Special Issue "Fatty Liver Disease: Diagnostic, Predictive and Prognostic Markers"

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

Deadline for manuscript submissions: 31 May 2021.

Special Issue Editor

Dr. Kento Imajo
Website
Guest Editor
Department of Gastroenterology and Hepatology, Yokohama City University School of Medicine, 3-9 Fukuura, Kanazawaku, Yokohama 236 Kanagawa, Japan
Interests: Fibrosis; Lipids

Special Issue Information

Dear Colleagues,

Fatty liver disease (FLD) is generally considered as the hepatic manifestation of metabolic syndrome and it is associated with a high prevalence of advanced fibrosis, hepatocellular carcinoma (HCC), and atherosclerotic diseases including cardiovascular disease. FLD includes steatosis, hepatic inflammation, hepatocellular ballooning, as well as liver fibrosis, which are diagnosed and evaluated by analyzing a liver biopsy. However, because the procedure to obtain liver biopsies has several disadvantages, such as a high cost and associated complications, alternatives to biopsy analysis are required. This Special Issue will include papers that investigate new biomarkers or imaging techniques to diagnose the presence of steatohepatitis, the severity of liver fibrosis, FLD-associated HCC, and extrahepatic complications including atherosclerosis and to identify predictive factors of FLD. Additionally, clinical studies examining potential new genetic biomarkers for FLD are welcome. This Special Issue will publish original research and review papers.

Dr. Kento Imajo
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Diagnostics is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Fatty liver disease
  • Nonalcoholic fatty liver disease
  • Nonalcoholic steatohepatitis
  • Steatosis
  • Hepatic inflammation
  • Ballooning

Published Papers (7 papers)

Order results
Result details
Select all
Export citation of selected articles as:

Research

Jump to: Review

Open AccessArticle
Prediction of Nonalcoholic Fatty Liver Disease Using Noninvasive and Non-Imaging Procedures in Japanese Health Checkup Examinees
Diagnostics 2021, 11(1), 132; https://doi.org/10.3390/diagnostics11010132 - 16 Jan 2021
Viewed by 306
Abstract
Access to imaging is limited for diagnosing nonalcoholic fatty liver disease (NAFLD) in general populations. This study evaluated the diagnostic performance of noninvasive and nonimaging indexes to predict NAFLD in the general Japanese population. Health checkup examinees without hepatitis virus infection or habitual [...] Read more.
Access to imaging is limited for diagnosing nonalcoholic fatty liver disease (NAFLD) in general populations. This study evaluated the diagnostic performance of noninvasive and nonimaging indexes to predict NAFLD in the general Japanese population. Health checkup examinees without hepatitis virus infection or habitual alcohol drinking were included. Fatty liver was diagnosed by ultrasonography. The hepatic steatosis index (HSI), Zhejiang University (ZJU) index, and fatty liver index (FLI) were determined, and risk of advanced liver fibrosis was evaluated by the fibrosis-4 index. NAFLD was diagnosed in 1935 (28.0%) of the 6927 subjects. The area under the receiver operating characteristic (AUROC) curve of the HSI, ZJU index, and FLI was 0.874, 0.886, and 0.884, respectively. The AUROC of the ZJU index (p < 0.001) and FLI (p = 0.002) was significantly greater than that for the HSI. In subjects with a high risk of advanced fibrosis, the sensitivity of the HSI, ZJU index, and FLI were 88.8%, 94.4%, and 83.3% with a low cut-off value and the specificity was 98.5%, 100%, and 100% with a high cut-off value. In conclusion, all indexes were useful to diagnose NAFLD in the general Japanese population and in subjects with potentially advanced liver fibrosis. Full article
(This article belongs to the Special Issue Fatty Liver Disease: Diagnostic, Predictive and Prognostic Markers)
Show Figures

