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Page 6 of 16 Liu et al. Hepatoma Res 2020;6:7 I http://dx.doi.org/10.20517/2394-5079.2019.39

Hepatic hyperplasia described rather than histological HCC Alcoholic hepatitis and fibrosis in non- tumour tissue burden in male but not female DEN- treated mice Liver injury and fibrosis in non-tumour tissue 7.5% mortality rate Hepatitis at Day 60, fibrosis at Day 90, 100% cirrhosis at Day 120 in non- tumour tissue WG, IR and steatosis but no inflammation or fibrosis e.g., MCD, CD and WD Similar rate of tumours in male and femal

Comments Ethanol significantly increased tumour HCC not described in other single diets, WG, IR and steatosis and inflammation

Hepatic lesions with elevated AFP and

HCC development cellular proliferation No tumours at 24 weeks At 48 weeks, tumours displayed in: Males 93.7% Females 35.7% 100% moderate to well differentiated tumours at Day 150 1/40 (2.5%) displayed tumour at 12 months 19/75 (25%) displayed tumours at 12 months 30% displayed tumours at 6 months 35% displayed tumours at 9 months 89% displayed tumours at 32-52 weeks 100% displayed tumours at 6 months (2 had lung metastases)

Table 1. Examples of mouse models for hepatocellular carcinoma associated with alcoholic and metabolic liver diseases

then 100 mg/kg weekly (Weeks 7-9) 4% Lieber-Decarli DEN 75 mg/kg i.p. weekly (Weeks 4-6), DEN 50 mg/kg gavage single dose at CCl 4 gavage 5 mL/kg twice weekly at HFD from Week 6 DEN 25 mg/kg i.p. single dose at Week

Chemotoxin DEN 1 mg/kg i.p. single dose 21-25 days DEN 100 mg/kg i.p. single dose at Week Week 7, increased to 8 mL/kg at Week DEN 10 mg/kg i.p. single dose on Days DEN 25 mg/kg i.p. single dose at Week

Diet manipulation alcohol diet from Week 9 10/20% (v/v) old ethanol drinking water on alternate days at Week 16 or 40 for 8 weeks 9% ethanol 7 drinking water from Week 9 Week 9 10 - HFD from Week 4 - CD-HFD from Week 4 - CDAA from Weeks 6-8 - WD + high- fructose-glucose water from Weeks 8-12 12-15 2 CD-HFD from 3 Week 3

Genetic modification foz/foz (Alms1 mutant)

- - - - - - - - -
Strain C57BL/6 male B6C3 male and female BALB/c male C57BL/6 male and female C57BL/6 male and female C57BL/6J male B6/129 male NOD.B10 male C57BL/6J male and female C57BL/6J male

Mouse model* Alcohol HCC models Alcohol + DEN Ambade et al. [48] Alcohol + DEN Brandon-Warner et al. [50] Alcohol + DEN + CCl 4 Xin et al. [53] NASH HCC models HFD Wolf et al. [55] CD-HFD Wolf et al. [55] CDAA De Minicis et al. [56] DIAMOND Asgharpour et al. [59] foz/foz mouse + DEN Arfianti et al. [69] HFD + DEN Park et al. [62] CD-HFD + DEN Kishida et al. [61]