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. 2021 Jul 15;11(7):3711-3725.
eCollection 2021.

Predictors of long-term recurrence and survival after resection of HBV-related hepatocellular carcinoma: the role of HBsAg

I-Cheng Lee  1   2 , Hao-Jan Lei  3 , Gar-Yang Chau  3 , Yi-Chen Yeh  4 , Chi-Jung Wu  1 , Chien-Wei Su  1   2 , Teh-Ia Huo  1   5   6 , Yee Chao  7 , Han-Chieh Lin  1   2 , Ming-Chih Hou  1   2 , Yi-Hsiang Huang  1   2   8
Affiliations

Predictors of long-term recurrence and survival after resection of HBV-related hepatocellular carcinoma: the role of HBsAg

I-Cheng Lee et al. Am J Cancer Res. .

Abstract

The recurrence rate remains high even under nucleos(t)ide analogues (NUCs) therapy in patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) after resection. The aim of this study is to evaluate the prognostic role of HBsAg in patients undergoing surgical resection for HBV-related HCC in NUCs era. Consecutive 522 patients undergoing surgical resection for HBV-related HCC were retrospectively enrolled. Factors associated with early (within 2 years), late (year 2 to 5), very late (beyond 5 years) recurrence and early or late mortality (within or beyond 5 years) were evaluated. During a median follow-up period of 59 months, 308 (59%), and 146 (28%) patients developed recurrence and mortality, respectively. HBsAg level did not correlate with early recurrence and mortality. By multivariate analyses, HBsAg >200 IU/mL (hazard ratio (HR)=1.778, P=0.037) and presence of cirrhosis (HR=2.157, P=0.001) were independent predictors of late recurrence, while HBsAg >50 IU/mL (HR=4.658, P=0.038), body mass index >25 kg/m2 (HR=2.720, P=0.013) and significant hepatic fibrosis (HR=2.509, P=0.039) were independent predictors of very late recurrence. HBsAg >50 IU/mL (HR=11.427, P=0.017), age >60 years (HR=2.688, P=0.006), albumin ≤3.5 g/dL (HR=4.739, P<0.001) and presence of cirrhosis (HR=2.781, P=0.006) were independent predictors of late mortality beyond 5 years. Combining these factors could well predict patients with minimal risk of long-term recurrence and mortality. In conclusion, tumor factors, liver function surrogate markers, metabolic factors and serum HBsAg levels play distinct roles in recurrence and survival at different time intervals after surgical resection for HBV-related HCC. Pre-operative HBsAg level is an important predictor of long-term recurrence and survival in patients with HBV-related HCC undergoing surgical resection.

Keywords: Hepatitis B virus; hepatocellular carcinoma; recurrence; resection; survival.

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Conflict of interest statement

None.

Figures

Figure 1
Figure 1
Screening, enrollment and grouping of patients.
Figure 2
Figure 2
Kaplan-Meier curves of early, late and very late recurrence-free survival (RFS) in patients with HBV-related HCC receiving surgical resection. A. Overall RFS stratified by baseline HBsAg level. B. Late RFS stratified by baseline HBsAg level. C. Late RFS stratified by HBsAg level and cirrhosis status. D. Very late RFS stratified by baseline HBsAg level. E. Very late RFS stratified by body mass index (BMI). F. Very late RFS stratified by baseline HBsAg level, BMI and significant fibrosis.
Figure 3
Figure 3
Kaplan-Meier curves of early and late mortality in patients with HBV-related HCC receiving surgical resection. A. Overall survival stratified by baseline HBsAg level. B. Early mortality stratified by baseline HBsAg level. C. Late mortality stratified by baseline HBsAg level. D. Late mortality stratified by the number of risk factors.
Figure 4
Figure 4
Kaplan-Meier curves of late, very late recurrence-free survival (RFS) and late mortality in subgroup patients with NUC therapy. A. Late RFS stratified by baseline HBsAg level. B. Late RFS stratified by HBsAg level and cirrhosis status. C. Very late RFS stratified by baseline HBsAg level. D. Very late RFS stratified by baseline HBsAg level, BMI and significant fibrosis. E. Late mortality stratified by baseline HBsAg level. F. Late mortality stratified by the number of risk factors.
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