A new horizon for liver support in acute liver failure

Davies, Nathan; Bañares, Rafael

doi:10.1016/j.jhep.2015.05.020

Cited by 6 publications

(6 citation statements)

References 8 publications

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“…Acute liver failure, a severe form of liver damage caused by various factors, is an infrequent but life-threatening disease, with death occurring in up to 50% of the cases 18 , 19 . The standard therapy for liver failure, liver transplantation, has improved the survival rate by approximately 40%; however, this option is strongly limited because of the shortage of donor livers 20 , 21 .…”

Section: Discussionmentioning

confidence: 99%

Bifidobacterium pseudocatenulatum LI09 and Bifidobacterium catenulatum LI10 attenuate D-galactosamine-induced liver injury by modifying the gut microbiota

Fang

Shi

et al. 2017

Sci Rep

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The gut microbiota is altered in liver diseases, and several probiotics have been shown to reduce the degree of liver damage. We hypothesized that oral administration of specific Bifidobacterium strains isolated from healthy guts could attenuate liver injury. Five strains were tested in this study. Acute liver injury was induced by D-galactosamine after pretreating Sprague-Dawley rats with the Bifidobacterium strains, and liver function, liver and ileum histology, plasma cytokines, bacterial translocation and the gut microbiome were assessed. Two strains, Bifidobacterium pseudocatenulatum LI09 and Bifidobacterium catenulatum LI10, conferred liver protection, as well as alleviated the increase in plasma M-CSF, MIP-1α and MCP-1 and bacterial translocation. They also ameliorated ileal mucosal injury and gut flora dysbiosis, especially the enrichment of the opportunistic pathogen Parasutterella and the depletion of the SCFA-producing bacteria Anaerostipes, Coprococcus and Clostridium XI. Negative correlations were found between MIP-1α / MCP-1 and Odoribacter (LI09 group) and MIP-1α / M-CSF and Flavonifractor (LI10 group). Our results indicate that the liver protection effects might be mediated through gut microbiota modification, which thus affect the host immune profile. The desirable characteristics of these two strains may enable them to serve as potential probiotics for the prevention or adjuvant treatment of liver injury.

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Section: Discussionmentioning

confidence: 99%

Bifidobacterium pseudocatenulatum LI09 and Bifidobacterium catenulatum LI10 attenuate D-galactosamine-induced liver injury by modifying the gut microbiota

Fang

Shi

et al. 2017

Sci Rep

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“…Orthotopic liver transplantation is the only proven therapy for ALF, but its overall usage is limited by the need for major surgery, life-long immunosuppression, and the shortage of donor organs. The expanding gap between the number of patients on the waiting list for liver transplantation and available donor livers has highlighted the strong need for alternative therapies, especially in the setting of ALF 2 .…”

Section: Introductionmentioning

confidence: 99%

Novel spheroid reservoir bioartificial liver improves survival of nonhuman primates in a toxin-induced model of acute liver failure

Li¹,

Wu²,

Wang³

et al. 2018

Theranostics

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This study aims to evaluate the effectiveness and safety of the spheroid reservoir bioartificial liver (SRBAL) with porcine hepatocyte organoids in a preclinical nonhuman primate model of acute liver failure (ALF).Methods: Thirty healthy rhesus monkeys were infused with α-amanitin and lipopolysaccharide and randomized into five groups (ALF alone control group; sham no-cell SRBAL treatment group; groups A, B and C with SRBAL treatment started at 12 h, 24 h and 36 h after induction of ALF, respectively). Animals were continuously treated with the SRBAL device for 6 h and followed for up to 336 h.Results: Survival of ALF monkeys improved with hepatocyte SRBAL treatment compared to control groups. Blood ammonia and total bilirubin were lower, and albumin levels were higher in all hepatocyte SRBAL treatment groups. No evidence of porcine endogenous retrovirus was identified in monkey liver or blood after SRBAL treatment. Titers of monkey antibody (IgG, IgM) did not rise after SRBAL treatment. In survival cases, the proportion of necrotic and apoptotic hepatocytes was lower in SRBAL-treated groups, with earlier liver regeneration leading to recovery. Cytokines TNF-α, IL-6, IL-12, IL-1β, IL-8, IFN-γ and IL-2 were ameliorated by the SRBAL treatment, while levels of M-CSF; HGF, EGF and VEGF; IL-1RA and MIF rose on priming, proliferation and the late phase of liver regeneration.Conclusions: The benefit of SRBAL therapy included preventive effects and therapeutic effects. SRBAL improved survival rate and prolonged median survival time in a nonhuman primate model of drug-induced ALF, and these benefits declined with a delay in the initiation of therapy. Improved survival and recovery of ALF monkeys was associated with a reduction in blood ammonia levels, inhibition of the pro-inflammatory response of ALF, and provided a microenvironment more suitable for regeneration of the injured liver.

