We extend our sincere gratitude to Dr. Francesco Paolo Russo and Alberto Ferrarese for their thorough evaluation and professional insights on our study [1]. We are gratified by their recognition of the potential of the age-adjusted Charlson Comorbidity Index for Hepatitis B Virus-Related Acute-on-Chronic Liver Failure (aCCI-HBV-ACLF) score in enhancing the accuracy of short-term and medium-term prognostic predictions, particularly in integrating comorbidity factors and reducing variability among clinicians [2].

Previous research has established that multiple comorbidities are strongly associated with poor prognosis, with extrahepatic complications such as chronic renal failure and diabetes significantly elevating the mortality risk in patients with liver disease [3-5]. However, the relatively low incidence of these comorbidities presents challenges in fully incorporating them into prognostic models. Although the aCCI was initially designed for long-term prognostic evaluation, study has underscored its relevance in evaluating the prognosis of liver disease patients [6]. Similarly, our further analysis demonstrated that in the short-term prognosis of patients with HBV-related ACLF, nearly all comorbidities included in the aCCI are significantly correlated with short-term survival outcomes (Table 1). For instance, cardiovascular diseases were associated with a 287% increase in the 28-day mortality risk and a 267% increase in the 90-day mortality risk. Additionally, patients with chronic obstructive pulmonary disease, connective tissue diseases, diabetes, moderate to severe renal disease, tumours and haematological diseases exhibited substantially increased mortality risks. In contrast, although peptic ulcer disease showed a certain increase in risk, it did not reach statistical significance (p > 0.05).

We fully concur with the concern regarding the exclusion of liver transplant patients from the study population. Liver transplantation is a crucial therapeutic option for ACLF, demonstrating significant improvements in patient outcomes [7, 8]. Studies have demonstrated that liver transplantation markedly enhances survival rates compared to patients not receiving transplantation, with only a small proportion succumbing to surgical complications or postoperative issues [9]. Including liver transplant recipients in this study could disproportionately elevate the incidence of end-point events, potentially leading to an overestimation of associated risks. Moreover, differences in medical expertise and resources across centres can significantly influence transplant success rates and post-transplant survival outcomes. Critical determinants of transplantation outcomes include the quality of donor organs, the overall health status of recipients and the expertise of the surgical team [10]. Not all patients awaiting transplantation are eligible, and therefore, including liver transplant recipients might compromise the predictive accuracy of the model when applied to other medical centres. Consequently, liver transplant recipients were excluded from the model's development.

We also acknowledge the potential influence of regional and racial variations on the generalisability of the aCCI-HBV-ACLF score. To address this, we aim to expand our data collection in future studies to validate the score in diverse populations. Once again, we are grateful for their in-depth review and constructive suggestions on our study. Their feedback has further illuminated the applicability and avenues for optimisation of the aCCI-HBV-ACLF score in different populations. We firmly believe that the aCCI-HBV-ACLF score can provide a more accurate prognostic assessment tool for the treatment and management of patients with ACLF in clinical practice.

我们衷心感谢 Francesco Paolo Russo 博士和 Alberto Ferrarese 博士对我们研究的全面评估和专业见解 [1]。我们欣慰地看到他们认识到年龄调整后的乙型肝炎病毒相关慢加急性肝衰竭查尔森合并症指数 （aCCI-HBV-ACLF） 评分在提高短期和中期预后预测的准确性方面的潜力，特别是在整合合并症因素和减少临床医生之间的差异方面 [2]。

既往研究已确定，多种共存疾病与不良预后密切相关，肝外并发症（如慢性肾功能衰竭和糖尿病）显著增加了肝病患者的死亡风险[3-5]。然而，这些合并症的发生率相对较低，因此难以将其完全纳入预后模型。尽管 aCCI 最初是为长期预后评估而设计的，但研究强调了其在评估肝病患者预后的相关性 [6]。同样，我们的进一步分析表明，在 HBV 相关 ACLF 患者的短期预后中，aCCI 中包含的几乎所有合并症都与短期生存结果显着相关（表 1）。例如，心血管疾病与 287 天死亡风险增加 287% 和 90 天死亡风险增加 90% 有关。此外，患有慢性阻塞性肺病、结缔组织病、糖尿病、中度至重度肾病、肿瘤和血液病的患者死亡风险显着增加。相比之下，尽管消化性溃疡病的风险有一定的增加，但并未达到统计学意义 （p > 0.05）。

我们完全同意对将肝移植患者排除在研究人群之外的担忧。肝移植是 ACLF 的重要治疗选择，表明患者预后有显著改善 [7， 8]。研究表明，与未接受移植的患者相比，肝移植显著提高了生存率，只有一小部分患者死于手术并发症或术后问题 [9]。将肝移植受者纳入本研究可能会不成比例地提高终点事件的发生率，可能导致对相关风险的高估。此外，不同中心的医学专业知识和资源的差异会显著影响移植成功率和移植后生存结果。移植结果的关键决定因素包括供体器官的质量、受者的整体健康状况和手术团队的专业知识 [10]。并非所有等待移植的患者都符合条件，因此，当应用于其他医疗中心时，包括肝移植受者可能会损害模型的预测准确性。因此，肝移植受者被排除在该模型的开发之外。

我们还承认地区和种族差异对 aCCI-HBV-ACLF 评分普遍性的潜在影响。为了解决这个问题，我们的目标是在未来的研究中扩大我们的数据收集，以验证不同人群的评分。我们再次感谢他们对我们研究的深入审查和建设性建议。他们的反馈进一步阐明了 aCCI-HBV-ACLF 评分在不同人群中的适用性和优化途径。我们坚信 aCCI-HBV-ACLF 评分可为临床实践中 ACLF 患者的治疗和管理提供更准确的预后评估工具。