Tissue and serum metabolomic phenotyping for diagnosis and prognosis of hepatocellular carcinoma.

More than two-thirds of patients with hepatocellular carcinoma (HCC) cannot receive curative therapy and have poor survival due to late diagnosis and few prognostic directions. In our study, nontargeted and targeted metabolomics analyses were conducted by liquid chromatography-mass spectrometry to characterize metabolic features of HCC and identify diagnostic and prognostic biomarker candidate incorporating liver tissue and serum metabolites. A total of 552 subjects, including 432 with liver tissue and 120 with serum specimens, were recruited in China. In the discovery cohort, a series of 138 metabolites were identified to discriminate HCC tissues from matched nontumor tissues. Retinol presented with the highest area under the curve (AUC) of 0.991 and associated with Edmondson grade. In the validation cohort, all metabolites in retinol metabolism pathway were examined and the levels of retinol and retinal in tumor tissue and serum decreased in the order of normal to cirrhosis to HCC of Edmondson Grades I to IV. Retinol and retinal levels could also differentiate between HCC and cirrhosis, with AUCs of 0.996 and 0.994, respectively, in tissue and 0.812 and 0.744, respectively, in serum. The AUC of the combined retinol and retinal panel in serum was 0.852. Univariate and multivariate Cox regression identified this panel as an independent predictor for HCC and showed that low expression of retinol and retinal correlated with decreased survival time. In conclusion, the retinol metabolic signature had considerable diagnostic and prognostic value for identifying HCC patients who would benefit from prompt therapy and optimal prognostic direction.

Long-Term Survival Outcomes After Liver Resection for Binodular Hepatocellular Carcinoma: A Multicenter Cohort Study.

BACKGROUND: The long-term prognosis after liver resection for multinodular (≥3 nodules) hepatocellular carcinoma (HCC) is generally considered to be unfavorable. However, the role of liver resection for binodular HCC is less investigated. SUBJECTS, MATERIALS, AND METHODS: From a multicenter database, consecutive patients who underwent curative-intent liver resection for binodular HCC and without macrovascular invasion between 2003 and 2015 were retrospectively reviewed. Patients' clinical variables as well as perioperative and long-term survival outcomes were analyzed. Univariable and multivariable analyses were performed to identify the risk factors associated with overall survival (OS) and recurrence-free survival (RFS) after curative resection. RESULTS: Of 263 enrolled patients, the perioperative 30-day mortality and morbidity rates were 1.5% and 28.5%. The 1-, 3-, and 5-year OS and RFS rates were 81.5%, 52.4%, and 39.1% and 57.1%, 35.8%, and 26.6%, respectively. Multivariable Cox-regression analyses identified preoperative alpha-fetoprotein level >400 µg/L, tumor size with a sum of two nodules >8 cm, tumor size ratio of large/small nodule >1.5 (asymmetrical proportion), unilateral hemiliver distribution of two nodules, distance of ≤3 cm between two nodules, and microvascular invasion in any nodule as independent risk factors associated with decreased OS and RFS. CONCLUSION: Liver resection was safe and feasible in patients with binodular HCC, with acceptable perioperative and long-term outcomes. Sum of two tumor sizes, size ratio and distribution, and distance between two nodules were independent risk factors associated with long-term survival outcomes after surgery. These results may guide clinicians to make individualized surgical decisions and estimate long-term prognosis for these patients. IMPLICATIONS FOR PRACTICE: Liver resection was safe and feasible in patients with binodular hepatocellular carcinoma, with acceptable perioperative and long-term outcomes. The sum of two tumor sizes, the size ratio and distribution of the two nodules, and the distance between two nodules were independent risk factors associated with long-term overall survival and recurrence-free survival after liver resection. The results of this study may guide clinicians to make individualized surgical decisions, estimate long-term prognosis, and plan recurrence surveillance and adjuvant therapy for these patients.

The impact of resection margin and microvascular invasion on long-term prognosis after curative resection of hepatocellular carcinoma: a multi-institutional study.

