Single-nodule hepatitis B virus-associated hepatocellular carcinoma smaller than 3 cm: two phenotypes defined by cluster analysis and their association with the outcome of ablation as the first-line therapy,International Journal of Hyperthermia

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Single-nodule hepatitis B virus-associated hepatocellular carcinoma smaller than 3 cm: two phenotypes defined by cluster analysis and their association with the outcome of ablation as the first-line therapy
International Journal of Hyperthermia ( IF 3.0 ) Pub Date : 2021-02-04 , DOI: 10.1080/02656736.2021.1876930
Shuanggang Chen _{1,

2} , Ying Wu _{1,

2} , Han Qi _{1,

2} , Lujun Shen _{1,

2} , Weimei Ma _{2,

3} , Fei Cao _{1,

2} , Yuhong Diao _{1,

2} , Ting Wang _{1,

2} , Shunling Ou _{1,

2} , Weijun Fan _{1,

2}

Affiliation

Abstract

Objectives

Hepatocellular carcinoma (HCC) is a heterogeneous disease. This study aimed to identify the heterogeneity related to the prognosis of ablation in patients with single-nodule hepatitis B virus (HBV)-associated HCC ≤3 cm.

Methods

A total of 359 patients with single-nodule HBV-associated HCC ≤3 cm treated with curative thermal ablation were retrospectively investigated. Hierarchical cluster analysis was applied to obtain more homogeneous patient clusters concerning demographic and physiological characteristics. Discriminant analysis was performed to identify the relatively important variables for cluster analysis. Multiple correspondence analysis (MCA) was used to clarify the relationship between clusters and categorical variables. Overall survival (OS) was compared among clusters using the Kaplan–Meier model.

Results

A two-cluster model was identified. Cluster 1 (n = 85) showed a higher percentage of female and older patients, higher inflammation response (higher prognostic nutritional index [PNI] and Glasgow prognostic score [GPS]), worse liver function (higher albumin–bilirubin grade and Child–Pugh grade), and relatively poorer immune status (higher neutrophil-to-lymphocyte ratio [NLR]) than cluster 2 (n = 274). NLR and GPS were the two most influential variables for cluster analysis (p < .0001). Cluster 2 had a significantly better prognosis than cluster 1. MCA revealed a clear negative correlation between inflammation status and liver function. Compared with cluster 1, the hazard ratios for OS of cluster 2 were 0.47 and 0.52 before and after adjusting for age, respectively (p < .05).

Conclusions

This study identified two sub-phenotypes of patients with single-nodule HBV-associated HCC ≤3 cm and their association with the outcome of thermal ablation alone as the first-line therapy.

Key points
Thermal ablation alone as the first-line therapy is not suitable for all patients with single-nodule hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC) ≤3 cm.
Patients with single-nodule HBV-associated HCC ≤3 cm can be identified as two sub-phenotypes associated with the outcome of thermal ablation alone as the first-line therapy, based on key preoperative clinical characteristics, especially inflammatory response and immune status.
Patients with single-nodule HBV-associated HCC ≤3 cm characterized by late-onset disease, worse liver function, poorer immune status, and higher inflammatory response (with higher inflammatory response being the most important factor) are not suitable for thermal ablation alone as the first-line therapy. In contrast, patients with single-nodule HBV-associated HCC ≤3 cm characterized by early-onset disease, better liver function, lower inflammatory response, and good immune status (with lower inflammatory response being the most important factor) are particularly suitable for thermal ablation alone.

Implications for patient care
In the treatment of patients with single-nodule HBV-associated HCC ≤3 cm, thermal ablation alone as the first-line therapy should be carefully considered after recognizing the key clinical characteristics, among which inflammatory response and immune status are the two most important factors involved in clinical heterogeneity, and inflammatory response is closely related to the prognosis of thermal ablation alone as the first-line therapy for these patients.

中文翻译：

小于3 cm的单结节性乙型肝炎病毒相关肝细胞癌：通过聚类分析定义的两种表型及其与作为一线治疗方法的消融结果的关系

摘要

目标

肝细胞癌（HCC）是一种异质性疾病。本研究旨在确定与单结节性乙型肝炎病毒（HBV）相关的HCC≤3 cm的患者与消融预后相关的异质性。

方法

回顾性研究了359例经根治性热消融治疗的单结节性HBV相关肝癌≤3cm的患者。应用层次聚类分析获得有关人口统计和生理特征的更均一的患者聚类。进行判别分析以识别用于聚类分析的相对重要的变量。多重对应分析（MCA）用于阐明聚类与分类变量之间的关系。使用Kaplan-Meier模型比较了群集之间的总生存期（OS）。

结果

确定了两个群集模型。第一组（n = 85）显示女性和老年患者百分比更高，炎症反应更高（预后营养指数[PNI]和格拉斯哥预后评分[GPS]更高），肝功能较差（白蛋白-胆红素等级较高和Child-Pugh）等级），且免疫状态较聚类2相对较差（中性白细胞与淋巴细胞之比[NLR]高）（n = 274）。NLR和GPS是两个最有影响力的聚类分析变量（p < .0001）。聚类2的预后明显优于聚类1。MCA显示炎症状态与肝功能之间存在明显的负相关。与群集1相比，群集2的OS在调整年龄前后的危险比分别为0.47和0.52（p <.05）。

结论

这项研究确定了单结节HBV相关性HCC≤3 cm的患者的两种亚表型，并将它们与仅热消融的结果相关联作为一线治疗。

关键点
仅热消融作为一线治疗方法并不适合于所有单结节性乙型肝炎病毒（HBV）相关性肝细胞癌（HCC）≤3 cm的患者。
基于关键的术前临床特征，尤其是炎症反应和免疫状态，可以将单结节HBV相关性HCC≤3 cm的患者识别为仅与热消融相关的两种亚表型，作为一线治疗。
单结节HBV相关性HCC≤3 cm的患者，其特征在于迟发性疾病，肝功能较差，免疫状况较差以及炎症反应较高（炎症反应较高是最重要的因素），不适合单独进行热消融，因为一线疗法。相比之下，单结节HBV相关性HCC≤3 cm的患者特别适合于热疗，其特征是早发疾病，更好的肝功能，较低的炎症反应和良好的免疫状态（较低的炎症反应是最重要的因素）。单独消融。