Abstract:Summary
Background
No blood test has been shown to be effective in the prediction of primary liver cancer in patients without cirrhosis.
Aim
To construct and internally validate two sequential tests for early prediction of liver cancer. These tests enable an algorithm which could improve the performance of the standard surveillance protocol recommended (imaging with or without AFP), limited to patients with cirrhosis.
Methods
We … Show more
“…We constructed two high performance tests in patients with chronic liver disease, LCR1 for the early stratification of the risk of cancer in patients without cirrhosis and LCR2 to increase the sensitivity of alfa‐foeto‐protein (AFP) alone, in patients with cirrhosis and in patients without cirrhosis but with a high LCR1 (above the optimal cut‐off) …”
Section: Introductionmentioning
confidence: 78%
“…Because these two types of surveillance were already assessed in the first FibroFrance cohort, we compared the sensitivities and specificities obtained in those two cohorts . We assessed the number of patients needed to be screened in a case‐control scenario with a fixed incidence of 33% HCC (one HCC for two controls).The sample size was determined as at least 50 cases with incident HCC and 100 matched controls to be included to have sufficient power for the assessment of sensitivity and the 5‐year prognostic value of the FT‐LCR1‐LCR2 algorithm.…”
Section: Methodsmentioning
confidence: 99%
“…We assessed the number of patients needed to be screened in a case‐control scenario with a fixed incidence of 33% HCC (one HCC for two controls).The sample size was determined as at least 50 cases with incident HCC and 100 matched controls to be included to have sufficient power for the assessment of sensitivity and the 5‐year prognostic value of the FT‐LCR1‐LCR2 algorithm. This number of incident HCC was derived from the 43 cases observed in the internal validation …”
Section: Methodsmentioning
confidence: 99%
“…One hundred sixty‐seven cancers (113 with cirrhosis, 54 without cirrhosis) were detected in 2,027 patients with high‐LCR1 and then high‐LCR2, thus 12 patients needed to be screened for one cancer. The negative predictive value was 99.5% (95% CI 99.0‐99.7) in the 2,026 unscreened patients (11 cancers without cirrhosis) and was higher than the standard surveillance in USA ref, which detected 113 cancers in 755 screened patients, that is seven patients screened for one cancer, but the negative predictive value was lower 98.0% (97.5‐98.5;Z = 4.3; P < 0.001) in 3,298 unscreened patients (42 cancers without cirrhosis) …”
Section: Introductionmentioning
confidence: 99%
“…3 We constructed two high performance tests in patients with chronic liver disease, LCR1 for the early stratification of the risk of cancer in patients without cirrhosis and LCR2 to increase the sensitivity of alfa-foeto-protein (AFP) alone, in patients with cirrhosis and in patients without cirrhosis but with a high LCR1 (above the optimal cut-off). 4 LCR1 combined proteins involved in liver cell repair (apolipopro-teinA1, haptoglobin), known HCC risk factors (gender, age, gammaglutamyl-transpeptidase) and a marker of fibrosis (alpha2-macroglobulin).…”
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.
“…We constructed two high performance tests in patients with chronic liver disease, LCR1 for the early stratification of the risk of cancer in patients without cirrhosis and LCR2 to increase the sensitivity of alfa‐foeto‐protein (AFP) alone, in patients with cirrhosis and in patients without cirrhosis but with a high LCR1 (above the optimal cut‐off) …”
Section: Introductionmentioning
confidence: 78%
“…Because these two types of surveillance were already assessed in the first FibroFrance cohort, we compared the sensitivities and specificities obtained in those two cohorts . We assessed the number of patients needed to be screened in a case‐control scenario with a fixed incidence of 33% HCC (one HCC for two controls).The sample size was determined as at least 50 cases with incident HCC and 100 matched controls to be included to have sufficient power for the assessment of sensitivity and the 5‐year prognostic value of the FT‐LCR1‐LCR2 algorithm.…”
Section: Methodsmentioning
confidence: 99%
“…We assessed the number of patients needed to be screened in a case‐control scenario with a fixed incidence of 33% HCC (one HCC for two controls).The sample size was determined as at least 50 cases with incident HCC and 100 matched controls to be included to have sufficient power for the assessment of sensitivity and the 5‐year prognostic value of the FT‐LCR1‐LCR2 algorithm. This number of incident HCC was derived from the 43 cases observed in the internal validation …”
Section: Methodsmentioning
confidence: 99%
“…One hundred sixty‐seven cancers (113 with cirrhosis, 54 without cirrhosis) were detected in 2,027 patients with high‐LCR1 and then high‐LCR2, thus 12 patients needed to be screened for one cancer. The negative predictive value was 99.5% (95% CI 99.0‐99.7) in the 2,026 unscreened patients (11 cancers without cirrhosis) and was higher than the standard surveillance in USA ref, which detected 113 cancers in 755 screened patients, that is seven patients screened for one cancer, but the negative predictive value was lower 98.0% (97.5‐98.5;Z = 4.3; P < 0.001) in 3,298 unscreened patients (42 cancers without cirrhosis) …”
Section: Introductionmentioning
confidence: 99%
“…3 We constructed two high performance tests in patients with chronic liver disease, LCR1 for the early stratification of the risk of cancer in patients without cirrhosis and LCR2 to increase the sensitivity of alfa-foeto-protein (AFP) alone, in patients with cirrhosis and in patients without cirrhosis but with a high LCR1 (above the optimal cut-off). 4 LCR1 combined proteins involved in liver cell repair (apolipopro-teinA1, haptoglobin), known HCC risk factors (gender, age, gammaglutamyl-transpeptidase) and a marker of fibrosis (alpha2-macroglobulin).…”
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.
Hepatocellular carcinoma (HCC) mortality remains high primarily due to late diagnosis as a consequence of failed early detection. Professional societies recommend semi-annual HCC screening in at-risk patients with chronic liver disease to increase the likelihood of curative treatment receipt and improve survival. However, recent dynamic shift of HCC etiologies from viral to metabolic liver diseases has significantly increased the potential target population for the screening, whereas annual incidence rate has become substantially lower. Thus, with the contemporary HCC etiologies, the traditional screening approach might not be practical and cost-effective. HCC screening consists of (i) definition of rational at-risk population, and subsequent (ii) repeated application of early detection tests to the population at regular intervals. The suboptimal performance of the currently available HCC screening tests highlights an urgent need for new modalities and strategies to improve early HCC detection. In this review, we overview recent developments of clinical, molecular, and imaging-based tools to address the current challenge, and discuss conceptual framework and approaches of their clinical translation and implementation. These encouraging progresses are expected to transform the current "one-size-fits-all" HCC screening into
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