Prospect of Animal Models for Acute-on-chronic Liver Failure: A Mini-review

Hassan, Hozeifa Mohamed; Li, Jun

doi:10.14218/jcth.2022.00086

Cited by 4 publications

(2 citation statements)

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“…In the absence of specific HBV-CLF animal models [ 55 ], we applied our previously established ACLF rat model [ 22 ], to further assess the potential key role of THBS1 in ACLF pathogenesis. The THBS1 biomarker identified from the human PBMC transcriptome in the COSSH multicenter cohort was externally validated in the serum and liver tissues of ACLF rats, which further confirmed the functional association between THBS1, the immune response and cellular apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Thrombospondin 1 enhances systemic inflammation and disease severity in acute-on-chronic liver failure

Hassan,

Liang,

Xin

et al. 2024

BMC Med

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Background The key role of thrombospondin 1 (THBS1) in the pathogenesis of acute-on-chronic liver failure (ACLF) is unclear. Here, we present a transcriptome approach to evaluate THBS1 as a potential biomarker in ACLF disease pathogenesis. Methods Biobanked peripheral blood mononuclear cells (PBMCs) from 330 subjects with hepatitis B virus (HBV)-related etiologies, including HBV-ACLF, liver cirrhosis (LC), and chronic hepatitis B (CHB), and normal controls (NC) randomly selected from the Chinese Group on the Study of Severe Hepatitis B (COSSH) prospective multicenter cohort underwent transcriptome analyses (ACLF = 20; LC = 10; CHB = 10; NC = 15); the findings were externally validated in participants from COSSH cohort, an ACLF rat model and hepatocyte-specific THBS1 knockout mice. Results THBS1 was the top significantly differentially expressed gene in the PBMC transcriptome, with the most significant upregulation in ACLF, and quantitative polymerase chain reaction (ACLF = 110; LC = 60; CHB = 60; NC = 45) was used to verify that THBS1 expression corresponded to ACLF disease severity outcome, including inflammation and hepatocellular apoptosis. THBS1 showed good predictive ability for ACLF short-term mortality, with an area under the receiver operating characteristic curve (AUROC) of 0.8438 and 0.7778 at 28 and 90 days, respectively. Enzyme-linked immunosorbent assay validation of the plasma THBS1 using an expanded COSSH cohort subjects (ACLF = 198; LC = 50; CHB = 50; NC = 50) showed significant correlation between THBS1 with ALT and γ-GT (P = 0.01), and offered a similarly good prognostication predictive ability (AUROC = 0.7445 and 0.7175) at 28 and 90 days, respectively. ACLF patients with high-risk short-term mortality were identified based on plasma THBS1 optimal cut-off value (< 28 µg/ml). External validation in ACLF rat serum and livers confirmed the functional association between THBS1, the immune response and hepatocellular apoptosis. Hepatocyte-specific THBS1 knockout improved mouse survival, significantly repressed major inflammatory cytokines, enhanced the expression of several anti-inflammatory mediators and impeded hepatocellular apoptosis. Conclusions THBS1 might be an ACLF disease development-related biomarker, promoting inflammatory responses and hepatocellular apoptosis, that could provide clinicians with a new molecular target for improving diagnostic and therapeutic strategies. Graphical Abstract

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Section: Discussionmentioning

confidence: 99%

Thrombospondin 1 enhances systemic inflammation and disease severity in acute-on-chronic liver failure

Hassan,

Liang,

Xin

et al. 2024

BMC Med

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“…Acute hepatic failure (AHF) is associated with an alarmingly high mortality rate of 80% [ 9 ]. Many studies have been conducted on animal models of acute hepatic failure, but implementing any model in practice is not an easy task [ 10 , 11 ]. Each model typically focuses on a specific aspect of AHF, lacking a comprehensive representation of the syndrome as a whole.…”

Section: Introductionmentioning

confidence: 99%

Ethanol Extract of the Microalga Phaeodactylum tricornutum Shows Hepatoprotective Effects against Acetaminophen-Induced Acute Liver Injury in Mice

Kim,

Park,

Eom

et al. 2024

IJMS

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Acute liver failure is an infrequent yet fatal condition marked by rapid liver function decline, leading to abnormalities in blood clotting and cognitive impairment among individuals without prior liver ailments. The primary reasons for liver failure are infection with hepatitis virus or overdose of certain medicines, such as acetaminophen. Phaeodactylum tricornutum (PT), a type of microalgae known as a diatom species, has been reported to contain an active ingredient with anti-inflammatory and anti-obesity effects. In this study, we evaluated the preventive and therapeutic activities of PT extract in acute liver failure. To achieve our purpose, we used two different acute liver failure models: acetaminophen- and D-GalN/LPS-induced acute liver failure. PT extract showed protective activity against acetaminophen-induced acute liver failure through attenuation of the inflammatory response. However, we failed to demonstrate the protective effects of PT against acute liver injury in the D-GalN/LPS model. Although the PT extract did not show protective activity against two different acute liver failure animal models, this study clearly demonstrates the importance of considering the differences among animal models when selecting an acute liver failure model for evaluation.

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Liver Regeneration in Acute on Chronic Liver Failure

Blake¹,

Steer²

2023

Clinics in Liver Disease

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Prospect of Animal Models for Acute-on-chronic Liver Failure: A Mini-review

Cited by 4 publications

References 84 publications

Thrombospondin 1 enhances systemic inflammation and disease severity in acute-on-chronic liver failure

Thrombospondin 1 enhances systemic inflammation and disease severity in acute-on-chronic liver failure

Ethanol Extract of the Microalga Phaeodactylum tricornutum Shows Hepatoprotective Effects against Acetaminophen-Induced Acute Liver Injury in Mice

Liver Regeneration in Acute on Chronic Liver Failure

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