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Diminished accuracy of biomarkers of fibrosis in low replicative chronic hepatitis B.

ABSTRACT: We evaluated the diagnostic accuracy of aspartate aminotransferase (AST)-to-platelet ratio index (APRI), fibrosis-4 index (FIB-4), AST/alanine aminotransferase (ALT) ratio (AAR), and age-platelet index (API) for significant fibrosis (Metavir F2-4) in low-replicative (HBV DNA <20,000 IU/mL) chronic hepatitis B virus (HBV) patients.The sensitivity, specificity, and area under the receiver-operating characteristic curve (AUROC) of HBeAg-negative, low-replicative (n = 213) and high-replicative (HBV DNA ?20,000 IU/mL, n = 153) patients was assessed.Overall, 113 patients (30.9%) had F2-4 fibrosis. Of the low and high-replicative patients, 40 (18.8%) and 73 (47.7%) had F2-4, respectively (P < 0.0001). APRI ?0.5 less frequently identified F2-4 fibrosis in low vs. high-replicative patients (48.7% vs. 69.6%, P = 0.032) and AAR identified it more frequently in low-replicative patients (37.5% vs. 19.4%, P = 0.037). FIB-4 and API were not different (P > 0.05) for identifying F2-4 fibrosis in low and high-replicative patients. Higher specificities were seen at the lowest cut-offs in low vs. high-replicative states for APRI (?0.5, 98% vs. 68.9%), AAR (84.3% vs. 76.6%), FIB-4 (?1.45, 97.5% vs. 87.8%) and API (>4, 94.8% vs. 93.8%). At ROC-defined thresholds, APRI (?0.33), AAR (?0.93), FIB-4 (?0.70) and API (>2) showed greater AUROCs for F2-4 diagnosis in low replicative (0.80, 0.62, 0.81 and 0.71, respectively) vs. high-replicative patients (0.73, 0.52, 0.67 and 0.69, respectively).All 4 biomarkers in both, low and high-replicative HBV demonstrate modest accuracy for fibrosis diagnosis at conventional cut-offs. Lowering the cut-offs may increase the diagnostic relevance of these biomarkers, particularly for APRI and FIB-4 in low-replicative disease.

SUBMITTER: Sanai FM

PROVIDER: S-EPMC5574089 | biostudies-other | 2017 Aug

REPOSITORIES: biostudies-other

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Diminished accuracy of biomarkers of fibrosis in low replicative chronic hepatitis B.

Sanai Faisal M FM Farah Taha T Albeladi Khalid K Batwa Faisal F Dahlan Yaser Y Babatin Mohammed A MA Al-Ashgar Hamad H AlMana Hadeel H Alsaad Khaled S KS AlSwat Khalid K Aljumah Abdulrahman A AlTraif Ibrahim H IH Kailani Bahaa E BE Bzeizi Khalid I KI

BMC gastroenterology 20170825 1

<h4>Background</h4>We evaluated the diagnostic accuracy of aspartate aminotransferase (AST)-to-platelet ratio index (APRI), fibrosis-4 index (FIB-4), AST/alanine aminotransferase (ALT) ratio (AAR), and age-platelet index (API) for significant fibrosis (Metavir F2-4) in low-replicative (HBV DNA <20,000 IU/mL) chronic hepatitis B virus (HBV) patients.<h4>Methods</h4>The sensitivity, specificity, and area under the receiver-operating characteristic curve (AUROC) of HBeAg-negative, low-replicative ( ...[more]

