Advances in the Diagnosis of Steatotic Liver Disease

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

Deadline for manuscript submissions: 30 November 2024 | Viewed by 4113

Special Issue Editor


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Guest Editor
Department of Internal Medicine, School of Medicine, Federal University of Bahia, Salvador, BA, Brazil
Interests: steatotic liver disease; hepatocellular carcinoma; hepatotoxicity

Special Issue Information

Dear Colleagues,

Steatotic liver disease (SLD has emerged as the novel nomenclature for NAFLD, defined by the “A multi-society Delphi consensus statement on new fatty liver disease nomenclature". It includes sub classification such as metabolic-associated steatotic liver disease (MASLD); alcohol related SLD (SLD-ALD); specific etiology SLD (DILI; monogenetic diseases, miscellaneous); cryptogenic SLD: unknown causes.

Our knowledge of SLD, considered the most frequent liver disease today, has been enhanced in all aspects of the disease, including epidemiology, clinical profile, diagnosis, and treatment. Advances also have been reached in precision medicine, which soon will be integrated into SLD clinical practice. However, unmet practical needs are still present in most clinical aspects of this liver disease.

In this Special Issue, all relevant aspects of SLD examined through original research articles, reviews, short communications, case reports, and your contributions are welcome.

We look forward to your collaboration.

Dr. Helma Pinchemel Cotrim
Guest Editor

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Keywords

  • steatotic liver disease—SLD
  • steatohepatitis
  • steatosis

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Published Papers (4 papers)

