Performance status as a prognostic surrogate in hepatocellular carcinoma: Role of albumin-bilirubin and easy-albumin-bilirubin grade.

BACKGROUND: Performance status (PS) is associated with the severity of liver cirrhosis and is also an important survival determinant in hepatocellular carcinoma (HCC). Albumin-bilirubin (ALBI) grade and easy (EZ)-ALBI grade have been proposed to evaluate liver dysfunction in HCC, but their role in patients with different PS is unclear. We aimed to investigate the prognostic role of ALBI and EZ-ALBI grade in a large HCC cohort with variable PS. METHODS: A total of 3355 newly diagnosed HCC patients between 2002 and 2018 were identified and retrospectively analyzed. Independent prognostic predictors associated with survival were investigated using the Cox proportional hazards model. RESULTS: Patients with poor PS had decreased survival compared with those with good PS. In the Cox model, creatinine ≥1.2 mg/dL, α-fetoprotein (AFP) ≥20 ng/mL, vascular invasion, distant metastasis, total tumor volume >100 cm 3 , presence of ascites, ALBI grades 2 and 3, EZ-ALBI grade 2 and grade 3, PS 1-4, and noncurative treatment were independently associated with higher mortality in the entire cohort (all p < 0.001). ALBI grade and EZ-ALBI grade can well stratify overall survival in subgroup patients with PS 0, PS 1-2, and PS 3-4 (all p < 0.001). CONCLUSION: Patients with good PS have better long-term survival compared with those with poor PS. ALBI and EZ-ALBI grade can discriminate long-term outcome in the entire cohort as well as in patients with different PS. ALBI and EZ-ALBI are objective and feasible prognostic models to evaluate liver dysfunction in HCC patients independent of PS.

Surgical resection versus transarterial chemoembolization for patients with hepatocellular carcinoma beyond Milan criteria: prognostic role of tumor burden score.

Tumor burden score (TBS) has been recently introduced to indicate the extent of tumor burden in different cancers, but its role in advanced hepatocellular carcinoma (HCC) is unclear. We aimed to determine the prognostic role of TBS in patients with HCC beyond the Milan criteria receiving surgical resection (SR) or transarterial chemoembolization (TACE). A total of 1303 newly diagnosed HCC patients beyond Milan criteria receiving SR or TACE as the primary therapy were retrospectively analyzed. Independent prognostic predictors were examined by the multivariate Cox proportional hazards model. SR was associated with better overall survival compared with TACE in these patients. Multivariate Cox analysis of the entire cohort revealed that age > 66 years (hazard ratio [HR]: 1.145, 95% confidence interval [CI]: 1.004-1.305, p = 0.043), serum α-fetoprotein > 200 ng/mL (HR: 1.602, 95% CI: 1.402-1.831, p < 0.001), performance status 2-4 (HR: 1.316, 95% CI: 1.115-1.553, p < 0.001), medium TBS (HR: 1.225, 95% CI:1.045-1.436, p = 0.012), high TBS (HR: 1.976, 95% CI: 1.637-2.384, p < 0.001), albumin-bilirubin (ALBI) grade 2-3 (HR: 1.529, 95% CI: 1.342-1.743, p < 0.001), presence of vascular invasion (HR: 1.568, 95% CI: 1.354-1.816, p < 0.001), and TACE (HR: 2.396, 95% CI: 2.082-2.759, p < 0.001) were linked with decreased survival. SR consistently predicted a significantly better survival in different TBS subgroups. TBS is a feasible and independent prognostic predictor in HCC beyond the Milan criteria. SR provides better long-term outcome compared with TACE in these patients independent of TBS grade, and should be considered as the primary treatment modality in this special patient group.

Comparison of Four Albumin-Based Liver Reserve Models (ALBI/EZ-ALBI/PALBI/PAL) against MELD for Patients with Hepatocellular Carcinoma Undergoing Transarterial Chemoembolization.

