初治慢性乙型肝炎患者共存乙型肝炎表面抗原和抗体与严重

StephenW

初治慢性乙型肝炎患者共存乙型肝炎表面抗原和抗体与严重肝纤维化和肝硬化的关系
王建 1 2 , 丁伟茂 3 , 刘家成 1 4 , 刘勇 2 5 , 严晓敏 1 2 , 夏娟 1 2 , 吴卫华 1 2 , 北家 1 2 , 陈雨欣 2 5 , 高冬梅 6 , 洪淑琴7 , 王晓红 8 , 王丽 1 , 欣彤 1 2 , 盛夏尹 1 2 , 张兆平 1 , 李洁 1 2 , 黄睿 1 2 4 , 吴超 1 2 4
隶属关系

    PMID: 35696167 DOI: 10.1001/jamanetworkopen.2022.16485

抽象的

重要性：乙型肝炎表面抗原 (HBsAg) 和抗 HBsAg 抗体 (anti-HBs) 共存构成慢性乙型肝炎病毒感染的非典型血清学特征，并且共存的 HBsAg 和抗 HBs 与患者的严重肝纤维化和肝硬化之间存在关联与慢性乙型肝炎 (CHB) 的关系尚不清楚。

目的：探讨 HBsAg 和抗 HBs 共存与慢性乙型肝炎患者严重肝纤维化和肝硬化的关系。

设计、设置和参与者：2015 年 1 月 10 日至 2021 年 3 月 31 日期间，来自中国 2 家医疗机构的连续初治 CHB 患者被纳入研究。使用天冬氨酸转氨酶 (AST) 到血小板确定严重肝纤维化和肝硬化比率指数 (APRI)，基于 4 个因素（FIB-4；因素包括年龄、AST 水平、丙氨酸氨基转移酶 [ALT] 水平和血小板计数）、瞬时弹性成像或超声检查的纤维化指数。数据分析时间为 2021 年 8 月 1 日至 2022 年 4 月 15 日。

主要结果和措施：主要结果是有 HBsAg 和抗 HBs 的患者与没有共存 HBsAg 和抗 HBs 的患者严重肝纤维化和肝硬化的发生率。严重肝纤维化定义为 APRI 评分为 1.5 或更高，FIB-4 评分为 3.25 或更高，或肝脏硬度测量为 8 kPa 或更高；肝硬化定义为 APRI 评分为 2.0 或更高，FIB-4 评分为 6.5 或更高，肝脏硬度测量为 11 kPa 或更高，或提示肝硬化的超声检查结果。

结果：在 6534 名入组患者中，4033 名患者（61.7%）为男性，中位（IQR）年龄为 41.0（33.0-52.0）岁。共有 277 名患者（4.2%）同时存在 HBsAg 和抗 HBs。有抗 HBs 与无抗 HBs 的患者年龄较大（中位 [IQR]，46.0 [33.0-55.5] 岁 vs 41.0 [33.0-52.0] 岁）并且乙型肝炎 e 抗原 (HBeAg) 阳性比例更高（277 名患者中的 123 名） [44.4%] 对比 6257 名患者中的 2115 名 [33.8%]；P < .001)，ALT 水平较高（中位数 [IQR]，45.1 [24.6-119.0] U/L 对比 36.7 [22.0-77.0] U/L；P = .001) 和 AST 水平（中位数 [IQR]，35.0 [23.5-68.4] U/L vs 28.3 [21.6-51.0] U/L；P < .001），以及较低的血小板计数（中位数 [IQR]，173.0 × 103/μL [129.0-212.5 × 103/μL] vs 185.0 × 103/μL [141.0-224.0 × 103/μL]；P = .004)，白蛋白水平（中位数 [IQR]，4.37 [4.11-4.56] g /dL vs 4.43 [4.17-4.61] g/dL；P = .02）和 HBsAg 水平（中位数 [IQR]、2.8 log10 [1.6-3.4 log10] IU/mL vs 3.3 log10 [2.6-3.9 log10] IU/毫升；P < .001)。与没有抗 HBs 的患者相比，有抗 HBs 的患者 APRI 评分更高（中位数 [IQR]，0.5 [0.3-1.4] vs 0.4 [0.3-0.9]；P < .001），FIB-4 评分（中位数 [ IQR]，1.4 [0.9-2.6] vs 1.1 [0.7-2.1]；P < .001)，以及肝脏硬度值（中值 [IQR]，7.5 [6.2-9.8] kPa vs 6.3 [5.2-8.1] kPa；P = .003)。抗 HBs 患者的严重肝纤维化比例也更高（277 名患者中的 102 名 [36.8%] vs 6207 名患者中的 1397 名 [22.5%]；P < .001）和肝硬化（277 名患者中的 87 名 [31.4%] vs 1194 6213 名患者 [19.2%]；P < .001) 与没有抗 HBs 的患者相比。 HBsAg 和抗 HBs 的共存与严重肝纤维化（优势比 [OR]，2.29；95% CI，1.56-3.38；P < .001）和肝硬化（OR，1.73；95% CI，1.12- 2.68；P = .01）在多变量分析中。然而，仅在 HBeAg 阴性患者（OR，1.66；95% CI，1.05-2.62；P = .03）中观察到并存的 HBsAg 和抗 HBs 与肝硬化的关联，而在 HBeAg 阳性患者（OR，1.45）中未观察到；95% CI，0.87-2.43；P = .16)。

结论和相关性：在这项横断面研究中，HBsAg 和抗 HBs 的共存在乙型肝炎病毒感染中并不常见，并且与更晚期的肝脏疾病有关，例如严重的肝纤维化和肝硬化，尤其是在 HBeAg 阴性的患者中。这些结果表明，有必要对具有这种血清学特征的 CHB 患者进行肝纤维化和肝硬化的密切监测。