PMID: 28841822

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Project description:Chronic hepatitis B (CHB) virus continues to be a leading cause of morbidity and mortality worldwide. The diagnosis of liver fibrosis has a key role in selecting patients with CHB for antiviral treatment. However, serum biomarkers demonstrate limited diagnostic utility. The present study aimed to compare the performances of fibrosis biomarkers for diagnosing significant liver fibrosis that indicates the need for antiviral therapy in patients with CHB and to identify the most appropriate biomarker for these patients. The current study included 96 antiviral-naïve patients with CHB who underwent liver biopsy. METAVIR scoring system was used to assess liver fibrosis and necroinflammation. The diagnostic performances were evaluated of the platelet (PLT) count; the levels of hyaluronan, serum 7S domain of type 4 collagen, procollagen type III N-terminal peptide, tissue inhibitor of metalloproteinases 1, Mac-2 binding protein glycosylation isomer (M2BPGi) and N-terminal type III collagen propeptide (Pro-C3); the fibrosis index based on four factors; the aspartate aminotransferase-to-platelet ratio index; and enhanced liver fibrosis score for identifying significant liver fibrosis [?fibrosis stage 2 (F2)]. All fibrosis biomarkers, except the Pro-C3 level, correlated with the fibrosis stage. M2BPGi was better than other biomarkers for diagnosing ?F2, with the highest area under the curve of 0.902. M2BPGi demonstrated a higher diagnostic accuracy for significant fibrosis than mild/severe fibrosis or cirrhosis. However, no significant correlation was observed between the M2BPGi level and fibrosis stage in patients with CHB having significant liver necroinflammation defined as ? necroinflammatory activity 2. The M2BPGi level and PLT count were exclusively correlated with the fibrosis stage in 73 patients without significant liver necroinflammation. M2BPGi demonstrated the highest diagnostic performance for significant fibrosis in patients having significant liver fibrosis with no significant liver necroinflammation. In conclusion, the M2BPGi level can accurately diagnose significant liver fibrosis that indicates the need for antiviral therapy in patients with CHB.

Project description:BackgroundNon-invasive tests have been constructed and evaluated mainly for binary diagnoses such as significant fibrosis. Recently, detailed fibrosis classifications for several non-invasive tests have been developed, but their accuracy has not been thoroughly evaluated in comparison to liver biopsy, especially in clinical practice and for Fibroscan. Therefore, the main aim of the present study was to evaluate the accuracy of detailed fibrosis classifications available for non-invasive tests and liver biopsy. The secondary aim was to validate these accuracies in independent populations.MethodsFour HCV populations provided 2,068 patients with liver biopsy, four different pathologist skill-levels and non-invasive tests. Results were expressed as percentages of correctly classified patients.ResultsIn population #1 including 205 patients and comparing liver biopsy (reference: consensus reading by two experts) and blood tests, Metavir fibrosis (FM) stage accuracy was 64.4% in local pathologists vs. 82.2% (p < 10-3) in single expert pathologist. Significant discrepancy (? 2FM vs reference histological result) rates were: Fibrotest: 17.2%, FibroMeter2G: 5.6%, local pathologists: 4.9%, FibroMeter3G: 0.5%, expert pathologist: 0% (p < 10-3). In population #2 including 1,056 patients and comparing blood tests, the discrepancy scores, taking into account the error magnitude, of detailed fibrosis classification were significantly different between FibroMeter2G (0.30 ± 0.55) and FibroMeter3G (0.14 ± 0.37, p < 10-3) or Fibrotest (0.84 ± 0.80, p < 10-3). In population #3 (and #4) including 458 (359) patients and comparing blood tests and Fibroscan, accuracies of detailed fibrosis classification were, respectively: Fibrotest: 42.5% (33.5%), Fibroscan: 64.9% (50.7%), FibroMeter2G: 68.7% (68.2%), FibroMeter3G: 77.1% (83.4%), p < 10-3 (p < 10-3). Significant discrepancy (? 2 FM) rates were, respectively: Fibrotest: 21.3% (22.2%), Fibroscan: 12.9% (12.3%), FibroMeter2G: 5.7% (6.0%), FibroMeter3G: 0.9% (0.9%), p < 10-3 (p < 10-3).ConclusionsThe accuracy in detailed fibrosis classification of the best-performing blood test outperforms liver biopsy read by a local pathologist, i.e., in clinical practice; however, the classification precision is apparently lesser. This detailed classification accuracy is much lower than that of significant fibrosis with Fibroscan and even Fibrotest but higher with FibroMeter3G. FibroMeter classification accuracy was significantly higher than those of other non-invasive tests. Finally, for hepatitis C evaluation in clinical practice, fibrosis degree can be evaluated using an accurate blood test.

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Diminished accuracy of biomarkers of fibrosis in low replicative chronic hepatitis B.

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Diminished accuracy of biomarkers of fibrosis in low replicative chronic hepatitis B.

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