TABLE 2.
Diet-induced NASH-associated fibrosis1
| Diet and species (ref) | Fibrosis (time to development) | Comments/applicable to advanced NASH fibrosis? |
|---|---|---|
| HFD | ||
| Mice (37) | Slight perivenular fibrosis (50 wk) | No progression beyond early/mild fibrosis; not applicable |
| Rats (39) | Mild perisinusoidal fibrosis (24 wk) | — |
| High-fat, high-cholesterol ± cholate | ||
| Hamsters (43) | Bridging fibrosis (12 wk) | Periportal microvesicular steatosis unlike adult NASH; not applicable if using toxic levels of dietary cholesterol |
| Mice (42) | Mild perisinusoidal fibrosis (week 30); bridging fibrosis (week 24, with dietary cholate) | Increased glucose and insulin tolerance; very high cholesterol content; cholate may be liver toxic; other models seem more applicable |
| Rabbits (48) | Central-central and portal-central bridging fibrosis (week 36) | Liver triglycerides not increased; nominal reduction of ALT and AST; improved insulin sensitivity and blood glucose; not applicable |
| Rats (45, 46) | Mild perisinusoidal fibrosis in one-third of animals (week 16); mild/moderate central and portal fibrosis (week 24–48); mild/moderate fibrosis in most and cirrhosis in some animals (week 9 with dietary cholate) | No progression beyond early fibrosis unless using very high levels of cholesterol and cholate; cholate may be liver toxic; not applicable |
| Western | ||
| DIAMOND mice (16) | Central perisinusoidal fibrosis (week 16–24); bridging fibrosis (week 52) | Histology and transcriptome mirror human NASH; long feeding time to achieve advanced fibrosis; applicable |
| Guinea pig (55) | Central perisinusoidal fibrosis (week 16); central-central and central-portal bridging fibrosis (week 25) | Histology and gene expression mirror human NASH; not obese; glucose tolerance not compromised; applicable |
| Hamster (17) | Bridging fibrosis (week 12–16) | No ballooning and predominantly microvesicular; could be applicable |
| Mice (52–54) | Central and portal perisinusoidal fibrosis (week 16–50); minority of animals (2/9) develop advanced fibrosis (week 50) | Advanced fibrosis requires lengthy feeding regimens and only develops in few animals; no advantages over other models |
| Rat (51) | Absent (week 16) | No fibrosis; periportal steatosis (unlike adult NASH); not applicable |
| Ossabaw pigs and Ossabaw miniature pig(56–58) | Mild fibrosis in half (3/6) of animals (week 16); periportal sinusoidal/moderate fibrosis (week 24); possibly bridging fibrosis (week 34)2 | Metabolic profile mimics human; predominantly microvesicular steatosis unlike humans; normal liver anatomy differs substantially from humans; portal-portal bridges present in normal liver; fibrosis pattern does not mimic adult NASH; not applicable |
| MCD | ||
| Mice (59) | Periportal fibrosis (week 10); perisinusoidal and periportal fibrosis (week 14); bridging fibrosis (week 16) | No ballooning; extensive weight loss; enhanced glucose and insulin tolerance; dissimilar molecular signaling pathways; fibrosis originating periportally (mice) unlike adult NASH; disease etiology does not mimic humans; not applicable |
| Rat (60, 61) | Central pericellular fibrosis (week 12); bridging fibrosis (week 17); cirrhosis (week 20) | — |
| CD-HFD | ||
| Mice (62) | Mild perisinusoidal (52 wk) | No advanced fibrosis; disease etiology does not mimic humans; not applicable |
| CDAA | ||
| Mice (63) | Mild/moderate (week 20) | No advanced fibrosis; disease etiology does not mimic humans; glucose/insulin tolerance not affected; not applicable |
| Rats (54) | Bridging fibrosis with nodular formation (week 12) | Rapid induction of advanced fibrosis and histology and mirror human NASH; disease etiology does not mimic humans; weight gain is decreased; other models may reflect dietary NASH etiology more closely |
| CDAA-HFD | ||
| Mice (64–66) | Perisinusoidal and periportal fibrosis (week 24); portal-portal bridging fibrosis (week 48) | Disease induction is faster compared with CDAA in mice; weight gain decreased; could be applicable, but other models seem more suitable |
| Göttingen minipigs (67) | Chicken-wire fibrosis (week 8) | Normal liver anatomy differs substantially from humans; weight gain decreased; no hepatocyte ballooning; no advanced fibrosis; not applicable |
1
ALT, alanine aminotransferase; AST, aspartate aminotransferase; CD-HFD, choline-deficient, high-fat diet; CDAA, choline-deficient, l-amino acid–defined; CDAA-HFD, choline-deficient, l-amino acid–defined high-fat diet; DIAMOND, diet-induced animal model of nonalcoholic fatty liver disease; HFD, high-fat diet; MCD, methionine and choline deficient; NASH, nonalcoholic steatohepatitis; Ref, reference.
2
Scoring system not defined, complicating the determination of fibrosis stage.