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Abstract Details
External validation of LCR1-LCR2, a multivariable HCC risk calculator, in patients with chronic HCV
JHEP Rep. 2021 Apr 24;3(4):100298. doi: 10.1016/j.jhepr.2021.100298. eCollection 2021 Aug.
Thierry Poynard12, Jean Marc Lacombe3, Olivier Deckmyn4, Valentina Peta24, Sepideh Akhavan1, Victor de Ledinghen5, Fabien Zoulim6, Didier Samuel78, Philippe Mathurin9, Vlad Ratziu12, Dominique Thabut12, Chantal Housset2, Hélène Fontaine10, Stanislas Pol10, Fabrice Carrat3
Author information
1Assistance Publique-Hôpitaux de Paris (AP-HP), Department of Hepato-Gastroenterology, Pitié-Salpêtrière Hospital, Paris, France.
2Sorbonne Université, INSERM, Centre de Recherche Saint-Antoine (CRSA), Institute of Cardiometabolism and Nutrition (ICAN), Paris, France.
3Sorbonne Université, INSERM, Institut Pierre Louis d'Épidémiologie et de Santé Publique, Paris, France.
4BioPredictive, Paris, France.
5Hepatology Unit Hôpital Haut-Lévêque, Pessac, and INSERM U1053, Université Bordeaux Segalen, Bordeaux, France.
6Hospices civils de Lyon, Hôpital Croix Rousse, Department of Hepatology, INSERM U1052, Université de Lyon, Lyon, France.
7AP-HP, Hospital Paul Brousse, Hepatology Department, UMR-S1193, Villejuif, France.
8Université Paris-Saclay, and Hepatinov, Villejuif, France.
9CHRU Claude Huriez, Hepatology Department Lille, France.
10Assistance Publique-Hôpitaux de Paris (AP-HP), Department of Hepato-Gastroenterology, AP-HP, Hôpital Cochin, Hepatology Department, Paris, France.
Abstract
Background & aims: The Liver Cancer Risk test algorithm (LCR1-LCR2) is a multianalyte blood test combining proteins involved in liver cell repair (apolipoprotein-A1 and haptoglobin), known hepatocellular carcinoma (HCC) risk factors (sex, age, and gamma-glutamyl transferase), a marker of fibrosis (alpha2-macroglobulin) and alpha-fetoprotein (AFP), a specific marker of HCC. The aim was to externally validate the LCR1-LCR2 in patients with chronic HCV (CHC) treated or not with antivirals.
Methods: Pre-included patients were from the Hepather cohort, a multicentre prospective study in adult patients with CHC in France. LCR1-LCR2 was assessed retrospectively in patients with the test components and AFP, available at baseline. The co-primary study outcome was the negative predictive value (NPV) of LCR1-LCR2 for the occurrence of HCC at 5 years and for survival without HCC according to the predetermined LCR1-LCR2 cut-offs. The cut-offs were adjusted for risk covariables and for the response to HCV treatment, and were quantified using time-dependent proportional hazards models.
Results: In total, 4,903 patients, 1,026 (21.9%) with baseline cirrhosis, were included in the study. Patients were followed for a median of 5.7 (IQR 4.2-11.3) years. A total of 3,788/4,903 (77.3%) patients had a sustained virological response. There were 137 cases of HCC at 5 years and 214 at the end of follow-up. HCC occurred at 5 years in 24/3,755 patients with low-risk LCR1-LCR2 compared with 113/1,148 patients with high-risk LCR1-LCR2. The NPV was 99.4% (95% CI 99.1-99.6). Similar findings (hazard ratio, 10.8; 95% CI, 8.1-14.3; p <0.001) were obtained after adjustment for exposure to antivirals, age, sex, geographical origin, HCV genotype 3, alcohol consumption, and type 2 diabetes mellitus.
Conclusions: The results showed that LCR1-LCR2 can be used to successfully identify patients with HCV at very low risk of HCC at 5 years.
Lay summary: Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related death worldwide and the fastest growing cause of cancer death in many countries. We constructed and internally validated a new multianalyte blood test to assess this Liver Cancer Risk (LCR1-LCR2). This study confirmed the performance of LCR1-LCR2 in patients with chronic HCV in the national French cohort Hepather, and its ability to identify patients at a very low risk of HCC at 5 years.
Clinical trials registration: The study is registered at ClinicalTrials.gov (NCT01953458).