Figure 1

Open AccessArticle
Predictive Value of Serum Ferritin in Combination with Alanine Aminotransferase and Glucose Levels for Noninvasive Assessment of NAFLD: Fatty Liver in Obesity (FLiO) Study
Diagnostics 2020, 10(11), 917; https://doi.org/10.3390/diagnostics10110917 - 08 Nov 2020
Viewed by 646
Abstract
The identification of affordable noninvasive biomarkers for the diagnosis and characterization of nonalcoholic fatty liver disease (NAFLD) is a major challenge for the research community. This study aimed to explore the usefulness of ferritin as a proxy biomarker of NAFLD condition, alone or [...] Read more.
The identification of affordable noninvasive biomarkers for the diagnosis and characterization of nonalcoholic fatty liver disease (NAFLD) is a major challenge for the research community. This study aimed to explore the usefulness of ferritin as a proxy biomarker of NAFLD condition, alone or in combination with other routine biochemical parameters. Subjects with overweight/obesity and ultrasound-confirmed liver steatosis (n = 112) from the Fatty Liver in Obesity (FLiO) study were assessed. The hepatic evaluation considered magnetic resonance imaging, ultrasonography, and credited routine blood liver biomarkers. Anthropometry and body composition, dietary intake (by means of a validated 137-item food frequency questionnaire), and specific biochemical markers were also determined. Serum ferritin levels were analyzed using a chemiluminescent microparticle immunoassay kit. Lower serum ferritin concentrations were associated with general better liver health and nutritional status. The evaluation of ferritin as a surrogate of liver damage by means of quantile regression analyses showed a positive association with alanine aminotransferase (ALT) (β = 19.21; p ≤ 0.001), liver fat content (β = 8.70; p = 0.008), and hepatic iron (β = 3.76; p ≤ 0.001), after adjusting for potential confounders. In receiver operating characteristic (ROC) analyses, the panel combination of blood ferritin, glucose, and ALT showed the best prediction for liver fat mass (area under the curve (AUC) 0.82). A combination of ferritin and ALT showed the higher predictive ability for estimating liver iron content (AUC 0.73). This investigation demonstrated the association of serum ferritin with liver health as well as with glucose and lipid metabolism markers in subjects with NAFLD. Current findings led to the identification of ferritin as a potential noninvasive predictive biomarker of NAFLD, whose surrogate value increased when combined with other routine biochemical measurements (glucose/ALT). Full article
(This article belongs to the Special Issue Fatty Liver Disease: Diagnostic, Predictive and Prognostic Markers)
Show Figures

Figure 1

Open AccessArticle
The Appropriate Opportunity for Evaluating Liver Fibrosis by Using the FIB-4 Index in Patients with Nonalcoholic Fatty Liver Disease in Japan
Diagnostics 2020, 10(10), 842; https://doi.org/10.3390/diagnostics10100842 - 19 Oct 2020
Viewed by 356
Abstract
In patients with nonalcoholic fatty liver disease (NAFLD), liver fibrosis is the predictive factor for liver-related events and prognosis. This retrospective study aimed to evaluate longitudinal changes in the FIB-4 index and to determine a strategy for diagnosing and following patients with NAFLD [...] Read more.
In patients with nonalcoholic fatty liver disease (NAFLD), liver fibrosis is the predictive factor for liver-related events and prognosis. This retrospective study aimed to evaluate longitudinal changes in the FIB-4 index and to determine a strategy for diagnosing and following patients with NAFLD using this index. We analyzed the FIB-4 index at baseline and after 1 and 5 years in 272 consecutive patients with biopsy-proven NAFLD. Of these, 52 patients underwent serial biopsies. The change in the FIB-4 index was correlated with changes in the fibrosis stage among these patients (p = 0.048). The median FIB-4 index was 1.64 at baseline, 1.45 at 1 year, and 1.74 at 5 years. The negative predictive value for advanced fibrosis at a low cutoff point was 90.4/90.1 at baseline/1 year. Its specificity at a high cutoff point increased from 65.0% at baseline to 82.3% at 1 year. Multivariate analysis identified the FIB-4 index at 1 year as a predictive factor for a FIB-4 index > 2.67 at 5 years. A FIB-4 index < 1.30 was acceptable for excluding advanced fibrosis at baseline. In contrast, to evaluate and predict advanced liver fibrosis with the FIB-4 index at a high cutoff point, we should use the index at 1 year after appropriate therapy. Full article
(This article belongs to the Special Issue Fatty Liver Disease: Diagnostic, Predictive and Prognostic Markers)
Show Figures

