Liver manipulation during liver surgery in humans is associated with hepatocellular damage and hepatic inflammation

Broek, Maartje A. J. van den; Shiri-Sverdlov, Ronit; Schreurs, J J W; Bloemen, Johanne G.; Bieghs, Veerle; Rensen, Sander S.; Dejong, Cornelis H. C.; Damink, Steven W. M. Olde

doi:10.1111/liv.12051

Cited by 25 publications

(16 citation statements)

References 35 publications

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“…Liver manipulation in itself also can give rise to hepatocellular injury, as previously reported which is most likely a greater determinant of peak levels in longer and major liver surgery since these result in more extensive liver manipulation. [19][20][21] These could all contribute to the contrasting results in several reports on the predictive value of peak ALT and AST. 16,22 In the present study, postoperative peak ALT and AST levels showed a good discriminative value for postoperative mortality, especially in major liver resections and resections for PHC.…”

Section: Discussionmentioning

confidence: 61%

Postoperative peak transaminases correlate with morbidity and mortality after liver resection

Olthof

Huiskens

Schulte

et al. 2016

HPB

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Section: Discussionmentioning

confidence: 61%

Postoperative peak transaminases correlate with morbidity and mortality after liver resection

Olthof

Huiskens

Schulte

et al. 2016

HPB

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“…Prolonged clamping should nonetheless be avoided since ischemia-reperfusion injury has been shown to induce severe hepatic damage [141]. Hepatic manipulation per se elicits an inflammatory response [142]. Methods to minimize mobilisation of the liver include laparoscopic surgery and the hanging method [143].…”

Section: Providing Optimal Perioperative Carementioning

confidence: 99%

Liver resection for cancer: New developments in prediction, prevention and management of postresectional liver failure

Mierlo

Schaap

Dejong

et al. 2016

Journal of Hepatology

103

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“…Recently, the pre- dictive and prognostic value of L-FABP in liver diseases has attracted considerable attention. Numerous studies have demonstrated that L-FABP can be used as a new diagnostic biomarker for hepatic injury and impaired function of hepatocytes (53)(54)(55). However, to date, there has been no study examining the change of L-FABP expression in TB patients.…”

Section: Discussionmentioning

confidence: 99%

Liver Fatty Acid Binding Protein Deficiency Provokes Oxidative Stress, Inflammation, and Apoptosis-Mediated Hepatotoxicity Induced by Pyrazinamide in Zebrafish Larvae

Zhang

Liu

Hassan

et al. 2016

Antimicrob Agents Chemother

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g Pyrazinamide (PZA) is an essential antitubercular drug, but little is still known about its hepatotoxicity potential. This study examined the effects of PZA exposure on zebrafish (Danio rerio) larvae and the mechanisms underlying its hepatotoxicity. A transgenic line of zebrafish larvae that expressed enhanced green fluorescent protein (EGFP) in the liver was incubated with 1, 2.5, and 5 mM PZA from 72 h postfertilization (hpf). Different endpoints such as mortality, morphology changes in the size and shape of the liver, histological changes, transaminase analysis and apoptosis, markers of oxidative and genetic damage, as well as the expression of certain genes were selected to evaluate PZA-induced hepatotoxicity. Our results confirm the manner of PZA dose-dependent hepatotoxicity. PZA was found to induce marked injury in zebrafish larvae, such as liver atrophy, elevations of transaminase levels, oxidative stress, and hepatocyte apoptosis. To further understand the mechanism behind PZA-induced hepatotoxicity, changes in gene expression levels in zebrafish larvae exposed to PZA for 72 h postexposure (hpe) were determined. The results of this study demonstrated that PZA decreased the expression levels of liver fatty acid binding protein (L-FABP) and its target gene, peroxisome proliferator-activated receptor ␣ (PPAR-␣), and provoked more severe oxidative stress and hepatitis via the upregulation of inflammatory cytokines such as tumor necrosis factor alpha (TNF-␣) and transforming growth factor ␤ (TGF-␤). These findings suggest that L-FABP-mediated PPAR-␣ downregulation appears to be a hepatotoxic response resulting from zebrafish larva liver cell apoptosis, and L-FABP can be used as a biomarker for the early detection of PZA-induced liver damage in zebrafish larvae. P yrazinamide (PZA) is an important first-line drug in tuberculosis (TB) combination chemotherapy and is used during the initial 2 months of treatment for its remarkable sterilizing activity (1). Hepatotoxicity is the major adverse effect of PZA and usually occurs in the first 2 months of treatment (2). Previously reported studies showed a high incidence of hepatotoxicity with a high dosage of 40 to 70 mg/kg of body weight and a low rate of liver injury with a daily dose of Ͻ35 mg/kg (3). Although a reduction of the clinical dose considerably decreased the rate of PZA-induced hepatotoxic side effects, PZA is still considered to induce higher hepatotoxicity than other first-line antituberculosis drugs (4, 5). PZA hepatotoxicity cannot be ignored; however, little is known about the exact mechanism of PZA-induced hepatotoxicity.Previous research, by using microarray analyses and proteomics studies, found that metabolism, inflammation, and oxidative stress pathways were probably involved in PZA-induced hepatotoxicity (6, 7). A recent investigation showed that the metabolite 5-hydroxypyrazinoic acid (5-OH-PA) is responsible for PZAinduced hepatotoxicity (8). Despite an increasing number of researchers who are trying to reevaluate the hepatotoxic potentia...

show abstract

Liver manipulation during liver surgery in humans is associated with hepatocellular damage and hepatic inflammation

Abstract: Liver mobilization is associated with hepatocellular damage and liver inflammation, as shown by infiltration of inflammatory cells and upregulation of genes involved in acute inflammation.

Cited by 25 publications

References 35 publications

Postoperative peak transaminases correlate with morbidity and mortality after liver resection

Postoperative peak transaminases correlate with morbidity and mortality after liver resection

Liver resection for cancer: New developments in prediction, prevention and management of postresectional liver failure

Liver Fatty Acid Binding Protein Deficiency Provokes Oxidative Stress, Inflammation, and Apoptosis-Mediated Hepatotoxicity Induced by Pyrazinamide in Zebrafish Larvae

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