The GALAD Score as Potential Screening Test for Hepatocellular Carcinoma in Nonalcoholic Steatohepatitis: An International Multicenter Study

The prevalence of nonalcoholic steatohepatitis (NASH) is rising rapidly and is currently the most common chronic liver disease in Western populations. Hepatocellular carcinoma (HCC) is a major complication of NASH and the current performance of screening approaches based on ultrasound shows limitations. To facilitate earlier diagnosis, this international multicenter study, with eight German and one Japanese center participating, tests the potential benefit of applying the biomarkers AFP, AFP-L3, DCP and related scores for HCC screening in NASH patients. In the retrospective German cohort, 126 NASH patients with newly diagnosed HCC and 231 NASH control patients without HCC were enrolled. In the prospective Japanese cohort, 389 NASH patients underwent HCC screening, among those 26 patients developed HCC during a 5-year screening period. AFP, AFP-L3 and DCP were measured using an automated immunoanalyzer. The performance of the diagnostic algorithm (GALAD) based on gender, age and the biomarkers was assessed in both NASH cohorts. AFP, AFP-L3 and DCP showed comparable sensitivities and specificities for HCC detection in the retrospective NASH cohort. Here, the GALAD score achieved an AUROC of 0.96, a significant improvement on individual application of AFP (0.88), AFP-L3 (0.86) or DCP (0.86). In the prospective serial dataset, the GALAD score in those who develop HCC is significantly raised , compared to those not developing HCC, several years before HCC is diagnosed. This international multicenter study demonstrates that the GALAD model represents a potential future HCC screening approach in the mostly obese NASH population, in which the sensitivity of ultrasound is limited. Funding Statement: This work was supported by the Deutsche Forschungsgemeinschaft (CA267/14-1 ) and by the Wilhelm-Laupitz Foundation to AC as well as the Werner Jackstaedt Foundation to LPB. Declaration of Interests: The authors declare they have nothing to disclose. Ethics Approval Statement: The study was institutional review board approved by the ethics committee of each center individually, and carried out in accordance with the 1964 Helsinki Declaration.