Liang LB, Zhang HJ, Liu F, Su QL. Hepatitis B core-related antigen as a predictive biomarker for recurrence in primary hepatocellular carcinoma: A meta-analysis. World J Gastrointest Oncol 2025; 17(5): 105148 [DOI: 10.4251/wjgo.v17.i5.105148]
Corresponding Author of This Article
Qiao-Li Su, MD, General Practice Ward/International Medical Center Ward, General Practice Medical Center, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Wuhou District, Chengdu 610041, Sichuan Province, China. cuxf27@163.com
Research Domain of This Article
Oncology
Article-Type of This Article
Meta-Analysis
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Ling-Bo Liang, Feng Liu, Qiao-Li Su, General Practice Ward/International Medical Center Ward, General Practice Medical Center, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
Hai-Jun Zhang, General Practice Ward/International Medical Center Ward, West China Healthcare Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
Author contributions: Liang LB and Su QL contributed to the conception of the study; Liang LB contributed significantly to literature search, data extraction, quality assessment, data analyses, and manuscript preparation; Liang LB and Zhang HJ contributed improving the article for language and style and protocol preparation; Liang LB and Liu F helped perform the analysis with constructive discussions; Su QL revised the manuscript and approved the final version.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Qiao-Li Su, MD, General Practice Ward/International Medical Center Ward, General Practice Medical Center, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Wuhou District, Chengdu 610041, Sichuan Province, China. cuxf27@163.com
Received: January 13, 2025 Revised: February 24, 2025 Accepted: April 11, 2025 Published online: May 15, 2025 Processing time: 122 Days and 17.7 Hours
Abstract
BACKGROUND
Hepatocellular carcinoma (HCC) is one of the most common malignancies, with high recurrence rates after treatment. Identifying reliable biomarkers for predicting recurrence is essential for improving patient outcomes. Hepatitis B core-related antigen (HBcrAg) has shown potential as a predictive marker for HCC recurrence.
AIM
To evaluate the association between HBcrAg levels and the risk of HCC recurrence.
METHODS
A systematic review was conducted following PRISMA guidelines. PubMed, EMBASE, Web of Science, and the Cochrane Library were searched without restrictions on date or language. Observational studies reporting hazard ratios (HRs) for HBcrAg as a predictor of HCC recurrence were included. Data extraction and quality assessment were performed independently by two reviewers. Statistical analyses used a random-effects model to account for heterogeneity (I² ≥ 50%), and sensitivity analysis was performed to ensure the robustness of the results.
RESULTS
A total of 1339 articles were initially identified, and 17 studies were included in the final meta-analysis after screening. The pooled analysis showed a significant association between elevated HBcrAg levels and HCC recurrence (HR = 4.42, 95% confidence interval: 3.43-5.41) with substantial heterogeneity (I² = 92.6%). Subgroup analysis revealed higher pooled HRs in studies with ≥ 500 participants (HR = 4.18) and HBcrAg cut-offs ≥ 4.0 LogU/mL (HR = 5.29). Studies with ≥ 10 years of follow-up showed a lower HR (2.89) compared to those with < 10 years (3.27). Patients treated with nucleos(t)ide analogs had a pooled HR of 1.98, while those without nucleos(t)ide analog had a higher HR of 3.87. Sensitivity analysis confirmed the robustness of the results, with no significant publication bias detected.
CONCLUSION
This meta-analysis provides strong evidence that elevated HBcrAg levels are associated with an increased risk of HCC recurrence. HBcrAg may serve as a valuable biomarker for predicting recurrence, aiding personalized management and surveillance strategies for HCC patients.
Core Tip: Our research compiles robust data from various studies to assess the prognostic significance of hepatitis B core-related antigen in predicting recurrence in hepatocellular carcinoma patients. This meta-analysis synthesizes evidence from 17 studies encompassing diverse populations and methodologies to offer a comprehensive understanding of hepatitis B core-related antigen’s role as a predictive biomarker. Given the high heterogeneity and recurrence rate of hepatocellular carcinoma, our findings are crucial for clinicians in tailoring patient-specific management strategies, potentially revolutionizing current surveillance and treatment protocols.
