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Randomized Trial of Spheroid Reservoir Bioartificial Liver in Porcine Model of Posthepatectomy Liver Failure
Open accessAbstract
Acute liver failure (ALF) is a catastrophic condition that can occur after major liver resection. The aim of this study was to determine the effects of the spheroid reservoir bio‐artificial liver (SRBAL) on survival, serum chemistry, and liver regeneration in posthepatectomy ALF pigs. Wild‐type large white swine (20 kg‐30 kg) underwent intracranial pressure (ICP) probe placement followed by 85% hepatectomy. Computed tomography (CT) volumetrics were performed to measure the extent of resection, and at 48 hours following hepatectomy to assess regeneration of the remnant liver. Animals were randomized into three groups based on treatment delivered 24‐48 hours after hepatectomy: Group1—standard medical therapy (SMT, n = 6); Group2—SMT plus bio‐artificial liver treatment using no hepatocytes (0 g, n = 6); and Group3—SMT plus SRBAL treatment using 200 g of primary porcine hepatocyte spheroids (200 g, n = 6). The primary endpoint was survival to 90 hours following hepatectomy. Death equivalent was defined as unresponsive grade 4 hepatic encephalopathy or ICP greater than 20 mmHg with clinical evidence of brain herniation. All animals in both (SMT and 0 g) control groups met the death equivalent before 51 hours following hepatectomy. Five of 6 animals in the 200‐g group survived to 90 hours ( P < 0.01). The mean ammonia, ICP, and international normalized ratio values were significantly lower in the 200‐g group. CT volumetrics demonstrated increased volume regeneration at 48 hours following hepatectomy in the 200‐g group compared with the SMT ( P < 0.01) and 0‐g (P < 0.01) groups. Ki‐67 staining showed increased positive staining at 48 hours following hepatectomy ( P < 0.01). Conclusion: The SRBAL improved survival, reduced ammonia, and accelerated liver regeneration in posthepatectomy ALF. Improved survival was associated with a neuroprotective benefit of SRBAL therapy. These favorable results warrant further clinical testing of the SRBAL.
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The pig hepatectomy model faithfully reflects liver regeneration in humans.
“We next aimed to probe HRX215’s capacity to enhance liver regeneration in a porcine hepatectomy model, which faithfully reflects liver regeneration in humans.41”
From First-in-class MKK4 inhibitors enhance liver regeneration and prevent liver failure (2024) · cites this paper as [41]
The Discussion describes a reproducible porcine hepatectomy model, and the Results (CT Volumetrics; page unavailable) measure liver regeneration in that model. Our copy does not establish that regeneration in the pigs faithfully reflects regeneration in humans. (LLM, conf=0.82)
Experimental — accuracy not yet measured85% hepatectomy in pigs results in a lethal PHLF with a collapse of liver protein synthesis, impaired hepatic metabolism, increased bilirubin levels, and a subsequent increase of intracranial pressure.
“85% hepatectomy in pigs results in a lethal PHLF with a collapse of liver protein synthesis, impaired hepatic metabolism, increase in bilirubin levels, and a subsequent increase of intracranial pressure (ICP).41”
From First-in-class MKK4 inhibitors enhance liver regeneration and prevent liver failure (2024) · cites this paper as [41]
The Results (Survival; Laboratory Values; AST/Total Bilirubin, page unavailable) show that untreated pigs reached a death-equivalent endpoint, while ammonia, bilirubin, INR, and intracranial pressure rose after 85% hepatectomy. The paper does not directly show a collapse of liver protein synthesis—elevated INR is an indirect indicator—and the lethal course applies to the control groups, not all pigs: five of six treated pigs survived to 90 hours. (LLM, conf=0.86)
Experimental — accuracy not yet measuredLiver regeneration after hepatectomy in pigs seems to reflect the situation in humans after hepatectomy very well.
“In particular, liver regeneration after hepatectomy in pigs seems to reflect the situation in humans after hepatectomy very well.41”
From First-in-class MKK4 inhibitors enhance liver regeneration and prevent liver failure (2024) · cites this paper as [41]
The Discussion reports liver regeneration in pigs after hepatectomy, supported by CT volumetrics and Ki-67 staining. It does not compare that regeneration with regeneration in humans after hepatectomy, so the claim that the pig model reflects the human situation very well is unsupported. (LLM, conf=0.82)
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Metadata
- Authors
- Chen, H. S., Joo, D. J., Shaheen, M., Li, Y., Wang, Y., Yang, J., Nicolas, C. T., Predmore, K., Amiot, B., Michalak, G., Mounajjed, T., Fidler, J., Kremers, W. K., & Nyberg, S. L.
- Affiliations
- Mayo Clinic (US)
- Corresponding author
- Nyberg, Scott L.
- ORCID
- Venue
- Hepatology
- Published
- 2018-12-27
- Volume
- 69
- Issue
- 1
- Pages
- 329-342
- ISSN
- 0270-9139 (ISSN-L)
- 1527-3350
- PMC
- PMC6527364
- OpenAlex
- W2884404363
- Cited by
- 77
- References
- 31
- Citations by year
- 2026: 4 · 2025: 7 · 2024: 11 · 2023: 10 · 2022: 6 · 2021: 12 · 2020: 17 · 2019: 9 · 2018: 1
- FWCI
- 10.13
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Hepatology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- YUHSpace (Yonsei University Medical Library) (submittedVersion, cc-by-nc-nd)
- Funders
- Mayo Foundation for Medical Education and Research
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK106667, R01DK056733)
- NIH Clinical Center
- Topics
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Health Sciences › Medicine › Hepatology › Liver Disease and Transplantation
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Keywords
- post-hepatectomy liver failure, acute liver failure, hepatectomy, porcine model, hepatocyte spheroids, liver regeneration, survival, intracranial pressure, hepatic encephalopathy, ammonia, Ki-67, neuroprotection
- MeSH terms
- Animals, Female, Hepatectomy, Liver Regeneration, Random Allocation, Swine, Survival Rate, Liver Failure, Spheroids, Cellular, Liver, Artificial, Bioartificial Organs, Hepatocytes
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