BACKGROUND: The resection margin (RM) status and microscopic vascular invasion (MVI) are known prognostic factors for hepatocellular carcinoma (HCC). An enhanced understanding of their impact on long-term prognosis is required to improve oncological outcomes. METHODS: Using multi-institutional data, the different impact of the RM status (narrow, <1 cm, or wide, ≥1 cm) and MVI (positive or negative) on overall survival (OS) and recurrence-free survival (RFS) after curative liver resection of solitary HCC without macrovascular invasion was analyzed. RESULTS: In 801 patients, 306 (38%) had a narrow RM and 352 (44%) had positive MVI. The median OS and RFS were 109.8 and 74.8 months in patients with wide RM & negative MVI, 93.5 and 53.1 months with wide RM & positive MVI, 79.2 and 41.6 months with narrow RM & negative MVI, and 69.2 and 37.5 months with narrow RM & positive MVI (both P < 0.01). On multivariable analyses, narrow RM & positive MVI had the highest hazard ratio with reduced OS and RFS (HR 2.96, 95% CI 2.11-4.17, and HR 3.15, 95% CI, 2.09-4.67, respectively). CONCLUSIONS: Concomitant having narrow RM and positive MVI increases the risks of postoperative death and recurrence by about 2-fold in patients with solitary HCC.

Protein induced by vitamin K absence or antagonist-II versus alpha-fetoprotein in the diagnosis of hepatocellular carcinoma: A systematic review with meta-analysis.

BACKGROUND: As a promising biomarker of hepatocellular carcinoma (HCC), protein induced by vitamin K absence or antagonist-II (PIVKA-II) has been studied extensively. However, its diagnostic capability varies across HCC studies. This study aimed to compare the performance of PIVKA-II with alpha-fetoprotein (AFP) in the diagnosis of HCC. DATA SOURCES: A systematic literature search was conducted to identify the studies from MEDLINE, Embase and Cochrane Library Databases, which were published up to December 20, 2017 to compare the diagnostic capability of PIVKA-II and AFP for HCC. The data were pooled using random effects model. Pooled sensitivity and specificity were calculated. Summary receiver operating characteristic curve (ROC) was employed to evaluate the diagnostic accuracy of each marker. RESULTS: Thirty-one studies were included. The pooled sensitivity (95% CI) of PIVKA-II and AFP was 0.66 (0.65-0.68) and 0.66 (0.65-0.67), respectively in diagnosis of HCC; and the corresponding pooled specificity (95% CI) was 0.89 (0.88-0.90) and 0.84 (0.83-0.85), respectively. The area under the ROC curve (AUC) of PIVKA-II and AFP was 0.856 (0.817-0.895) and 0.770 (0.728-0.811), respectively. Subgroup analysis showed that PIVKA-II was superior to AFP in terms of the AUC for both small HCC (< 3 cm) [0.863 (0.825-0.901) vs 0.717 (0.658-0.776)] and large HCC (≥ 3 cm) [0.854 (0.811-0.897) vs 0.729 (0.682-0.776)]; for American [0.926 (0.897-0.955) vs 0.698 (0.594-0.662)], European [0.772 (0.743-0.801) vs 0.628 (0.594-0.662)], Asian [0.838 (0.812-0.864) vs 0.785 (0.764-0.806)] and African [0.812 (0.794-0.840) vs 0.721 (0.675-0.767)] HCC patients; and for HBV-related [0.909 (0.866-0.951) vs 0.714 (0.673-0.755)] and mixed-etiology [0.847 (0.821-0.873) vs 0.794 (0.772-0.816)] HCC. CONCLUSION: This meta-analysis indicates that PIVKA-II is better than AFP in terms of the accuracy for diagnosing HCC, regardless of tumor size, patient ethnic group, or HCC etiology.

Hydrogel Crosslinked with Nanoparticles for Prevention of Surgical Hemorrhage and Recurrence of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is acknowledged as an immunosuppressive neoplasm, whereby the inactive microenvironment facilitates immune tolerance and evasion of HCC. Post-surgical resected liver cancer exhibits a proclivity for relapse, rendering prevention of recurrence challenging as it may transpire at any point subsequent to surgery. Among the various anti-recurrence interventions, the primary clinical approach involving the administration of regimens atezolizumab and bevacizumab (A+T) is deemed the most efficacious in reversing the tumor microenvironment, albeit still lacking in complete satisfaction. Therefore, the objective is to utilize a recently developed block copolymer as a protective carrier for two specific monoclonal antibody drugs. Subsequently, a modified hemostatic hydrogel will be synthesized for application during hepatic surgery. The immunotherapy impact of this approach is significantly prolonged and intensified due to the combined hemostasis properties and controlled release of the constituents within the synthesized nanocomposite hydrogel. Furthermore, these nanocomposite hydrogels exhibit remarkable efficacy in preventing postoperative wound bleeding and substantially enhancing the safety of liver cancer resection. This research on the anti-recurrence hydrogel system presents a novel therapeutic approach for addressing local recurrence of liver cancer, potentially offering a substantial contribution to the field of surgical treatment for liver cancer in the future.

