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Non-alcoholic Fatty Liver Disease: Diagnosis and Management
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Non-alcoholic Fatty Liver Disease: Diagnosis and Management

A special issue of Diagnostics (ISSN 2075-4418). This special issue belongs to the section "Pathology and Molecular Diagnostics".

Deadline for manuscript submissions: closed (31 December 2022) | Viewed by 14478

Special Issue Editor

Prof. Dr. Carol Stanciu

E-Mail Website
Guest Editor
1. Gastroenterology Department “Grigore T. Popa”, University of Medicine and Pharmacy, 700111 Iasi, Romania
2. Institute of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700111 Iasi, Romania
Interests: non-alcoholic fatty liver disease; gastrointestinal motility; viral hepatitis; liver cirrhosis; liver transplant; acute-on chronic liver failure; non-invasive assessment of liver fibrosis; inflammatory bowel disease; biliary tract disorders; Clostridium difficile infection

Special Issue Information

Dear Colleagues,

Nonalcoholic fatty liver disease (NAFLD) is a major cause of chronic liver disease and has now become a global epidemic affecting 1 in 4 adults worldwide. NAFLD encompasses two distinct conditions with distinct histologic features and prognosis: 1) nonalcoholic fatty liver (NAFL), which includes steatosis only, and 2) nonalcoholic steatohepatitis (NASH) characterized by steatosis and inflammation with hepatocyte ballooning, with or without fibrosis, which can progress to liver fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). However, the true prevalence of NASH is not yet known due to the need for liver biopsy (LB) to set the diagnosis, but current data show that 1 in 3 patients with NAFLD have NASH, while the global prevalence of NASH in general population ranges between 3% and 5%. Liver biopsy (LB) is the “gold standard” for the diagnosis of NASH. However, liver biopsy is an invasive method, with high costs, inter- and intra-observer variability of histopathological interpretation, sampling errors, and the risk of rare but potentially life-threatening complications. The abovementioned drawbacks of LB have led to the development of several noninvasive methods for liver fibrosis evaluation ranging from serum markers assay to advanced imaging techniques. Based on the above, we would like to invite you to contribute to this Special Issue on “Non-Alcoholic Fatty Liver Disease: Diagnosis and Management” of Diagnostics.

Prof. Dr. Carol Stanciu
Guest Editor

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Published Papers (5 papers)

