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肝脂肪变性和 2 型糖尿病的发展:慢性乙型肝炎和病毒特异性因素的影响。

Hepatic steatosis and development of type 2 diabetes: Impact of chronic hepatitis B and viral specific factors.

机构信息

Graduate Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan.

Department of Gastroenterology, Ren-Ai Branch, Taipei City Hospital, Taipei, Taiwan.

出版信息

J Formos Med Assoc. 2022 Aug;121(8):1478-1487. doi: 10.1016/j.jfma.2021.10.014. Epub 2021 Nov 8.

Abstract

BACKGROUND

Chronic hepatitis B (CHB) was associated with a lower prevalence of nonalcoholic fatty liver disease (NAFLD). The impact of CHB on the link between NAFLD and type 2 diabetes (T2D) and related virological implications remain unclear.

METHODS

We recruited 2255 middle-to older-aged individuals who were examined serially for hepatic steatosis by ultrasonography and blood biochemistry as part of a population-based hepatocellular-carcinoma cohort study. In CHB patients, hepatitis B surface antigen (HBsAg) seroclearance and variation in viral load trajectory were also evaluated.

RESULTS

During the average follow-up of 6 years, 168 participants developed T2D. CHB, as compared with uninfected subjects, was associated with lower risks for both new development and persistence of hepatic steatosis. Furthermore, the risk of steatosis decreased with higher levels of past viral load trajectories (p for trend = 0.0002). However, concomitant steatosis at baseline in CHB patients was still significantly associated with a 1.98-fold increased risk for T2D after multivariate adjustment including age, impaired fasting glucose, cirrhosis, and time-varying body mass index, although CHB reduced the propensity of hepatic steatosis to develop diabetes, especially for patients with high levels of past viral-load trajectory. In CHB, the functional cure of HBV infection, as indicated by HBsAg seroclearance, was associated with a 1.41-fold (95% CI 1.12-1.79) increased risk of steatosis. In addition, the increased risk for progressive impairment of glucose metabolism due to steatosis was especially prominent after HBsAg seroclearance.

CONCLUSION

The data showed that HBV interferes with fatty liver disease and modulates its related T2D risk, offering additional insight into the interplay between NAFLD and CHB.

摘要

背景

慢性乙型肝炎(CHB)与非酒精性脂肪性肝病(NAFLD)的患病率较低相关。CHB 对 NAFLD 和 2 型糖尿病(T2D)之间关联的影响及其相关病毒学意义尚不清楚。

方法

我们招募了 2255 名中年及以上个体,他们作为基于人群的肝细胞癌队列研究的一部分,通过超声和血液生化检查连续检查肝脂肪变性。在 CHB 患者中,还评估了乙型肝炎表面抗原(HBsAg)血清清除和病毒载量轨迹的变化。

结果

在平均 6 年的随访期间,有 168 名参与者发生了 T2D。与未感染者相比,CHB 与新发生和持续存在肝脂肪变性的风险较低相关。此外,随着过去病毒载量轨迹水平的升高,发生脂肪变性的风险降低(趋势 p 值=0.0002)。然而,在多变量调整包括年龄、空腹血糖受损、肝硬化和随时间变化的体重指数后,CHB 患者基线时同时存在的脂肪变性仍与 T2D 的风险增加 1.98 倍显著相关,尽管 CHB 降低了脂肪变性发展为糖尿病的倾向,特别是对于过去病毒载量轨迹水平较高的患者。在 CHB 中,HBsAg 血清清除表明乙型肝炎病毒感染的功能性治愈,与脂肪变性的风险增加 1.41 倍(95%CI 1.12-1.79)相关。此外,由于脂肪变性导致葡萄糖代谢进行性受损的风险增加在 HBsAg 血清清除后尤为突出。

结论

数据表明,HBV 干扰脂肪性肝病并调节其相关的 T2D 风险,为 NAFLD 和 CHB 之间的相互作用提供了更多的见解。

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