Abnormal liver tests after liver transplantation

Fedoravicius, Andrew; Charlton, Francesca

doi:10.1002/cld.540

Cited by 18 publications

(11 citation statements)

References 10 publications

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“…Some of the human livers perfused for 1 week displayed a course of laboratory parameters and histology that was similar to those observed in the clinical setting of liver transplantation. For example, as in some of the livers perfused for 1 week, AST and ALT levels peak at around day 1, likely owing to some hepatocyte injury upon reperfusion, but decline rapidly thereafter similar to successful clinical liver transplantation 31,37 . Likewise, blood bilirubin increased during ex vivo perfusion with a delay in some livers as compared to liver enzymes 37 .…”

Section: Discussionmentioning

confidence: 99%

An integrated perfusion machine preserves injured human livers for 1 week

et al. 2020

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tandard preservation of donor livers is performed by flushing the organ with a cold solution at the time of procurement, which is followed by static storage on ice. This approach reduces liver metabolic activity, allowing safe storage for up to 12-18 h (refs. 1,2). Recently, the combination of supercooling with subzero storage (−4 °C) and hypothermic, as well as subnormothermic, machine perfusion achieved an extension of the preservation time of human livers up to 27 h (ref. 2). By contrast, human livers can also be kept metabolically fully active for up to 24 h by supplying normothermic blood or oxygenated fluids in a controlled environment by machine perfusion 1,3-5. The possibility of repairing poor-quality livers sufficiently to enable transplantation requires preserving metabolically active livers 1,3 for several days. Accordingly, the need for long-term organ preservation technology has been endorsed by multiple private and governmental initiatives 1. However, currently used normothermic machine perfusion technologies have been used only for a relatively short time period (for example, a median perfusion time of 9 h (ref. 5)), to successfully maintain hemodynamics, perfusate oxygenation and temperature. We sought to extend perfusion time beyond 24 h by engineering a perfusion machine that recapitulates additional core body functions that are critical to liver health. We chose 7-d as a target because this time period has been shown to offer a credible time frame for inducing clinically relevant liver regeneration in patients undergoing complex liver resection 6-8. Under physiologic conditions, the liver, which constitutes 2.5% of body weight, receives 25% of the blood output of the heart and performs >5,000 functions 9. It has a unique dual vascular supply with high-pressure, oxygen-rich arterial blood entering through the hepatic artery and low-pressure, oxygen-reduced portal vein blood draining the abdominal viscera. Its high metabolic activity produces waste products that are excreted in the bile or removed by hepatic macrophages or the kidneys. The metabolic profile is largely controlled by pancreatic hormones, including insulin and glucagon. Our perfusion technology, developed in the "Liver4Life project", includes automated control of glucose levels by injection of insulin and glucagon, a dialysis membrane for waste-product removal, regulation of oxygenation and liver movement to prevent pressure necrosis. Results Liver perfusion machine. Our perfusion machine (Fig. 1a,b) recapitulates blood supply through the two vascular entries of the liver, the hepatic artery and portal vein. The hepatic artery is supplied with oxygen-rich blood at elevated pressure (mean arterial pressure (MAP) ≥ 65 mmHg) in a pulsatile manner (Fig. 1c), whereas the portal vein receives blood at low pressure (around 5-10 mmHg) with a reduced oxygen content (venous blood, non-pulsatile). The system maintains oxygen saturation of 65% in the vena cava by continuously adjusting oxygen content in the portal vein (Fig. 1d). In vivo, nutr...