Citation: Liang LB, Zhang HJ, Liu F, Su QL. Hepatitis B core-related antigen as a predictive biomarker for recurrence in primary hepatocellular carcinoma: A meta-analysis. World J Gastrointest Oncol 2025; 17(5): 105148
Primary hepatocellular carcinoma (HCC) is one of the most prevalent and highly lethal forms of liver cancer worldwide, representing a significant health burden, particularly in regions with a high prevalence of hepatitis B virus (HBV) infection. Chronic HBV infection is recognized as a principal etiological factor for HCC, and despite advancements in early identification and treatment, recurrence remains a serious issue, adversely impacting patient prognosis[1-3]. The recurrence rates after therapy for HCC may attain 70% within five years, underscoring the urgent need for reliable biomarkers to stratify patients by recurrence risk and to tailor follow-up and treatment strategies accordingly[4].
The recurrence of HCC may arise from intrahepatic metastases of the initial tumor or from de novo carcinogenesis in the afflicted liver. Identifying reliable predictive indications for HCC recurrence may inform individualized surveillance tactics and early intervention, potentially improving outcomes. The hepatitis B core-related antigen (HBcrAg) has shown promise as a biomarker for predicting disease progression and recurrence risk[5,6]. HBcrAg, a viral protein associated with active HBV replication and covalently closed circular DNA (cccDNA) status, has emerged as a surrogate diagnostic for assessing HBV activity independently of blood HBV DNA levels, which may be undetectable in patients on antiviral therapy. Recent studies demonstrate that elevated HBcrAg levels correlate with an increased risk of HCC recurrence, highlighting its potential as a predictive biomarker. HBcrAg signifies both the replicative activity of HBV and the persistence of cccDNA in hepatocytes, which operate as a vital reservoir for HBV that is resistant to standard antiviral therapies[7-9]. Thus, HBcrAg detection may provide a more accurate assessment of active viral replication and related carcinogenic risk, making it a crucial tool in HCC management, especially for patients with low or undetectable HBV DNA levels due to effective antiviral therapy. This systematic review and meta-analysis seek to consolidate existing information regarding the predictive significance of HBcrAg for HCC recurrence. This study aims to clarify the predictive value of HBcrAg levels for HCC recurrence by synthesizing data from existing studies and evaluating its potential as a reliable biomarker for guiding clinical management.
MATERIALS AND METHODS
Search strategy
The systematic review followed PRISMA guidelines[10], utilizing PubMed, EMBASE, Web of Science, and the Cochrane Library for data sources. A comprehensive search was conducted on September 19, 2023, without restrictions on publication dates or language. The search strategy was: (“Hepatitis B virus core-related antigen” OR “Hepatitis B core-related antigen” OR “HBcrAg”) AND (“hepatocellular carcinoma” OR “primary hepatocellular carcinoma” OR “HCC” OR “liver cancer”) AND (“recurrence” OR “recurrent” OR “relapse” OR “prognosis” OR “predictive value” OR “risk factors”). This approach was consistent with the PICO framework in order to include all pertinent studies in the meta-analysis. Additionally, reference lists of pertinent articles were manually reviewed to identify additional studies.
Inclusion criteria and exclusion criteria
Inclusion criteria: (1) Studies that investigated the predictive value of HBcrAg for recurrence in patients with primary HCC; (2) Observational studies, including cohort and case-control studies, which provided sufficient data on HBcrAg levels and recurrence outcomes; (3) Studies that reported quantitative measures [e.g., hazard ratios (HRs), relative risks, or odds ratios] of HBcrAg as a predictor for HCC recurrence; and (4) Studies published in any language, with full-text availability.
Exclusion criteria: (1) Studies that did not specifically evaluate the role of HBcrAg in predicting HCC recurrence; (2) Case reports, review articles, editorials, letters, conference abstracts, and non-peer-reviewed studies; (3) Studies involving patients with secondary or metastatic liver cancers, or other primary liver diseases; and (4) Studies lacking sufficient data for extraction or studies with duplicated data across publications.
Data extraction
Data extraction was performed separately by two reviewers, with results verified for consistency. Discrepancies were addressed through dialogue among the reviewers, and a third-party reviewer was engaged if consensus was unattainable. The extracted data comprised the author, year, sample size, country, study type, follow-up period, intervention, baseline HBeAg status, cut-off value, and measurement method. When necessary data were absent from the published reports, the original study authors were approached via email to acquire unpublished material.
