Current noninvasive liver reserve models do not predict histological fibrosis severity in hepatocellular carcinoma.

The Ishak scoring system has been used to stage liver fibrosis. Ten noninvasive liver reserve models were proposed to assess the severity of liver fibrosis, but their performance in hepatocellular carcinoma (HCC) is unknown. We aimed to evaluate the correlation between these models and severity of fibrosis in patients with HCC. A total 464 patients with HCC undergoing surgical resection were retrospectively analyzed. Multivariate logistic regression analysis was performed to determine independent factors associated with advanced fibrosis (Ishak score 4 or higher). There were no significant correlations between all noninvasive models and severity of fibrosis in HCC (p for trend all >0.1). In subgroup analysis, cirrhosis discriminant index (CDS) and Lok's index in hepatitis B-, and fibrosis index based on 4 factors (FIB-4), CDS and Lok's index in hepatitis C-associated HCC, best correlated with the severity of liver fibrosis. Low platelet count, prolonged prothrombin time, hepatitis C and multiple tumors were independently associated with advanced fibrosis. Among the 10 models, CDS was the best model to predict cirrhosis. Currently used noninvasive liver reserve models do not well correlate with severity of histological fibrosis in HCC. New noninvasive models are required to improve the predictive accuracy of liver fibrosis in HCC.

Metastasis in patients with hepatocellular carcinoma: Prevalence, determinants, prognostic impact and ability to improve the Barcelona Clinic Liver Cancer system.

BACKGROUND & AIM: Patients with hepatocellular carcinoma and metastasis are classified as advanced or terminal stage by the Barcelona Clinic Liver Cancer system. This study investigates the prevalence, determinants, and prognostic effect of metastasis and its ability to improve the Barcelona Clinic Liver Cancer system. METHODS: A total of 3414 patients were enrolled. The Kaplan-Meier and Cox regression methods were used to determine survival predictors. Akaike information criterion was used to compare the prognostic performance of staging systems. RESULTS: There were 357 (10%) patients having extrahepatic metastasis at the time of diagnosis. Metastases were associated with old age, alcoholism, hepatitis B, poorer liver function, higher α-foetoprotein level and larger tumour burden (all P < .05). Vascular invasion was associated with metastasis regardless of total tumour volume, and higher α-foetoprotein level and multiple tumours were associated with metastasis in patients with smaller tumour volume (all P < .05). Patients with both vascular invasion and metastasis had significantly worse outcome compared to patients with either vascular invasion or metastasis (P < .05). In the Cox proportional model, the co-existence of vascular invasion and metastasis was an independent predictor of decreased survival (P < .05). Re-allocating 181 Barcelona Clinic Liver Cancer stage C patients with both vascular invasion and metastasis into stage D was associated with lower Akaike information criterion, indicating enhanced prognostic power of the Barcelona Clinic Liver Cancer. CONCLUSIONS: Metastasis is not uncommon, and is strongly associated with tumoural factors and poor long-term survival in hepatocellular carcinoma. Modification of the Barcelona Clinic Liver Cancer system based on vascular invasion and metastasis may further improve its predictive accuracy in advanced stage patients.

Using nomogram of the Barcelona Clinic Liver Cancer system for treatment selection in patients with stage C hepatocellular carcinoma.

BACKGROUND: The nomogram of the Barcelona Clinic Liver Cancer (BCLC) for hepatocellular carcinoma (HCC) has been used for outcome prediction. Patients with BCLC stage C HCC often undergo anti-cancer therapy against current treatment guidelines in real world practice. We aimed to use the nomogram to provide guidance on treatment selection for BCLC stage C patients. METHODS: A total of 1317 patients with stage C HCC were retrospectively analyzed and divided into four groups by nomogram points. One-to-one matched pairs between patients receiving different treatments were generated by the propensity score with matching model within these groups. Survival analysis was performed by Kaplan-Meier method with log-rank test. RESULTS: Patients with higher nomogram points were more often treated with targeted or supportive therapies (p <  0.001). Patients receiving targeted or supportive therapies had a decreased survival compared to patients undergoing aggressive treatments (surgical resection, ablation, transarterial chemo-embolization or transplantation) across all four groups (p <  0.001). After matching for baseline differences in the propensity model, patients receiving different treatments had comparable age, gender, etiology of liver disease, tumor burden, severity of cirrhosis and performance status. Survival analyses were re-performed and disclosed that patients with nomogram points < 15 had better overall outcome after aggressive treatments (p <  0.05). For patients with nomogram points > 15, there was no significant difference in survival between patients receiving two different treatment strategies. CONCLUSIONS: The nomogram of BCLC system is a feasible tool to help stage C HCC patients to select primary anti-cancer treatment in pursuance of better overall survival.

