Sequential Combination of FIB-4 Followed by M2BPGi Enhanced Diagnostic Performance for Advanced Hepatic Fibrosis in an Average Risk Population

Abstract

The fibrosis-4 (FIB-4) index is the most widely used estimated formula to screen for advanced hepatic fibrosis; however, it has a considerable intermediate zone. Here, we propose an algorithm to reduce the intermediate zone and improve the diagnostic performance of screening for advanced liver fibrosis by incorporating Mac-2-binding protein glycan isomer (M2BPGi) into a FIB-4 based screening strategy in an average risk group. Four-hundred eighty-eight healthy and chronic liver disease subjects were analyzed using a 1:1 propensity score matched for age and sex. Advanced liver fibrosis (≥F3) was defined by magnetic resonance elastography (MRE, ≥3.6 kPa). Classification tree analysis was employed to improve diagnostic performance using a combination of the FIB-4 index and M2BPGi. The median serum M2BPGi levels of healthy subjects, patients without advanced fibrosis, and those with the condition were 0.48, 0.94, and 2.93, respectively. The area under the receiver operating characteristic (AUROC) curve of M2BPGi (0.918) for advanced fibrosis was the highest compared to those of the FIB-4 index (0.887), APRI (0.873), and AST/ALT ratio (0.794). When M2BPGi was incorporated following the FIB-4 index, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 87.1%, 82.5%, 54.0%, and 96.4%, respectively. Moreover, 74.3% (133/179) of cases in the intermediate zone of the FIB-4 index avoided unnecessary referrals. Two-step pathway (FIB-4 followed by M2BPGi) could reduce unnecessary referrals and/or liver biopsies in an average-risk population.

Epidemiology, Pathogenesis, and Diagnostic Strategy of Diabetic Liver Disease in Japan

“…However, this two-step algorithm should be validated by international, multi-center, and prospective trials. Other candidates as the second step modality include type IV collagen 7S, CA-fibrosis index, Mac-2 binding protein glycan isomer (M2BPGi) [ 113 ] and ELF test [ 114 ]. M2BPGi, a novel hepatic fibrosis marker, has been developed in Japan.…”

“…M2BPGi can predict fibrosis stage in CLD, including NAFLD [ 115 , 116 , 117 ]. In the Korean population with CLD, sequential combination of FIB-4 index followed by M2BPGi can identify advanced fibrosis (≥F3) evaluated by MRE [ 113 ]. We are now planning to validate this two-step algorithm using FIB-4 index and M2BPGi in Japanese population with biopsy-proven NAFLD.…”

“…The enhanced liver fibrosis (ELF) test is a non-invasive blood test that measures three direct markers of fibrosis: hyaluronic acid (HA), procollagen III amino-terminal peptide (PIIINP), and tissue inhibitor of matrix metalloproteinase 1 (TIMP-1) [ 98 ]. According to a two-step algorithm from EU [ 113 ], ELF test can be applied to the intermediate group of FIB-4 index (1.3–3.25). If NAFLD patients have an ELF score of 10.35 or above, they are likely to have advanced fibrosis [ 113 ].…”

“…According to a two-step algorithm from EU [ 113 ], ELF test can be applied to the intermediate group of FIB-4 index (1.3–3.25). If NAFLD patients have an ELF score of 10.35 or above, they are likely to have advanced fibrosis [ 113 ]. Recently, the usefulness of ELF test was validated in a Japanese NAFLD population [ 118 ].…”

FIB-4 First in Diagnostic Algorithm of MAFLD at the Era of “Global Metabodemic “

“…FIB-4 first strategy would decrease costs and decrease unnecessary referrals as well as increase access to screening in non-specialized facilities. It remains unknown which parameters are the most appropriate as 2 nd step among a variety of NITs, including ELF test [15], Mac-2 binding protein glycated isomer (M2BPGi) [95][96][97], type IV collagen 7S [88,96], ProC3 [98], and autotaxin [99,100].…”