Quality assessment
The quality of studies included in this meta-analysis was meticulously assessed by two independent reviewers using the Newcastle-Ottawa Scale (NOS)[11]. The NOS is a dependable instrument for assessing study quality, rating studies based on nine criteria under three main categories: Selection, comparability, and outcome. These categories enabled the identification of potential sources of bias in each study. Each asterisk in the NOS evaluation table signified one point, with overall quality scores varying from 0 to 9. According to these scores, studies were categorized as follows: Scores of 0-3 denoted low quality, 4-6 denoted moderate quality, and 7-9 denoted excellent quality.
Statistical analysis
Statistical analyses were performed using Stata version 17 (StataCorp, College Station, TX, United States). The variability of study was assessed using χ2 statistics and quantified with the I² statistic. When the I² was below 50% and the P value was 0.10 or above, indicating no significant heterogeneity, a fixed-effect model was employed to compute the pooled effect size. When I² reached 50% or higher, or the P value fell below 0.10, signifying substantial heterogeneity, a random-effects model was utilized for effect size calculation. Sensitivity analysis was conducted to evaluate the robustness of the results and to determine the influence of individual studies on the overall effect size by systematically excluding each study and recalculating the pooled effect. The symmetry of the funnel plot was studied to assess potential publishing bias, with symmetrical distribution indicating a less likelihood of publication bias. In addition to the funnel plot, Egger’s test was performed to statistically assess the presence of publication bias. All statistical tests were bilateral, and a P value below 0.05 was deemed statistically significant.
RESULTS
Search results and study selection
During the preliminary stage of this systematic review and meta-analysis, an extensive search of several electronic databases produced 1339 possibly pertinent papers. Following the elimination of duplicate entries, a meticulous assessment of titles and abstracts was performed according to explicitly established inclusion and exclusion criteria, which took into account study methodology, demographic factors, clinical results, and overall research quality. This procedure identified 48 articles for additional examination. A comprehensive evaluation of the whole texts by several researchers resulted in the deletion of 31 articles due to factors including review articles (n = 11), sequential publishing (n = 8), inadequate data (n = 6), and absence of control groups in clinical trials (n = 6). Seventeen publications ultimately satisfied all criteria and were incorporated into the final meta-analysis[12-28] (Figure 1).
Figure 1
Flowchart showing the process of study selection for inclusion in the meta-analysis.
Study characteristics
This meta-analysis incorporated a total of 17 studies, primarily cohort studies conducted in Japan and China. The focus of these studies was on the evaluation of HBcrAg as a clinical biomarker. The average age of participants varied across studies, ranging from 40.0 to 61.3 years, with most studies reporting a male-to-female ratio. The follow-up durations differed significantly, with median follow-up times spanning from 4.8 to 15.95 years, indicating extensive long-term monitoring of HBcrAg levels. The studies employed various cut-off values for HBcrAg, reflecting differences in clinical and research objectives. Measurement methods predominantly utilized chemiluminescent enzyme immunoassay, alongside some employing the innovative immunoassay for HBcrAg using a new technology technology (Table 1).
Table 1 Characteristics of studies included in the meta-analysis.
The quality evaluation of the studies included in this meta-analysis employed a systematic method, assessing multiple factors that indicate the strength of each study’s design and implementation. The studies shown a commendable degree of representativeness for the exposed cohorts, with the majority attaining high ratings for cohort selection and exposure ascertainment. The capacity to verify that the outcome of interest was nonexistent at the commencement of the study was also firmly established. The comparability among cohorts was usually positive, with numerous research employing suitable design or analytical techniques. The evaluation of outcomes was regularly documented, and the follow-up time was considered sufficient in most instances, facilitating a thorough assessment of long-term impacts. The total scores across studies ranged from 7 to 9, signifying a predominantly good level of evidence. Significantly, research conducted by Yi-Chung Hsieh and Ka-Shing Cheung attained optimal scores, demonstrating their methodological precision. The overall quality of the studies used in this meta-analysis substantiates the validity of the findings about the clinical importance of HBcrAg in the management of hepatitis B (Table 2).
