Supplementary Material for: Incorporating ALBI Grade with Geriatric Nutritional Risk Index Enhances Hepatocellular Carcinoma Risk Stratification

Introduction
Despite its prognostic impact, nutritional status has not yet been integrated into the assessment of hepatocellular carcinoma (HCC). This study investigated the association between geriatric nutritional risk index (GNRI) and overall survival (OS) in patients with HCC using a nationwide registry.
Methods
Data from the Korea Central Cancer Registry between 2008 and 2019 were analyzed. We explored the integration of the GNRI with the albumin–bilirubin (ALBI) grade for prognostic stratification. Restricted cubic spline regression was used to assess the association between GNRI and survival, stratified by ALBI grade.
Results
Among the 16,416 treatment-naïve HCC patients, the ALBI grades were distributed as follows: grade 1, 7,409; grade 2, 7,445; and grade 3, 1,562. Patients were categorized according to Barcelona Clinic Liver Cancer (BCLC) stages: 5,132 stage 0/A, 2,608 stage B, 5,289 stage C, and 968 stage D. The median OS for all patients was 3.1 years (95% CI: 3.0–3.2) and significantly differed with the inclusion of ALBI grade and GNRI (P < 0.001). The effect of combining ALBI grade and GNRI was further evaluated for each BCLC stage. This risk stratification showed a significant correlation with OS for each BCLC stage (all P < 0.001), except for stage D (P = 0.082). Multivariate analysis revealed that a combination of favorable ALBI grade and high GNRI score was independently associated with decreased mortality risk.
Conclusion
The GNRI was significantly correlated with OS across ALBI grades and BCLC stages. Integrating the GNRI into the ALBI grade may enhance risk stratification for patients with HCC.

引言
尽管营养状况具有预后评估价值，但目前尚未被纳入肝细胞癌（hepatocellular carcinoma, HCC）的临床评估体系。本研究依托全国性登记数据库，探讨老年营养风险指数（geriatric nutritional risk index, GNRI）与肝细胞癌患者总生存期（overall survival, OS）的关联。

方法
本研究分析了2008年至2019年韩国中央癌症登记处（Korea Central Cancer Registry）的存档数据。我们探索了将GNRI与白蛋白-胆红素（albumin–bilirubin, ALBI）分级相结合以实现更精准预后分层的方案。采用限制性立方样条回归模型，按ALBI分级分层分析GNRI与患者生存结局的相关性。

结果
本研究共纳入16416例初治肝细胞癌患者，ALBI分级分布如下：1级7409例，2级7445例，3级1562例。按巴塞罗那临床肝癌（Barcelona Clinic Liver Cancer, BCLC）分期进行分组：0/A期5132例，B期2608例，C期5289例，D期968例。所有患者的中位总生存期为3.1年（95%置信区间：3.0~3.2），联合ALBI分级与GNRI可显著区分患者生存预后（P < 0.001）。我们进一步针对各BCLC分期评估了二者联合的预后价值。除D期外（P = 0.082），该联合分层模型与各BCLC分期患者的总生存期均存在显著相关性（所有P < 0.001）。多因素分析结果显示，良好ALBI分级联合高GNRI评分可独立降低患者的死亡风险。

结论
GNRI与不同ALBI分级及BCLC分期的肝细胞癌患者总生存期均存在显著相关性。将GNRI整合至ALBI分级体系中，可进一步提升肝细胞癌患者的风险分层效能。