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

Abstract

BackgroundWe 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.MethodsThe 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.ResultsOverall, 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).ConclusionAll 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12876-017-0658-x) contains supplementary material, which is available to authorized users.

Serum markers for predicting advanced fibrosis in patients with chronic hepatitis B and nonalcoholic fatty liver disease

“…[14,17] Although our study patients shared some clinical features of those with CHB, the NAFLD status may have effects on hepatitis B progression and serum markers related to hepatic necroinflammatory activities. [19,20] Therefore, our findings on the best performing marker differed from those in studies that enrolled CHB patients without NAFLD or NAFLD patients without CHB. In the present study, the best performing marker in NAFLD patients without CHB was FIB-4, which has been well documented as the best choice in many studies and also recommended by recent published association guidelines for NAFLD patients.…”

“…However, the role of APRI for predicting advanced fibrosis in CHB patients without NAFLD remains controversial as 2 meta-analyses showed conflicting results [14,17] . Although our study patients shared some clinical features of those with CHB, the NAFLD status may have effects on hepatitis B progression and serum markers related to hepatic necroinflammatory activities [19,20] . Therefore, our findings on the best performing marker differed from those in studies that enrolled CHB patients without NAFLD or NAFLD patients without CHB.…”

The relationship between serum hepatitis B virus DNA level and liver histology in patients with chronic HBV infection

“…The assessment of liver fibrosis and cirrhosis was performed at low magnification by three senior pathologists unaware of the clinical and virological results. According to the Laennec staging system (grades L0-L4C), liver fibrosis and cirrhosis were divided into 7 grades [ 6 – 9 ]. If there were different opinions on the stage of the liver biopsy, the patient was excluded.…”