Jan Best1, Lars P Bechmann1, Jan-Peter Sowa1, Svenja Sydor1, Alexander Dechêne2, Kristina Pflanz3, Sotiria Bedreli3, Clemens Schotten3, Andreas Geier4, Thomas Berg5, Janett Fischer5, Arndt Vogel6, Heike Bantel6, Arndt Weinmann7, Jörn M Schattenberg7, Yvonne Huber7, Henning Wege8, Johann von Felden8, Kornelius Schulze8, Dominik Bettinger9, Robert Thimme10, Friedrich Sinner1, Kerstin Schütte1, Karl Heinz Weiss11, Hidenori Toyoda12, Satoshi Yasuda12, Takashi Kumada13, Sarah Berhane14, Marc Wichert15, Dominik Heider16, Guido Gerken3, Philip Johnson14, Ali Canbay17. 1. Department of Gastroenterology, Hepatology and Infectious Diseases, University Hospital Magdeburg, Magdeburg, Germany. 2. Department of Gastroenterology and Hepatology, University Hospital Essen, University Duisburg-Essen, Essen, Germany; Department of Gastroenterology, Hepatology and Endocrinology, Paracelsus Medical University, Klinikum Nürnberg, Nürnberg, Germany. 3. Department of Gastroenterology and Hepatology, University Hospital Essen, University Duisburg-Essen, Essen, Germany. 4. Division of Hepatology, Department of Internal Medicine II, University Hospital Würzburg, Würzburg, Germany. 5. Section of Hepatology, Division of Gastroenterology and Rheumatology, University Hospital Leipzig, Leipzig, Germany. 6. Clinic of Gastroenterology, Hepatology and Endocrinology, Hannover Medical High School, Hannover, Germany. 7. Department of Medicine I, University Medical Center Johannes Gutenberg University, Mainz, Germany. 8. Department of Medicine I, University Medical Center, Hamburg-Eppendorf, Germany. 9. Department of Medicine II, Medical Center University of Freiburg, Freiburg, Germany; Berta-Ottenstein-Programme, Faculty of Medicine, University of Freiburg, Freiburg, Germany. 10. Department of Medicine II, Medical Center University of Freiburg, Freiburg, Germany. 11. Department of Internal Medicine IV, University Hospital Heidelberg, Heidelberg, Germany. 12. Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan. 13. Department of Nursing, Gifu Kyoritsu University, Ogaki, Japan. 14. Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool, United Kingdom. 15. Central Laboratory, University Hospital Essen, University Duisburg-Essen, Essen, Germany. 16. Department of Mathematics and Computer Science, Philipps-University Marburg, Marburg, Germany. 17. Department of Gastroenterology, Hepatology and Infectious Diseases, University Hospital Magdeburg, Magdeburg, Germany. Electronic address: ali.canbay@kk-bochum.de.
Abstract
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.
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.
Authors: Sven H Loosen; Mirco Castoldi; Markus S Jördens; Sanchary Roy; Mihael Vucur; Jennis Kandler; Linda Hammerich; Raphael Mohr; Frank Tacke; Tom F Ulmer; Ulf P Neumann; Tom Luedde; Christoph Roderburg Journal: PLoS One Date: 2021-03-12 Impact factor: 3.240
Authors: Neehar D Parikh; Anand S Mehta; Amit G Singal; Timothy Block; Jorge A Marrero; Anna S Lok Journal: Cancer Epidemiol Biomarkers Prev Date: 2020-04-01 Impact factor: 4.254