BALAD and BALAD-2 predict survival of hepatocellular carcinoma patients: a North American cohort study

Wongjarupong, Nicha; Negron-Ocasio, Gabriela M.; Mara, Kristin C.; Prasai, Kritika; Abdallah, Mohamed; Ahn, Keun Soo; Yang, Ju Dong; Addissie, Benyam D.; Giama, Nasra H.; Harmsen, William S.; Therneau, Terry M.; Roberts, Lewis R.

doi:10.1016/j.hpb.2020.09.014

Cited by 14 publications

(16 citation statements)

References 10 publications

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“… 34 Otherwise, among these algorithms, Balad scores exhibit promising results regarding their predictive value of overall survival in patients with HCC. 35 These latter scores require further validation, but it would be interesting to compare their performances to the results obtained with HSPG-related biomarkers revealed from our study in patients with advanced HCC.…”

Section: Discussionmentioning

confidence: 83%

Sulfatase 2 Along with Syndecan 1 and Glypican 3 Serum Levels are Associated with a Prognostic Value in Patients with Alcoholic Cirrhosis-Related Advanced Hepatocellular Carcinoma

Mouhoubi

Bamba‐Funck

Sutton

et al. 2022

JHC

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Sulfatase 2 (SULF2) is an enzyme related to heparan sulfate modifications. Its expression, as for some heparan sulfate proteoglycans expression, has been linked to hepatocellular carcinoma (HCC) at mRNA level and immunohistochemistry staining on biopsy samples. This study aims to evaluate the prognostic value of serum levels of SULF2 in patients with alcoholic cirrhosis with or without HCC. Patients and Methods: Two hundred and eighty-seven patients with alcoholic cirrhosis were enrolled in this study: 164 without HCC, 57 with early HCC, and 66 with advanced HCC at inclusion. We analyzed the association between SULF2 serum levels and prognosis using Kaplan-Meier method and univariate and multivariate analysis using a Cox model. Results: Child-Pugh C Patients have higher serum levels of SULF2 than Child-Pugh A patients. Serum levels of SULF2 were also higher in patients with advanced HCC compared with the other groups. In patients with advanced HCC, high serum levels of SULF2 were associated with less favorable overall survival. Combination of SULF2 with Glypican 3 (GPC3) and Syndecan 1 (SDC1) serum levels enhanced the ability to discriminate worst prognostic in advanced HCC. Conclusion: SULF2 along with GPC3 and SDC1 serum levels have been shown to be associated with a prognostic value in advanced HCC.

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Section: Discussionmentioning

confidence: 83%

Sulfatase 2 Along with Syndecan 1 and Glypican 3 Serum Levels are Associated with a Prognostic Value in Patients with Alcoholic Cirrhosis-Related Advanced Hepatocellular Carcinoma

Mouhoubi

Bamba‐Funck

Sutton

et al. 2022

JHC

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“…The usefulness of incorporating all 3 biomarkers with relevant clinical characteristics has been previously shown through the gender, age, AFP-L3, AFP, and DCP model (gender, age, AFP-L3, AFP, and DCP) to predict the presence of any HCC 12,13 as well as early-stage HCC 26 . Similarly, the validated BALAD score (bilirubin, albumin, AFP-L3, AFP, and DCP) has been shown to predict HCC-related survival 23 . Therefore, in the present study, we assessed the association of BALAD score with waitlist dropout risk.…”

Section: Discussionmentioning

confidence: 91%

“…Cox proportional hazards models estimated the risk of waitlist dropout with HR and 95% CI for each explanatory variable as well as separately for the validated BALAD score, which includes bilirubin, albumin, AFP-L3, AFP, and DCP. [23] Multiple cutoffs for AFP ( ≥ 20, ≥ 100, ≥ 250 ng/mL), AFP-L3 ( ≥ 15% and ≥ 35%), and DCP ( ≥ 7.5 ng/mL) were tested. [6,20,21] Factors with a univariate p value less than 0.1 were evaluated in the multivariable analysis with the final model selected by backward elimination (p for removal greater than 0.05).…”

Section: Outcomes and Statistical Analysismentioning

confidence: 99%

“…Using the parameter estimates from the MV dropout model (Table 3), we created a biomarker-based rounded point risk score for manual calculation (6* (AFP ≥ 100 ng/mL) + 8*(AFP-L3 ≥ 35%) + 8*(DCP ≥ 7.5 ng/mL) + 5*(initial tumor stage beyond Milan criteria) +10*(Time to listing after HCC dx ≥ 1y) + 1*(MELD-Na at listing) + 1*(Child-Pugh score at listing). The median risk score of the entire cohort was 23 (IQR [16][17][18][19][20][21][22][23][24][25][26][27][28][29]. We then split the cohort (n = 257) into quintiles with median values of 13, 17, 23, 27, and 40 for the lowest to highest-risk quintiles.…”

Section: Probability Of Waitlist Dropout Stratified By Biomarkers At ...mentioning

confidence: 99%

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AFP-L3 and DCP are superior to AFP in predicting waitlist dropout in HCC patients: Results of a prospective study