Figure 1

Open AccessArticle
An Improved qFibrosis Algorithm for Precise Screening and Enrollment into Non-Alcoholic Steatohepatitis (NASH) Clinical Trials
Diagnostics 2020, 10(9), 643; https://doi.org/10.3390/diagnostics10090643 - 28 Aug 2020
Viewed by 990
Abstract
Background: Many clinical trials with potential drug treatment options for non-alcoholic fatty liver disease (NAFLD) are focused on patients with non-alcoholic steatohepatitis (NASH) stages 2 and 3 fibrosis. As the histological features differentiating stage 1 (F1) from stage 2 (F2) NASH fibrosis are [...] Read more.
Background: Many clinical trials with potential drug treatment options for non-alcoholic fatty liver disease (NAFLD) are focused on patients with non-alcoholic steatohepatitis (NASH) stages 2 and 3 fibrosis. As the histological features differentiating stage 1 (F1) from stage 2 (F2) NASH fibrosis are subtle, some patients may be wrongly staged by the in-house pathologist and miss the opportunity for enrollment into clinical trials. We hypothesized that our refined artificial intelligence (AI)-based algorithm (qFibrosis) can identify these subtle differences and serve as an assistive tool for in-house pathologists. Methods: Liver tissue from 160 adult patients with biopsy-proven NASH from Singapore General Hospital (SGH) and Peking University People’s Hospital (PKUH) were used. A consensus read by two expert hepatopathologists was organized. The refined qFibrosis algorithm incorporated the creation of a periportal region that allowed for the increased detection of periportal fibrosis. Consequently, an additional 28 periportal parameters were added, and 28 pre-existing perisinusoidal parameters had altered definitions. Results: Twenty-eight parameters (20 periportal and 8 perisinusoidal) were significantly different between the F1 and F2 cases that prompted a change of stage after a careful consensus read. The discriminatory ability of these parameters was further demonstrated in a comparison between the true F1 and true F2 cases as 26 out of the 28 parameters showed significant differences. These 26 parameters constitute a novel sub-algorithm that could accurately stratify F1 and F2 cases. Conclusion: The refined qFibrosis algorithm incorporated 26 novel parameters that showed a good discriminatory ability for NASH fibrosis stage 1 and 2 cases, representing an invaluable assistive tool for in-house pathologists when screening patients for NASH clinical trials. Full article
(This article belongs to the Special Issue Fatty Liver Disease: Diagnostic, Predictive and Prognostic Markers)
Show Figures

