Table 1.
Factors that influence the development and severity of liver diseases.
| Liver disease | Geneticsa | Lifestyle/comorbiditiesb | Environmental toxicantsc | Microbiomed |
|---|---|---|---|---|
| Inherited liver diseases | +++2,3 | +4 | – | +3 |
| Biliary atresia | ++5,6 | +(+)5 | ++7 | +8 |
| Primary biliary cholangitis | ++9 | – | ++10, 11, 12, 13, 14, 15 | +16 |
| Primary sclerosing cholangitis | ++17,18 | – | – | +19,20 |
| Autoimmune hepatitis | ++21, 22, 23, 24 | ++21, 22, 23, 24 | +23, 24, 25 | ++26 |
| Direct DILI | +27, 28, 29 | ++30, 31, 32 | +33, 34, 35 | ++36 |
| Idiosyncratic DILI | +37 | +38 | – | – |
| Viral hepatitis | ++39,40 | ++41,42 | +(+)43,44 | – |
| NAFLD/MAFLD | ++45 | +++45 | ++(+)46, 47, 48, 49 | ++(+)50,51 |
| ALD | ++52 | +++52 | – | +++51,53 |
| TAFLD/TASH | – | – | +++46,54 | +55 |
–, no known association or not classifiable. Evidence inadequate in humans and limited in experimental models.
+, possible association. Limited evidence in humans and in experimental models.
++, probable association. Limited evidence in humans and sufficient in experimental models.
+++, known association and/or primary cause. Clear cause and effect association is known.
Sexual dimorphism, familial associations, linkage disequilibrium, etc.
Viral infections, metabolic syndrome, alcohol, underlying liver disease, etc.
Exposure to environmental/occupational chemicals or toxins, natural or anthropogenic, that was not self-administered.
Altered microbiome/dysbiosis in diseased patients or in animal models.