Table 2.
Summary data on the potential implication of estrogen in chronic liver disease and hepatocellular carcinoma.
| Liver Disease | Risk | Mechanism(s) | Reference |
|---|---|---|---|
| HBV | ↑ | ↑ in situ estrogen synthesis | Murakami et al., 2020 [49] |
| HCC | ↑ | Hypermethylation of the ESR1 gene | Hishida et al., 2013 [46] |
| HCC | ↑ | Variant estrogen receptor(s) | Villa et al., 1995 [47] |
| Cirrhosis/HCC | ↑ | ERα36 splice variant | Miceli et al., 2011 [55] |
| HCC | ↑ | Promoter-driven ↑ aromatase expression | Koh et al., 2011 [48] |
| HCC | ↑ | ↑ aromatase expression and activity | Catagnetta et al., 2003 [50] |
| HCC | ↑ | Estrogen-induced ↑ AREG expression | Carruba et al., 2011 [52] |
| HCC | ↑ | AREG-induced ↑ liver cancer cell growth | Cocciadiferro et al., 2017 [54] |
| HCC | ↑ | Liver-specific deletion of NF2 (NF2/KO) | Benhamouche et al., 2010 [66] |
| HCC | ↓ | NF2 (Merlin) regulation of liver stem/progenitor cell niche | Villanueva, 2010 [86] |
| HCC | ↑ | Persistently ↑ estrogen formation and NF2 (Merlin) upregulation | Cocciadiferro et al., 2017 [54] |
| HCC | ↓ | FOXA-dependent ERα-mediated estrogen signaling | Zhao & Li, 2015 [88] |
| HCC | ↑ | FOXA1/2-deficient mice | Li et al., 2012 [90] |
HBV, chronic hepatitis B virus; HCV, chronic hepatitis C virus; HCC, hepatocellular carcinoma; ESR1, estrogen steroid receptor 1; ERα36, estrogen receptor α 36; AREG, amphiregulin; NF2, neurofibromatosis type 2; FOXA, Forkhead bOX protein A.