Screening and follow-up of chronic liver diseases with understanding their etiology in clinics and hospitals

Abstract

Background and aim: Considering the increasing prevalence of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis (NASH), the development of an effective screening and follow-up system that enables the recognition of etiological changes by primary physicians in clinics and specialists in hospitals is required.

Methods: Chronic hepatitis B (HBV) and C (HCV), NASH, and alcoholic steatohepatitis (ASH) patients who were assayed for Mac-2-binding protein glycosylation isomer (M2BPGi) (n = 272) and underwent magnetic resonance elastography (MRE) (n = 119) were enrolled. Patients who underwent MRE were also tested by ultrasound elastography (USE) (n = 80) and for M2BPGi (n = 97), autotaxin (ATX) (n = 62), and platelet count (n = 119), and their fibrosis-4 (FIB-4) index was calculated (n = 119).

Results: FIB-4 index >2, excluding HBV-infected patients, M2BPGi >0.5, ATX >0.5, and platelet count <20 × 10⁴/μL were the benchmark indices, and we took into consideration other risk factors, such as diabetes mellitus and age, to recommend further examinations, such as USE, based on the local situation to avoid overlooking hepatocellular carcinoma (HCC) in the clinic. During specialty care in the hospital, MRE exhibited high diagnostic ability for fibrosis stages >F3 or F4; it could efficiently predict collateral circulation with high sensitivity, which can replace USE. We also identified etiological features and found that collateral circulation in NASH/ASH patients tended to exceed high-risk levels; moreover, these patients exhibited more variation in HCC-associated liver stiffness than the HBV and HCV patients.

Conclusions: Using appropriate markers and tools, we can establish a stepwise, practical, noninvasive, and etiology-based screening and follow-up system in primary and specialty care.

Keywords: Mac‐2‐binding protein glycosylation isomer; autotaxin; fibrosis‐4 index; hepatocellular carcinoma; magnetic resonance elastography.

Figure 1

Relatively convenient fibrosis markers for primary physicians. M2BPGi (a), ATX (b), FIB‐4 index (b), and platelet count (d) with or without hepatocellular carcinoma (HCC). M2BPGi (e, f), ATX (g, h), FIB‐4 index (i, j), and platelet count (k, l) without (e, g, i, k) or with HCC (f, h, j, l) depending on etiology. Red dotted lines in (f) indicate the 0.5 cut‐off index (COI) and 1.0 COI; in (h), 0.5 mg/L and 1.0 mg/L; in (j), 2 FIB‐4 index; and in (l), 20 × 10⁴/μL on the y axis.

Figure 2

Correlation between magnetic resonance elastography (MRE) and ultrasound elastography (USE) data and between tissue fibrosis stages and MRE data of each etiology. MRE (a) and USE (b) data show that liver stiffness increased with increasing fibrosis stage. Liver stiffness measured by MRE (c) and USE (d) categorized by each etiology.

Figure 3

Evaluation of the ability of magnetic resonance elastography (MRE) in high fibrosis stage patients. Liver stiffness of F0–2 and F3–4 (a). AUROC for predicting fibrosis states higher than F3 by MRE (b), ultrasound elastography (USE) (c), M2BPGi (d), ATX (e), FIB‐4 index (f), and platelet count (g).

Figure 4

Liver stiffness and Child‐Pugh classification and correlation between magnetic resonance elastography (MRE) and each tested parameter. Liver stiffness in Child‐Pugh grade B patients differs based on etiology (a). Blue dotted circles represent non‐alcoholic steatohepatitis and alcoholic steatohepatitis patients, and red dotted circles represent hepatitis B virus and hepatitis C virus patients. Correlation between MRE and ultrasound elastography (USE) (b), M2BPGi (c), ATX (d), FIB‐4 index (e), and platelet count (f).

Figure 5

Relationship between clinical parameters and collateral circulation. Data for clinical parameters with or without collateral circulation are shown as follows: magnetic resonance elastography (MRE) (a), ultrasound elastography (USE) (b), M2BPGi (c), ATX (d), FIB‐4 index (e), and platelet count (f). AUROC values for predicting collateral circulation were analyzed as follows: MRE (g), USE (h), M2BPGi (i), ATX (j), FIB‐4 index (k), and platelet count (l).

Figure 6

Magnetic resonance elastography (MRE) and ultrasound elastography (USE) data with and without hepatocellular carcinoma (HCC). MRE (a) and USE (b) data with and without HCC are shown. AUROC values of MRE (c) and USE (d) for predicting HCC are shown. MRE (e) and USE (f) data with and without HCC categorized by etiologies. Red dotted lines indicate liver stiffness level of 4000 Pa. The percentages indicated in blue are the frequency of patients with MRE value above 4000 Pa (indicated by red dotted line) in each etiology.

Figure 7

Highlight of this study. ASH, alcoholic steatohepatitis; HBV, hepatitis B virus; HCC, hepatocellular carcinoma; MRE, magnetic resonance elastography; NASH, non‐alcoholic steatohepatitis.