Table 2 The quality assessment according to Newcastle-Ottawa Scale of each cohort study.
Ref.
Representativeness of the exposed cohort
Selection of the non-exposed cohort
Ascertainment of exposure
Demonstration that outcome of interest was not present at start of study
Comparability of cohorts on the basis of the design or analysis
Association between HBcrAg and recurrence of primary HCC
A total of 17 studies were included in this meta-analysis, all investigating the relationship between HBcrAg and recurrence in HCC[12-28]. There was significant heterogeneity across the studies (I2 = 92.6%, P < 0.001), and thus a random-effects model was applied to synthesize the data. The pooled results demonstrated that elevated HBcrAg levels were associated with an increased risk of HCC recurrence. Specifically, the HR for HBcrAg as a potential predictor of recurrence was 4.42 [95% confidence interval (CI): 3.43-5.41], indicating a substantial association between higher HBcrAg levels and recurrence risk. This finding suggests that HBcrAg could serve as a valuable biomarker for predicting recurrence in patients with primary HCC, offering insights into disease management and surveillance strategies (Figure 2).
Figure 2 Forest plot displaying the association between hepatitis B core-related antigen and recurrence of primary hepatocellular carcinoma.
CI: Confidence interval.
Subgroup analysis of factors influencing HBcrAg and HCC recurrence
A subgroup analysis was conducted to explore the factors influencing the relationship between HBcrAg and recurrence of primary HCC. The results showed that studies with a sample size of ≥ 500 had a pooled HR of 4.18 (95%CI: 1.68-6.53) with significant heterogeneity (I² = 65.9%, random-effects model), while studies with fewer than 500 participants reported a pooled HR of 3.26 (95%CI: 1.39-5.66) with higher heterogeneity (I² = 76.2%). For follow-up duration, studies with follow-up times of ≥ 10 years showed a pooled HR of 2.89 (95%CI: 1.38-5.31; I² = 82.3%, random-effects model), compared to those with less than 10 years of follow-up, which had a pooled HR of 3.27 (95%CI: 1.98-6.79; I² = 51.1%). Regarding HBcrAg cut-off values, studies with a cut-off of ≥ 4.0 LogU/mL showed a higher pooled HR of 5.29 (95%CI: 2.17-8.56; I² = 55.8%), while studies with a cut-off value < 4.0 LogU/mL reported a pooled HR of 1.78 (95%CI: 1.25-4.42; I² = 51.68%). In terms of treatment, patients treated with nucleos(t)ide analogs (NAs) had a pooled HR of 1.98 (95%CI: 1.38-4.98; I² = 71.56%), while those without NAs treatment had a higher pooled HR of 3.87 (95%CI: 1.96-8.53; I² = 38.94%, fixed-effects model). Lastly, when considering baseline HBeAg status, HBeAg-negative patients showed a pooled HR of 3.15 (95%CI: 1.88-5.16; I² = 67.75%), while HBeAg-positive patients had a pooled HR of 2.52 (95%CI: 1.21-7.18; I² = 0.00%, fixed-effects model). These results highlight that HBcrAg is a consistent predictor of recurrence across various subgroups (Table 3).
Table 3 Subgroup analysis of hepatitis B core-related antigen and primary hepatocellular carcinoma recurrence.
Subgroup factor
Divided standard
Pooled HR (95%CI)
Heterogeneity (I²)
Effects model
Sample size
≥ 500
4.18 (1.68-6.53)
65.90%
Random-effect
< 500
3.26 (1.39-5.66)
76.20%
Random-effect
Follow-up time
≥ 10 years
2.89 (1.38-5.31)
82.30%
Random-effect
< 10 years
3.27 (1.98-6.79)
51.10%
Random-effect
HBcrAg cut-off value
≥ 4.0 LogU/mL
5.29 (2.17-8.56)
55.80%
Random-effect
< 4.0 LogU/mL
1.78 (1.25-4.42)
51.68%
Random-effect
Treatment
With NAs
1.98 (1.38-4.98)
71.56%
Random-effect
Without NAs
3.87 (1.96-8.53)
38.94%
Fixed-effect
Baseline HBeAg
Negative
3.15 (1.88-5.16)
67.75%
Random-effect
Positive
2.52 (1.21-7.18)
0.00%
Fixed-effect
Sensitivity analysis
A sensitivity analysis was conducted to assess the robustness and consistency of the pooled results, owing to the significant heterogeneity among the studies in the meta-analysis. This approach entailed the methodical exclusion of each trial individually, followed by the recalibration of the overall effect estimates using the residual data. The sensitivity analysis results revealed that the aggregated estimates were stable, suggesting that the omission of any individual study did not substantially affect the outcomes. This indicates that no single study exerted excessive effect on the overall results, hence bolstering the credibility of the meta-analysis. The consistency of the results throughout all sensitivity studies underscores the robustness and dependability of the key conclusions derived from this study (Figure 3).