(1) Background: The severity of liver functional reserve plays an important role in the management of hepatocellular carcinoma (HCC). Noninvasive models such as the model for end-stage liver disease (MELD), albumin-bilirubin (ALBI) grade and easy (EZ)-ALBI grade, platelet-albumin-bilirubin (PALBI) and platelet-albumin (PAL) are used to evaluate liver dysfunction. We aimed to compare the prognostic performance of these four albumin-based models against MELD in HCC patients undergoing transarterial chemoembolization (TACE). (2) Methods: A total of 1038 treatment naïve HCC patients who received TACE as the primary treatment were enrolled. A multivariate Cox model was used to determine independent survival predictors. (3) Results: Multivariate analysis revealed that higher serum creatinine and α-fetoprotein level, vascular invasion, large tumor size, ALBI grades 2-3, EZ-ALBI grades 2-3, PALBI grades 2-3, PAL grades 2-3, but not the MELD score, were independent predictors associated with decreased survival in different Cox models. Among these models, the PALBI grade had the highest homogeneity and lowest corrected Akaike information criteria value, followed by EZ-ALBI, PAL, ALBI and, lastly, MELD. (4) Conclusions: All four albumin-based liver reserve models are better prognostic tools than MELD score in HCC patients undergoing TACE. Of these, the PALBI score is the best model to evaluate the liver reserve and should be considered a surrogate marker in these patients.

Prognostic Prediction for Patients with Hepatocellular Carcinoma and Ascites: Role of Albumin-Bilirubin (ALBI) Grade and Easy (EZ)-ALBI Grade.

Patients with hepatocellular carcinoma (HCC) often have co-existing ascites, which is a hallmark of liver decompensation. The albumin-bilirubin (ALBI) grade and EZ (easy)-ALBI grade are used to assess liver functional reserve in HCC, but the predictive accuracy of these two models in HCC patients with ascites is unclear. We aimed to determine the prognostic role of ALBI and EZ-ALBI grades in these patients. A total of 4431 HCC patients were prospectively enrolled and retrospectively analyzed. Independent prognostic predictors were identified by the multivariate Cox proportional hazards model. Of all patients, 995 (22.5%) patients had ascites. Grade 1, 2, and 3 ascites were found in 16%, 4%, and 3% of them, respectively. A higher ascites grade was associated with higher ALBI and EZ-ALBI scores and linked with decreased overall survival. In the Cox multivariate analysis, serum bilirubin level > 1.1 mg/dL, creatinine level ≥ 1.2 mg/dL, α-fetoprotein ≥ 20 ng/mL, total tumor volume > 100 cm3, vascular invasion, distant metastasis, poor performance status, ALBI grade 2 and 3, EZ-ALBI grade 2 and 3, and non-curative treatments were independently associated with increased mortality (all p < 0.05) among HCC patients with ascites. The ALBI and EZ-ALBI grade can adequately stratify overall survival in both the entire cohort and specifically in patients with ascites. Ascites is highly prevalent and independently predict patient survival in HCC. The ALBI and EZ-ALBI grade are feasible markers of liver dysfunction and can stratify long-term survival in HCC patients with ascites.

Cryptogenic hepatocellular carcinoma: characteristics, outcome, and prognostic role of albumin-bilirubin (ALBI) grade vs easy ALBI grade.

BACKGROUND: The characteristics and prognosis of cryptogenic hepatocellular carcinoma (HCC) remain unclear. The albumin-bilirubin (ALBI) grade and its updated version, the easy ALBI (EZ-ALBI) grade, are important prognostic predictors for HCC. We aimed to investigate the long-term survival of patients with cryptogenic HCC and the prognostic role of ALBI and EZ-ALBI grade in these patients. METHODS: A prospective cohort of 2,937 HCC patients with viral or cryptogenic etiology were retrospectively analyzed. The multivariate Cox model was used to determine prognostic predictors. RESULTS: Cryptogenic HCC patients were often older and diabetic, had lower serum ɑ-fetoprotein (AFP) levels, larger tumor burden, poor performance status, advanced cancer stage, and received non-curative treatments compared with hepatitis B or C-related HCC. The Cox analysis showed that age > 65 years, serum AFP > 400 ng/mL, presence of vascular invasion or distant metastasis, presence of ascites, performance status 2-4, ALBI grade 2 and 3, EZ-ALBI grade 2 and 3, and non-curative treatment, were independent predictors of decreased survival in cryptogenic HCC (p < .001). Significant survival differences were found across ALBI grade and EZ-ALBI grade in cryptogenic HCC and subgroup patients receiving curative or non-curative treatments. The Cancer of Liver Italian Program was the best staging system for patients with cryptogenic HCC. CONCLUSIONS: Patients with cryptogenic HCC have a larger tumor burden and advanced cancer stage at disease presentation compared with those with viral HCC. The ALBI and EZ-ALBI score are robust models to evaluate liver functional reserve for these patients independent of treatment modality.

