Special Issue "Diagnosing NAFLD: Which Tool, Where, When and Why to Use It"

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 2020).

Special Issue Editor

Prof. Dr. Giovanni Tarantino
Website
Guest Editor
Department of Clinical Medicine and Surgery, University of Naples Federico II | UNINA, Naples, Italy
Interests: nonalcoholic fatty liver disease; metabolic syndrome; obesity; atherosclerosis and NAFLD; PCOS and NAFLD; HCV-related chronic hepatitis; HCV-related arthritis; therapy of liver cirrhosis; portal hypertension; hepatic encephalopathy; imaging ultrasonography of liver and spleen; psoriatic arthritis and NAFLD; cytokines in obesity
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Special Issue Information

Dear Colleagues,

Non-alcoholic fatty liver disease (NAFLD) is an important cause of chronic liver disease, hepatocellular carcinoma, and liver transplant worldwide. Furthermore, it is associated with increased risk of heart disease, type 2 diabetes (T2DM), chronic kidney disease, and malignancies including, among others, prostate cancer. NAFLD is highly prevalent among patients with obesity and related co-morbidities, such as PCOS and OSAS. The more aggressive form of NAFLD, including non-alcoholic steatohepatitis (NASH) and advanced fibrosis, is linked to high risk for all-cause and liver-related mortality. Weight loss via lifestyle changes comprehending dietary modification and exercise is the first-line intervention used in treating and improving NAFLD/NASH.

Currently, there are no approved pharmacological interventions for NASH, but there are various ongoing trials to try to reduce the progression of this form. The rationale for these efforts consists of separating simple fatty liver from NASH. However, there are at least three schools of thought on that approach: The first one is the aforementioned. The second one emphasizes the preventive approach, thus promptly diagnosing the simple form (i.e., NAFLD). The third addresses the major causes of NAFLD/NASH (i.e., obesity (mainly abdominal) and T2DM) in the very initial phase. For this very reason, the discovery of NAFLD/NASH is of pivotal importance. Nevertheless, the skyrocketing health costs of this disease force physicians and health care providers to find simple and possibly inexpensive tools to apply, even though they do not always have complete reliability in diagnosing such diseases.

Prof. Dr. Giovanni Tarantino
Guest Editor

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Keywords

  • Histology: Liver Biopsy
  • Imaging: CT, MRI, MRE, PDFF, Ultrasound, TE, ARFI
  • Surrogate markers: NAFLD ridge score, NAFLD liver Fat Score, Hepatic steatosis Index, Fatty Liver Index, Lipid accumulation product index, FLIP algoritm, CHeK score, NFS, Fib-4, APRI, BARD score, ELF, Hepascore, Fibrotest, fibroSURE/Actitest, FibroMeter NAFLD index
  • Micro RNA, polymorfisms, cytokines, growth factors, hormones, genomics, transcriptomics, lipidomics, proteomics, and metabolomics

Published Papers (5 papers)

