External validation of LCR1-LCR2, a multivariable HCC risk calculator, in patients with chronic HCV.
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).
Keywords — author-chosen AFP, AFP, alpha-fetoprotein, AUROC, area under the receiver operating curve, CHC, chronic HCV, Cirrhosis, DAA, direct-acting antivirals, EASL, European Association for the Study of the Liver, FIB4, Fibrosis-4, FibroTest™, Fibrosis progression, HCC, hepatocellular carcinoma, LCR, Liver Cancer Risk, LCR1-LCR2, Liver Cancer Risk, Multi-analyte blood test, NNS, needed to screen, NPV, negative predictive value, SIR, standardised incidence ratio, STARD, Standards for the Reporting of Diagnostic Accuracy Studies, STROBE, Strengthening the Reporting of Observational Studies in Epidemiology, SVR, sustained virological response, Surveillance, VCTE, vibration-controlled transient elastography
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