Radiofrequency Ablation versus Transarterial Chemoembolization for Hepatocellular Carcinoma within Milan Criteria: Prognostic Role of Tumor Burden Score.

Tumor burden score (TBS), estimated by the diameter and number of tumor nodules, was recently proposed to assess the tumor burden in hepatocellular carcinoma (HCC). We aimed to evaluate the prognostic impact of TBS on HCC patients within the Milan criteria undergoing radiofrequency ablation (RFA) or transarterial chemoembolization (TACE). A total of 883 patients undergoing RFA and TACE were included. The multivariate Cox proportional hazards model was used to determine independent prognostic predictors in different patient cohorts. The TACE group had significantly higher TBS compared with the RFA group. The RFA group had better long-term survival than the TACE group in patients within the Milan criteria in univariate survival analysis. In the Cox model, serum α-fetoprotein (AFP) > 20 ng/mL, performance status 1−2, medium and high TBS, albumin−bilirubin (ALBI) grade 2 and grade 3 were independent predictors linked with mortality (all p < 0.001). Overall, TACE was not an independent predictor; among patients with low TBS, TACE was independently associated with decreased survival compared with RFA (p = 0.034). Conclusions: TBS is a feasible prognostic marker for HCC patients within the Milan criteria. TACE may be an effective treatment alternative for these patients. Among patients with low TBS, RFA should be considered the priority treatment modality.

Tumor burden score as a new prognostic surrogate in patients with hepatocellular carcinoma undergoing radiofrequency ablation: role of albumin-bilirubin (ALBI) grade vs easy ALBI grade.

INTRODUCTION: Tumor burden score (TBS) was proposed to represent tumor burden in solid tumors, including hepatocellular carcinoma (HCC). The prognostic role of TBS in HCC patients in relation to recently introduced liver reserve markers, albumin-bilirubin (ALBI) grade, and easy (EZ)-ALBI grade, is unclear. We aimed to investigate the feasibility of TBS in HCC patients undergoing radiofrequency ablation (RFA). RESEARCH DESIGN AND METHODS: A total of 576 treatment-naïve patients with HCC undergoing RFA were analyzed. The multivariate Cox analysis was used to identify independent predictors associated with tumor recurrence and long-term survival. RESULTS: Patients with high TBS had increased risk of tumor recurrence and mortality compared with those with low TBS. The Cox analysis showed that serum ɑ-fetoprotein (AFP) level >20 ng/mL, medium and high TBS, ALBI grade 2 and grade 3, EZ-ALBI grade 2 and grade 3 were associated with tumor recurrence and decreased patient survival (all p <0.05). In addition, TBS can reliably stratify tumor recurrence and overall survival in different ALBI and EZ-ALBI grade groups. CONCLUSIONS: TBS is a simple and feasible prognostic surrogate to predict tumor recurrence and survival in HCC patients undergoing RFA. Its prognostic ability remains stable in patients with variable liver functional reserve.

A New Tumor Burden Score and Albumin-Bilirubin Grade-Based Prognostic Model for Hepatocellular Carcinoma.

The prognosis of hepatocellular carcinoma (HCC) varies widely due to variable tumor extent and liver reserve. We aimed to develop and validate a new prognostic model based on tumor burden score (TBS) and albumin-bilirubin (ALBI) grade for HCC. We prospectively identified 3794 HCC patients who were randomized into derivation and validation groups. Survival predictors were evaluated by a multivariate Cox model. The TBS-ALBI system allocated two points for high TBS and ALBI grade 3, and one point each for the presence of ascites, serum α-fetoprotein ≥ 400 ng/mL, vascular invasion or distant metastasis, performance status 2-4, medium TBS, and ALBI grade 2, with a maximal score of 8 points. Significant survival differences were found across different TBS-ALBI score groups in the validation cohort (all p < 0.001). The TBS-ALBI system had the lowest corrected Akaike information criterion (AICc) and the highest homogeneity compared with other proposed staging models. The discriminative ability of the TBS-ALBI system was consistently stable across different viral etiologies, cancer stages, and treatment strategies. Conclusions: This new TBS-ALBI system is a feasible and robust prognostic system in comparison with other systems; it is a user-friendly tool for long-term outcome assessment independent of treatment modality and cancer stage in HCC.