External validation of LCR1-LCR2, a multivariable HCC risk calculator, in patients with chronic hepatitis C

Abstract Background and aim The liver cancer risk test algorithm (LCR1-LCR2) is a multi-analyte blood test combining proteins involved in liver cell repair (apolipoprotein-A1, haptoglobin), known HCC risk factors (gender, age, GGT), a marker of fibrosis (alpha2-macroglobulin) and AFP, a specific marker of HCC. The aim was to externally validate LCR1-LCR2 in patients with chronic hepatitis C, (CHC) treated or not with antivirals. Patients and methods Pre-included patients were from the Hepather cohort, a multicenter 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 cutoffs. The cutoffs were adjusted for risk covariables and for the response to HCV treatment and quantified using time-dependent proportional hazards models. Results A total of 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. 137 HCC occurred at 5 years and 214 at the end of follow-up. HCC occurred at 5 years in 24/3,755 patients with a low-risk LCR1-LCR2 compared to 113/1,148 patients with a high-risk LCR1-LCR2. The NPV was 99.4% (95%CI 99.1-99.6). Similar findings (hazard-ratio=10.8;8.1-14.3; P Conclusion The performance of LCR1-LCR2 to identify patients with hepatitis-C at a very low risk of HCC at 5 years was externally validated. NCT01953458 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 multi-analyte blood test to assess this Liver Cancer Risk (LCR1-LCR2). This study confirmed the performance of LCR1-LCR2 in patients with chronic hepatitis C in the national French cohort Hepather, and its ability to identify patients at a very low risk of HCC at 5 years.