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“…2h). To further assess key metabolic functions of hepatocytes in BEL scaffolds, ammonia detoxification and urea production assays were adapted to bioreactor scale culture based on prior 2D culture and hepatocyte spheroid studies 19 . In brief, BELs were challenged with fresh co-culture media supplemented with 0.8 mM ammonium chloride 16-20 h following hepatocyte seeding and samples were taken at intervals up to 23 h after the challenge for quantification of ammonia and urea (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…In addition to showing sustained perfusion of a hepatocyte/endothelial BEL in vivo, the survival and functionality of hepatocytes were assessed. Previous studies have correlated the relationship between intracranial pressure (ICP) and blood ammonia levels during acute liver failure 19 . Therefore, a totally internal intracranial probe (NEUROVENT-P-tel, Raumedic, Mills River, NC) was implanted 5 days prior to surgery to allow monitoring of the intracranial pressure (ICP).…”

Section: Resultsmentioning

confidence: 99%

Functional characterization of a bioengineered liver after heterotopic implantation in pigs

et al. 2021

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Organ bioengineering offers a promising solution to the persistent shortage of donor organs. However, the progression of this technology toward clinical use has been hindered by the challenges of reconstituting a functional vascular network, directing the engraftment of specific functional cell types, and defining appropriate culture conditions to concurrently support the health and phenotypic stability of diverse cell lineages. We previously demonstrated the ability to functionally reendothelialize the vasculature of a clinically scaled decellularized liver scaffold with human umbilical vein endothelial cells (HUVECs) and to sustain continuous perfusion in a large animal recovery model. We now report a method for seeding and engrafting primary porcine hepatocytes into a bioengineered liver (BEL) scaffold previously reendothelialized with HUVECs. The resulting BELs were competent for albumin production, ammonia detoxification and urea synthesis, indicating the presence of a functional hepatocyte compartment. BELs additionally slowed ammonia accumulation during in vivo perfusion in a porcine model of surgically induced acute liver failure. Following explant of the graft, BEL parenchyma showed maintenance of canonical endothelial and hepatocyte markers. Taken together, these results support the feasibility of engineering a clinically scaled functional BEL and establish a platform for optimizing the seeding and engraftment of additional liver specific cells.

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A new horizon for liver support in acute liver failure

Abstract: Please cite this article as: Davies, N., Bañares, R., A new horizon for liver support in acute liver failure, Journal of Hepatology (2015), doi: http://dx.

Cited by 6 publications

References 8 publications

Bifidobacterium pseudocatenulatum LI09 and Bifidobacterium catenulatum LI10 attenuate D-galactosamine-induced liver injury by modifying the gut microbiota

Bifidobacterium pseudocatenulatum LI09 and Bifidobacterium catenulatum LI10 attenuate D-galactosamine-induced liver injury by modifying the gut microbiota

Novel spheroid reservoir bioartificial liver improves survival of nonhuman primates in a toxin-induced model of acute liver failure

Functional characterization of a bioengineered liver after heterotopic implantation in pigs

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