Figure 1

Review

Jump to: Research

Open AccessReview
Diagnostic Accuracy of FibroScan and Factors Affecting Measurements
Diagnostics 2020, 10(11), 940; https://doi.org/10.3390/diagnostics10110940 - 12 Nov 2020
Cited by 1 | Viewed by 452
Abstract
Evaluating liver steatosis and fibrosis is important for patients with non-alcoholic fatty liver disease. Although liver biopsy and pathological assessment is the gold standard for these conditions, this technique has several disadvantages. The evaluation of steatosis and fibrosis using ultrasound B-mode imaging is [...] Read more.
Evaluating liver steatosis and fibrosis is important for patients with non-alcoholic fatty liver disease. Although liver biopsy and pathological assessment is the gold standard for these conditions, this technique has several disadvantages. The evaluation of steatosis and fibrosis using ultrasound B-mode imaging is qualitative and subjective. The liver stiffness measurement (LSM) and controlled attenuation parameter (CAP) determined using FibroScan are the evidence-based non-invasive measures of liver fibrosis and steatosis, respectively. The LSM and CAP measurements are carried out simultaneously, and the median values of more than ten valid measurements are used to quantify liver fibrosis and steatosis. Here, we demonstrate that the reliability of the LSM depends on the interquartile range to median ratio (IQR/Med), but CAP values do not depend on IQR/Med. In addition, the LSM is affected by inflammation, congestion, and cholestasis in addition to fibrosis, while CAP values are affected by the body mass index in addition to steatosis. We also show that the M probe provides higher LSM values but lower CAP values than the XL probe in the same population. However, there was no statistically significant difference between the diagnostic accuracies of the two probes. These findings are important to understand the reliability of FibroScan measurements and the factors influencing measurement values for all patients. Full article
(This article belongs to the Special Issue Fatty Liver Disease: Diagnostic, Predictive and Prognostic Markers)
Open AccessReview
Complications of Non-Alcoholic Fatty Liver Disease in Extrahepatic Organs
Diagnostics 2020, 10(11), 912; https://doi.org/10.3390/diagnostics10110912 - 07 Nov 2020
Viewed by 707
Abstract
Non-alcoholic fatty liver disease (NAFLD) is now recognized as the most common chronic liver disease worldwide, along with the concurrent epidemics of metabolic syndrome and obesity. Patients with NAFLD have increased risks of end-stage liver disease, hepatocellular carcinoma, and liver-related mortality. However, the [...] Read more.
Non-alcoholic fatty liver disease (NAFLD) is now recognized as the most common chronic liver disease worldwide, along with the concurrent epidemics of metabolic syndrome and obesity. Patients with NAFLD have increased risks of end-stage liver disease, hepatocellular carcinoma, and liver-related mortality. However, the largest cause of death among patients with NAFLD is cardiovascular disease followed by extrahepatic malignancies, whereas liver-related mortality is only the third cause of death. Extrahepatic complications of NAFLD include chronic kidney disease, extrahepatic malignancies (such as colorectal cancer), psychological dysfunction, gastroesophageal reflux disease, obstructive sleep apnea syndrome, periodontitis, hypothyroidism, growth hormone deficiency, and polycystic ovarian syndrome. The objective of this narrative review was to summarize recent evidences about extrahepatic complications of NAFLD, with focus on the prevalent/incident risk of such diseases in patients with NAFLD. To date, an appropriate screening method for extrahepatic complications has not yet been determined. Collaborative care with respective experts seems to be necessary for patient management because extrahepatic complications can occur across multiple organs. Further studies are needed to reveal risk profiles at baseline and to determine an appropriate screening method for extrahepatic diseases. Full article
(This article belongs to the Special Issue Fatty Liver Disease: Diagnostic, Predictive and Prognostic Markers)
Open AccessReview
Surveillance of Hepatocellular Carcinoma in Nonalcoholic Fatty Liver Disease
Diagnostics 2020, 10(8), 579; https://doi.org/10.3390/diagnostics10080579 - 10 Aug 2020
Cited by 3 | Viewed by 1101
Abstract
Nonalcoholic fatty liver disease (NAFLD) is becoming the leading cause of hepatocellular carcinoma (HCC), liver-related mortality, and liver transplantation. There is sufficient epidemiological cohort data to recommend the surveillance of patients with NAFLD based upon the incidence of HCC. The American Gastroenterology Association [...] Read more.
Nonalcoholic fatty liver disease (NAFLD) is becoming the leading cause of hepatocellular carcinoma (HCC), liver-related mortality, and liver transplantation. There is sufficient epidemiological cohort data to recommend the surveillance of patients with NAFLD based upon the incidence of HCC. The American Gastroenterology Association (AGA) expert review published in 2020 recommends that NAFLD patients with cirrhosis or advanced fibrosis estimated by non-invasive tests (NITs) consider HCC surveillance. NITs include the fibrosis-4 (FIB-4) index, the enhanced liver fibrosis (ELF) test, FibroScan, and MR elastography. The recommended surveillance modality is abdominal ultrasound (US), which is cost effective and noninvasive with good sensitivity. However, US is limited in obese patients and those with NAFLD. In NAFLD patients with a high likelihood of having an inadequate US, or if an US is attempted but inadequate, CT or MRI may be utilized. The GALAD score, consisting of age, gender, AFP, the lens culinaris-agglutinin-reactive fraction of AFP (AFP-L3), and the protein induced by the absence of vitamin K or antagonist-II (PIVKA-II), can help identify a high risk of HCC in NAFLD patients. Innovative parameters, including a Mac-2 binding protein glycated isomer, type IV collagen 7S, free apoptosis inhibitor of the macrophage, and a combination of single nucleoside polymorphisms, are expected to be established. Considering the large size of the NAFLD population, optimal screening tests must meet several criteria, including high sensitivity, cost effectiveness, and availability. Full article
(This article belongs to the Special Issue Fatty Liver Disease: Diagnostic, Predictive and Prognostic Markers)
Show Figures

Figure 1

Back to TopTop