External validation of an algorithm combining multi‐analyte blood tests (FibroTest‐LCR1‐LCR2) to identify subjects at risk of hepatocellular carcinoma in patients with chronic liver disease

Abstract

Summary Background and Aims The early non‐invasive prediction of hepatocellular carcinoma in patients with chronic liver disease, without or with cirrhosis, is needed. The algorithm FT‐LCR1‐LCR2 which sequentially combines the FibroTest and two multi‐analyte‐tests (LCR1‐LCR2) and increased the performance of alfa‐foeto‐protein (AFP) alone, was constructed and internally validated in the prospective FibroFrance cohort. The first aim was to externally validate the sensitivity and the 5‐year prognostic value of FT‐LCR1‐LCR2. Methods We selected patients included in HCC surveillance programs from the ongoing prospective cohort at Bondy‐Hospital, France. All patients had paired serum samples drawn before incidental cases of HCC detected during follow‐up (cases). Cases were blindly matched to controls who had not developed HCC during a similar follow‐up based on gender, age and fibrosis stages. The performance of the FT‐LCR1‐LCR algorithm was assessed and compared with the standard AASLD surveillance (F4+/+‐AFP). Results 159 patients were followed prospectively (median 5.1 yr), including 51 who had developed HCC (31 with cirrhosis and 20 without) and 108 controls (56 with cirrhosis and 52 without). Sensitivity of the FT‐LCR1‐LCR2 algorithm was higher than standard surveillance 51/51; 100% (95% CI 93.0‐1.00) vs 31/51; 60.8 (46.1‐74.2; P < 0.001), and 5 yr‐survival without HCC was 90% (81‐99) vs 77% (67‐86;P = 0.003) according to the FT‐LCR1‐LCR2. When the algorithm was repeated in the same 159 patients 1.5 years later, cases who developed cancer had a significant yearly increase in LCR2 = +0.014(SE = 0.02) compared to 0.00 (0.01) in controls P = 0.003). Conclusion The FT‐LCR1‐LCR2 algorithm was validated in an independent external cohort for the prediction of HCC.

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

“…LCR1-LCR2 has also been externally validated in a case control study of 149 prospectively enrolled patients in the Bondy Cohort. 12 The aim of the present study was to externally validate LCR1-LCR2 with the previously identified cutoffs of the Original-Study, in a sustainability analysis of patients with chronic hepatitis C, prospectively included in the large Hepather cohort, whatever the stage of fibrosis at inclusion. 7…”

“…22 Our ambispective (both prospective and retrospective) analysis was useful to assess health outcomes with a long induction period and exposures. 12…”

“…LCR1-LCR2 has also been externally validated in a case-control study of 149 patients prospectively enrolled in the Bondy Cohort. 12 …”

HCC risk prediction using biomarkers in non-cirrhotic patients following HCV eradication: Reassuring the patient or the doctor?

“…The HECAM-FibroFrance Group previously reported and externally validated the LCR1 and LCR2 tests to identify individuals at high risk of HCC in a cohort of patients with any cause of chronic liver disease (7,8) potentially curable, all were smaller than 30 mm.…”

“…The HECAM-FibroFrance Group previously reported and externally validated the LCR1 and LCR2 tests to identify individuals at high risk of HCC in a cohort of patients with any cause of chronic liver disease. 7 , 8 LCR1-LCR2 is a multi-analyte blood test combining proteins involved in liver cell repair (apolipoprotein-A1, haptoglobin), known HCC risk factors (gender, age, gamma-glutamyltransferase), a marker of fibrosis (alpha2-macroglobulin) and alfa-fetoprotein, a specific marker of HCC. In this issue of JHEP Reports , the HECAM consortium and the ANRS CO22 Hepather cohort present an external validation of LCR1-LCR2 in patients with chronic hepatitis C from the ANRS CO22 Hepather cohort.…”