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

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.

Keywords:

• Carcinoma
• Hepatocellular
• Phenotype
• Cluster Analysis
• Ablation Techniques
• Treatment Outcome

Acknowledgements

We would like to thank Ms Binyan Shen for her support of Shuanggang Chen.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The datasets used and analyzed in the current study are available from the corresponding author on reasonable request.

Additional information

Funding

This work was funded by the National Natural Science Foundation of China (grant number 81771954).