Diagnostic and prognostic values of noninvasive biomarkers of fibrosis in patients with alcoholic liver disease.

FibroTest has been validated as a biomarker of fibrosis in patients with chronic viral hepatitis, with a similar prognostic value as biopsy. The aim of the study was to compare the diagnostic and prognostic values of FibroTest versus the recently patented biomarkers, FibrometerA, and Hepascore. A total of 218 consecutive patients with ALD and available liver biopsy examination were included. Biomarkers were compared using univariate area under the ROC curves (AUROC) and multivariate analysis (logistic regression and Cox). The median follow-up was 8.2 years. Eighty-five patients died, including 42 deaths related to liver complications. The diagnostic values of FibrometerA and Hepascore did not differ from that of FibroTest for advanced fibrosis (all AUROC = 0.83 +/- 0.03) and cirrhosis (FibroTest and FibrometerA = 0.94 +/- 0.02, Hepascore = 0.92 +/- 0.02), and were significantly greater than those of nonpatented biomarkers (APRI, Forns, FIB4; P < 0.01). In multivariate analysis the most significant was FibroTest (P = 0.001), without independent diagnostic value for FibrometerA (P = 0.19), and Hepascore (P = 0.40). The prognostic values of FibroTest (AUROC for survival or non liver disease-related death = 0.79 +/- 0.04), FibrometerA (0.80 +/- 0.04), Hepascore (0.78 +/- 0.04), did not differ from that of biopsy fibrosis staging (0.77 +/- 0.04). In multivariate analysis the most significant were FibroTest (P = 0.004) and biopsy (P = 0.03), without independent prognostic values for FibrometerA (P = 0.41) and Hepascore (P = 0.28). In patients with alcoholic liver disease, FibrometerA and Hepascore did not improve the diagnostic and prognostic values of FibroTest.

The diagnostic value of biomarkers (SteatoTest) for the prediction of liver steatosis.

BACKGROUND: Biopsy is the usual gold standard for liver steatosis assessment. The aim of this study was to identify a panel of biomarkers (SteatoTest), with sufficient predictive values, for the non-invasive diagnosis of steatosis in patients with or without chronic liver disease. Biomarkers and panels were assessed in a training group of consecutive patients with chronic hepatitis C and B, alcoholic liver disease, and non-alcoholic fatty liver disease, and were validated in two independent groups including a prospective one. Steatosis was blindly assessed by using a previously validated scoring system. RESULTS: 310 patients were included in the training group; 434 in three validation groups; and 140 in a control group. SteatoTest was constructed using a combination of the 6 components of FibroTest-ActiTest plus body mass index, serum cholesterol, triglycerides, and glucose adjusted for age and gender. SteatoTest area under the ROC curves was 0.79 (SE = 0.03) in the training group; 0.80 (0.04) in validation group 1; 0.86 (0.03) in validation group 2; and 0.72 (0.05) in the validation group 3 - all significantly higher than the standard markers: gamma-glutamyl-transpeptidase or alanine aminotransferase. The median SteatoTest value was 0.13 in fasting controls; 0.16 in non-fasting controls; 0.31 in patients without steatosis; 0.39 in grade 1 steatosis (0-5%); 0.58 in grade 2 (6-32%); and 0.74 in grade 3-4 (33-100%). For the diagnosis of grade 2-4 steatosis, the sensitivity of SteatoTest at the 0.30 cut-off was 0.91, 0.98, 1.00 and 0.85 and the specificity at the 0.70 cut-off was 0.89, 0.83, 0.92, 1.00, for the training and three validation groups, respectively. CONCLUSION: SteatoTest is a simple and non-invasive quantitative estimate of liver steatosis and may reduce the need for liver biopsy, particularly in patients with metabolic risk factor.

The diagnostic value of combining carbohydrate-deficient transferrin, fibrosis, and steatosis biomarkers for the prediction of excessive alcohol consumption.

