The Effectiveness of Noninvasive Biomarkers to Predict Hepatitis B-Related Significant Fibrosis and Cirrhosis: A Systematic Review and Meta-Analysis of Diagnostic Test Accuracy

Abstract

Noninvasive biomarkers have been developed to predict hepatitis B virus (HBV)-related fibrosis owing to the significant limitations of liver biopsy. Those biomarkers were initially derived from evaluation of hepatitis C virus (HCV)-related fibrosis, and their accuracy among HBV-infected patients was under constant debate. A systematic review was conducted on records in PubMed, EMBASE and the Cochrane Library electronic databases, up until April 1st, 2013, in order to systematically assess the effectiveness and accuracy of these biomarkers for predicting HBV-related fibrosis. The questionnaire for quality assessment of diagnostic accuracy studies (QUADAS) was used. Out of 115 articles evaluated for eligibility, 79 studies satisfied the pre-determined inclusion criteria for meta-analysis. Eventually, our final data set for the meta-analysis contained 30 studies. The areas under the SROC curve for APRI, FIB-4, and FibroTest of significant fibrosis were 0.77, 0.75, and 0.84, respectively. For cirrhosis, the areas under the SROC curve for APRI, FIB-4 and FibroTest were 0.75, 0.87, and 0.90, respectively. The heterogeneity of FIB-4 and FibroTest were not statistically significant. The heterogeneity of APRI for detecting significant fibrosis was affected by median age (P = 0.0211), and for cirrhosis was affected by etiology (P = 0.0159). Based on the analysis we claim that FibroTest has excellent diagnostic accuracy for identification of HBV-related significant fibrosis and cirrhosis. FIB-4 has modest benefits and may be suitable for wider scope implementation.

LCR1 and LCR2, two multi‐analyte blood tests to assess liver cancer risk in patients without or with cirrhosis

“…were based on the first serum samples obtained at inclusion. In the integrated database, AUROCt of LCR1 was assessed among patients without cirrhosis, and AUROCt of LCR2 was assessed among the clinical population at risk, patients with cirrhosis as defined by the standard FibroTest cut-off of 0.74, [5][6][7][8][9] and in patients without cirrhosis but with a cancer high risk defined as LCR1 above the optimal cut-off. To improve the efficiency of surveillance, we also assessed the NNS in patients 50 years old or older, a well-known risk factor of PLC.…”

“…The development of non-invasive tests of fibrosis could improve the prediction of the cancer risk in large populations. 3 In 1997 we constructed a fibrosis blood test (FibroTest ® , Fibro-Sure in USA), 4 which has been validated in chronic hepatitis C (CHC) 5,6 and B (CHB), 5,7 alcoholic liver disease (ALD), 8 and non-alcoholic fatty liver disease (NAFLD), 9 with similar prognostic values. 10,11 Therefore, the FibroTest can replace a biopsy to determine the presence or absence of cirrhosis when constructing new tests to predict candidates at risk who require surveillance .…”

Systematic review with meta‐analysis: direct comparisons of biomarkers for the diagnosis of fibrosis in chronic hepatitis C and B

“…To improve the access to fibrosis staging, and replace liver function test and biopsy, many non‐invasive fibrosis biomarkers have been assessed since 1991, including systematic reviews since 2002 . Most of these reviews focused on a specific liver disease such as CHC, CHB, NAFLD, and ALD …”

The γ-glutamyl transpeptidase to platelet ratio (GPR) in HBV patients: just adding up?

“…Yet, proper external validation of new biomarkers is a crucial and essential step before its widespread application to clinical care. Indeed, the diagnostic accuracy of serum fibrosis markers in CHB seems to vary significantly across distinct populations 3. These discrepancies might be explained by some relevant factors, such as variations in laboratory methods and aminotransferases levels, different proportions of HBeAg-negative subjects and diverse HBV genotype distribution and demographic characteristics.…”