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Section: Discussionmentioning

confidence: 99%

An integrated perfusion machine preserves injured human livers for 1 week

et al. 2020

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“…Despite initial transaminitis upon reperfusion, plateau of all markers of liver injury during XC indicates that injury was transient, within expectations for organ reperfusion, and analogous to initial hepatic biomarker elevations observed clinically after liver transplantation. 22,23 Although plateau ALT levels remained at the upper limit of normal and plateau AST levels remained above normal ranges reported for swine, 24 these changes are likely explained by contributions from both the in situ host liver and the ex vivo donor liver, as well as from other tissues, for example, AST also arises from muscle, heart, brain, red blood cells. 25 The maintenance of hepatic arterial pressure and flow within physiologic ranges reflects intact autoregulatory functions of the myogenic response and the hepatic arterial buffer response.…”

Section: Discussionmentioning

confidence: 89%

Cross-Circulation for Extracorporeal Liver Support in a Swine Model

Tumen

Stokes

et al. 2021

ASAIO Journal

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Although machine perfusion has gained momentum as an organ preservation technique in liver transplantation, persistent organ shortages and high waitlist mortality highlight unmet needs for improved organ salvage strategies. Beyond preservation, extracorporeal organ support platforms can also aid the development and evaluation of novel therapeutics. Here, we report the use of veno-arterial-venous (V-AV) cross-circulation (XC) with a swine host to provide normothermic support to extracorporeal livers. Functional, biochemical, and morphological analyses of the extracorporeal livers and swine hosts were performed over 12 hours of support. Extracorporeal livers maintained synthetic function through alkaline bile production and metabolic activity through lactate clearance and oxygen consumption. Beyond initial reperfusion, no biochemical evidence of hepatocellular injury was observed. Histopathologic injury scoring showed improvements in sinusoidal dilatation and composite acute injury scores after 12 hours. Swine hosts remained hemodynamically stable throughout XC support. Altogether, these outcomes demonstrate the feasibility of using a novel V-AV XC technique to provide support for extracorporeal livers in a swine model. V-AV XC has potential applications as a translational research platform and clinical biotechnology for donor organ salvage.

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“…Oral prednisolone was gradually tapered to 10 mg/d for 1 month. In this study, the cases of suspicious rejection (not confirmed by a biopsy) were defined as “suspected acute rejection (SAR),” which showed the increase of aspartate aminotransferase (AST) or alanine aminotransferase (ALT) level more than 2‐fold above the upper baseline value within 6 months after LT. We have ruled out other possible causes of elevated enzymes, such as nonimmune primary parenchymal injuries possibly caused by bacterial infection; viral infection such as cytomegalovirus or Epstein‐Barr virus infection; exacerbation of primary diseases, including hepatitis B or alcoholic liver diseases; drug‐induced injuries; and/or biliary problems after transplantation surgery . Importantly, all patients with SAR in our study were rescued by steroid pulse therapy.…”

Section: Methodsmentioning

confidence: 99%

Early reduction of regulatory T cells is associated with acute rejection in liver transplantation under tacrolimus-based immunosuppression with basiliximab induction

Han

Joo

Kim

et al. 2020

American Journal of Transplantation

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The liver has been considered a tolerogenic allograft because many intrahepatic components, such as intrahepatic dendritic cells with immature phenotype, hepatocytes with decreased expression of major histocompatibility complex, Kupffer cells, relatively anergic effector T cells, and regulatory T cells (Tregs), contribute to the immune tolerance. 1-3 However, liver transplantation (LT) leads to the activation of effector T cells, effector B cells, and natural killer cells, which are associated with liver allograft damage. 1,2 To suppress this immune activation, pharmacological interventions, including glucocorticoids, antimetabolites such as mycophenolic acid and

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Abnormal liver tests after liver transplantation

Abstract: http://aasldpubs.onlinelibrary.wiley.com/hub/journal/10.1002/(ISSN)2046-2484/video/7-4-reading-charlton.html a video presentation of this article

Cited by 18 publications

References 10 publications

An integrated perfusion machine preserves injured human livers for 1 week

An integrated perfusion machine preserves injured human livers for 1 week

Cross-Circulation for Extracorporeal Liver Support in a Swine Model

Early reduction of regulatory T cells is associated with acute rejection in liver transplantation under tacrolimus-based immunosuppression with basiliximab induction

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