Mesoporous Nanoparticles for Diagnosis and Treatment of Liver Cancer in the Era of Precise Medicine.

Primary liver cancer is the seventh-most-common cancer worldwide and the fourth-leading cause of cancer mortality. In the current era of precision medicine, the diagnosis and management of liver cancer are full of challenges and prospects. Mesoporous nanoparticles are often designed as specific carriers of drugs and imaging agents because of their special morphology and physical and chemical properties. In recent years, the design of the elemental composition and morphology of mesoporous nanoparticles have greatly improved their drug-loading efficiency, biocompatibility and biodegradability. Especially in the field of primary liver cancer, mesoporous nanoparticles have been modified as highly tumor-specific imaging contrast agents and targeting therapeutic medicine. Various generations of complexes and structures have been determined for the complicated clinical management requirements. In this review, we summarize these advanced mesoporous designs in the different diagnostic and therapeutic fields of liver cancer and discuss the relevant advantages and disadvantages of transforming applications. By comparing the material properties, drug-delivery characteristics and application methods of different kinds of mesoporous materials in liver cancer, we try to help determine the most suitable drug carriers and information media for future clinical trials. We hope to improve the fabrication of biomedical mesoporous nanoparticles and provide direct evidence for specific cancer management.

Responsive Hydrogels Based on Triggered Click Reactions for Liver Cancer.

Globally, liver cancer, which is one of the major cancers worldwide, has attracted the growing attention of technological researchers for its high mortality and limited treatment options. Hydrogels are soft 3D network materials containing a large number of hydrophilic monomers. By adding moieties such as nitrobenzyl groups to the network structure of a cross-linked nanocomposite hydrogel, the click reaction improves drug-release efficiency in vivo, which improves the survival rate and prolongs the survival time of liver cancer patients. The application of a nanocomposite hydrogel drug delivery system can not only enrich the drug concentration at the tumor site for a long time but also effectively prevents the distant metastasis of residual tumor cells. At present, a large number of researches have been working toward the construction of responsive nanocomposite hydrogel drug delivery systems, but there are few comprehensive articles to systematically summarize these discoveries. Here, this systematic review summarizes the synthesis methods and related applications of nanocomposite responsive hydrogels with actions to external or internal physiological stimuli. With different physical or chemical stimuli, the structural unit rearrangement and the controlled release of drugs can be used for responsive drug delivery in different states.

Impact of Surveillance in Chronic Hepatitis B Patients on Long-Term Outcomes After Curative Liver Resection for Hepatocellular Carcinoma.

BACKGROUND: Clinical guidelines recommend surveillance in high-risk population to early detect hepatocellular carcinoma (HCC), when curative treatment such as liver resection can be applied. However, it is largely unknown whether surveillance would provide long-term survival benefits to these high-risk patients who have received curative liver resection for HCC. METHODS: A prospectively maintained database on patients with chronic hepatitis B infection who underwent curative liver resection for HCC from 2003 to 2014 was reviewed. Patients' overall survival and recurrence were compared between the groups of patients whose HCCs were diagnosed by surveillance or non-surveillance, as well as between the groups of patients operated in the first (2003-2008) and second (2009-2014) 6-year periods. RESULTS: Of 1075 chronic hepatitis B patients with HCC, 452 (42.0%) patients were diagnosed by preoperative surveillance. Compared with the non-surveillance group, the OS and RFS rates were significantly better in the surveillance group (both P < 0.001). Surveillance was associated with a 55% decrease in the overall survival risk and a 48% decrease in the recurrence risk (HR 0.45, 95% CI 0.38-0.53, and HR 0.52, 95% CI 0.44-0.61). Compared with the first period, a significant reduction of 12% and 19% in the overall death and recurrence risks, respectively, was observed in the second period (HR 0.88, 95% CI 0.78-0.97, and HR 0.81, 95% CI 0.70-0.95). CONCLUSION: Surveillance for HCC was associated with favorable long-term overall and recurrence-free survival rates after curative liver resection of HCC in patients with chronic hepatitis B.