Figure 3 Sensitivity analysis graph evaluating the stability of the meta-analysis findings.
CI: Confidence interval.
Assessment of publication bias
Funnel plots were created from the research included in the meta-analysis, revealing a symmetrical distribution of results. This symmetry suggests the absence of substantial evidence for publication bias among the papers considered (Figure 4). The lack of asymmetry in the funnel plots indicates that the results of this meta-analysis are improbable to be affected by selective reporting or other types of publication bias. Additionally, Egger’s test was conducted to more rigorously assess publication bias. The results of Egger’s test (P > 0.05 for all) indicated no significant publication bias, further reinforcing the conclusion that the findings of this meta-analysis are not substantially influenced by publication bias.
Figure 4
Funnel plot assessing the presence of publication bias among studies included in the meta-analysis.
DISCUSSION
HCC is among the most common and fatal malignancies worldwide, particularly in regions with high HBV infection rates. Recurrence following therapy is a significant challenge, with rates ascending to 70% within five years. Thus, the development of reliable biomarkers for predicting recurrence is crucial for improving patient outcomes. HBcrAg has emerged as a viable contender as it signifies viral replication and the presence of cccDNA, even in patients undergoing antiviral therapy[29-31]. This meta-analysis assessed the prognostic relevance of HBcrAg for recurrence in primary HCC, analyzing data from 17 studies. The aggregated findings indicated a substantial correlation between increased HBcrAg levels and the probability of HCC recurrence, implying that HBcrAg could serve as a dependable biomarker for predicting recurrence in patients with primary HCC. The overall HR for HBcrAg as a predictor of recurrence was 4.42 (95%CI: 3.43-5.41), signifying a significant elevation in recurrence risk correlated with elevated levels of this antigen. These findings have significant implications for the clinical management and surveillance of HCC patients.
HBcrAg indicates the replicative activity of HBV, even in individuals receiving antiviral treatment. This marker is linked to cccDNA in hepatocytes, a viral reservoir crucial for HBV persistence. Notwithstanding the successful reduction of HBV DNA levels with NA therapy, cccDNA may endure in hepatocytes, enabling ongoing low-level viral activity. This persistent viral presence can promote oncogenesis through chronic inflammation, immune modulation, and hepatocyte regeneration, hence increasing the likelihood of cancer recurrence following first treatment. Additionally, HBcrAg has been recognized as associated with other established risk factors for HCC recurrence, including HBV-related cirrhosis and liver fibrosis. Patients with elevated HBcrAg levels may have increased liver damage, creating an environment conducive to tumor recurrence[32,33]. The interaction between viral persistence and liver damage creates a favorable setting for the recurrence of HCC, even after successful resection or limited treatment of the primary tumor.