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Research

13 pages, 770 KiB  
Article
Clinical Model for the Prediction of Severe Liver Fibrosis in Adult Patients with Type II Diabetes Mellitus
by Ovidiu Paul Calapod, Andreea Maria Marin, Anca Pantea Stoian and Carmen Fierbinteanu-Braticevici
Diagnostics 2022, 12(8), 1829; https://doi.org/10.3390/diagnostics12081829 - 29 Jul 2022
Cited by 1 | Viewed by 2193
Abstract
Background and Objectives: Non-alcoholic fatty liver disease (NAFLD)-related severe liver fibrosis is associated with a higher risk of progressing to decompensated cirrhosis and hepatic failure and developing NAFLD-related hepatocellular carcinoma (HCC), particularly in populations with diabetes. Our pilot study aims to evaluate the [...] Read more.
Background and Objectives: Non-alcoholic fatty liver disease (NAFLD)-related severe liver fibrosis is associated with a higher risk of progressing to decompensated cirrhosis and hepatic failure and developing NAFLD-related hepatocellular carcinoma (HCC), particularly in populations with diabetes. Our pilot study aims to evaluate the performances of various noninvasive methods in predicting liver fibrosis in a population of patients with diabetes and to establish a new scoring system for the prediction of severe fibrosis (>F3). Materials and Methods: A total of 175 patients with diabetes were enrolled for liver fibrosis evaluation. Using the degree of agreement (concordance) between a noninvasive score based on serum biomarkers (NAFLD fibrosis score) and point shear-wave elastography (pSWE) as the reference method, we generated receiver operating characteristic (ROC) curves and performed a multivariate analysis to predict severe liver fibrosis. Results: In our population of patients with diabetes, gamma-glutamyltransferase (GGT), age, body mass index (BMI), the homeostatic model assessment of insulin resistance (HOMA-IR), and glycosylated hemoglobin (HbA1C) were significant predictors for the diagnosis of the F3/F4 group (area under the ROC: 0.767, 0.743, 0.757, 0.772, and 0.7, respectively; p < 0.005 for all). Moreover, the combined composite score (the sum of GGT, age, BMI, HOMA index, and HbA1C) had the highest diagnostic performance at a cut-off value of 3 (AUROC—0.899; p < 0001). The sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) were 91.20%, 79%, 79%, and 89%, respectively, and 89% of patients were correctly classified as having severe liver fibrosis. In contrast with the Fibrosis 4 (FIB-4) score and the AST-to-platelet ratio index (APRI), the composite score had the best accuracy in discriminating advanced fibrosis. Conclusions: The proposed composite score had a reliable and acceptable diagnostic accuracy in identifying patients with diabetes at risk of having severe fibrosis using readily available laboratory and clinical data. Full article
(This article belongs to the Special Issue Non-alcoholic Fatty Liver Disease: Diagnosis and Management)
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10 pages, 877 KiB  
Article
Characteristics of Urine Organic Acid Metabolites in Nonalcoholic Fatty Liver Disease Assessed Using Magnetic Resonance Imaging with Elastography in Korean Adults
by Ji-Hee Haam, Yun Kyong Lee, Eunkyung Suh and Young-Sang Kim
Diagnostics 2022, 12(5), 1199; https://doi.org/10.3390/diagnostics12051199 - 11 May 2022
Cited by 4 | Viewed by 2046
Abstract
The liver is an essential organ that manufactures energy through various metabolic pathways; thus, exploring the intermediate metabolites in nonalcoholic fatty liver disease (NAFLD) may help discover novel parameters in hepatic steatosis or fibrosis. The present study aimed to investigate the traits of [...] Read more.
The liver is an essential organ that manufactures energy through various metabolic pathways; thus, exploring the intermediate metabolites in nonalcoholic fatty liver disease (NAFLD) may help discover novel parameters in hepatic steatosis or fibrosis. The present study aimed to investigate the traits of urine organic acid metabolites in participants with hepatic steatosis and fibrosis in nonalcoholic Korean adults. Hepatic steatosis and fibrosis, in 68 men and 65 women, were evaluated using quantification by proton density fat fraction with magnetic resonance (MR) imaging and MR elastography, respectively. Urine metabolites were obtained using a high-performance liquid