We thank Dr. Lo for the interest in our manuscripts that explored the association of COVID-19 vaccination and mortality.^{[1, 2]} As correctly pointed out, the study reflects the distribution of cirrhosis in the entire Veterans Health Administration without a referral or tertiary care bias.^[1-3] Therefore, as expected, the majority of participants included in both studies had compensated cirrhosis.

Our results showed that, among patients with compensated cirrhosis, postvaccination COVID-19 was associated with an 81% reduction in hazard of death [adjusted hazard ratio (aHR) 0.19, 95% confidence interval (CI) 0.08–0.45, p = 0.0001] and 84% reduction in COVID-19–related death (aHR 0.16, 95% CI 0.06–0.46, p = 0.0001).^[1] Among patients with decompensated cirrhosis, postvaccination COVID-19 was associated with a 73% reduction in hazard of death (aHR 0.27, 95% CI 0.08–0.90, p = 0.03) but not COVID-19–related death (aHR 0.51, 95% CI 0.14–1.88, p = 0.31). We believe that the lack of significance with COVID-19–related death among participants with decompensated cirrhosis is likely a Type II error; the power to identify differences between postvaccination and unvaccinated COVID-19 in this subgroup was only 48.7%, and the sample size required to identify differences between the two groups with 80% power was 366, which was higher than our study sample. Our retrospective study was not designed to identify vaccine safety.

However, a follow-up study from our group using data from the same cohort compared vaccination-induced immunity and infection-induced immunity among participants with cirrhosis and was adequately powered.^[4] The vaccine-associated immunity group was fully vaccinated participants with cirrhosis with no documented severe acute respiratory syndrome coronavirus 2 infection. The infection-induced immunity group was unvaccinated participants who had prior COVID-19. A subgroup analysis among the participants with decompensated cirrhosis in this study showed that vaccine-induced immunity was associated with a reduction in odds of developing COVID-19 [adjusted odds ratio (aOR) 0.10, 95% CI 0.07–0.13, p < 0.0001] and symptomatic (aOR 0.49, 95% CI 0.35–0.70, p < 0.0001), moderate/severe/critical (aOR 0.42, 95% CI 0.26–0.69, p = 0.0004), and severe or critical COVID-19 (aOR 0.15, 95% CI 0.07–0.31, p < 0.0001) compared with infection-induced immunity. This study, done later in the pandemic, had a larger sample size and more outcomes to demonstrate statistical significance.

The above findings suggest that COVID-19 vaccines appear to be protective among participants with decompensated cirrhosis in an adequately powered study cohort, but we agree with the need for more studies in this highly vulnerable population.

我们感谢 Lo 博士对我们探索 COVID-19 疫苗接种与死亡率关联的手稿的兴趣。^{[ 1, 2 ]}正如正确指出的那样，该研究反映了整个退伍军人健康管理局中肝硬化的分布，没有转诊或三级护理偏差。^{[ 1-3 ]}因此，正如预期的那样，两项研究中的大多数参与者都患有代偿性肝硬化。

我们的结果表明，在代偿期肝硬化患者中，接种疫苗后 COVID-19 与死亡风险降低 81% 有关 [调整后的风险比 (aHR) 0.19，95% 置信区间 (CI) 0.08–0.45，p  = 0.0001] COVID-19 相关死亡减少 84%（aHR 0.16，95% CI 0.06–0.46，p  = 0.0001）。^{[ 1 ]}在失代偿期肝硬化患者中，接种疫苗后 COVID-19 与死亡风险降低 73%（aHR 0.27，95% CI 0.08–0.90，p  = 0.03）相关，但与 COVID-19 相关的死亡无关（aHR 0.51 , 95% CI 0.14–1.88, p = 0.31）。我们认为失代偿性肝硬化参与者中与 COVID-19 相关的死亡缺乏显着性可能是 II 类错误；在该亚组中识别接种后和未接种 COVID-19 之间差异的能力仅为 48.7%，以 80% 的能力识别两组之间差异所需的样本量为 366，高于我们的研究样本。我们的回顾性研究并非旨在确定疫苗的安全性。

然而，我们小组使用来自同一队列的数据进行的一项后续研究比较了肝硬化参与者中疫苗接种诱导的免疫力和感染诱导的免疫力，并且具有足够的说服力。^{[ 4 ]}疫苗相关免疫组是完全接种疫苗的肝硬化参与者，没有记录的严重急性呼吸系统综合症冠状病毒 2 感染。感染诱导免疫组是未接种过 COVID-19 疫苗的参与者。本研究中失代偿性肝硬化参与者的亚组分析表明，疫苗诱导的免疫力与发生 COVID-19 的几率降低有关 [调整后的优势比 (aOR) 0.10，95% CI 0.07–0.13，p  < 0.0001]和症状（aOR 0.49，95% CI 0.35–0.70，p  < 0.0001）、中度/重度/危重（aOR 0.42，95% CI 0.26–0.69，p  = 0.0004）和重度或重度 COVID-19（aOR 0.15，95% CI 0.07–0.31，p  < 0.0001）与感染引起的免疫。这项研究是在大流行后期进行的，样本量更大，结果更多，可以证明具有统计学意义。

上述发现表明，COVID-19 疫苗似乎在足够有力的研究队列中对失代偿性肝硬化参与者具有保护作用，但我们同意需要对这一高度脆弱的人群进行更多研究。