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Research

Open AccessArticle
Liver Fibrosis Biomarkers Accurately Exclude Advanced Fibrosis and Are Associated with Higher Cardiovascular Risk Scores in Patients with NAFLD or Viral Chronic Liver Disease
Diagnostics 2021, 11(1), 98; https://doi.org/10.3390/diagnostics11010098 - 09 Jan 2021
Abstract
Liver fibrosis predicts liver-related and cardiovascular outcomes in chronic liver disease patients. We compared the diagnostic performance of various liver fibrosis biomarkers for identifying histological significant/advanced fibrosis. Additionally, the correlations of such liver fibrosis biomarkers with cardiovascular risk (CVR) scores were evaluated. 173 [...] Read more.
Liver fibrosis predicts liver-related and cardiovascular outcomes in chronic liver disease patients. We compared the diagnostic performance of various liver fibrosis biomarkers for identifying histological significant/advanced fibrosis. Additionally, the correlations of such liver fibrosis biomarkers with cardiovascular risk (CVR) scores were evaluated. 173 patients with viral hepatitis (157 HCV and 16 HBV) and 107 with a non-alcoholic fatty liver disease (NAFLD) were consecutively enrolled. Various liver fibrosis biomarkers: aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio (ARR), AST to Platelet Ratio Index (APRI), Fibrosis-4 (FiB-4), Forns index, NAFLD fibrosis score (NFS), BARD (body mass index (BMI), AAR, Diabetes) score, and Hepamet fibrosis score (HFS), were used to identify significant/advanced fibrosis. CVR was assessed by using the SCORE, the Progetto CUORE, or the Framingham risk scoring systems. Liver fibrosis biomarkers performed better in predicting advanced rather than significant liver fibrosis in all patients, regardless of chronic liver disease aetiology. Forns index and HFS performed best in predicting advanced fibrosis in patients with viral chronic liver disease and NAFLD. Lower cut-offs of these liver fibrosis biomarkers had high negative predictive values for advanced fibrosis overall, as well as in patients with NAFLD or viral chronic liver disease. FIB-4, Forns index, NFS, and HFS were positively correlated with SCORE and Framingham risk scores. In conclusion, liver fibrosis biomarkers accurately exclude advanced fibrosis and positively correlate with CVR scores in patients with chronic liver disease. Full article
(This article belongs to the Special Issue Diagnosing NAFLD: Which Tool, Where, When and Why to Use It)
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Open AccessArticle
Periostin Circulating Levels and Genetic Variants in Patients with Non-Alcoholic Fatty Liver Disease
Diagnostics 2020, 10(12), 1003; https://doi.org/10.3390/diagnostics10121003 - 25 Nov 2020
Abstract
Circulating periostin has been suggested as a possible biomarker in non-alcoholic fatty liver disease (NAFLD) in Asian studies. In the present study, we aimed to test its still controversial relevance in a Caucasian population. In patients with histologically-proven NAFLD (N. = 74; 10 [...] Read more.
Circulating periostin has been suggested as a possible biomarker in non-alcoholic fatty liver disease (NAFLD) in Asian studies. In the present study, we aimed to test its still controversial relevance in a Caucasian population. In patients with histologically-proven NAFLD (N. = 74; 10 with hepatocellular carcinoma, HCC) plasma periostin concentrations were analyzed. POSTN haplotype analysis was based on rs9603226, rs3829365, and rs1029728. Hepatitis C patients (N. = 81, 7 HCC) and healthy subjects (N. = 27) were used as controls. The median plasma periostin concentration was 11.6 ng/mL without differences amongst groups; it was not influenced by age, liver fibrosis or steatosis. However, possession of haplotype two (rs9603226 = G, rs3829365 = C, rs1028728 = A) was associated with lower circulating periostin compared to other haplotypes. Moreover, periostin was higher in HCC patients. At multivariate analysis, HCC remained the only predictor of high periostin. In conclusion, plasma periostin concentrations in Caucasians NAFLD patients are not influenced by the degree of liver disease, but are significantly higher in HCC. Genetically-determined differences may account for some of the variability. These data suggest extreme caution in predicting a possible future role of periostin antagonists as a rational therapeutic alternative for NAFLD, but show a potential periostin role in the management of NAFLD-associated HCC. Full article
(This article belongs to the Special Issue Diagnosing NAFLD: Which Tool, Where, When and Why to Use It)
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Open AccessArticle
Liver Biopsy Hydroxyproline Content Is a Diagnostic for Hepatocellular Carcinoma in Murine Models of Nonalcoholic Steatohepatitis
