輔助二甲雙胍不能加速乙型肝炎表面抗原清除

StephenW

輔助二甲雙胍不能加速乙型肝炎表面抗原清除
瑪麗亞·阿里尼·洛佩茲，PT，DPT，CSCS，CMTPT
| 2022 年 9 月 23 日
在接受恩替卡韋的慢性乙型肝炎病毒感染患者中，輔助二甲雙胍未能加速乙型肝炎表面抗原清除。

根據發表在《肝髒病學年鑑》上的研究結果，二甲雙胍作為恩替卡韋治療的輔助藥物不會加速乙型肝炎 e 抗原 (HBeAG) 陰性慢性乙型肝炎病毒 (HBV) 感染患者的乙型肝炎表面抗原 (HBsAg) 清除。

中國的研究人員在 2020 年 1 月至 2020 年 9 月期間進行了一項雙盲、單中心、隨機、安慰劑對照試驗，以評估輔助二甲雙胍對接受恩替卡韋 12 個月以上的慢性 HBV 患者的影響。患者以 1:1 的方式隨機分配接受輔助二甲雙胍 (n=29) 或安慰劑 (n=31) 治療 24 週。主要結果是第 24 周和第 36 週的血清 HBsAg 水平。

在二甲雙胍和安慰劑組的患者中，平均 (SD) 年齡分別為 49.4 (6.3) 和 50.5 (7.7) 歲，其中 82.8% 和 83.9% 為男性，基線時的中位血清 HBsAg 水平 (log IU/mL) 為分別為 2.43（IQR，1.64-2.73）和 2.47（IQR，1.64-2.76）。

在第 24 週，二甲雙胍（2.18；95% CI，2.12-2.24）和安慰劑（2.13；95% CI，2.07-2.19）組患者之間調整後的平均血清 HBsAg 水平沒有顯著差異。對第 36 週調整後的平均血清 HBsAg 水平的進一步分析顯示，二甲雙胍（2.17；95% CI，2.11-2.23）和安慰劑（2.11；95% CI，2.05-2.17）組患者的結果相似。

這些發現提出了一個問題，即為什麼二甲雙胍的這些有影響的抗病毒和免疫調節作用不能轉化為臨床益處。

儘管在二甲雙胍組的患者中觀察到較高的不良事件 (AE) 發生率，但與安慰劑組的患者相比沒有顯著差異（31.0% 對 16.1%；P =.227）。最常見的 AE 包括腹瀉（10.3% 對 6.5%）、腹脹（6.9% 對 0%）和 HBeAg 血清逆轉（10.3% 對 6.5%）。兩個患者組均未報告嚴重的 AE。

敏感性分析結果還顯示，二甲雙胍組和安慰劑組患者在第 24 週或第 36 週時血清 HBsAg 水平沒有顯著差異。

研究限制包括樣本量小、單中心設置和有限的普遍性。此外，24 週的輔助二甲雙胍療程可能不足以清除血清 HBsAg。

據研究人員稱，“這些發現提出了一個問題，即為什麼二甲雙胍的這些有影響的抗病毒和免疫調節作用不能轉化為臨床益處。”

披露：一位作者宣布獲得了國家自然科學基金創新研究組項目的資助，該項目支持這項研究。
參考：

張W，李YY，尚QH，等。隨機對照試驗：二甲雙胍附加療法對恩替卡韋治療的慢性乙型肝炎患者功能性治癒的影響。Ann Hepatol。 2022；27(6):100745。 doi:10.1016/j.aohep.2022.100745

StephenW

Adjunctive Metformin Fails to Accelerate Hepatitis B Surface Antigen Clearance
Maria Arini Lopez, PT, DPT, CSCS, CMTPT
| September 23rd, 2022
Adjunctive metformin failed to accelerate hepatitis B surface antigen clearance in patients infected with chronic hepatitis B virus receiving entecavir.

Metformin as an adjunct to entecavir therapy does not accelerate hepatitis B surface antigen (HBsAg) clearance in patients with hepatitis B e antigen (HBeAG)-negative chronic hepatitis B virus (HBV) infection, according to study findings published in Annals of Hepatology.

Researchers in China conducted a double-blind, single-center, randomized, placebo-controlled trial between January 2020 and September 2020 to evaluate the effects of adjunctive metformin in patients with chronic HBV who were receiving entecavir for more than 12 months. Patients were randomly assigned in a 1:1 fashion to receive either adjunctive metformin (n=29) or placebo (n=31) for 24 weeks. The primary outcome was serum HBsAg levels at weeks 24 and 36.

Among patients in the metformin and placebo groups, the mean (SD) age was 49.4 (6.3) and 50.5 (7.7) years, 82.8% and 83.9% were men, and the median serum HBsAg level (log IU/mL) at baseline was 2.43 (IQR, 1.64-2.73) and 2.47 (IQR, 1.64-2.76), respectively.

At week 24, adjusted mean serum HBsAg levels did not significantly differ between patients in the metformin (2.18; 95% CI, 2.12-2.24) and placebo (2.13; 95% CI, 2.07-2.19) groups. Further analysis of adjusted mean serum HBsAg levels at week 36 showed similar results among patients in the metformin (2.17; 95% CI, 2.11-2.23) and placebo (2.11; 95% CI, 2.05-2.17) groups.

These findings raise the question of why those impactful antiviral and immunomodulatory effects of metformin do not translate into a clinical benefit.

Although a higher rate of adverse events (AEs) was observed among patients in the metformin group, it was not significantly different vs those in the placebo group (31.0% vs 16.1%; P =.227). The most common AEs included diarrhea (10.3% vs 6.5%), abdominal distension (6.9% vs 0%), and HBeAg seroreversion (10.3% vs 6.5%). No severe AEs were reported in either patient group.

Results of sensitivity analyses also showed no significant differences in serum HBsAg levels at week 24 or 36 between patients in the metformin and placebo groups.

Study limitations include the small sample size, the single-center setting, and limited generalizability. In addition, the 24-week course of adjunctive metformin may have been insufficient in regard to serum HBsAg clearance.

According to the researchers, “these findings raise the question of why those impactful antiviral and immunomodulatory effects of metformin do not translate into a clinical benefit.”

Disclosure: One author declared receipt of a grant from the Innovative Research Group Project of the National Natural Science Foundation of China, which supported this study.
References:

Zhang W, Li YY, Shang QH, et al. Randomised controlled trial: effect of metformin add-on therapy on functional cure in entecavir-treated patients with chronic hepatitis B. Ann Hepatol. 2022;27(6):100745. doi:10.1016/j.aohep.2022.100745