StephenW

Association of Coexistent Hepatitis B Surface Antigen and Antibody With Severe Liver Fibrosis and Cirrhosis in Treatment-Naive Patients With Chronic Hepatitis B
Jian Wang  1   2 , Weimao Ding  3 , Jiacheng Liu  1   4 , Yong Liu  2   5 , Xiaomin Yan  1   2 , Juan Xia  1   2 , Weihua Wu  1   2 , Bei Jia  1   2 , Yuxin Chen  2   5 , Dongmei Gao  6 , Shuqin Hong  7 , Xiaohong Wang  8 , Li Wang  1 , Xin Tong  1   2 , Shengxia Yin  1   2 , Zhaoping Zhang  1 , Jie Li  1   2 , Rui Huang  1   2   4 , Chao Wu  1   2   4
Affiliations

    PMID: 35696167 DOI: 10.1001/jamanetworkopen.2022.16485

Abstract

Importance: Coexistence of hepatitis B surface antigen (HBsAg) and antibody against HBsAg (anti-HBs) constitutes an atypical serological profile in chronic hepatitis B virus infection, and the association between coexistent HBsAg and anti-HBs with severe liver fibrosis and cirrhosis in patients with chronic hepatitis B (CHB) remains unclear.

Objective: To investigate the association of coexistent HBsAg and anti-HBs with severe liver fibrosis and cirrhosis in patients with CHB.

Design, setting, and participants: Consecutive treatment-naive patients with CHB from 2 medical institutions in China were enrolled between January 10, 2015, and March 31, 2021. Severe liver fibrosis and cirrhosis were identified using the aspartate transaminase (AST) to platelet ratio index (APRI), the fibrosis index based on 4 factors (FIB-4; factors comprise age, AST level, alanine aminotransferase [ALT] level, and platelet count), transient elastography, or ultrasonography. Data were analyzed from August 1, 2021, to April 15, 2022.

Main outcomes and measures: The primary outcomes were rates of severe liver fibrosis and cirrhosis among patients with vs patients without coexistant HBsAg and anti-HBs. Severe liver fibrosis was defined as an APRI score of 1.5 or higher, a FIB-4 score of 3.25 or higher, or a liver stiffness measurement of 8 kPa or higher; cirrhosis was defined as an APRI score of 2.0 or higher, a FIB-4 score of 6.5 or higher, a liver stiffness measurement of 11 kPa or higher, or ultrasonographic findings suggestive of cirrhosis.

Results: Of 6534 enrolled patients, 4033 patients (61.7%) were male, and the median (IQR) age was 41.0 (33.0-52.0) years. A total of 277 patients (4.2%) had coexistent HBsAg and anti-HBs. Patients with vs without anti-HBs were older (median [IQR], 46.0 [33.0-55.5] years vs 41.0 [33.0-52.0] years) and had a higher proportion of hepatitis B e antigen (HBeAg) positivity (123 of 277 patients [44.4%] vs 2115 of 6257 patients [33.8%]; P < .001), higher ALT levels (median [IQR], 45.1 [24.6-119.0] U/L vs 36.7 [22.0-77.0] U/L; P = .001) and AST levels (median [IQR], 35.0 [23.5-68.4] U/L vs 28.3 [21.6-51.0] U/L; P < .001), and lower platelet counts (median [IQR], 173.0 × 103/μL [129.0-212.5 × 103/μL] vs 185.0 × 103/μL [141.0-224.0 × 103/μL]; P = .004), albumin levels (median [IQR], 4.37 [4.11-4.56] g/dL vs 4.43 [4.17-4.61] g/dL; P = .02), and HBsAg levels (median [IQR], 2.8 log10 [1.6-3.4 log10] IU/mL vs 3.3 log10 [2.6-3.9 log10] IU/mL; P < .001). Compared with patients without anti-HBs, those with anti-HBs had higher APRI scores (median [IQR], 0.5 [0.3-1.4] vs 0.4 [0.3-0.9]; P < .001), FIB-4 scores (median [IQR], 1.4 [0.9-2.6] vs 1.1 [0.7-2.1]; P < .001), and liver stiffness values (median [IQR], 7.5 [6.2-9.8] kPa vs 6.3 [5.2-8.1] kPa; P = .003). Patients with anti-HBs also had higher proportions of severe liver fibrosis (102 of 277 patients [36.8%] vs 1397 of 6207 patients [22.5%]; P < .001) and cirrhosis (87 of 277 patients [31.4%] vs 1194 of 6213 patients [19.2%]; P < .001) compared with patients without anti-HBs. The coexistence of HBsAg and anti-HBs was independently associated with severe liver fibrosis (odds ratio [OR], 2.29; 95% CI, 1.56-3.38; P < .001) and cirrhosis (OR, 1.73; 95% CI, 1.12-2.68; P = .01) in the multivariate analysis. However, the association of coexistent HBsAg and anti-HBs with cirrhosis was only observed in patients with HBeAg negativity (OR, 1.66; 95% CI, 1.05-2.62; P = .03) and not in patients with HBeAg positivity (OR, 1.45; 95% CI, 0.87-2.43; P = .16).

Conclusions and relevance: In this cross-sectional study, the coexistence of HBsAg and anti-HBs was unusual in hepatitis B virus infection and was associated with more advanced liver diseases, such as severe liver fibrosis and cirrhosis, especially among patients with HBeAg negativity. These results suggest that close monitoring for liver fibrosis and cirrhosis is warranted in patients with CHB who have this serological profile.

StephenW

https://jamanetwork.com/journals ... 654527274.69024.pdf