External validation of LCR1-LCR2, a multivariable HCC risk calculator, in patients with chronic HCV
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 fib...
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Elsevier
2021-08-01
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Series: | JHEP Reports |
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Online Access: | http://www.sciencedirect.com/science/article/pii/S2589555921000744 |
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doaj-2a6493e2f7954175b1cb400a894224aa |
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record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Thierry Poynard Jean Marc Lacombe Olivier Deckmyn Valentina Peta Sepideh Akhavan Victor de Ledinghen Fabien Zoulim Didier Samuel Philippe Mathurin Vlad Ratziu Dominique Thabut Chantal Housset Hélène Fontaine Stanislas Pol Fabrice Carrat |
spellingShingle |
Thierry Poynard Jean Marc Lacombe Olivier Deckmyn Valentina Peta Sepideh Akhavan Victor de Ledinghen Fabien Zoulim Didier Samuel Philippe Mathurin Vlad Ratziu Dominique Thabut Chantal Housset Hélène Fontaine Stanislas Pol Fabrice Carrat External validation of LCR1-LCR2, a multivariable HCC risk calculator, in patients with chronic HCV JHEP Reports Fibrosis progression Cirrhosis Multi-analyte blood test LCR1-LCR2 Surveillance AFP |
author_facet |
Thierry Poynard Jean Marc Lacombe Olivier Deckmyn Valentina Peta Sepideh Akhavan Victor de Ledinghen Fabien Zoulim Didier Samuel Philippe Mathurin Vlad Ratziu Dominique Thabut Chantal Housset Hélène Fontaine Stanislas Pol Fabrice Carrat |
author_sort |
Thierry Poynard |
title |
External validation of LCR1-LCR2, a multivariable HCC risk calculator, in patients with chronic HCV |
title_short |
External validation of LCR1-LCR2, a multivariable HCC risk calculator, in patients with chronic HCV |
title_full |
External validation of LCR1-LCR2, a multivariable HCC risk calculator, in patients with chronic HCV |
title_fullStr |
External validation of LCR1-LCR2, a multivariable HCC risk calculator, in patients with chronic HCV |
title_full_unstemmed |
External validation of LCR1-LCR2, a multivariable HCC risk calculator, in patients with chronic HCV |
title_sort |
external validation of lcr1-lcr2, a multivariable hcc risk calculator, in patients with chronic hcv |
publisher |
Elsevier |
series |
JHEP Reports |
issn |
2589-5559 |
publishDate |
2021-08-01 |
description |
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). |
topic |
Fibrosis progression Cirrhosis Multi-analyte blood test LCR1-LCR2 Surveillance AFP |
url |
http://www.sciencedirect.com/science/article/pii/S2589555921000744 |
work_keys_str_mv |
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doaj-2a6493e2f7954175b1cb400a894224aa2021-08-18T04:22:51ZengElsevierJHEP Reports2589-55592021-08-0134100298External validation of LCR1-LCR2, a multivariable HCC risk calculator, in patients with chronic HCVThierry Poynard0Jean Marc Lacombe1Olivier Deckmyn2Valentina Peta3Sepideh Akhavan4Victor de Ledinghen5Fabien Zoulim6Didier Samuel7Philippe Mathurin8Vlad Ratziu9Dominique Thabut10Chantal Housset11Hélène Fontaine12Stanislas Pol13Fabrice Carrat14Assistance Publique-Hôpitaux de Paris (AP-HP), Department of Hepato-Gastroenterology, Pitié-Salpêtrière Hospital, Paris, France; Sorbonne Université, INSERM, Centre de Recherche Saint-Antoine (CRSA), Institute of Cardiometabolism and Nutrition (ICAN), Paris, France; Corresponding author. Address: Hepatology Department, Pitié Salpêtrière Hospital, 57 Bd Hôpital, 75013, Paris, France. Tel.: +33-1-48899118; Fax: +33-1-42161427.Sorbonne Université, INSERM, Institut Pierre Louis d’Épidémiologie et de Santé Publique, Paris, FranceBioPredictive, Paris, FranceSorbonne Université, INSERM, Centre de Recherche Saint-Antoine (CRSA), Institute of Cardiometabolism and Nutrition (ICAN), Paris, France; BioPredictive, Paris, FranceAssistance Publique-Hôpitaux de Paris (AP-HP), Department of Hepato-Gastroenterology, Pitié-Salpêtrière Hospital, Paris, FranceHepatology Unit Hôpital Haut-Lévêque, Pessac, and INSERM U1053, Université Bordeaux Segalen, Bordeaux, FranceHospices civils de Lyon, Hôpital Croix Rousse, Department of Hepatology, INSERM U1052, Université de Lyon, Lyon, FranceAP-HP, Hospital Paul Brousse, Hepatology Department, UMR-S1193, Villejuif, France; Université Paris-Saclay, and Hepatinov, Villejuif, FranceCHRU Claude Huriez, Hepatology Department Lille, FranceAssistance Publique-Hôpitaux de Paris (AP-HP), Department of Hepato-Gastroenterology, Pitié-Salpêtrière Hospital, Paris, France; Sorbonne Université, INSERM, Centre de Recherche Saint-Antoine (CRSA), Institute of Cardiometabolism and Nutrition (ICAN), Paris, FranceAssistance Publique-Hôpitaux de Paris (AP-HP), Department of Hepato-Gastroenterology, Pitié-Salpêtrière Hospital, Paris, France; Sorbonne Université, INSERM, Centre de Recherche Saint-Antoine (CRSA), Institute of Cardiometabolism and Nutrition (ICAN), Paris, FranceSorbonne Université, INSERM, Centre de Recherche Saint-Antoine (CRSA), Institute of Cardiometabolism and Nutrition (ICAN), Paris, FranceAssistance Publique-Hôpitaux de Paris (AP-HP), Department of Hepato-Gastroenterology, AP-HP, Hôpital Cochin, Hepatology Department, Paris, FranceAssistance Publique-Hôpitaux de Paris (AP-HP), Department of Hepato-Gastroenterology, AP-HP, Hôpital Cochin, Hepatology Department, Paris, FranceSorbonne Université, INSERM, Institut Pierre Louis d’Épidémiologie et de Santé Publique, Paris, FranceBackground & 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).http://www.sciencedirect.com/science/article/pii/S2589555921000744Fibrosis progressionCirrhosisMulti-analyte blood testLCR1-LCR2SurveillanceAFP |