GALAD Score Detects Early Hepatocellular Carcinoma in an International Cohort of Patients With Nonalcoholic Steatohepatitis

Jan Best, Lars P Bechmann, Jan-Peter Sowa, Svenja Sydor, Alexander Dechêne, Kristina Pflanz, Sotiria Bedreli, Clemens Schotten, Andreas Geier, Thomas Berg, Janett Fischer, Arndt Vogel, Heike Bantel, Arndt Weinmann, Jörn M Schattenberg, Yvonne Huber, Henning Wege, Johann von Felden, Kornelius Schulze, Dominik BettingerRobert Thimme, Friedrich Sinner, Kerstin Schütte, Karl Heinz Weiss, Hidenori Toyoda, Satoshi Yasuda, Takashi Kumada, Sarah Berhane, Marc Wichert, Dominik Heider, Guido Gerken, Philip Johnson, Ali Canbay, Sarah Berhane

Research output: Contribution to journalArticlepeer-review

30 Citations (Scopus)


BACKGROUND & AIMS: The prevalence of nonalcoholic steatohepatitis (NASH) associated hepatocellular carcinoma (HCC) is increasing. However, strategies for detection of early-stage HCC in patients with NASH have limitations. We assessed the ability of the GALAD score, which determines risk of HCC based on patient sex; age; and serum levels of α-fetoprotein (AFP), AFP isoform L3 (AFP-L3), and des-gamma-carboxy prothrombin (DCP), to detect HCC in patients with NASH.

METHODS: We performed a case-control study of 125 patients with HCC (20% within Milan Criteria) and 231 patients without HCC (NASH controls) from 8 centers in Germany. We compared the performance of serum AFP, AFP-L3, or DCP vs GALAD score to identify patients with HCC using receiver operating characteristic curves and corresponding area under the curve (AUC) analyses. We also analyzed data from 389 patients with NASH under surveillance for HCC in Japan, followed for a median of 167 months. During the 5-year screening period, 26 patients developed HCC. To compensate for irregular intervals of data points, we performed locally weighted scatterplot smoothing, linear regression, and a non-linear curve fit to assess development of GALAD before HCC development.

RESULTS: The GALAD score identified patients with any stage HCC with an AUC of 0.96 - significantly greater than values for serum levels of AFP (AUC, 0.88), AFP-L3 (AUC, 0.86) or DCP (AUC, 0.87). AUC values for the GALAD score were consistent in patients with cirrhosis (AUC, 0.93) and without cirrhosis (AUC, 0.98). For detection of HCC within Milan Criteria, the GALAD score achieved an AUC of 0.91, with a sensitivity of 68% and specificity of 95% at a cutoff of -0.63. In a pilot Japanese cohort study, the mean GALAD score was higher in patients with NASH who developed HCC than in those who did not develop HCC as early as 1.5 years before HCC diagnosis. GALAD scores were above -0.63 approximately 200 days before the diagnosis of HCC.

CONCLUSIONS: In a case-control study performed in Germany and a pilot cohort study in Japan, we found the GALAD score may detect HCC with high levels of accuracy in patients with NASH, with and without cirrhosis. The GALAD score can detect patients with early-stage HCC, and might facilitate surveillance of patients with NASH, who are often obese, which limits the sensitivity of detection of liver cancer by ultrasound.

Original languageEnglish
Pages (from-to)728-735.e4
JournalClin Gastroenterol Hepatol
Issue number3
Publication statusPublished - Mar 2020

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Copyright © 2020 AGA Institute. Published by Elsevier Inc. All rights reserved.


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