A reproducible, clinically relevant, intensively managed, pig model of acute liver failure for testing of therapies aimed to prolong survival

Lee, Karla C. L.; Jiménez, Carolina Palacios; Alibhai, Hatim; Chang, Yu‐Mei; Leckie, P; Baker, Luisa A.; Stanzani, Giacomo; Priestnall, Simon L.; Mookerjee, Rajeshwar P.; Jalan, Rajiv; Davies, Nathan

doi:10.1111/liv.12042

Cited by 26 publications

(35 citation statements)

References 23 publications

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“…Previous attempts to establish a standardized APAP intoxication model[13-15,20] were unsuccessful. Thiel et al[20] administered APAP directly into the upper jejunum via an implanted catheter, and this route of administration was affected by anesthesia, laparotomy and jejunotomy.…”

Section: Discussionmentioning

confidence: 99%

“…Thiel et al[20] administered APAP directly into the upper jejunum via an implanted catheter, and this route of administration was affected by anesthesia, laparotomy and jejunotomy. Lee et al[15] used an oro-duodenal feeding tube that was placed for APAP dosing without any surgery. The way a gastric tube is used for APAP injection not only avoids a complex operation but also facilitates basic anesthesia intubation, thus greatly facilitating the induction of hepatic failure.…”

Section: Discussionmentioning

confidence: 99%

“…Newsome et al[13] induced ALF in pigs by maintaining steady blood concentrations of APAP without fatal methemoglobinemia. Thiel et al[14] used jejunal administration of APAP, and Lee et al[15] successfully made an APAP-induced ALF porcine model.…”

Section: Introductionmentioning

confidence: 99%

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Artificial liver support in pigs with acetaminophen-induced acute liver failure

He¹,

Feng²,

Cai³

et al. 2017

WJG

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AIMTo establish a reversible porcine model of acute liver failure (ALF) and treat it with an artificial liver system.METHODSSixteen pigs weighing 30-35 kg were chosen and administered with acetaminophen (APAP) to induce ALF. ALF pigs were then randomly assigned to either an experimental group (n = 11), in which a treatment procedure was performed, or a control group (n = 5). Treatment was started 20 h after APAP administration and continued for 8 h. Clinical manifestations of all animals, including liver and kidney functions, serum biochemical parameters and survival times were analyzed.RESULTSTwenty hours after APAP administration, the levels of serum aspartate aminotransferase, total bilirubin, creatinine and ammonia were significantly increased, while albumin levels were decreased (P < 0.05). Prothrombin time was found to be extended with progression of ALF. After continuous treatment for 8 h (at 28 h), aspartate aminotransferase, total bilirubin, creatinine, and ammonia showed a decrease in comparison with the control group (P < 0.05). A cross-section of livers revealed signs of vacuolar degeneration, nuclear fragmentation and dissolution. Concerning survival, porcine models in the treatment group survived for longer times with artificial liver system treatment (P < 0.05).CONCLUSIONThis model is reproducible and allows for quantitative evaluation of new liver systems, such as a bioartificial liver. The artificial liver system (ZHJ-3) is safe and effective for the APAP-induced porcine ALF model.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Artificial liver support in pigs with acetaminophen-induced acute liver failure

He¹,

Feng²,

Cai³

et al. 2017

WJG

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show abstract

“…Although the results of this study were performed using a porcine liver model, we think that our results can be transferred to humans, since porcine animal models have broadly and successfully been used in translational research [24][25][26]. The use of intravenous agents for general anesthesia denotes a further limitation of this study as they may have altered hepatic perfusion parameters.…”

Section: Discussionmentioning

confidence: 91%

Characterization of benign periablational enhancement following multipolar radiofrequency ablation using perfusion CT in an in-vivo porcine liver model

Vahldiek

Thieme

Gemeinhardt

et al. 2017

JCB

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Abstract. PURPOSE:Thermal ablation is an important interventional option in the management of liver tumors. Immediate postablational imaging regularly shows periablational enhancement. This peripheral hyperperfusion may induce heat-sink effects which could contribute to incomplete tumor ablation. To reduce the effect of hyperperfusion the feeding vessels source must be known. The aim of this study was to dynamically characterize the type of blood supply of the periablational enhancement zone immediately after hepatic radiofrequency ablation (RFA) using perfusion CT. METHODS:We used an in-vivo porcine liver model. Multipolar RFA was performed in healthy pig livers. Immediate postablational perfusion CT was acquired. The contrast enhancement over time of the peripheral ablation zone, the aorta and the portal vein were recorded. Time differences of the peak periablational enhancement to the peak arterial perfusion and to the peak portalvenous perfusion were calculated and analyzed. RESULTS: The perfusion peak of the periablational enhancement zone always occurred in mean 8.1 s after the arterial peak in the aorta and in mean 16.9 s before the peak in the portal vein. CONCLUSIONS: Benign periablational enhancement is a result of primary arterial and not portalvenous hyperperfusion. In order to reduce heat sink effects, peri-ablational arterial balloon occlusion or transarterial chemoembolization may be beneficial during RFA.

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“…In the described study (Baker et al 2015) a clinically relevant porcine model of acetaminophen (APAP)-induced ALF (Lee et al 2013) was used to investigate temporal changes in both global miRNA and tissue-specific miRNAs in plasma samples from induction of ALF, through acute liver injury (ALI) and ALF to death. Six pigs received oral APAP with ALF occurring after 19h±2h and death after a further 13h±3h, whilst three control pigs underwent the same protocols except for receiving water instead of APAP and were maintained for 20h up to 'ALF' and 20h thereafter ( Fig.…”

mentioning

confidence: 99%