Abstract：
Portal hypertension progression can be relieved after controlling the etiology of liver cirrhosis. Whether beta-blockers could additionally enhance the effects during treatment, particularly for small esophageal varices (EV), was unclear. This study aims to assess the efficacy of add-on carvedilol to delay EV progression during anti-hepatitis B virus (HBV) treatment in HBV-related cirrhosis.
This randomized controlled trial enrolled patients with virologically suppressed HBV-compensated cirrhosis and small/medium EV. The participants were randomly assigned to receive nucleos(t)ide analog (NUC) or carvedilol 12.5 mg plus NUC (1:1 allocation ratio). The primary end point was the progression rate of EV at 2 years of follow-up.
A total of 238 patients (small EV, 77.3%) were randomized into 119 NUC and 119 carvedilol plus NUC (carvedilol [CARV] combination group). Among them, 205 patients (86.1%) completed paired endoscopies. EV progression rate was 15.5% (16/103) in the NUC group and 12.7% (13/102) in the CARV combination group (relative risk = 0.79, 95% confidence interval 0.36-1.75, P = 0.567). Subgroup analysis on medium EV showed the CARV combination group had a more favorable effect in promoting EV regression (43.5% vs 13.1%, P = 0.022) than NUC alone, but not in small cases ( P = 0.534). The incidence of liver-related events (decompensation, hepatocellular carcinoma, or death/liver transplantation) within 2 years was similar between the 2 groups (11.2% vs 10.4%, P = 0.881).
The overall results did not show statistically significant differences between the added carvedilol strategy and NUC monotherapy in preventing EV progression in patients with virologically suppressed HBV-compensated cirrhosis. However, the carvedilol-added approach might offer improved outcomes specifically for patients with medium EV (NCT03736265).
This randomized controlled trial enrolled patients with virologically suppressed HBV-compensated cirrhosis and small/medium EV. The participants were randomly assigned to receive nucleos(t)ide analog (NUC) or carvedilol 12.5 mg plus NUC (1:1 allocation ratio). The primary end point was the progression rate of EV at 2 years of follow-up.
A total of 238 patients (small EV, 77.3%) were randomized into 119 NUC and 119 carvedilol plus NUC (carvedilol [CARV] combination group). Among them, 205 patients (86.1%) completed paired endoscopies. EV progression rate was 15.5% (16/103) in the NUC group and 12.7% (13/102) in the CARV combination group (relative risk = 0.79, 95% confidence interval 0.36-1.75, P = 0.567). Subgroup analysis on medium EV showed the CARV combination group had a more favorable effect in promoting EV regression (43.5% vs 13.1%, P = 0.022) than NUC alone, but not in small cases ( P = 0.534). The incidence of liver-related events (decompensation, hepatocellular carcinoma, or death/liver transplantation) within 2 years was similar between the 2 groups (11.2% vs 10.4%, P = 0.881).
The overall results did not show statistically significant differences between the added carvedilol strategy and NUC monotherapy in preventing EV progression in patients with virologically suppressed HBV-compensated cirrhosis. However, the carvedilol-added approach might offer improved outcomes specifically for patients with medium EV (NCT03736265).
摘要：
背景：控制肝硬化的病因后，门脉高压的进展可以得到缓解。β受体阻滞剂是否可以在治疗期间额外增强效果，特别是对于小的食管静脉曲张（EV），不清楚。本研究旨在评估加卡维地洛在抗乙型肝炎病毒（HBV）治疗期间延迟EV进展的疗效。
方法：这项随机对照试验招募了病毒学抑制的HBV代偿性肝硬化和小/中EV患者。参与者被随机分配接受核苷（t）ide类似物（NUC）或卡维地洛12.5mg加NUC（分配比1：1）。主要终点是随访2年的EV进展率。
结果：共238例患者（小EV，77.3％）被随机分为119个NUC和119个卡维地洛+NUC（卡维地洛[CARV]组合组）。其中,205例患者（86.1％）完成了配对内窥镜检查。NUC组EV进展率为15.5%(16/103)，CARV组合组为12.7%(13/102)(相对危险度=0.79，95%置信区间为0.36-1.75，P=0.567)。对中EV的亚组分析显示，CARV组合组在促进EV消退方面具有更有利的作用（43.5％vs13.1％，P=0.022）比单独的NUC，但不是在小的情况下（P=0.534）。肝脏相关事件的发生率（失代偿，肝细胞癌，或死亡/肝移植）在2年内两组之间相似（11.2％vs10.4％，P=0.881)。
结论：总体结果未显示添加卡维地洛策略和NUC单一疗法在预防病毒学抑制的HBV代偿性肝硬化患者的EV进展方面的统计学差异。然而,添加卡维地洛的方法可能会改善中等EV患者的结局(NCT03736265).
方法：这项随机对照试验招募了病毒学抑制的HBV代偿性肝硬化和小/中EV患者。参与者被随机分配接受核苷（t）ide类似物（NUC）或卡维地洛12.5mg加NUC（分配比1：1）。主要终点是随访2年的EV进展率。
结果：共238例患者（小EV，77.3％）被随机分为119个NUC和119个卡维地洛+NUC（卡维地洛[CARV]组合组）。其中,205例患者（86.1％）完成了配对内窥镜检查。NUC组EV进展率为15.5%(16/103)，CARV组合组为12.7%(13/102)(相对危险度=0.79，95%置信区间为0.36-1.75，P=0.567)。对中EV的亚组分析显示，CARV组合组在促进EV消退方面具有更有利的作用（43.5％vs13.1％，P=0.022）比单独的NUC，但不是在小的情况下（P=0.534）。肝脏相关事件的发生率（失代偿，肝细胞癌，或死亡/肝移植）在2年内两组之间相似（11.2％vs10.4％，P=0.881)。
结论：总体结果未显示添加卡维地洛策略和NUC单一疗法在预防病毒学抑制的HBV代偿性肝硬化患者的EV进展方面的统计学差异。然而,添加卡维地洛的方法可能会改善中等EV患者的结局(NCT03736265).