Liver Resection for Hepatocellular Carcinoma in Non-alcoholic Fatty Liver Disease: a Multicenter Propensity Matching Analysis with HBV-HCC.

BACKGROUND: The incidence of hepatocellular carcinoma (HCC) in non-alcoholic fatty liver disease (NAFLD) is increasing worldwide. Higher perioperative risks may be anticipated due to underlying steatohepatitis, while long-term outcomes after liver resection are unknown. We sought to investigate outcomes after liver resection for NAFLD-HCC versus hepatitis B virus (HBV)-HCC using propensity score matching (PSM). METHODS: Consecutive patients who underwent liver resection for HCC between 2003 and 2014 were identified from a multicenter database. Patients with NAFLD-HCC were matched one-to-one to patients with HBV-HCC. RESULTS: Among 1483 patients identified, 96 (6.5%) had NAFLD-HCC and 1387 (93.5%) had HBV-HCC. Patients with NAFLD-HCC were older (median age 57 vs. 50 years), more often overweight (50.0% vs. 37.5%), less often to have cirrhosis (30.2% vs. 72.5%) and liver dysfunction (Child-Pugh B: 4.2% vs. 10.7%), had larger tumor size (median 7.2 vs. 6.2 cm) yet had better tumor differentiation (27.1% vs. 17.6%) compared with patients with HBV-HCC (all P < 0.05). Perioperative mortality and morbidity were comparable between the two groups (1.0% vs. 1.4% and 20.8% vs. 23.2%, both P > 0.05). No differences were noted in median OS and RFS among patient with NAFLD-HCC versus HBV-HCC before or after PSM. CONCLUSION: While patients with NAFLD-HCC had different clinical characteristics than patients with HBV-HCC, liver resection resulted in similar perioperative outcomes and comparable OS and RFS among patients with NAFLD-HCC and HBV-HCC.

Association of family history with long-term prognosis in patients undergoing liver resection of HBV-related hepatocellular carcinoma.

BACKGROUND: Family history is a risk factor for the development of hepatocellular carcinoma (HCC). The aim of the current study was to investigate the association between family history of HCC and long-term oncologic prognosis among patients undergoing curative liver resection for hepatitis B virus (HBV)-related HCC. METHODS: Patients who underwent curative liver resection of HBV-related HCC between 2003 and 2013 were consecutively enrolled. Family history was defined as a self-reported history of HCC in a first-degree relative. Propensity score matching (PSM) and multivariable Cox-regression analyses were performed to compare overall survival (OS) and recurrence-free survival (RFS) among patients with and without a family history. RESULTS: Among 1,112 patients, 183 (16.5%) patients had a family history of HCC. Using PSM, 179 pairs of patients with and without a family history were created that had no differences in the baseline characteristics and operative variables. On matched analysis, family history was associated with decreased OS and RFS after curative-intent resection of HBV-related HCC in the propensity matching cohort (P=0.042 and 0.006, respectively). On multivariable Cox-regression analyses, a family history of HCC was associated with decreased OS (HR: 1.574; 95% CI: 1.171-2.116; P=0.003) and RFS (HR: 1.534; 95% CI: 1.176-2.002; P=0.002) after adjusting for other prognostic risk factors. CONCLUSIONS: Family history was associated with decreased OS and RFS rates among patients undergoing curative liver resection of HBV-related HCC.

Sex difference in recurrence and survival after liver resection for hepatocellular carcinoma: A multicenter study.

BACKGROUND: There is a striking sex difference in the incidence of hepatocellular carcinoma, with a strong predominance for men; however, the impact of sex on the incidence of recurrence after curative resection of hepatocellular carcinoma remains controversial. This study aimed to assess sex differences in the risks of recurrence and mortality for patients treated with curative resection of hepatocellular carcinoma. METHODS: We retrospectively reviewed data from 1,435 hepatocellular carcinoma patients treated with curative resection (1,228 men and 207 women) between 2004 and 2014 at 5 institutions in China. Patients' baseline characteristics, operative variables, and rates of early recurrence (≤2 years after resection), late recurrence (>2 years after resection), and cancer-specific mortality were evaluated and compared. To clarify the true oncologic impact of sex, multivariable competing-risks regression analyses were performed to identify predictors associated with early and late recurrence, as well as cancer-specific mortality. RESULTS: The early recurrence rates between men and women were similar (43.3% vs 42.0%, P = .728), but the late recurrence and rates of cancer-specific mortality in men were greater compared with women (17.2% vs 11.2%, P = .044; and 42.8% vs 34.3%, P = .022, respectively). Multivariable competing-risks regression analyses revealed no sex difference in early recurrence; however, men had greater late recurrence rate (hazard ratio, 1.752; 95% confidence interval, 1.145-2.682; P = .010) and rate of cancer-specific mortality (hazard ratio, 1.307; 95% confidence interval, 1.015-1.683; P = .038). CONCLUSION: There was no difference in early recurrence rate (≤2 years after resection between men and women, but men had significantly greater late recurrence (>2 years) and rates of cancer-specific mortality after hepatocellular carcinoma resection than women.