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Research

10 pages, 1363 KiB  
Article
Sequential Diagnostic Approach Using FIB-4 and ELF for Predicting Advanced Fibrosis in Metabolic Dysfunction-Associated Steatotic Liver Disease
by Yeo-Wool Kang, Yang-Hyun Baek and Sang-Yi Moon
Diagnostics 2024, 14(22), 2517; https://doi.org/10.3390/diagnostics14222517 - 11 Nov 2024
Viewed by 436
Abstract
Background and Aims: Multiple non-invasive tests (NITs) for identifying advanced fibrosis in patients with non-alcoholic fatty liver disease (NAFLD) are available, but, due to the limitations of single NITs, the American Association for the Study of Liver Disease (AASLD) guidelines suggest a [...] Read more.
Background and Aims: Multiple non-invasive tests (NITs) for identifying advanced fibrosis in patients with non-alcoholic fatty liver disease (NAFLD) are available, but, due to the limitations of single NITs, the American Association for the Study of Liver Disease (AASLD) guidelines suggest a two-step strategy, combining the Fibrosis-4 Index (FIB-4) score with the Enhanced Liver Fibrosis (ELF) test to improve diagnostic accuracy and minimize unnecessary liver biopsies. However, few real-world studies have used such a sequential approach. We here evaluated the diagnostic accuracy of the ELF test in patients with recently established metabolic dysfunction-associated steatotic liver disease (MASLD) and assessed the clinical utility of applying a two-step strategy, including the ELF test following the FIB-4 score assessment, in patients with MASLD. Methods: We enrolled 153 patients diagnosed with MASLD who underwent liver biopsy at the Dong-A University Hospital between June 2018 and August 2023. The degree of fibrosis was determined based on liver biopsy results. Various NITs were used, including the Aminotransferase-to-Platelet Ratio Index (APRI), FIB-4 score, NAFLD Fibrosis score (NFS) and ELF test. The diagnostic efficacy of these NITs was evaluated based on the area under the receiver operating characteristic curve (AUROC). Additionally, the performance of each test was further examined both when applied individually and in a two-step approach, where FIB-4 was used followed by ELF testing. Key metrics such as sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were used for this analysis. Results: Overall, 153 patients with MASLD (mean age: 46.62 years; 52.3% men; 28.1% with type 2 diabetes) were included. The performance of the NITs in identifying advanced fibrosis was as follows: the AUROC of the APRI, FIB-4, NFS, and ELF tests were 0.803 (95% confidence interval (CI), 0.713–0.863), 0.769 (95% CI, 0.694–0.833), 0.699 (95% CI, 0.528–0.796), and 0.829 (95% CI, 0.760–0.885), respectively. The combination of the FIB-4 score ≥ 1.30 and the ELF score ≥ 9.8 showed 67.86% sensitivity, 90.40% specificity, a PPV of 75.18%, an NPV of 86.78%, an accuracy of 83.64%, and an AUROC of 0.791 for predicting the diagnosis of advanced fibrosis. This approach excluded 28 patients (71.8%) from unnecessary liver biopsies. Conclusions: Our study demonstrated that ELF testing maintained diagnostic accuracy in assessing liver fibrosis in patients with MASLD in real-world practice. This test was used as a second step in the evaluation, reducing clinically unnecessary invasive liver biopsies and referrals to tertiary institutions. This approach allows assessment of MASLD severity in primary care settings without requiring additional equipment. Full article
(This article belongs to the Special Issue Advances in the Diagnosis of Steatotic Liver Disease)
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13 pages, 946 KiB  
Article
A Mediterranean Diet-Oriented Intervention Rescues Impaired Blood Cell Bioenergetics in Patients with Metabolic Dysfunction-Associated Steatotic Liver Disease
by Agnese Segala, Marika Vezzoli, Alice Vetturi, Emirena Garrafa, Barbara Zanini, Emanuela Bottani, Monica Marullo, Silvia Marconi, Chiara Ricci and Alessandra Valerio
Diagnostics 2024, 14(18), 2041; https://doi.org/10.3390/diagnostics14182041 - 14 Sep 2024
Viewed by 625
Abstract
Background: Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD), a novel term for Non-Alcoholic Fatty Liver Disease (NAFLD), is associated with liver mitochondrial dysfunction. We previously demonstrated that mitochondrial respiratory capacity in peripheral blood mononuclear cells (PBMCs) was significantly reduced in patients with MASLD [...] Read more.
Background: Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD), a novel term for Non-Alcoholic Fatty Liver Disease (NAFLD), is associated with liver mitochondrial dysfunction. We previously demonstrated that mitochondrial respiratory capacity in peripheral blood mononuclear cells (PBMCs) was significantly reduced in patients with MASLD compared to non-MASLD controls. For MASLD treatment, guidelines recommend behavioral and dietary changes to reduce body weight. A recent 12-month clinical trial demonstrated that ameliorating patients’ lifestyles through improved adherence to the Mediterranean diet and encouraged physical activity results in MASLD remission or regression. Methods: As a sub-study of the 12-month clinical trial, we evaluated the effects of the Mediterranean diet-oriented intervention on PBMC mitochondrial DNA content and respiratory parameters and on various biomarkers associated with MASLD. Results: Contrary to what was found at the baseline, after twelve months of intervention, systemic inflammatory and bioenergetics parameters did not differ between MASLD patients (N = 15) and control subjects (N = 17). PBMCs from MASLD subjects showed rescued basal respiration, ATP-linked respiration, maximal respiration, and spare respiratory capacity. The observed recovery coincided with a significant increase in the patients’ adherence to the Mediterranean diet (Medscore). Conclusions: Our findings indicate that a Mediterranean diet-oriented intervention, without calorie reduction, preserves blood cell mitochondrial function in MASLD subjects. Thus, PBMC bioenergetics-based assays might be taken into account not only for diagnosing but also for monitoring therapeutic responses in MASLD. Full article