The subgroup analysis provided further insights into the factors influencing the relationship between HBcrAg and HCC recurrence. Larger studies (sample size ≥ 500) demonstrated a slightly higher pooled HR (4.18) compared to smaller studies (HR = 3.26), though both results indicate a significant association. This consistency across different study sizes strengthens the overall conclusion that HBcrAg is a strong predictor of recurrence. The analysis also showed that studies with follow-up times of ≥ 10 years reported a lower pooled HR (2.89) than those with shorter follow-up durations (3.27). This may suggest that the risk of recurrence associated with HBcrAg diminishes over time, possibly due to the eventual clearance of HBV cccDNA in some patients or the long-term effects of antiviral therapies[34]. However, the high heterogeneity (I² = 82.3%) in the longer follow-up group indicates that further studies are needed to clarify this potential trend. When comparing HBcrAg cut-off values, studies with a threshold of ≥ 4.0 LogU/mL reported a higher pooled HR (5.29), indicating that patients with higher antigen levels are at a substantially greater risk of recurrence. This highlights the importance of identifying an optimal cut-off value for HBcrAg in clinical practice to accurately stratify patients by their recurrence risk[35,36]. While a cut-off value of ≥ 4.0 LogU/mL appears to be associated with higher recurrence risk in this cohort of studies, we recommend that clinicians consider adjusting this threshold based on specific patient characteristics and clinical context. Further research with larger, more diverse populations would be essential to validate these findings and determine the most appropriate HBcrAg cut-off value for predicting HCC recurrence in different settings.
The impact of antiviral treatment was also significant in the subgroup analysis. Patients who received NA therapy had a lower pooled HR (1.98) compared to those without NA treatment (3.87). This suggests that while antiviral therapy can reduce the risk of recurrence, it does not completely eliminate it, particularly in patients with elevated HBcrAg levels. Therefore, even patients on antiviral therapy may benefit from more intensive surveillance and management if their HBcrAg levels are high. Lastly, the baseline HBeAg status was another factor influencing recurrence risk. HBeAg-negative patients had a slightly higher pooled HR (3.15) compared to HBeAg-positive patients (HR = 2.52). This may be due to the fact that HBeAg-negative status often reflects a more advanced stage of chronic HBV infection, where immune control of the virus has led to lower serum viral loads, but cccDNA persists in the liver, maintaining the risk of carcinogenesis[37,38].
The sensitivity analysis performed in this meta-analysis validated the robustness of the results. Sequential exclusion of each study revealed that no one study significantly affected the pooled results, demonstrating the stability and reliability of the overall conclusions derived from this analysis. This stability reinforces the significance of HBcrAg as a reliable and pertinent predictor of HCC recurrence across diverse patient cohorts and research methodologies. This meta-analysis indicates that HBcrAg should be regarded as a significant biomarker for predicting recurrence in patients with initial HCC. Its application could assist in identifying high-risk individuals who may require more intense follow-up measures, enhanced monitoring, or supplementary medications. Moreover, considering the correlation between elevated HBcrAg levels and the risk of recurrence, subsequent research should concentrate on formulating therapeutic approaches that directly address viral cccDNA to further diminish the likelihood of HCC recurrence in individuals with chronic HBV infection.
This meta-analysis possesses multiple limitations. Initially, considerable heterogeneity existed among the investigations, which may have impacted the aggregated results. Moreover, discrepancies in HBcrAg cut-off values and follow-up periods may influence comparability. Finally, certain studies were deficient in comprehensive data regarding patient characteristics, constraining the capacity for more nuanced subgroup analyses. To address the limitations identified, future research should aim to standardize HBcrAg cut-off values, follow-up periods, and patient demographics, while also incorporating additional biomarkers such as alpha-fetoprotein, protein induced by vitamin K absence II, and microRNAs to enable a more multifactorial risk assessment for HCC recurrence. Additionally, exploring the combined predictive value of HBcrAg with other biomarkers, including HBeAg and HBV DNA, may further improve the accuracy and clinical utility of recurrence prediction models.
CONCLUSION
This meta-analysis conclusively demonstrates a significant correlation between elevated HBcrAg levels and heightened recurrence risk in patients with initial HCC. The strong results across several subgroups, along with the consistency shown in sensitivity analyses, highlight the significance of HBcrAg as an essential instrument in controlling the long-term outcomes of HCC patients.
ACKNOWLEDGEMENTS
We thank everyone who participated in this research and completed it together.
Footnotes
Provenance and peer review: Unsolicited article; Externally peer reviewed.
Peer-review model: Single blind
Specialty type: Oncology
Country of origin: China
Peer-review report’s classification
Scientific Quality: Grade B, Grade B
Novelty: Grade B, Grade B
Creativity or Innovation: Grade B, Grade B
Scientific Significance: Grade B, Grade B
P-Reviewer: Liu HD; Zhou L S-Editor: Wang JJ L-Editor: A P-Editor: Zhang L
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