Comparison of twelve liver functional reserve models for outcome prediction in patients with hepatocellular carcinoma undergoing surgical resection.

Various noninvasive liver functional reserve models have been proposed, but their prognostic ability in patients with hepatocellular carcinoma (HCC) is unclear. We aimed to investigate the performance of twelve noninvasive liver reserve models in HCC patients undergoing surgical resection. A total of 645 patients undergoing resection were prospectively identified and retrospectively analyzed. Tumor recurrence, overall survival, and independent prognostic factors were evaluated by the Cox proportional hazards model. Of the twelve models, the King's score showed the highest homogeneity and lowest corrected Akaike information criterion (AICc) value, suggesting a better predictive ability for tumor recurrence. In multivariate Cox analysis, we confirmed that King's score, tumor size and serum alpha-fetoprotein level were independent predictors associated with recurrence. In survival prediction, albumin-bilirubin (ALBI) revealed the highest homogeneity and lowest value among twelve invasive models, indicating a better prognostic performance. In the Cox model, ALBI grade, tumor burden, alpha-fetoprotein, vascular invasion, diabetes mellitus and performance status were independent predictors linked with overall survival. In summary, the currently used liver function models have differential predictive ability for HCC patients undergoing surgical resection. The King's score is a feasible tool to predict tumor recurrence, whereas ALBI grade is a more robust model for prognostic prediction.

Prognostic Performance of Ten Liver Function Models in Patients with Hepatocellular Carcinoma Undergoing Radiofrequency Ablation.

Liver functional capacity is a crucial survival determinant for hepatocellular carcinoma (HCC). Noninvasive models were proposed to assess hepatic reserve, but their performance in outcome prediction is unclear. We aimed to investigate 10 currently used liver function models in HCC patients undergoing radiofrequency ablation (RFA). A total 499 HCC patients were prospectively identified. Homogeneity and corrected Akaike information criteria (AICc) were compared. Cox proportional hazards model was used to identify independent survival predictors. Significance survival differences were found across 10 noninvasive models (all p < 0.001) except for GUCI and APRI grade 2 vs 3, and King's score grade 1 vs 2. Among these models, ALBI grade showed the highest homogeneity and lowest AICs value, indicating a better prognostic performance. Within Child-Turcotte-Pugh (CTP) score 5 group, significant survival difference was demonstrated between ALBI grade 1 and 2 (p < 0.001); for those with CTP score 6 or higher, only ALBI grade 2 and 3 showed survival difference (p < 0.001). Cox analysis disclosed that ALBI grade, tumor size and performance status were independent prognostic predictors. There was significant correlation between CTP score and other 9 models. We conclude that ALBI grade may serve as objective and feasible surrogate for prognostic prediction in HCC patients undergoing RFA.

Impact of tumor burden on prognostic prediction for patients with terminal stage hepatocellular carcinoma: A nomogram study.

BACKGROUND: The recently proposed nomogram of Barcelona Clinic Liver Cancer (BCLC) lacks predictive accuracy for patients with stage D hepatocellular carcinoma (HCC). Tumor burden is crucial in prognostic prediction but is not included in the criteria of stage D HCC. This study aims to develop a nomogram with tumor burden as the core element for BCLC stage D patients. METHODS: A total of 386 patients were randomly grouped into derivation and validation sets (1:1 ratio). The multivariate Cox proportional hazards model was used to select factors with significant prognostic effect and generate the nomogram. Concordance indices and calibration plots were used to evaluate the performance of nomogram. RESULTS: Overall survival of study patients was significantly associated with tumor burden as well as hepatitis B, serum α-fetoprotein level, cirrhosis and performance status in multivariate Cox regression (all p<0.05). Beta-coefficients of these variables in derivation set were used to generate the nomogram. Each patient was assigned with a total nomogram point that predicted individualized 6-month and 1-year survival. The derivation and validation sets had a c-index of 0.759 (95% confidence interval [CI]: 0.552-0.923) and 0.741 (95% CI: 0.529-0.913), respectively. The calibration plots were close to the 45-degree line for 6-month and 1-year survival prediction for all quarters of patients in both derivation and validation sets. CONCLUSION: Tumor burden is significantly associated with the outcome for patients with stage D HCC. The tumor burden-incorporated nomogram may serve as a feasible and easy-to-use tool in predicting survival on an individual level.

