Liver Cancer: Therapeutic Challenges and the Importance of Experimental Models

Table 1

Pathophysiological characteristics between cytotoxic HCC experimental models.

Model						HCC time development	Highlights	Ref
MRHM	+	+	+	−	+	5–12 months	Infiltration, preneoplasia at 30 days, high number of positive fields for GGT. Fibrosis, inflammation, metabolic alterations. Allows the study of early and late HCC.	[39, 40]
DEN	+	−	−	−	+	9 months	Chronic inflammation, chromosomal instability, disruption of cell cycle, DNA damage, neutrophil infiltration, bile duct proliferation, centrilobular hemorrhagic necrosis, bridging necrosis.	[41]
CCl4	+	+/−	+	−	+	1-2 years	Hepatic collagen accumulation, periportal fibrosis, hepatocyte necrosis, stellate hepatic cell activation, macrophage infiltration.	[42]
TAA	+	+/−	+	+	+	6–12 months	Strong centrally driven fibrotic component, progressing to cirrhosis prior to HCC.	[43]
STAM	+	+	+	−	+	20 weeks	Hepatic fat deposit whilst increased lobular inflammation with foam cell-like macrophages.	[44]
CDE	+	+/−	+/−	−	+	14 months	Major steatosis, periportal injury, fibrosis, strong liver progenitor cell component.	[43]
ALIOS	+	+/−	+/−	−	+	1 year	Ballooning hepatocytes, fibrosis, later liver progenitor cell involvement.	[45]
DIAMOND	+	+/−	+	−	+	1 year	Ballooning and progressive fibrosis. Strong histologic and transcriptomic similarities with human NASH and HCC.	[46]
DEN + HFD	+	+	+	+	+	9 months	Characterized model of enhancing IL-6 and TNF expression.	[47]
DEN + CCl4	+	+/−	+	−	+	5–9 months	Inflammation, fibrogenesis, oxidative stress, shortened HCC latency, and increased presence of progenitor cells.	[48, 49]

⁺Present;  ⁻absent;  ^+/−may or may not develop in experimental models (relative incidence). DEN: diethylnitrosamine; CCl₄: carbon tetrachloride; MRHM: modified resistant hepatocyte model; TAA: thioacetamide; STAM: streptozotocin + HFD-treated mice; CDE: choline-deficient ethionine-supplemented diet; ALIOS: American lifestyle-induced obesity syndrome model; DIAMOND: diet-Induced animal model of nonalcoholic fatty liver disease; and HFD: high-fat diet.