chromatography–mass spectrometry analysis. The candidate metabolites were included in the logistic regression models for hepatic steatosis and fibrosis. The association between high p-hydroxyphenyllactate levels and hepatic steatosis was not independent of body mass index and Homeostatic Model Assessment-insulin resistance. High ethylmalonate, β-hydroxybutyrate, and sulfate levels were significantly related to a low probability of hepatic fibrosis, independent of covariates. In conclusion, urine metabolites were not related to hepatic steatosis independent of obesity and insulin resistance, while several metabolites were specifically associated with hepatic fibrosis. Further study is required to verify the diagnostic value of the metabolites in a population with wide-spectrum NAFLD. Full article
(This article belongs to the Special Issue Non-alcoholic Fatty Liver Disease: Diagnosis and Management)
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13 pages, 1147 KiB  
Article
Clinical and Laboratory Characteristics of Normal Weight and Obese Individuals with Non-Alcoholic Fatty Liver Disease
by Anca Trifan, Adrian Rotaru, Remus Stafie, Ermina Stratina, Sebastian Zenovia, Robert Nastasa, Laura Huiban, Tudor Cuciureanu, Cristina Muzîca, Stefan Chiriac, Irina Gîrleanu, Ana-Maria Sîngeap, Catalin Sfarti, Camelia Cojocariu and Carol Stanciu
Diagnostics 2022, 12(4), 801; https://doi.org/10.3390/diagnostics12040801 - 24 Mar 2022
Cited by 8 | Viewed by 2655
Abstract
Non-alcoholic fatty liver disease (NAFLD) has had, over the past few decades, a progressively growing prevalence among the general population all over the world, in parallel with metabolic conditions such as type 2 diabetes mellitus (T2DM), dyslipidemia, and obesity. However, NAFLD is also [...] Read more.
Non-alcoholic fatty liver disease (NAFLD) has had, over the past few decades, a progressively growing prevalence among the general population all over the world, in parallel with metabolic conditions such as type 2 diabetes mellitus (T2DM), dyslipidemia, and obesity. However, NAFLD is also detected in 10–13% of subjects with a body mass index (BMI) ≤ 25 kg/m² (lean-NAFLD), whose major risk factors remain unknown. In this study, we aimed to characterize the clinical features and associated risk factors of lean-NAFLD in comparison with obese-NAFLD patients. Consecutive patients diagnosed with NAFLD by vibration-controlled transient elastography and controlled attenuation parameter were prospectively enrolled. Biological and clinical data obtained from the participants were stratified according to their BMI in two groups: lean-NAFLD and obese-NAFLD. In total, 331 patients (56.8% males) were included in the final analysis. Most of the subjects were obese-NAFLD (n = 258, 77.9%) and had a higher prevalence of T2DM, dyslipidemia, and components of the metabolic syndrome, together with abnormal biological parameters. Regarding liver stiffness measurements, the proportion of subjects with at least significant fibrosis (≥F2) was approximately twofold higher among obese-NAFLD (43.81%) in comparison with lean-NAFLD patients (23.29%). Moreover, obese individuals had a higher risk for liver fibrosis (OR = 2.6, 95%, CI 1.5–4.42, p < 0.001) than lean individuals. Although associated metabolic conditions and at least significant liver fibrosis were present in approximately one-quarter of the patients, these were more frequent among obese-NAFLD patients. Therefore, individualized screening strategies for NAFLD should be established according to BMI. Full article
(This article belongs to the Special Issue Non-alcoholic Fatty Liver Disease: Diagnosis and Management)
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13 pages, 1266 KiB  
Article
Evaluation of a Whole-Liver Dixon-Based MRI Approach for Quantification of Liver Fat in Patients with Type 2 Diabetes Treated with Two Isocaloric Different Diets
by Valentina Brancato, Giuseppe Della Pepa, Lutgarda Bozzetto, Marilena Vitale, Giovanni Annuzzi, Luca Basso, Carlo Cavaliere, Marco Salvatore, Angela Albarosa Rivellese and Serena Monti
Diagnostics 2022, 12(2), 514; https://doi.org/10.3390/diagnostics12020514 - 16 Feb 2022
Cited by 2 | Viewed by 3364
Abstract
Dixon-based methods for the detection of fatty liver have the advantage of being non-invasive, easy to perform and analyze, and to provide a whole-liver coverage during the acquisition. The aim of the study was to assess the feasibility of a whole-liver Dixon-based approach [...] Read more.