A New Treatment-integrated Prognostic Nomogram of the Barcelona Clinic Liver Cancer System for Hepatocellular Carcinoma.

The nomogram of the Barcelona Clinic Liver Cancer (BCLC) has accurate outcome prediction. This study aims to propose a treatment-integrated nomogram derived from BCLC for patients with hepatocellular carcinoma (HCC). A total of 3,371 patients were randomly grouped into derivation (n = 2,247) and validation (n = 1,124) sets. Multivariate Cox proportional hazards model was used to generate the nomogram from tumor burden, cirrhosis, performance status (PS) and primary anti-cancer treatments. Concordance indices and calibration plots were used to evaluate the performance of nomogram. The derivation and validation sets had the same concordance index of 0.774 (95% confidence intervals: 0.717-0.826 and 0.656-0.874, respectively). In calibration plots, survival distributions predicted by the nomogram and observed by the Kaplan-Meier method were similar at 3- and 5-year for patients from derivation and validation sets. Validation group patients divided into 10 subgroups by the original and new treatment-integrated BCLC nomogram were used to evaluate the prognostic performance of integrating primary anti-cancer treatments. Compared to the nomogram of original BCLC system, the treatment-integrated nomogram of BCLC system had larger linear trend and likelihood ratio X2. In conclusion, based on the results of concordance index tests, integrating primary anti-cancer treatments into the BCLC system provides similar discriminatory ability.

Prognostic role of noninvasive liver reserve markers in patients with hepatocellular carcinoma undergoing transarterial chemoembolization.

BACKGROUND: Various noninvasive liver reserve markers were proposed to indicate the severity of liver damage. However, the role and feasibility of these markers to predict the prognosis of patients with hepatocellular carcinoma (HCC) are unknown. We aimed to identify the prognostic role of the 8 currently used hepatic reserve markers in patients with HCC undergoing transarterial chemoembolization (TACE). METHODS: Between 2002 and 2013, a total of 881 patients with HCC undergoing TACE were prospectively identified and retrospectively analyzed. The baseline characteristics, tumor status and noninvasive markers were collected. Homogeneity and corrected Akaike information criteria (AICc) were compared between these markers. The Cox proportional hazards model was used to identify independent predictors of survival. RESULTS: Significant differences in survival distribution were found for albumin-bilirubin (ALBI) grade, Child-Turcotte-Pugh (CTP) class, Lok index, fibrosis index based on 4 factors (FIB-4), Göteborg University cirrhosis index (GUCI), cirrhosis discriminant index (CDI) and model for end-stage liver disease (MELD) score (all p values <0.05). Among these markers, the ALBI grade showed the highest homogeneity and lowest AICc value, indicating a better prognostic performance. Cox multivariate analysis confirmed that ALBI grade 2, ascites, serum alkaline phosphatase and α-fetoprotein level, tumor diameter, vascular invasion and performance status were significant independent prognostic predictors. The distribution of the ALBI score well correlated with baseline CTP and MLED scores. CONCLUSIONS: Our data suggest that among the currently used liver reserve markers, ALBI grade may serve as an objective and feasible surrogate to predict the prognosis of HCC patients undergoing TACE.

Prognostic impact of diabetes mellitus on hepatocellular carcinoma: Special emphasis from the BCLC perspective.

