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多囊肝疾病中的雌激素:未来治疗的靶点?

Estrogens in polycystic liver disease: A target for future therapies?

机构信息

Department of Nephrology, University Medical Center Groningen, University Hospital Groningen, Groningen, the Netherlands.

Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, the Netherlands.

出版信息

Liver Int. 2021 Sep;41(9):2009-2019. doi: 10.1111/liv.14986. Epub 2021 Jul 10.

Abstract

BACKGROUND AND AIMS

Patients suffering from polycystic liver disease (PLD) can develop large liver volumes, leading to physical and psychological complaints, reducing quality of life. There is an unmet need for new therapies in these patients. Estrogen seems to be a promising target for new therapies. In this review, we summarize the available experimental and epidemiological evidence to unravel the role of estrogens and other female hormones in PLD, to answer clinical questions and identify new targets for therapy.

METHODS

We identified all experimental and epidemiologial studies concerning estrogens or other female hormones and PLD, to answer pre-defined clinial questions.

RESULTS

Female sex is the most important risk factor for the presence and severity of disease; estrogen supplementation enhances liver growth and after menopause, liver growth decreases. Experimental studies show the presence of the estrogen receptors alfa and beta on cystic cholangiocytes, and increased in vitro growth after administration of estrogen.

CONCLUSIONS

Based on the available evidence, female PLD patients should be discouraged from taking estrogen-containing contraceptives or hormone replacement therapy. Since liver growth rates decline after menopause, treatment decisions should be based on measured liver growth in postmenopausal women. Finally, blockage of estrogen receptors or estrogen production is a promising target for new therapies.

摘要

背景和目的

患有多囊性肝病 (PLD) 的患者可能会出现肝脏体积增大,导致身体和心理不适,降低生活质量。这些患者需要新的治疗方法。雌激素似乎是新疗法的一个有前途的靶点。在这篇综述中,我们总结了现有的实验和流行病学证据,以阐明雌激素和其他女性激素在 PLD 中的作用,回答临床问题,并确定新的治疗靶点。

方法

我们确定了所有关于雌激素或其他女性激素与 PLD 相关的实验和流行病学研究,以回答预先确定的临床问题。

结果

女性是该病存在和严重程度的最重要危险因素;雌激素补充会促进肝脏生长,而绝经后肝脏生长会减少。实验研究表明,囊性胆管细胞上存在雌激素受体阿尔法和贝塔,并且在给予雌激素后体外生长增加。

结论

基于现有证据,应劝阻患有多囊性肝病的女性服用含有雌激素的避孕药或激素替代疗法。由于绝经后肝脏生长速度下降,因此应根据绝经后女性的肝生长测量值来做出治疗决策。最后,阻断雌激素受体或雌激素的产生是新疗法的一个有前途的靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dddd/8456902/0aa456babe7d/LIV-41-2009-g004.jpg

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