BACKGROUND AND AIM: The validity of biomarkers of excessive alcohol drinking (EAD) (30 g/day or more), such as carbohydrate-deficient transferrin (CDT%), is confounded by liver disease severity. The aim was to improve the accuracy of the percentage of CDT by taking into account the presence of fibrosis and steatosis, estimated using biomarkers FibroTest and SteatoTest. METHODS: Three hundred and twenty consecutive patients, 97 with alcoholic liver disease (ALD), and 223 non-ALD, were included. In ALD, 58% had advanced fibrosis and 58% had steatosis; in non-ALD, 25% had advanced fibrosis and 25% had steatosis. RESULTS: The mean percentage of CDT was lower in ALD with advanced fibrosis [2.4 (SE=0.2)] versus without [4.1 (0.3) P<0.0001], and lower in ALD with steatosis versus without (2.4 vs. 3.9; P=0.0007). Among non-ALD, there was no difference in the percentage of CDT according to fibrosis or steatosis. gamma-glutamyl-transpeptidase was higher in patients with advanced fibrosis or with steatosis both in ALD and non-ALD. Aspartate aminotransferase/alanine aminotransferase (AST/ALT) was higher in ALD patients with fibrosis versus without (2.5 vs. 1.3 P<0.0001) but not in non-ALD (1.01 vs. 0.98). AST/ALT was higher in ALD patients with steatosis versus without (2.2 vs. 1.6 P=0.04) and the inverse was observed in non-ALD (0.6 vs. 1.1 P<0.0001). In the entire population the percentage of CDT, gamma-glutamyl-transpeptidase, AST/ALT was associated with EAD, the area under the receiver operating characteristic curve =0.89 (95% CI: 0.84-0.93), 0.93 (0.89-0.93) and 0.77 (0.71-0.82). An algorithm combining the percentage of CDT, FibroTest and SteatoTest permitted to obtain area under the receiver operating characteristic curve=0.92 versus 0.88 for the percentage of CDT (P=0.004) with 87.4% of patients classified correctly. CONCLUSION: Biomarkers of EAD are confounded by fibrosis and steatosis. Accuracy of the percentage of CDT is significantly increased when combined with biomarkers of fibrosis and steatosis.

The diagnostic value of biomarkers (AshTest) for the prediction of alcoholic steato-hepatitis in patients with chronic alcoholic liver disease.

BACKGROUND/AIMS: The aim was to identify a panel of biomarkers (AshTest) for the diagnosis of alcoholic steato-hepatitis (ASH), in patients with chronic alcoholic liver disease. METHODS: Biomarkers were assessed in patients with an alcohol intake>50 g/d, in a training group, and in two validation groups. Diagnosis of ASH (polymorphonuclear infiltrate and hepatocellular necrosis) and its histological severity (four classes: none, mild, moderate and severe) were assessed blindly. RESULTS: Two hundred and twenty-five patients were included, 70 in the training group, 155 in the validation groups, and 299 controls. AshTest was constructed using a combination of the six components of FibroTest-ActiTest plus aspartate aminotransferase. The AshTest area under the ROC curves for moderate-severe ASH was 0.90 in the training group, 0.88 and 0.89 in the validation groups. The median AshTest value was 0.005 in controls, 0.05 in patients without or with mild ASH, 0.64 in moderate, and 0.84 in severe ASH grade 3, (P<0.05 between all groups). At a 0.50 cut-off, the sensitivity of AshTest was 0.80 and the specificity was 0.84. CONCLUSIONS: In heavy drinkers, AshTest is a simple and non-invasive quantitative estimate of alcoholic hepatitis. The use of AshTest may reduce the need for liver biopsy, and therefore allow an earlier treatment of alcoholic hepatitis.

Biomarkers for the prediction of liver fibrosis in patients with chronic alcoholic liver disease.

BACKGROUND & AIMS: The aim of this study was to determine the diagnostic use of noninvasive markers of fibrosis in patients with chronic alcoholic liver disease. METHODS: A total of 221 consecutive patients with an alcohol intake of >50 g/day (median, 100 g/day) and available liver biopsy examination and FibroTest FibroSure (FT) results were included prospectively. Fibrosis was assessed blindly on a 5-stage histologic scale similar to that of the METAVIR scoring system. Hyaluronic acid was measured and used as a standard serum marker of fibrosis. RESULTS: Advanced fibrosis (F2-F4) was present at biopsy examination in 63% of patients. The mean FT value (SE) was F0 = .29 (.05); F1 = .29 (.03), F2 = .40 (.03), F3 = .53 (.04); and F4 = .88 (.02) (P < .05 between all groups, except between F0 and F1). As opposed to FT, there was no significant difference for hyaluronic acid between F2 and F1 and between F2 and F0. For F2-F4 vs. F0-F1, the FT area under the ROC curves (AUROC) = .84 (.03) and .79 (.03) for hyaluronic acid. For the diagnosis of F4, the AUROC was very high, .95 for FT and .93 for hyaluronic acid. The discordances of the 2 stages were attributed to biopsy failures in 26 cases and to FT failures in 13 cases. CONCLUSIONS: In heavy drinkers, FT is a simple and noninvasive quantitative estimate of liver fibrosis. The use of FT may decrease the need for liver biopsy examination.