BACKGROUND: Diabetes mellitus (DM) is associated with higher incidence and poorer prognosis of hepatocellular carcinoma (HCC). The influence of DM on patient survival in different HCC stages is not known. METHODS: A prospective dataset of 3,182 HCC patients was collected between 2002 and 2014. Patients were divided into three groups according to BCLC stages (BCLC stage 0 and stage A, BCLC stage B, BCLC stage C and stage D). We compared the cumulative survival rate of diabetic and non-diabetic patients in different BCLC groups. The correlation between DM and overall survival was also analyzed by multivariate Cox regression model within each group. RESULTS: DM is present in 25.2% of all patients. Diabetic patients had lower cumulative survival in BCLC stage 0 plus BCLC stage A group (log rank p<0.001), and BCLC stage B group (log rank p = 0.012), but not in BCLC stage C plus BCLC stage D group (log rank p = 0.132). Statistically significant differences in overall survival are found between diabetic and non-diabetic patients in BCLC stage 0 plus stage A group (adjusted hazard ratio [HR] = 1.45, 95% confidence interval [CI] 1.08-1.93, p = 0.013), and BCLC stage B (adjusted HR = 1.77, 95% CI 1.24-2.51, p = 0.002). In contrast, the survival difference is not seen in BCLC stage C plus stage D group (adjusted HR = 1.09, 95% CI 0.90-1.30, p = 0.387). CONCLUSIONS: DM is prevalent in HCC, and is associated with lower survival rate in HCC patients with BCLC stage 0 plus stage A and B, but not in those with BCLC stage C plus stage D.

ALBI and PALBI grade predict survival for HCC across treatment modalities and BCLC stages in the MELD Era.

BACKGROUND AND AIM: The severity of liver dysfunction in hepatocellular carcinoma (HCC) is often estimated with Child-Turcotte-Pugh (CTP) classification or model for end-stage liver disease (MELD) score. We aim to investigate the performance of albumin-bilirubin (ALBI) and platelet-albumin-bilirubin (PALBI) grade, which are recently reported to be simple and objective measurements for liver reserve in HCC. METHODS: Between 2002 and 2014, consecutive 3182 HCC patients were enrolled to follow up their survival. The area under receiver-operator-characteristic curve (AUC) was calculated to test the discriminatory powers over 1-year, 3-year, and 5-year survival. RESULTS: Significant survival differences were found across all ALBI and PALBI grades (both P < 0.001). The majority (73%) of patients were CTP class A. Within CTP class A, ALBI revealed two prognostic groups while PALBI segregated three prognostic groups. The PABLI grade also identified three different survival groups for patients undergoing resection, ablation, and chemoembolization. Both ALBI and PALBI grade were capable of discerning survival among different HCC stages. The PALBI grade had significantly higher AUC compared with CTP classification and ALBI grade at 1, 3, and 5 years. For CTP class A patients, the PALBI grade was also associated with significantly higher AUC compared with ALBI grade at 1-year and 3-year intervals. The MELD score has the lowest AUC compared with other systems. CONCLUSIONS: Both ALBI and PALBI grade are adequate models to assess liver dysfunction in HCC. The PALBI grade is consistently better in all patients, in patients with minimally decreased liver function, and in patients receiving different aggressive therapies.

Proposal and validation of a new model to estimate survival for hepatocellular carcinoma patients.

BACKGROUND AND AIMS: The survival of hepatocellular carcinoma (HCC) patients is heterogeneous. We aim to develop and validate a simple prognostic model to estimate survival for HCC patients (MESH score). METHODS: A total of 3182 patients were randomised into derivation and validation cohort. Multivariate analysis was used to identify independent predictors of survival in the derivation cohort. The validation cohort was employed to examine the prognostic capabilities. RESULTS: The MESH score allocated 1 point for each of the following parameters: large tumour (beyond Milan criteria), presence of vascular invasion or metastasis, Child-Turcotte-Pugh score ≥6, performance status ≥2, serum alpha-fetoprotein level ≥20 ng/ml, and serum alkaline phosphatase ≥200 IU/L, with a maximal of 6 points. In the validation cohort, significant survival differences were found across all MESH scores from 0 to 6 (all p < 0.01). The MESH system was associated with the highest homogeneity and lowest corrected Akaike information criterion compared with Barcelona Clínic Liver Cancer, Hong Kong Liver Cancer (HKLC), Cancer of the Liver Italian Program, Taipei Integrated Scoring and model to estimate survival in ambulatory HCC Patients systems. The prognostic accuracy of the MESH scores remained constant in patients with hepatitis B- or hepatitis C-related HCC. The MESH score can also discriminate survival for patients from early to advanced stages of HCC. CONCLUSIONS: This newly proposed simple and accurate survival model provides enhanced prognostic accuracy for HCC. The MESH system is a useful supplement to the BCLC and HKLC classification schemes in refining treatment strategies.