Tissue and serum metabolite profiling reveals potential biomarkers of human hepatocellular carcinoma.

BACKGROUND AND AIMS: Metabolomics serves as an important tool in distinguishing changes in metabolic pathways and the diagnosis of human disease. Hepatocellular carcinoma (HCC) is a malignance present of heterogeneous metabolic disorder and lack of effective biomarker for surveillance and diagnosis. In this study, we searched for potential metabolite biomarkers of HCC using tissue and serum metabolomics approach. METHODS: A total of 30 pairs of matched liver tissue samples from HCC patients and 90 serum samples (30 HCC patients, 30 liver cirrhosis patients, and 30 healthy individuals) were assessed. Metabolomics was performed through ultra performance liquid chromatography-mass spectrometry in conjunction with multivariate and univariate statistical analyses. RESULTS: A total of six differential metabolites including chenodeoxycholic acid (CDCA), glycocholic acid (GCA), LPC20:5, LPE18:0, succinyladenosine and uridine were present in HCC tissue and serum samples. CDCA, LPC20:5, succinyladenosine and uridine were used to construct a diagnostic model based on logistic regression. The four-metabolite panel discriminated HCC from liver cirrhosis with an AUC score of 0.938, sensitivity of 93.3% and specificity of 86.7%. For all HCC and cirrhosis patients, the diagnostic accuracy increased to 96.7% and 90.0%, respectively. CONCLUSION: The combination of CDCA, LPC20:5, succinyladenosine and uridine can be used as a biomarker panel to improve HCC sensitivity and specificity. This panel significantly benefits HCC diagnostics and reveals new insight into HCC pathogenesis.

Risk Factors, Patterns, and Outcomes of Late Recurrence After Liver Resection for Hepatocellular Carcinoma: A Multicenter Study From China.

Importance: Late recurrence (more than 2 years) after liver resection for hepatocellular carcinoma (HCC) is generally considered as a multicentric tumor or a de novo cancer. Objective: To investigate the risk factors, patterns, and outcomes of late recurrence after curative liver resection for HCC. Design, Setting, and Participants: This study was a multicenter retrospective analysis of patients who underwent curative liver resection for HCC at 6 hospitals in China from January 2001 to December 2015. Among 734 patients who were alive and free of recurrence at 2 years after resection, 303 patients developed late recurrence. Data were analyzed from June 2017 to February 2018. Interventions: Liver resection for HCC. Main Outcomes and Measures: Risk factors of late recurrence as well as patterns, treatments, and long-term outcomes of patients with late recurrence. Univariate and multivariate Cox regression analyses were performed to identify independent risk factors of late recurrence. Results: Of the included 734 patients, 652 (88.8%) were male, and the mean (SD) age was 51.0 (10.3) years. At a median (interquartile range) follow-up of 78.0 (52.8-112.5) months, 303 patients (41.3%) developed late recurrence. Multivariate analysis revealed that male sex, cirrhosis, multiple tumors, satellite nodules, tumor size greater than 5 cm, and macroscopic and microscopic vascular invasion were independent risk factors of late recurrence. Of the 303 patients with late recurrence, 273 (90.1%) had only intrahepatic recurrence, 30 (9.9%) had both intrahepatic and extrahepatic recurrence, and none had only extrahepatic recurrence. Potentially curative treatments were given to 165 of 303 patients (54.5%) with late recurrence, which included reresection, transplant, and local ablation. Multivariate Cox regression analysis showed that regular surveillance for postoperative recurrence (hazard ratio [HR], 0.470; 95% CI, 0.310-0.713; P = .001), cirrhosis (HR, 1.381; 95% CI, 1.049-1.854; P = .02), portal hypertension (HR, 2.424; 95% CI, 1.644-3.574; P < .001), Child-Pugh grade of B or C (HR, 1.376; 95% CI, 1.153-1.674; P < .001), Barcelona Clinic Liver Cancer stage B (HR, 1.304; 95% CI, 1.007-1.708; P = .04) and stage C (HR, 2.037; 95% CI, 1.583-2.842; P < .001), and potentially curative treatment (HR, 0.443; 95% CI, 0.297-0.661; P < .001) were independent predictors of overall survival for patients with late recurrence. Conclusions and Relevance: Late recurrence after HCC resection was associated with sex, cirrhosis, and several aggressive tumor characteristics of the initial HCC. The patterns of late recurrence suggested surveillance for recurrence after 2 years of surgery should be targeted to the liver. Postoperative surveillance improved the chance of potentially curative treatments, with improved survival outcomes in patients with late recurrence.