Dixon-based methods for the detection of fatty liver have the advantage of being non-invasive, easy to perform and analyze, and to provide a whole-liver coverage during the acquisition. The aim of the study was to assess the feasibility of a whole-liver Dixon-based approach for liver fat quantification in type 2 diabetes (T2D) patients who underwent two different isocaloric dietary treatments: a diet rich in monosaturated fatty acids (MUFA) and a multifactorial diet. Thirty-nine T2D patients were randomly assigned to MUFA diet (n = 21) and multifactorial diet (n = 18). The mean values of the proton density fat fraction (PDFF) over the whole liver and over the ROI corresponding to that chosen for MRS were compared to MRS-PDFF using Spearman’s correlation (ρ). Before–after changes in percentage of liver volume corresponding to MRI-PDFF above thresholds associated with hepatic steatosis (LV%TH, with TH = 5.56%, 7.97% and 8.8%) were considered to assess the proposed approach and compared between diets using Wilcoxon rank-sum test. Statistical significance set at p < 0.05. A strong linear relationship was found between MRS-PDFF and MRI-PDFFs (ρ = 0.85, p < 0.0001). Changes in LV%TH% were significantly higher (p < 0.05) in the multifactorial diet than in MUFA diet (25% vs. 9%, 35% vs. 12%, and 38% vs. 13% decrease, respectively, for TH = 5.56%, 7.97%, and 8.8%) and this was reproducible compared to results obtained using the standard liver fat analysis. A volumetric approach based on Dixon method could be an effective, non-invasive technique that could be used for the quantitative analysis of hepatic steatosis in T2D patients. Full article
(This article belongs to the Special Issue Non-alcoholic Fatty Liver Disease: Diagnosis and Management)
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11 pages, 1523 KiB  
Article
Pemafibrate Ameliorates Liver Dysfunction and Fatty Liver in Patients with Non-Alcoholic Fatty Liver Disease with Hypertriglyceridemia: A Retrospective Study with the Outcome after a Mid-Term Follow-Up
by Suguru Ikeda, Takaaki Sugihara, Takuya Kihara, Yukako Matsuki, Takakazu Nagahara, Tomoaki Takata, Sonoko Kitao, Tsuyoshi Okura, Kazuhiro Yamamoto and Hajime Isomoto
Diagnostics 2021, 11(12), 2316; https://doi.org/10.3390/diagnostics11122316 - 9 Dec 2021
Cited by 11 | Viewed by 3342
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease related to metabolic syndrome. No standard pharmacological treatment has yet been established. We retrospectively evaluated the efficacy of pemafibrate in 16 NAFLD patients (11 men and 5 women; median age, 59 years; range, [...] Read more.
Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease related to metabolic syndrome. No standard pharmacological treatment has yet been established. We retrospectively evaluated the efficacy of pemafibrate in 16 NAFLD patients (11 men and 5 women; median age, 59 years; range, 27–81 years) who had taken pemafibrate for at least one year. They were all diagnosed with fatty liver according to imaging and clinical criteria. They were administered pemafibrate from October 2018 to October 2021 (median, 94 weeks; range, 56–157 weeks). Serum triglyceride was significantly decreased by −41.9% (342.3 ± 54.0 to 198.9 ± 20.4 mg/dL, p < 0.001). Aspartate aminotransferase (AST), alanine aminotransferase, and gamma-glutamyl transferase levels significantly decreased by −42.1% (49.6 ± 7.0 to 28.7 ± 3.4 U/L, p < 0.001), −57.1% (65.1 ± 10.8 to 27.9 ± 3.7 U/L, p < 0.001), and −43.2% (68.9 ± 10.9 to 39.1 ± 5.3 U/L, p < 0.05), respectively. The AST to platelet ratio (APRI) (0.8 ± 0.1 to 0.4 ± 0.1, p < 0.001) and fibrosis based on four factors (FIB-4) index (1.8 ± 0.3 to 1.4 ± 0.2, p < 0.05) also significantly decreased. Liver attenuation (39.1 ± 1.2 to 57.8 ± 2.7 HU, p = 0.028) and liver/spleen ratio (0.76 ± 0.04 to 1.18 ± 0.02, p = 0.012) significantly improved in three patients, as assessed by computed tomography. In conclusion, pemafibrate significantly improves serum triglyceride levels, liver function, FIB-4 index, APRI, and fatty liver in NAFLD patients with hypertriglyceridemia. Full article
(This article belongs to the Special Issue Non-alcoholic Fatty Liver Disease: Diagnosis and Management)
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