BACKGROUND & AIMS: GALAD and BALAD-2 are statistical models for estimating the likelihood of the presence of hepatocellular carcinoma (HCC) in individual patients with chronic liver disease and the survival of patients with HCC, respectively. Both models use objective measures, particularly the serum markers alpha-fetoprotein (AFP), AFP-L3, and des-gamma-carboxyprothrombin. We aimed to validate these models in an international cohort of patients with HCC and assess their clinical performance. METHODS: We collected data on cancer diagnosis and outcomes of 6834 patients (2430 with HCC and 4404 with chronic liver disease) recruited from Germany, Japan, and Hong Kong. We also collected data from 229 patients with other hepatobiliary tract cancers (cholangiocarcinoma or pancreatic adenocarcinoma) and 92 healthy individuals (controls). For reference, the original UK cohort (on which the GALAD model initially was built and BALAD-2 was validated) was included in the analysis. We assessed the effects of tumor size and etiology on GALAD model performance, and its ability to correctly discriminate HCC from other hepatobiliary cancers. We assessed the performance of BALAD-2 in patients with different stages of HCC. RESULTS: In all cohorts, the area under the receiver operating characteristic curve (AUROC), quantifying the ability of GALAD to discriminate patients with HCC from patients with chronic liver disease, was greater than 0.90-similar to the series on which the model originally was built (AUROC, 0.97). GALAD discriminated patients with HCC from those with other hepatobiliary cancers with an AUROC value of 0.95; values were slightly lower for patients with small unifocal HCCs, ranging from 0.85 to 0.95. Etiology and treatment of chronic viral hepatitis had no effect on the performance of this model. BALAD-2 analysis assigned patients with HCC to 4 distinct prognostic groups-overall and when patients were stratified according to disease stage. CONCLUSIONS: We validated the performance of the GALAD and BALAD-2 models for the diagnosis of HCC and predicting patient survival, respectively (based on levels of the serum markers AFP, AFP-L3, and des-gamma-carboxyprothrombin), in an international cohort of almost 7000 patients. These systems might be used in HCC surveillance and determination of patient prognosis.
Berhane, Sarah Toyoda, Hidenori Tada, Toshifumi Kumada, Takashi Kagebayashi, Chiaki Satomura, Shinji Schweitzer, Nora Vogel, Arndt Manns, Michael P Benckert, Julia Berg, Thomas Ebker, Maria Best, Jan Dechene, Alexander Gerken, Guido Schlaak, Joerg F Weinmann, Arndt Worns, Marcus A Galle, Peter Yeo, Winnie Mo, Frankie Chan, Stephen L Reeves, Helen Cox, Trevor Johnson, Philip eng Validation Study Clin Gastroenterol Hepatol. 2016 Jun;14(6):875-886.e6. doi: 10.1016/j.cgh.2015.12.042. Epub 2016 Jan 13.
- Adult Aged Asia Biomarkers/*blood Carcinoma, Hepatocellular/*diagnosis Cohort Studies *Decision Support Techniques Diagnostic Tests, Routine/*methods Europe Female Humans Liver Neoplasms/*diagnosis Male Middle Aged Survival Analysis *Diagnostic *Liver Cancer *Prognostic Marker *Quantification