Solitary Large Hepatocellular Carcinoma: Staging and Treatment Strategy.

BACKGROUND & AIMS: Controversies exist on staging and management of solitary large (>5 cm) hepatocellular carcinoma (HCC). This study aims to evaluate the impact of tumor size on Barcelona Clinic Liver Cancer (BCLC) staging and treatment strategy. METHODS: BCLC stage A and B patients were included and re-classified as single tumor 2-5 cm or up to 3 tumors ≤3 cm (group A; n = 657), single tumor >5 cm (group SL; n = 224), and multiple tumors >3 cm (group B; n = 351). Alternatively, 240 and 229 patients with solitary large HCC regardless of tumor stage received surgical resection (SR) and transarterial chemoembolization (TACE), respectively. The propensity score analysis identified 156 pairs of patients from each treatment arm for survival comparison. RESULTS: The survival was significantly higher for group A but was comparable between group SL and group B patients. Of patients with solitary large HCC, the 1-, 3- and 5-year survival rates were 88% versus 74%, 76% versus 44%, and 63% versus 35% between SR and TACE group, respectively (p<0.001). When baseline demographics were adjusted in the propensity model, the respective 1-, 3- and 5-year survival rates were 87% versus 79%, 76% versus 46%, and 61% versus 36% (p<0.001). The Cox proportional hazards model identified TACE with a 2.765-fold increased risk of mortality compared with SR (95% confidence interval: 1.853-4.127, p<0.001). CONCLUSIONS: Patients with solitary large HCC should be classified at least as intermediate stage HCC. SR provides significantly better survival than TACE for solitary large HCC regardless of tumor stage. Further amendment to the BCLC classification is mandatory.

Development and Validation of a New Prognostic System for Patients with Hepatocellular Carcinoma.

BACKGROUND: Prognostic assessment in patients with hepatocellular carcinoma (HCC) remains controversial. Using the Italian Liver Cancer (ITA.LI.CA) database as a training set, we sought to develop and validate a new prognostic system for patients with HCC. METHODS AND FINDINGS: Prospective collected databases from Italy (training cohort, n = 3,628; internal validation cohort, n = 1,555) and Taiwan (external validation cohort, n = 2,651) were used to develop the ITA.LI.CA prognostic system. We first defined ITA.LI.CA stages (0, A, B1, B2, B3, C) using only tumor characteristics (largest tumor diameter, number of nodules, intra- and extrahepatic macroscopic vascular invasion, extrahepatic metastases). A parametric multivariable survival model was then used to calculate the relative prognostic value of ITA.LI.CA tumor stage, Eastern Cooperative Oncology Group (ECOG) performance status, Child-Pugh score (CPS), and alpha-fetoprotein (AFP) in predicting individual survival. Based on the model results, an ITA.LI.CA integrated prognostic score (from 0 to 13 points) was constructed, and its prognostic power compared with that of other integrated systems (BCLC, HKLC, MESIAH, CLIP, JIS). Median follow-up was 58 mo for Italian patients (interquartile range, 26-106 mo) and 39 mo for Taiwanese patients (interquartile range, 12-61 mo). The ITA.LI.CA integrated prognostic score showed optimal discrimination and calibration abilities in Italian patients. Observed median survival in the training and internal validation sets was 57 and 61 mo, respectively, in quartile 1 (ITA.LI.CA score ≤ 1), 43 and 38 mo in quartile 2 (ITA.LI.CA score 2-3), 23 and 23 mo in quartile 3 (ITA.LI.CA score 4-5), and 9 and 8 mo in quartile 4 (ITA.LI.CA score > 5). Observed and predicted median survival in the training and internal validation sets largely coincided. Although observed and predicted survival estimations were significantly lower (log-rank test, p < 0.001) in Italian than in Taiwanese patients, the ITA.LI.CA score maintained very high discrimination and calibration features also in the external validation cohort. The concordance index (C index) of the ITA.LI.CA score in the internal and external validation cohorts was 0.71 and 0.78, respectively. The ITA.LI.CA score's prognostic ability was significantly better (p < 0.001) than that of BCLC stage (respective C indexes of 0.64 and 0.73), CLIP score (0.68 and 0.75), JIS stage (0.67 and 0.70), MESIAH score (0.69 and 0.77), and HKLC stage (0.68 and 0.75). The main limitations of this study are its retrospective nature and the intrinsically significant differences between the Taiwanese and Italian groups. CONCLUSIONS: The ITA.LI.CA prognostic system includes both a tumor staging-stratifying patients with HCC into six main stages (0, A, B1, B2, B3, and C)-and a prognostic score-integrating ITA.LI.CA tumor staging, CPS, ECOG performance status, and AFP. The ITA.LI.CA prognostic system shows a strong ability to predict individual survival in European and Asian populations.

