人类免疫缺陷病毒/丙型肝炎病毒合并感染女性生殖衰老与肝纤维化进展。
Reproductive Aging and Hepatic Fibrosis Progression in Human Immunodeficiency Virus/Hepatitis C Virus-Coinfected Women.
机构信息
Division of GI/Hepatology.
Department of Surgery.
出版信息
Clin Infect Dis. 2017 Oct 30;65(10):1695-1702. doi: 10.1093/cid/cix643.
BACKGROUND
Severity of hepatic fibrosis is greater in postmenopausal than in premenopausal women, perhaps owing to protective effects of estrogens. However, prior studies of estrogen and liver fibrosis lack serial fibrosis measures, adjustment for age, or longitudinal observations in coinfected populations.
METHODS
In a longitudinal cohort of women coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV), we assessed fibrosis progression across reproductive age, using validated serum fibrosis markers, aminotransferase platelet ratio index (APRI) and fibrosis 4 (FIB-4). Fibrosis rate was evaluated within each woman as she transitioned from pre- to postmenopause, defined by a biomarker of ovarian function.
RESULTS
The median follow-up (n = 405) was 9.1 years (interquartile range, 5.0-15.2 years), with a median menopausal age of 49 years (47-52 years). When fully controlled for chronologic aging, the fibrosis progression rate was accelerated during perimenopause, as shown using FIB-4 (0.12 units per year faster than during premenopause; 95% confidence interval [CI], .02-.21; P = .01) and APRI (0.05 units per year faster; -.002 to .09; P = .06). Accelerated fibrosis was also observed during postmenopause compared with premenopause, for FIB-4 (0.14 units per year faster; 95% CI, -.01 to .29; P = .07) and APRI (0.07 units per year faster; -.003 to .15; P = .06). Accelerated fibrosis in perimenopause persisted after adjustment for Hispanic ethnicity, antiretroviral use, and alcohol (0.10 FIB-4 units per year faster than during premenopause; 95% CI, .008-.20; P = .03).
CONCLUSIONS
In HIV/HCV-coinfected women, hepatic fibrosis accelerates with reproductive aging. Accelerated fibrosis begins in perimenopause, highlighting a previously unrecognized group of women at increased risk for advanced fibrosis and associated complications. Longitudinal analyses of fibrosis rates across reproductive age should be conducted in non-HCV-related liver diseases, given potential implications in a broader spectrum of women.
背景
绝经后女性的肝纤维化严重程度大于绝经前女性，这可能归因于雌激素的保护作用。然而，先前关于雌激素和肝纤维化的研究缺乏对纤维化的连续测量、对年龄的调整或对合并感染人群的纵向观察。
方法
在一项感染人类免疫缺陷病毒 (HIV) 和丙型肝炎病毒 (HCV) 的女性合并感染队列中，我们使用经过验证的血清纤维化标志物天冬氨酸转氨酶血小板比值指数 (APRI) 和纤维化 4 指数 (FIB-4)，评估了生育年龄期间的纤维化进展情况。通过卵巢功能的生物标志物，在每个女性从绝经前过渡到绝经后期间评估纤维化率。
结果
中位随访时间（n=405）为 9.1 年（四分位距，5.0-15.2 年），中位绝经年龄为 49 岁（47-52 岁）。当完全控制了chronologic aging（即，与时间相关的老化）后，围绝经期的纤维化进展速度加快，这一点在使用 FIB-4（每年比绝经前快 0.12 单位；95%置信区间，0.02-0.21；P=0.01）和 APRI（每年快 0.05 单位；-0.002 至 0.09；P=0.06）时均有所体现。与绝经前相比，绝经后也观察到纤维化加速，FIB-4 每年快 0.14 单位（95%置信区间，-0.01 至 0.29；P=0.07），APRI 每年快 0.07 单位（-0.003 至 0.15；P=0.06）。在调整了西班牙裔种族、抗逆转录病毒治疗和酒精使用后，围绝经期的纤维化加速仍然存在（每年 FIB-4 快 0.10 单位，比绝经前快 0.008-0.20；P=0.03）。
结论
在 HIV/HCV 合并感染的女性中，肝纤维化随生殖衰老而加速。纤维化加速始于围绝经期，这突出了一个以前未被认识到的、处于晚期纤维化和相关并发症风险增加的女性群体。鉴于在更广泛的女性人群中可能存在的影响，应该在非 HCV 相关肝病中进行生殖年龄期间纤维化率的纵向分析。
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