(This article belongs to the Special Issue Advances in the Diagnosis of Steatotic Liver Disease)
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13 pages, 226 KiB  
Article
Efficacy of Ultrasound for the Detection of Possible Fatty Liver Disease in Children
by Sarah B. Lowry, Shelly Joseph, Kevin J. Psoter, Emily Dunn, Sana Mansoor, S. Kathryn Smith, Wikrom Karnsakul, Gihan Naguib, Kenneth Ng and Ann O. Scheimann
Diagnostics 2024, 14(15), 1652; https://doi.org/10.3390/diagnostics14151652 - 31 Jul 2024
Viewed by 720
Abstract
Pediatric MASLD (previously referred to as NAFLD) incidence has continued to rise along with the obesity pandemic. Pediatric MASLD increases the risk of liver fibrosis and cirrhosis in adulthood. Early detection and intervention can prevent and reduce complications. Liver biopsy remains the gold [...] Read more.
Pediatric MASLD (previously referred to as NAFLD) incidence has continued to rise along with the obesity pandemic. Pediatric MASLD increases the risk of liver fibrosis and cirrhosis in adulthood. Early detection and intervention can prevent and reduce complications. Liver biopsy remains the gold standard for diagnosis, although imaging modalities are increasingly being used. We performed a retrospective study of 202 children seen in a pediatric gastroenterology clinic with a complaint of abdominal pain, elevated liver enzymes or MASLD, or a combination of the three to evaluate screening methods for MASLD. A total of 134 of the 202 patients included in the study underwent laboratory testing and abdominal ultrasound. Ultrasound images were reviewed with attention to liver size and echotexture by a fellowship-trained pediatric radiologist for liver size and echotexture. Overall, 76.2% of the initial radiology reports correctly identified hepatomegaly based on age and 75.4% of the initial radiology reports correctly described hepatic echogenicity that was consistent with increased hepatic fat deposition. Use of screening ultrasound in concert with other clinical evaluations can be helpful to identify children at risk of MASLD. Utilizing ranges for liver span according to age can help to diagnose hepatomegaly, and understanding how to identify hepatic echogenicity is important for identifying possible hepatic steatosis. Full article
(This article belongs to the Special Issue Advances in the Diagnosis of Steatotic Liver Disease)
18 pages, 2248 KiB  
Article
Mitochondrial Dysfunction in Peripheral Blood Mononuclear Cells as Novel Diagnostic Tools for Non-Alcoholic Fatty Liver Disease: Visualizing Relationships with Known and Potential Disease Biomarkers
by Emirena Garrafa, Agnese Segala, Marika Vezzoli, Emanuela Bottani, Barbara Zanini, Alice Vetturi, Renata Bracale, Chiara Ricci and Alessandra Valerio
Diagnostics 2023, 13(14), 2363; https://doi.org/10.3390/diagnostics13142363 - 13 Jul 2023
Cited by 5 | Viewed by 1823
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a health emergency worldwide due to its high prevalence and the lack of specific therapies. Noninvasive biomarkers supporting NAFLD diagnosis are urgently needed. Liver mitochondrial dysfunction is a central NAFLD pathomechanism that changes throughout disease progression. Blood-cell [...] Read more.
Non-alcoholic fatty liver disease (NAFLD) is a health emergency worldwide due to its high prevalence and the lack of specific therapies. Noninvasive biomarkers supporting NAFLD diagnosis are urgently needed. Liver mitochondrial dysfunction is a central NAFLD pathomechanism that changes throughout disease progression. Blood-cell bioenergetics reflecting mitochondrial organ dysfunction is emerging for its potential applications in diagnostics. We measured real-time mitochondrial respirometry in peripheral blood mononuclear cells (PBMCs), anthropometric parameters, routine blood analytes, and circulating cytokines from a cohort of NAFLD patients (N = 19) and non-NAFLD control subjects (N = 18). PBMC basal respiration, ATP-linked respiration, maximal respiration, and spare respiratory capacity were significantly reduced in NAFLD compared to non-NAFLD cases. Correlation plots were applied to visualize relationships between known or potential NAFLD-related biomarkers, while non-parametric methods were applied to identify which biomarkers are NAFLD predictors. Basal and ATP-linked mitochondrial respiration were negatively correlated with triglycerides and fasting insulin levels and HOMA index. Maximal and spare respiratory capacity were negatively correlated with IL-6 levels. All the mitochondrial respiratory parameters were positively correlated with HDL-cholesterol level and negatively correlated with fatty liver index. We propose including blood cell respirometry in panels of NAFLD diagnostic biomarkers to monitor disease progression and the response to current and novel therapies, including mitochondrial-targeted ones. Full article
(This article belongs to the Special Issue Advances in the Diagnosis of Steatotic Liver Disease)
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