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.

Huiyul Park, Eileen L. Yoon, Goh Eun Chung, Eun Kyung Choe, Jung Ho Bae, Seung Ho Choi, Mimi Kim, Woochang Hwang, Hye-Lin Kim, Sun Young Yang, Dae Won Jun. Gut and Liver 2024;18:316-27. https://doi.org/10.5009/gnl230044

Traditionally, sarcopenia has defined as amount of absolute muscle mass adjusted by height in the elderly people. However, relative muscle mass adjusted by weight has been used extensively in most non-alcoholic fatty liver disease (NAFLD) studies. Here, we attempted to investigate the pitfall of adjusted muscle mass by weight to evaluate association between sarcopenia and NAFLD. Adult subjects (n = 1343) who underwent a health check-up were finally included for analysis. The weight-adjusted skeletal muscle mass index (wSMI) and height-adjusted SMI (hSMI) calculated by dividing the total appendicular skeletal muscle (ASM) by weight or the square of height, respectively. Prevalence of sarcopenia defined by wSMI in the NAFLD group was significantly higher than in the control group (1.3% vs. 8.8%, p < 0.001). However, there was no difference in the prevalence of sarcopenia defined by hSMI between the control and NAFLD groups (2.0% vs. 0.8%, p = 0.055). Since body weight was the most potent independent risk factor for NAFLD in multivariable logistic regression analysis, abnormal rates (<−1 SD) of almost all parameters increased in the NAFLD population, after weight adjustment. However, abnormal rates of non-metabolic parameter did not increase in NAFLD, after height adjustment. Only metabolic parameters showed relationship with NAFLD, after height adjustment. As NAFLD is highly associated with body weight, careful attention should be given in the case of studying the relationship of NAFLD with sarcopenia adjusted by body weight.

Background: The fibrosis-4 index (FIB-4) and the NAFLD fibrosis score (NFS) have been used as noninvasive screening methods for advanced fibrosis in patients with NAFLD. However, their diagnostic performance has not been evaluated in at-risk individuals regardless of hepatic steatosis. This study evaluated the performance of the FIB-4 and NFS in at-risk groups of health check-up examinees at mass screening centers. Methods: This retrospective, cross-sectional study included 8545 participants who underwent voluntary magnetic resonance elastography at a discounted fee during their regular health check-ups at 13 mass screening centers nationwide. The at-risk group was defined as those with any of the following conditions: NAFLD, 2 or more metabolic abnormalities, diabetes mellitus, or abnormal aminotransferase levels. A magnetic resonance elastography cutoff of ≥3.6 kPa was used to define conventional advanced fibrosis. Results: According to the proposed criteria, the proportion of at-risk individuals was 67.4%–80.2% in the health check-up cohort without viral or alcohol-associated liver disease. The prevalence of individuals with advanced hepatic fibrosis in each at-risk group was ~2.3%–2.8% according to various criteria. It was higher in patients without NAFLD than in those with NAFLD. A total of 28.2%–39.6% of those in each at-risk group did not show hepatic steatosis on ultrasonography. The performance of FIB-4 for advanced fibrosis in the at-risk group was comparable with that in the NAFLD group. FIB-4 showed a better area under the receiver operating characteristic curve and sensitivity than NFS in the at-risk group. Conclusions: FIB-4 demonstrated superior performance compared with the NFS, and its performance in at-risk individuals was similar to that observed for patients with NAFLD.

Screening strategies for hepatic fibrosis are heavily focused on patients with fatty liver on sonography in primary care centers. This study aimed to investigate the target population for screening significant hepatic fibrosis in primary care centers. This retrospective cross-sectional cohort study used data from 13 nationwide centers. A total of 5111 subjects who underwent both abdominal sonography and magnetic resonance elastography as part of their health check-up were included. Subjects with viral hepatitis and/or a history of significant alcohol consumption were excluded. Significant and advanced hepatic fibrosis was defined as ≥3.0 kPa and ≥3.6 kPa in the MRE test, respectively. The prevalence of significant and advanced hepatic fibrosis was 7.3% and 1.9%, respectively. Among the subjects with significant hepatic fibrosis, 41.3% did not have fatty liver. Hepatic fibrosis burden increased according to the number of metabolic risk abnormalities. Nearly 70% of subjects with significant hepatic fibrosis also had two or more metabolic risk abnormalities and/or diabetes. However, the prevalence of fibrosis did not differ between the groups with and without fatty liver. The presence of two or more metabolic risk abnormalities was an independent risk factor for significant hepatic fibrosis regardless of the fatty liver. Therefore, in the setting of primary care centers, screening for hepatic fibrosis would better be extended to subjects with metabolically unhealthy status beyond those with fatty liver.