Mehta

Kotwani

Norman

et al. 2023

Liver Transplantation

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In patients with HCC awaiting liver transplantation (LT), there is a need to identify biomarkers that are superior to AFP in predicting prognosis. AFP-L3 and des-gamma-carboxyprothrombin (DCP) play a role in HCC detection, but their ability to predict waitlist dropout is unknown. In this prospective single-center study commenced in July 2017, 267 HCC patients had all 3 biomarkers obtained at LT listing. Among them, 96.2% received local-regional therapy, and 18.8% had an initial tumor stage beyond Milan criteria requiring tumor downstaging. At listing, median AFP was 7.0 ng/mL (IQR 3.4–21.5), median AFP-L3 was 7.1% (IQR 0.5–12.5), and median DCP was 1.0 ng/mL (IQR 0.2–3.8). After a median follow-up of 19.3 months, 63 (23.6%) experienced waitlist dropout, while 145 (54.3%) received LT, and 59 (22.1%) were still awaiting LT. Using Cox proportional hazards analysis, AFP-L3≥35% and DCP≥7.5 ng/mL were associated with increased waitlist dropout, whereas AFP at all tested cutoffs, including ≥20,≥ 100, and≥250 ng/mL was not. In a multivariable model, AFP-L3≥35% (HR 2.25, p=0.04) and DCP≥7.5 ng/mL (HR 2.20, p=0.02) remained associated with waitlist dropout as did time from HCC diagnosis to listing ≥ 1 year and increasing MELD-Na score. Kaplan-Meier probability of waitlist dropout within 2 years was 21.8% in those with AFP-L3<35% and DCP<7.5 ng/mL, 59.9% with either AFP-L3 or DCP elevated, and 100% for those with both elevated (p<0.001). In this prospective study, listing AFP-L3% and DCP were superior to AFP in predicting waitlist dropout with the combination of AFP-L3≥35% and DCP≥7.5 ng/mL associated with a 100% risk of waitlist dropout, thus clearly adding prognostic value to AFP alone.

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“…To address the diverse biomarker phenotypes, the numerical accumulation of biomarkers was utilized as recently described [ 19 ] and consistent with their use in the BALAD and GALAD prognosis/surveillance indices [ 18 , 44 , 45 ]. Biomarker accumulation was not associated with demographic or etiological factors.…”

Section: Discussionmentioning

confidence: 99%

Baseline Alpha-Fetoprotein, Alpha-Fetoprotein-L3, and Des-Gamma-Carboxy Prothrombin Biomarker Status in Bridge to Liver Transplant Outcomes for Hepatocellular Carcinoma

Nunez

Sandow

Fort

et al. 2021

Cancers

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The biomarkers α-fetoprotein (AFP), Lens culinaris agglutinin-reactive AFP fraction (AFP-L3), and des-γ-carboxy prothrombin (DCP) have emerging implications in hepatocellular carcinoma (HCC) surveillance, overall prognosis, and post-surgical recurrence risk. This retrospective study investigated treatment and bridge to liver transplant (LT) prognosis associated with AFP, AFP-L3%, and DCP biomarker profiles prior to liver-directed therapy (LDT). In a 140-patient cohort, each biomarker was associated with HCC progression risk using the established thresholds of AFP > 20 ng/mL, AFP-L3 > 15%, and DCP > 7.5 ng/mL. Over 60% of the cohort expressed at least one biomarker at baseline. Although most biomarker-positive patients expressed the clinical standard AFP (57/87), only 32% were positive for AFP alone. Biomarker accumulation increased HCC progression risk but was not associated with demographic factors or preserved liver function. Biomarker triple negative patients had smaller index HCC (p = 0.003), decreased multifocal burden (p = 0.010), and a higher objective response rate (ORR, 62% compared to 46%, p = 0.011). Expressing all three biomarkers at baseline was associated with dismal first-line ORR (12%) with a median time to progression (TTP) of only 181 days post-LDT. Patients with triple negative status for the HCC biomarkers AFP, AFP-L3%, and DCP have the highest first-line ORR with < 5% HCC progression 1-year post-LDT. Biomarker profiling can establish baseline prognosis for identifying optimal bridge to LT and downstaging to LT candidates with triple negative biomarker status and providing an ideal post-LDT target as a compliment to radiographic response.

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BALAD and BALAD-2 predict survival of hepatocellular carcinoma patients: a North American cohort study

Cited by 14 publications

References 10 publications

Sulfatase 2 Along with Syndecan 1 and Glypican 3 Serum Levels are Associated with a Prognostic Value in Patients with Alcoholic Cirrhosis-Related Advanced Hepatocellular Carcinoma

Sulfatase 2 Along with Syndecan 1 and Glypican 3 Serum Levels are Associated with a Prognostic Value in Patients with Alcoholic Cirrhosis-Related Advanced Hepatocellular Carcinoma

AFP-L3 and DCP are superior to AFP in predicting waitlist dropout in HCC patients: Results of a prospective study

Baseline Alpha-Fetoprotein, Alpha-Fetoprotein-L3, and Des-Gamma-Carboxy Prothrombin Biomarker Status in Bridge to Liver Transplant Outcomes for Hepatocellular Carcinoma

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