Table 1 Animal models proposed to replicate MetALD or MASLD+alcohol consumption

HFD + 5% EtOH in drinking water

♀ Balb⁄c

6 week

Yes

Very mild

Yes

No

Easy to set up. Short-term model. Significantly elevated endotoxin levels in the portal circulation, increased TLR4 expression.

No signs of advanced steatohepatitis.

Solid WD (2 weeks) followed by implantation of the intragastric catheter (27 g EtOH/kg body weight/day + liquid HFD) 8 week +  bonus dose 4-5 g EtOH/kg body weight/week

♂ C57BL/6

10 week

Yes

MNC infiltration

Yes

No

Important clinical features of ALD, including balloon cell degeneration and necrotic hepatocytes surrounded by PMN infiltrates, splenomegaly, hypoalbuminemia, bilirubinemia.

Heterogeneous responses to the treatment. No data about MetS. Not a physiological model, requiring skilled surgical implantation and extensive animal monitoring. Can be classified as severe procedure, thus have potential. Difficulties with local ethics committees.

HFD + EtOH gastric gavage twice a week (2 g EtOH/kg body weight  as a 30% solution in saline)

♂ C57BL/6

12 week

Yes

Yes (F4/80+ Kupffer cells, CD45 + , CD68+ infiltration)

Yes (histological and molecular)

No

Easy to establish in short term. Very relevant to the real-life setting. Increased body weight, hyperlipidaemia and hyperinsulinaemia. Potentially can be extended to produce more severe fibrosis by either increasing dose of alcohol or duration of treatment.

Inappropriate technique during the oral gavage can be cause of mortality.

WD + EtOH in drinking water (20% for 4 days and 10% for 3 days per week)

♂/♀ C57BL/6 J

16 week

Yes

Mild

Yes (pericellular fibrosis)

No

Easy to perform model. It reproduces a very slow and largely asymptomatic disease progression. Demonstrates significant similarly to human chronic ALD. It can be applied equally to both males and females and preserves gender differences in the disease phenotypes as seen in humans.

Reproduces a limited spectrum of human MetALD features due to the very mild gain of weight and the absence of MetS.

DUAL diet model (WD + 10%EtOH in sweetened drinking water)

♀ and ♂ C57BL/6 J

23 week

Yes

Yes

Yes

Yes (52 week)

Physiological, easy, affordable, highly reproducible diet with low mortality characterized by obesity, glucose intolerance, liver damage, prominent steatohepatitis and fibrosis, as well as inflammation and fibrosis in white adipose tissue.

Lengthy periods of feeding mice, demanding a significant amount of labor.

EtOH binge one single dose of ethanol (5 g/kg body weight as a 53% v/v solution in water) via oral gavage

♂ ob/ob (B6/JGpt-Lepem1Cd25/Gpt)

10 week 9 h after gavage

Yes

Mild neutrophil infiltration in the liver

No

No

Simplicity, low inter-individual heterogeneity.

The etiology of obesity in ob/ob mice can be incompatible with MetALD. Not really a chronical model.

WD + 5% EtOH in drinking water + weekly EtOH gavage (2.5 g EtOH/kg body weight)

♂ C57BL/6 J

12 week

Yes

No

No (only increasing expression of pro-fibrotic genes)

No

Experimental mouse model of early MetALD. Impairs glucose intolerance.

Recapitulates histologic steatosis without histologic inflammation or fibrosis.

WASH-diet model (liquid WD with 4.5% EtOH (vol/vol))

♂ C57BL/6

7 week

Yes

Upregulation of inflammatory factors IL6 and TGFB

Yes

No

Simple model. Mice display high adiposity, elevated serum cholesterol, TG and markers of liver injury.

Does not recapitulate histological inflammation. Liquid diet requires daily changes and significant amount of labor.

MetALD diet (high fat-cholesterol-sugar diet) + 10% EtOH in drinking water + 5 g/kg body weight EtOH gavage weekly

♂ C57BL/6

3 months

Yes

Yes

Yes

No

Mimics the features of MetALD and severe alcohol-associated hepatitis. Hepatic phenotype show molecular signatures of steatosis, inflammation, fibrosis, impaired liver synthetic function, and regeneration.

Survival rate is 85%. Mild MetS