/ob and db/db mice. Preliminary investigations performed in male and female wild-type, ob/ob, and db/db mice showed a selective increase in hepatic CYP2E1 activity in female db/db mice. However, liver triglycerides in these animals were significantly lower compared with ob/ob mice. Next, APAP (500 mg/kg) was administered in female wild-type, ob/ ob, and db/db mice, and investigations were carried out 0.5, 2, 4, and 8 h after APAP intoxication. Liver injury 8 h after APAP intoxication was higher in db/db mice, as assessed by plasma transaminases, liver histology, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay. In db/db mice, however, the extent of hepatic glutathione depletion, levels of APAP-protein adducts, c-Jun N-terminal kinase activation, changes in gene expression, and mitochondrial DNA levels were not greater compared with the other genotypes. Furthermore, in the db/db genotype plasma lactate and ␤-hydroxybutyrate were not specifically altered, whereas the plasma levels of APAP-glucuronide were intermediary between wild-type and ob/ob mice. Thus, early APAP-induced hepatotoxicity was greater in db/db than ob/ob mice, despite less severe fatty liver and similar basal levels of transaminases. Hepatic CYP2E1 induction could have an important pathogenic role when APAP-induced liver injury occurs in the context of obesity and related metabolic disorders.

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Section: Discussioncontrasting

confidence: 45%

Section: Discussionmentioning

confidence: 99%

Differences in Early Acetaminophen Hepatotoxicity between Obeseob/obanddb/dbMice

Aubert

Begriche

Delannoy

et al. 2012

J Pharmacol Exp Ther

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“…Activation of these receptors and intracellular pathways might take part in cytoprotective effects of midkine during Cd toxicity. Human and experimental studies have shown that apoptosis plays a role in hepatocyte death in alcoholic liver disease and nonalcoholic steatohepatitis and apoptosis levels correlate with the severity of the liver disease [23][24][25][26] . LDL receptor-related protein (LRP) is another midkine receptor.…”

Section: Discussionmentioning

confidence: 99%

Midkine secretion protects Hep3B cells from cadmium induced cellular damage

Yazıhan¹,

Ataoglu²,

Akçıl³

et al. 2008

WJG

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AIM:To evaluate role of midkine secretion during Cadmium (Cd) exposure in the human hepatocyte cell line Hep3B cells. METHODS:Different dosages of Cd (0.5-1-5-10 μg/mL) were applied to Hep3B cells and their effects to apoptosis, lactate dehydrogenase (LDH) leakage and midkine secretion were evaluated as time dependent m a n n e r. S a m e e x p e r i m e n t s w e re re p e a t e d w i t h exogenously applied midkine (250-5000 pg/mL) and/or 5 μg/mL Cd.

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“…24 It is also recognized that nonalcoholic fatty liver disease (NAFLD) can also increase susceptibility for DILI. 25 Thus, particular attention is needed when medicating patients with liver disease (reviewed by Gupta and Lewis). 26 However, the presence of pre-existing liver disease does not mean that potentially hepatotoxic medications cannot be used.…”

Section: Risk Factors For Drug-induced Liver Injurymentioning

confidence: 99%

Drug-Induced Liver Injury

Hamilton

Collins‐Yoder

Collins

2016

AACN Advanced Critical Care

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Drug-induced liver injury (DILI) is common and nearly all classes of medications can cause liver disease. Most cases of DILI are benign, and improve after drug withdrawal. It is important to recognize and remove the offending agent as quickly as possible to prevent the progression to chronic liver disease and/or acute liver failure. There are no definite risk factors for DILI, but preexisting liver disease and genetic susceptibility may predispose certain individuals. Although most patients have clinical symptoms that are identical to other liver diseases, some patients may present with symptoms of systemic hypersensitivity. Treatment of drug and herbal-induced liver injury consists of rapid drug discontinuation and supportive care targeted to alleviate unwanted symptoms. KeywordsDrug-induced liver injury (DILI); drug-induced hepatitis; drug-induced cholestasis; acetaminophen; vanishing bile duct syndrome; herbal toxicity Adverse drug reactions are an important cause of liver injury that may require discontinuation of the offending agent, hospitalization, or even liver transplantation. 1 Indeed, drug-induced hepatotoxicity is the most frequent cause of acute liver failure in US. 2 Because the liver is responsible for concentrating and metabolizing a majority of medications, it is a prime target for medication-induced damage. Among hepatotoxic drugs, acetaminophen (paracetamol) is the most often studied. However, a broad range of different pharmacological agents can induce liver damage, including anesthetics, anticancer drugs, antibiotics, antituberculosis agents, antiretrovirals, and cardiac medications. In addition, a plethora of traditional medical therapies and herbal remedies may also be hepatotoxic.Depending on the duration of injury and the histological location of damage, drug-induced liver injury (DILI) is categorized as acute or chronic, and either as hepatitis, cholestatic, or a mixed pattern of injury. The hepatitis pattern is characterized by hepatocyte necrosis and is associated with a poor prognosis. There are three types of acute cholestatic drug-induced injury: bland cholestasis is the result of abnormal biliary secretion, and is not accompanied by significant hepatocellular damage; cholestatic hepatitis (mixed type) refers to cholestasis with concomitant hepatic parenchymal damage; and the third form of acute cholestasis is

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A prospective study of acute drug‐induced liver injury in patients suffering from non‐alcoholic fatty liver disease

Abstract: NAFLD conveys a nearly fourfold increase of DILI risk in obese middle-aged patients. NAFLD, characterized by mitochondrial dysfunction, could predispose to drug-induced hepatotoxicity that probably shares the same pathophysiological mechanism.

Cited by 142 publications

References 29 publications

Differences in Early Acetaminophen Hepatotoxicity between Obeseob/obanddb/dbMice

Differences in Early Acetaminophen Hepatotoxicity between Obeseob/obanddb/dbMice

Midkine secretion protects Hep3B cells from cadmium induced cellular damage

Drug-Induced Liver Injury

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