Preoperative transcatheter arterial chemoembolization for surgical resection of huge hepatocellular carcinoma (≥ 10 cm): a multicenter propensity matching analysis.

BACKGROUND AND AIMS: Surgical resection for hepatocellular carcinoma (HCC) is potentially curative, but long-term survival remains unsatisfactory. There is currently no effective neoadjuvant or adjuvant therapy for HCC. We sought to evaluate the impact of preoperative transcatheter arterial chemoembolization (TACE) on long-term prognosis after surgical resection of huge HCCs (≥ 10 cm). METHODS: Using a multicenter database, consecutive patients who underwent curative-intent resection for huge HCC without macrovascular invasion between 2004 and 2014 were identified. The association between preoperative TACE with perioperative outcomes, long-term overall survival (OS), and recurrence-free survival (RFS) was assessed before and after propensity score matching (PSM). RESULTS: Among the 377 enrolled patients, 88 patients (23.3%) received preoperative TACE. The incidence of perioperative mortality and morbidity was comparable among patients who did and did not undergo preoperative TACE (3.4% vs. 2.4%, p= 0.704, and 33.0% vs. 31.1%, p= 0.749, respectively). PSM analysis created 84 matched pairs of patients. In examining the entire cohort as well as the PSM cohort, median OS (overall cohort: 32.8 vs. 22.3 months, p= 0.035, and PSM only: 32.8 vs. 18.1 months, p= 0.023, respectively) and RFS (12.9 vs. 6.4 months, p= 0.016, and 12.9 vs. 4.1 months, p= 0.009, respectively) were better among patients who underwent preoperative TACE vs. patients who did not. After adjustment for other confounding factors on multivariable analyses, preoperative TACE remained independently associated with a favorable OS and RFS after the resection of huge HCC. CONCLUSION: Preoperative TACE did not increase perioperative morbidity or mortality, yet was associated with an improved OS and RFS after liver resection of huge HCC (≥ 10 cm).

Identification of Actual 10-Year Survival After Hepatectomy of HBV-Related Hepatocellular Carcinoma: a Multicenter Study.

BACKGROUND: Hepatitis B virus (HBV) infection is the leading cause of hepatocellular carcinoma (HCC) worldwide. The aim of the study was to identify the incidence and predictive factors of actual 10-year survival following liver resection of HBV-related HCC. METHODS: A Chinese multicenter database of patients undergoing curative hepatectomy of HBV-related HCC was reviewed. Patients who survived ≥ 10 years and patients who died < 10 years after surgery were compared and analyzed. Univariable and multivariable regression analyses were performed to identify predictive factors associated with 10-year survival. RESULTS: Among all enrolled 1016 patients, the actuarial 10-year survival rate was 24.1%, while the actual 10-year survival rate was 16.6%. There were 169 patients who survived at least 10 years after surgery and 688 who died within 10 years from surgery. These patients constituted the study population of this study. Multivariable regression analysis revealed that cirrhosis, preoperative HBV viral load > 104 copies/mL, maximum tumor size > 5 cm, multiple tumors, macroscopic and microscopic vascular invasion, postoperative HBV reactivation, and early recurrence (< 2 years after surgery) were independent risk factors associated with actual 10-year survival, while postoperative antiviral therapy, regular recurrence surveillance, and curative treatments for initial recurrence were independent protective factors. CONCLUSIONS: The actual 10-year survival after curative resection of HBV-related HCC was calculated to be 16.6%. Postoperative antiviral therapy and regular recurrence surveillance were independent protective factors associated with actual 10-year survival after liver resection of HBV-related HCC.