INTRODUCTION The role of reproductive factors in the development of chronic hepatitis B (CHB) remains unknown. We assessed the potential contributions of gender, menopausal status, and menarche age to liver fibrosis in CHB. METHODS A cross-sectional prospective study included 716 women and 716 age-matched men with CHB who were not currently receiving antiviral therapy. Liver stiffness measurement using transient elastography was used to stage liver fibrosis as F0-F1 (<7.2 kPa), F ≥ 2 (7.2 kPa), F ≥ 3 (9.4 kPa), and F = 4 (12.2 kPa). Female patients were asked regarding their age at menarche and menopausal status using a questionnaire. RESULTS Of the 716 women, 121 (16.9%) were postmenopausal, and 80 (11.2%) had advanced liver fibrosis. Multivariate logistic regression analysis showed that the postmenopausal status compared with the premenopausal status (odds ratio [OR] = 3.65-8.83; P < 0.05) and age at menarche of >14 years compared with <13 years (OR = 2.85-3.95; P < 0.05) were significantly associated with advanced fibrosis. Compared with premenopausal women, age-matched men had a higher OR for advanced fibrosis (P < 0.05). Compared with postmenopausal women, age-matched men did not show a significant difference in the degree of liver fibrosis (P > 0.05). Longitudinal data analysis showed that postmenopausal women (n = 31) were significantly less likely to undergo regression of liver fibrosis after antiviral treatment vs premenopausal women (n = 19) (26.3% vs 74.2%, respectively; P < 0.001). DISCUSSION Menopause and late menarche aggravated liver fibrosis in untreated CHB, besides menopause delayed fibrosis regression under antiviral therapy. The protective effect of female gender against fibrosis was lost for postmenopausal women. TRANSLATIONAL IMPACT It is important to consider menopausal status and age at menarche in establishing surveillance strategies among CHB females. Postmenopausal estrogen therapy may be considered for the prevention or treatment of liver fibrosis.

中文翻译：

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性别和生殖因素对慢性乙型肝炎感染患者肝纤维化的影响。

引言生殖因子在慢性乙型肝炎（CHB）发生中的作用仍然未知。我们评估了性别，绝经状态和初潮年龄对CHB肝纤维化的潜在影响。方法一项横断面的前瞻性研究包括716例CHB患者和716例年龄相匹配的男性，他们目前未接受抗病毒治疗。F0-F1（<7.2 kPa），F≥2（7.2 kPa），F≥3（9.4 kPa）和F = 4（12.2 kPa）使用瞬时弹性成像测量肝硬度来进行肝纤维化分期。使用问卷调查询问女性患者初潮年龄和绝经状态。结果716名妇女中，绝经后为121名（16.9％），晚期肝纤维化为80名（11.2％）。多元logistic回归分析显示，绝经后状态与绝经前状态比较（几率[OR] = 3.65-8.83； P <0.05），月经初潮年龄大于14岁而小于13岁（OR = 2.85-3.95； P <0.05）与晚期纤维化显着相关。与绝经前女性相比，年龄相匹配的男性对晚期纤维化的OR更高（P <0.05）。与绝经后女性相比，年龄相配的男性在肝纤维化程度上没有显着差异（P> 0.05）。纵向数据分析显示，与绝经前妇女（n = 19）相比，抗病毒治疗后绝经后妇女（n = 31）发生肝纤维化的可能性显着降低（分别为26.3％和74.2％； P <0.001）。讨论未经治疗的CHB的更年期和月经初潮加剧了肝纤维化，而且在抗病毒治疗下更年期延迟了纤维化的消退。绝经后女性失去了女性抵抗纤维化的保护作用。翻译影响在建立慢性乙型肝炎女性监测策略时，考虑绝经状态和初潮年龄是很重要的。绝经后雌激素治疗可考虑用于预防或治疗肝纤维化。