Nomogram of the Barcelona Clinic Liver Cancer system for individual prognostic prediction in hepatocellular carcinoma.

BACKGROUND & AIMS: The predictive accuracy of the Barcelona Clinic Liver Cancer (BCLC) staging system on a single patient is not clear. This study aimed to develop a nomogram to predict individualized survival of patients with hepatocellular carcinoma (HCC) based on the BCLC system. METHODS: A total of 3179 patients were randomly grouped into derivation (n = 2119) and validation (n = 1060) sets. The multivariate Cox proportional hazards model was used to generate the nomogram from tumour burden, cirrhosis and performance status (PS). The performance of the nomogram was evaluated by concordance indices and calibration tests. RESULTS: Beta coefficients from the Cox model were used to assign nomogram points to different degrees of tumour burden, Child-Turcotte-Pugh classification and PS. A nomogram with a scale of 0-26 was developed and the predicted survival rates at 3 and 5 years were calculated. The derivation set had a concordance index of 0.766 (95% confidence interval [CI]: 0.686-0.838); and the validation set showed a concordance index of 0.775 (95% CI: 0.607-0.909). The calibration plots were close to the 45-degree line for 3- and 5-year survival prediction of BCLC stages 0-C patients in both derivation and validation groups. For BCLC stage D patients, calibration plots in both groups showed deviation from the 45-degree line for 3- and 5-year prediction. CONCLUSIONS: This study provides quantitative evidence to support the prognostic ability of BCLC system. This straightforward and easy-to-use nomogram may accurately predict the survival at 3 and 5 years for individual HCC patient except for BCLC stage D patients.

Surgical Resection is Better than Transarterial Chemoembolization for Patients with Hepatocellular Carcinoma Beyond the Milan Criteria: A Prognostic Nomogram Study.

BACKGROUND: The clinical outcomes in hepatocellular carcinoma (HCC) patients receiving surgical resection (SR) or transarterial chemoembolization (TACE) are diverse. This study aimed to develop a nomogram to predict individualized survival risk in patients with HCC beyond the Milan criteria undergoing aggressive treatments (SR and TACE). METHODS: A total of 1009 patients were enrolled in the study and randomly grouped into derivation (n = 505) and validation sets (n = 504). The multivariate Cox proportional hazards model was used to select significant prognostic predictors from the derivation set to generate the nomogram. The performance of the nomogram was evaluated by discrimination (concordance index) and calibration tests. RESULTS: Serum albumin <3.8 g/dL, α-fetoprotein ≥400 ng/mL, TACE, vascular invasion, multiple tumors, and tumor volume ≥200 cm(3) were associated with poor survival in the multivariate Cox model (all p < 0.05). A nomogram with a scale of 0-47 was developed with these six variables, and the predicted survival rates at 1 and 3 years were calculated. The derivation set with bootstrapping (B = 100) had a good concordance index of 0.694 [95% confidence interval (CI) 0.68-0.708]. Discrimination test in the validation set provided a concordance index of 0.71 (95 % CI 0.697-0.722), and the calibration plots well-matched the 45-degree line for 1- and 3-year survival prediction. The respective survival for patients undergoing SR or TACE could be predicted based on the nomogram across different risk scores. CONCLUSIONS: This easy-to-use nomogram may accurately predict survival at 1 and 3 years for individual HCC patients beyond the Milan criteria, and provide quantitative survival advantage of SR over TACE.

Surgical Resection Versus Radiofrequency Ablation for Single Hepatocellular Carcinoma ≤ 2  cm in a Propensity Score Model.

