Animal models applied to acute-on-chronic liver failure: Are new models required to understand the human condition?

Table 1 Current experimental acute-on-chronic liver failure animal models

Animal model	Liver chronic induction	Fibrosis establishment	AD	Immune response observed	Clear methodologyrandomized study	Ref.
Female Wistar rats	HSA subcutaneal and i.v.	Yes	LPS/D-GaIN i.p.	Inflammatory cytokines	Unclear methodology regarding randomization1, n = 60	Wang et al[56], 2012; Gao et al[83], 2016
Male NZ rabbit	CCl4 in oil i.p.	Yes	Not described	Not described	Unclear methodology	Zhu et al[71], 2013
Female Wistar rats	HSA subcutaneal and i.v.	Yes	LPS/D-GaIN i.p.	Inflammatory pathway through cytokines increase	Unclear methodology regarding randomization1, n = 15	Yang et al[57], 2014
Female SD rats	CCl4 in oil i.p.	Yes	LPS/D-GaIN i. p.	Not described	Unclear methodology	Zhang et al[67], 2014
Female Wistar rats	BD ligature	Yes	ischemia 70% liver reduction	Inflammatory cytokines	Unclear methodology regarding randomization, n = 10	Hu et al[58], 2014
Male SD rats	CCl4 in oil i.p.	Yes	LPS/D-GaIN i.p.	Treg/Th17 imbalance	Unclear methodology regarding randomization1, n = 80	Ni et al[59], 2017
Male Wistar rats	Cholestasis induced by BD ligature	Yes	Not described	CD45+ up regulation	Unclear methodology regarding randomization1, n = 20	Gilsanz et al[60], 2017
Male Wistar rats	PS i.p.	Yes	LPS/D-GaIN i.p.	Inflammatory cytokines	Unclear methodology regarding randomization1, n = 10 e 60	Li et al[61], 2017
Wistar rats	BD ligature	Yes	LPS i.p.	Not described	Unclear methodology regarding randomization1, n = 6/8	Nataj, et al[80], 2018
Wistar or SD rats	CCl4 or TAA or BD ligature	Yes	LPS i.p.	Neutrophil infiltration and NET	Unclear methodology regarding randomization1, n = 6-9	Tripathi et al [69],2018
Male C57BL/6J	CCl4 in olive oil i.p.	Yes	Ethyl alcohol	Inflammatory cytokines and neutrophil infiltration	Unclear methodology regarding randomization1	Furuya, et al[14], 2019; Schwarzkopf et al[73], 2020
Male SD rats	CCl4 in oil i.p.	Yes	LPS/D-GaIN i.p.	Not described†	Unclear methodology regarding randomization1, n = 10	Xue et al[43], 2019
Male SD rats	CCl4 in oil i.p.	Yes	LPS/D-GaIN i.p.	Not described†§	Unclear methodology regarding randomization1, n = 10	Xie et al[68], 2019
Male C57BL/6J	CCl4 in oil i.p.	Yes	Klebsiella pneumonia i.p.	Increase in IL-6 and IFN-γ pathway	Unclear methodology regarding randomization1, n = 4-8	Xiang, et al[70], 2020
SD rats	BD ligation	Yes	LPS i.p.	Inflammatory cytokines	Unclear methodology	Monteiro et al[62], 2021

¹There is no methodological description of the randomization that has been used. ^†The mitochondrial function was assessed relating with cell damage and systemic inflammatory response. ^§This model shows increased of vacuoles and damage liver mitochondrial, and downregulation in adenosine triphosphate and adenosine diphosphate source. AD: Acute decompensation; NZ: New Zealand; SD: Sprague Dawley; HAS: Human albumin serum; PS: Porcine serum; i.p.: Intraperitoneal injection; i.v.: Intravenous injection; TAA: Thioacetamide Administration; LPS: Lipopolysaccharide; D-GaIN: D- Galactosamine Hydrochloride; BD: Bile Duct; CCl₄: Carbon Tetrachloride; NET: Neutrophil extracellular trap; Treg: Regulatory T cell; Th17: T helper 17 lymphocyte.