Prevalence of liver fibrosis and risk factors in a general population using non-invasive biomarkers (FibroTest)

<p>Abstract</p> <p>Background</p> <p>FibroTest and elastography have been validated as biomarkers of liver fibrosis in the most frequent chronic liver diseases and in the fibrosis screening of patients with diabetes. One challenge was to use them for estimating the prevalence of fibrosis, identifying independent risk factors and to propose screening strategies in the general population.</p> <p>Methods</p> <p>We prospectively studied 7,463 consecutive subjects aged 40 years or older. Subjects with presumed advanced fibrosis (FibroTest greater than 0.48) were re-investigated in a tertiary center.</p> <p>Results</p> <p>The sample characteristics were similar to those of the French population. FibroTest was interpretable in 99.6%. The prevalence of presumed fibrosis was 2.8%, (209/7,463), including cirrhosis in 0.3% (25/7,463); 105/209 (50%) subjects with presumed fibrosis accepted re-investigation. Fibrosis was confirmed in 50, still suspected in 27, indeterminate in 25 and not confirmed with false positive FibroTest or false negative elastography in 3 subjects. False negative rate of FibroTest estimated using elastography was 0.4% (3/766). The attributable causes for confirmed fibrosis were both alcoholic and nonalcoholic fatty liver disease (NAFLD) in 66%, NAFLD in 13%, alcohol in 9%, HCV in 6%, and other in 6%. Factors independently associated (all P < 0.003) with confirmed fibrosis were age, male gender, waist circumference, HCV antibody and alcohol consumption estimated using carbohydrate-deficient transferrin, enabling efficient screening-oriented strategies to be compared and proposed.</p> <p>Conclusions</p> <p>Biomarkers have permitted to estimate prevalence of advanced fibrosis around 2.8% in a general population aged 40 years or older, and several risk factors which may be used for the validation of selective or non-selective screening strategies.</p

Applicability and precautions of use of liver injury biomarker FibroTest. A reappraisal at 7 years of age

<p>Abstract</p> <p>Background</p> <p>FibroTest (FT) is a validated biomarker of fibrosis. To assess the applicability rate and to reduce the risk of false positives/negatives (RFPN), security algorithms were developed. The aims were to estimate the prevalence of RFPN and of proven failures, and to identify factors associated with their occurrences.</p> <p>Methods</p> <p>Four populations were studied: 954 blood donors (P1), 7,494 healthy volunteers (P2), 345,695 consecutive worldwide sera (P3), including 24,872 sera analyzed in a tertiary care centre (GHPS) (P4). Analytical procedures of laboratories with RFPN > 5% and charts of P4 patients in with RFPN were reviewed.</p> <p>Results</p> <p>The prevalence of RFPN was 0.52% (5/954; 95%CI 0.17-1.22) in P1, 0.51% (38/7494; 0.36-0.70) in P2, and 0.97% (3349/345695; 0.94-1.00) in P3. Three a priori high-risk populations were confirmed: 1.97% in P4, 1.77% in HIV centre and 2.61% in Sub-Saharan origin subjects. RFPN was mostly associated with low haptoglobin (0.46%), and high apolipoproteinA1 (0.21%). A traceability study of a P3 laboratory with RFPFN > 5% permitted to correct analytical procedures.</p> <p>Conclusion</p> <p>The mean applicability rate of Fibrotest was 99.03%. Independent factors associated with the high risk of false positives/negatives were HIV center, subSaharan origin, and a tertiary care reference centre, although the applicability rate remained above 97%.</p

Awareness of the severity of liver disease re-examined using software-combined biomarkers of liver fibrosis and necroinflammatory activity

International audienceBackground Effective antiviral treatment (direct-acting antiviral agents (DAAs)), the requirement for a fibrosis score to support DDA reimbursement and a screening strategy, such as the USA baby boomer campaign, should lead to an increased awareness of liver disease severity.Objective To compare the awareness of liver disease severity between the USA and France, two countries with similar access to hepatitis C virus (HCV) and hepatitis B virus (HBV) treatments, similar rules for treatment reimbursement and similar availability of validated fibrosis tests, but with different policies, as France has no screening.Method The global database of the FibroTest–ActiTest, including 1 085 657 subjects between 2002 and 2014, was retrospectively analysed. Awareness was defined as the test prescription rate and was compared between the USA and France, according to year of birth, gender and dates of DAA availability and screening campaign (2013–2014).Results In the USA 252 688 subjects were investigated for HCV, with a dramatic increase (138%) in the test rate in 2013–2014 (119 271) compared with 2011–2012 (50 031). In France 470 762 subjects were investigated (subjects with HCV and other disease) and the rates were stable. In USA 82.4% of subjects and in France 84.6% were classified as either the highest or lowest priority. The most striking difference was the higher test rate in women born between 1935 and 1944 in France 30 384/200 672 (15.1%) compared with the USA 8035/97 079 (8.3%) (OR=1.98 (95% CI 1.93 to 2.03) p<0.0001). This resulted in twice as many cases of cirrhosis being detected, 2.6% (5191/200 672 women) and 1.3% (1303/97 079), respectively, despite the same prevalence of cirrhosis in this age group (17.1% vs 16.2%) and without any clear explanation as to why they had not been included in the USA screening.Conclusions This study highlighted in the USA the association between awareness of liver disease and both the HCV campaign and DAA availability. In comparison with France, there was a dramatically lower awareness of cirrhosis in the USA for women born between 1935 and 1944

Prospective external validation of a new non‐invasive test for the diagnosis of non‐alcoholic steatohepatitis in patients with type 2 diabetes

International audienceBackgroundOne of the unmet needs in patients with type 2 diabetes mellitus (T2DM) is the prediction of non-alcoholic liver disease by non-invasive blood tests, for each of the three main histological features, fibrosis, non-alcoholic steatohepatitis (NASH) and steatosis.AimsTo validate externally the performances of a recent panel, Nash-FibroTest, for the assessment of the severity of fibrosis stages, NASH grades and steatosis grades.MethodsWe prospectively analysed 272 patients with T2DM. Standard definitions of stages and grades were used, and analyses were centralised and blinded. The performances of the FibroTest, NashTest-2 and SteatoTest-2 were assessed using the Obuchowski measure (OM), the main outcome recommended as a summary measure of accuracy includeing all pairwise stages and grades comparisons, which is not provided par the extensively used binary area under the ROC curve.ResultsThe diagnostic performance of each component of the panel was significant. OM (SE; significance) of the FibroTest, the NashTest-2 and the SteatoTest-2 was 0.862 (0.012; P < 0.001), 0.827 (0.015; P < 0.001) and 0.794 (0.020; P < 0.01), respectively. For ballooning and lobular inflammation, OM was 0.794 (0.021; P < 0.001) and 0.821 (0.017; P < 0.001), respectively. In a post hoc analysis the FibroTest outperformed VCTE by 4.1% (2.5-6.5; P < 0.001) for reliability, with a non-significant difference for OM for fibrosis staging, 0.859 (0.012) for FibroTest vs 0.870 (0.009) for VCTE.ConclusionsFrom a single blood sample, the panel provides non-invasive diagnosis of the stages of fibrosis, and the grades of NASH and steatosis in patients with T2DM