OBJECTIVES: To evaluate the efficacy of surgical resection (SR) and radiofrequency ablation (RFA) for single hepatocellular carcinoma (HCC) 2  cm or less. BACKGROUND: The optimal management for Barcelona Clínic Liver Cancer (BCLC) very early-stage HCC is undetermined. METHODS: Between 2002 and 2013, a total of 237 (SR, 109; RFA, 128) patients with BCLC very early-stage HCC were enrolled. Their overall survival (OS) and recurrence-free survival (RFS) were compared. Propensity score matching analysis identified 79 matched pairs of patients to compare outcomes. RESULTS: At baseline, patients with SR were younger and had larger tumors (both P < 0.05). The 5-year OS rates were 81% versus 76% (P = 0.136), whereas 5-year RFS rates were 49% versus 24% (P < 0.001) for SR and RFA groups, respectively. In the propensity model, the baseline variables were well balanced between 2 groups. Surgical resection was significantly associated with better OS and RFS compared with RFA; the 5-year OS rates were 80% versus 66% (P = 0.034), and 5-year RFS rates were 48% versus 18% (P < 0.001) for SR and RFA groups, respectively. The Cox proportional hazards model identified RFA as an independent predictor for mortality and tumor recurrence in the propensity model (hazard ratio, 2.120 and 2.421, respectively; both P < 0.05). Patients with recurrent HCC had inferior prognosis compared with patients without recurrence (P = 0.001). However, the survival after recurrence was similar between patients initially treated with SR or RFA (P = 0.415). CONCLUSIONS: Surgical resection provides better long-term OS and RFS compared with RFA in patients with BCLC very early-stage HCC. Surgical resection should be considered as the first-line treatment for these patients.

Prognosis of hepatocellular carcinoma: Assessment of eleven staging systems.

BACKGROUND & AIMS: Multiple staging systems have been proposed for hepatocellular carcinoma (HCC). However there is no consensus regarding which system provides the best prognostic accuracy. We aimed to investigate the performance of 11 currently used HCC staging systems. METHODS: Between 2002 and 2013, a large prospective dataset of 3182 HCC patients were enrolled. The baseline characteristics and staging information were collected. Independent predictors of survival were identified. Homogeneity and corrected Akaike information criterion (AICc) were compared between each system. RESULTS: The median follow-up duration was 17months. Independent predictors of adverse outcome were serum albumin <3.5g/dl, bilirubin ⩾1mg/dl, creatinine ⩾1mg/dl, alpha-fetoprotein ⩾20ng/ml, alkaline phosphatase ⩾200IU/L, presence of ascites, multiple tumor nodules, maximal tumor size >5cm, presence of vascular invasion, presence of extrahepatic metastasis, and poor performance status (all p<0.001). Significant differences in survival were found across all stages of the 11 systems except between Hong Kong Liver Cancer stage IV and V, Japan Integrated Staging score 4 and 5, and Tokyo score 5 through 8. The Cancer of the Liver Italian Program (CLIP) score was associated with the highest homogeneity and lowest AICc value in the entire cohort. In subgroup analysis, the CLIP score was also superior in patients with hepatitis B- or hepatitis C-related HCC and in patients receiving curative or non-curative treatments. CONCLUSIONS: The CLIP staging system is stable and consistently the best prognostic model in all patients and in patients with different viral etiology and treatment strategy.

When to Perform Surgical Resection or Radiofrequency Ablation for Early Hepatocellular Carcinoma?: A Nomogram-guided Treatment Strategy.

Radiofrequency ablation (RFA) is indicated for early-stage hepatocellular carcinoma (HCC), but the comparative efficacy between RFA and surgical resection (SR) is inconclusive. We aim to develop a prognostic nomogram for predicting recurrence-free survival (RFS) after RFA. We also evaluate the possibility of using nomogram in improving treatment algorithm.We retrospectively enrolled 836 patients with Barcelona Clínic Liver Cancer very-early/early-stage HCC receiving SR or RFA. A visually-orientated nomogram was constructed with Cox proportional hazards model, and number and size of tumor, platelet count, albumin level, and model for end-stage liver disease score were included. The concordance index of the nomogram was 0.69.Radiofrequency ablation patients were stratified into low and high-risk groups by the median of nomogram scores. The RFS and overall survival (OS) of 2 risk groups were compared with SR patients with propensity score matching analysis. SR provided better RFS and OS compared with high-risk (nomogram score ≥9.8) RFA patients in the propensity model. The 5-year RFS rates were 36% versus 11%, whereas the 5-year OS rates were 74% versus 60% for SR and high-risk RFA groups, respectively (both P < 0.05). However, SR was associated with better RFS (5-year RFS rates 41% vs 29%), but similar OS (5-year OS rates 80% vs 81%), compared with low-risk (nomogram score <9.8) RFA patients in the propensity model (P < 0.05 and P > 0.05, respectively).In conclusion, this user-friendly nomogram offers individualized recurrence risk estimation and stratification for early HCC patients receiving curative RFA. The nomogram can be integrated into current treatment algorithm. SR should be considered the first-line treatment for high-risk patients to achieve better long-term survival.

Hong Kong Liver Cancer Staging System Is Associated With Better Performance for Hepatocellular Carcinoma: Special Emphasis on Viral Etiology.

Hong Kong Liver Cancer (HKLC) staging system was developed for prognostic and treatment evaluation for hepatocellular carcinoma (HCC) but is not externally validated. We aimed to evaluate and compare HKLC system with Barcelona Clínic Liver Cancer (BCLC) staging system. The prognostic performance, discriminatory ability, and efficacy of treatment recommendations were compared between the BCLC and HKLC systems. Significant differences in survival were found across all stages of BCLC and across stages I to IV of HKLC systems (P < 0.01). HKLC system was associated with higher homogeneity in prognostic accuracy. The survival was similar between patients treated according to the HKLC or BCLC system (P = 0.07). However, more patients were treated according to HKLC recommendations than to BCLC recommendations (57% vs. 47%, P < 0.001). In a hypothetical cohort created by random sampling, patients treated according to the HKLC scheme had better survival compared with patients treated according to the BCLC system (P < 0.001).Subgroup analyses between hepatitis B virus (HBV) and hepatitis C virus (HCV)-related HCC were performed. More HCV-related HCC were at earlier BCLC or HKLC stages (both P < 0.001). The HKLC system was more informative with greater homogeneity in predicting survival in both HBV and HCV cohorts. However, HKLC treatment recommendations were associated with better long-term survival only in HBV-related HCC but not in HCV-related HCC (P < 0.001 and P = 0.79, respectively).In conclusion, we provided external validation of the HKLC system. Compared with the BCLC system, the HKLC system has better prognostic accuracy and therapeutic efficacy in the entire cohort and in HBV-related HCC but not in HCV-related HCC. Due to high heterogeneity among patients of various etiologies, staging and treatment strategies tailored to specific HCC etiology are required.

Hepatocellular Carcinoma Patients With Performance Status 1 Deserve New Classification and Treatment Algorithm in the BCLC System.

Hepatocellular carcinoma (HCC) patients with performance status (PS) 1 or 2 are considered similar in the Barcelona Clinic Liver Cancer (BCLC) system. The rationales are not fully studied. A total of 693 and 335 HCC patients were classified as PS 1 and 2, respectively, in a prospectively followed up database. One-to-one matched pairs between HCC patients were generated by using the propensity score with matching model. Survival analysis was performed and the hazard ratio was calculated with the Cox proportional hazards model. Patients with PS 1 were significantly younger and had better liver and renal functions compared with patients with PS 2 (all P < 0.05). Patients with PS 1 had earlier BCLC stages and higher chances to undergo curative treatments (both P < 0.05). After matching, patients with PS 1 or 2 had similar age, gender, liver diseases, severity of cirrhosis, tumor burden, and treatments (all P > 0.05); patients with PS 1 had significantly better prognosis compared with patients with PS 2 (P < 0.05). There were 68% of patients with PS 1 that underwent aggressive treatments (resection, transplantation, percutaneous ablation, or transarterial chemoembolization), which were significantly correlated to better outcome with a hazard ratio of 0.539 in the matching model (P = 0.002). For patients with PS 2, aggressive treatments were not significantly associated with better long-term survival. Aggressive treatments provide survival benefits for patients with PS 1, but not for patients with PS 2. HCC patients with PS 1 or 2 should be considered clinically different disease entities in the BCLC system.