Diagnostics 2020, 10(10), 784; https://doi.org/10.3390/diagnostics10100784 - 04 Oct 2020
Abstract
There is increasing evidence that nonalcoholic steatohepatitis (NASH) is a risk factor for hepatocellular carcinoma (HCC) in the absence of cirrhosis, a phenomenon termed noncirrhotic HCC. Early diagnosis of HCC is critical to a favorable prognosis. We tested the hypothesis that hydroxyproline content [...] Read more.
There is increasing evidence that nonalcoholic steatohepatitis (NASH) is a risk factor for hepatocellular carcinoma (HCC) in the absence of cirrhosis, a phenomenon termed noncirrhotic HCC. Early diagnosis of HCC is critical to a favorable prognosis. We tested the hypothesis that hydroxyproline content of liver biopsy samples is diagnostic for HCC in murine models of NASH induced by diet or by diet and chemicals. The training set comprised mice fed a standard diet or a fast-food diet with or without administration of thioacetamide. At harvest, livers from the modified diet cohort exhibited NASH with a subset of NASH livers exhibiting HCC. Hydroxyproline content was measured in liver biopsy samples with tissue in the NASH+HCC cohort sampled from the remote, nontumor parenchyma. Plotting the receiver operating characteristics (ROC) with hydroxyproline as the continuous variable against the absence or presence of HCC yielded an area under ROC of 0.87, a threshold of >0.18 μg hydroxyproline/mg liver and sensitivity of 91% with a specificity of 83.3%. The use of liver hydroxyproline content as a diagnostic for HCC in a test set comprising healthy, NASH and NASH+HCC livers proved 87% accurate. Full article
(This article belongs to the Special Issue Diagnosing NAFLD: Which Tool, Where, When and Why to Use It)
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Open AccessArticle
Could SCGF-Beta Levels Be Associated with Inflammation Markers and Insulin Resistance in Male Patients Suffering from Obesity-Related NAFLD?
Diagnostics 2020, 10(6), 395; https://doi.org/10.3390/diagnostics10060395 - 11 Jun 2020
Cited by 1
Abstract
One of the pathologic hallmarks of obesity is macrophage infiltration of adipose tissue that has been confirmed as source of multipotent adult stem cells. Stem cell growth factor-beta (SCGF-β) shows activity on granulocyte/macrophage progenitor cells in combination with granulocyte macrophage colony-stimulating factor (GM-CSF) [...] Read more.
One of the pathologic hallmarks of obesity is macrophage infiltration of adipose tissue that has been confirmed as source of multipotent adult stem cells. Stem cell growth factor-beta (SCGF-β) shows activity on granulocyte/macrophage progenitor cells in combination with granulocyte macrophage colony-stimulating factor (GM-CSF) and macrophage colony-stimulating factor (M-CSF). Obesity-associated inflammation induces insulin resistance (IR), which is central to nonalcoholic fatty liver disease (NAFLD) or hepatic steatosis (HS). We searched for relationship between levels of SCGF-β and those of C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-β (TNF-β), interleukin-12p40 (IL-12p40), interleukin-10 (IL-10), ferritin, GM-CSF and M-CSF and between SCGF-β concentrations and IR in obese patients with HS. Eighty obese patients were retrospectively studied. Serum cytokines levels were appreciated by magnetic bead-based multiplex immunoassays. IR was evaluated by homeostatic model assessment (HOMA), HOMA-derived β-cell function (HOMA-B%), quantitative insulin sensitivity check Index (QUICKI) and single point insulin sensitivity estimator (SPISE). HS and spleen volume were assessed by ultrasonography (US). SCGF-β and IL-6 levels predicted HOMA values (p = 0.032 and 0.041, respectively) only in males. In male patients, CRP and IL-6 levels (p = 0.007) predicted SCGF-β concentrations (p = 0.03 and 0.007, respectively), which in turn predicted HS at US, p = 0.037. SCGF-β levels were linked to IR and HS severity with the mediation role of CRP. IL-10 levels negatively predicted SCGF-β concentrations (p = 0.033). M-CSF levels predicted serum concentration of both TNF-β and IL-12p40 (p = 0.00), but did not predict serum IL-10 (p = 0.30). Prediction of HOMA values by SCGF-β levels, likely mediated by markers of inflammation, characterizes this study, shedding some light on mechanisms inducing/worsening IR of male patients with obesity-related NAFLD. Full article
(This article belongs to the Special Issue Diagnosing NAFLD: Which Tool, Where, When and Why to Use It)
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Open AccessArticle
Non-Alcoholic Fatty Liver Disease in Patients with Type 2 Diabetes: Evaluation of Hepatic Fibrosis and Steatosis Using Fibroscan
Diagnostics 2020, 10(3), 159; https://doi.org/10.3390/diagnostics10030159 - 14 Mar 2020
Cited by 3
Abstract
Patients with type 2 diabetes mellitus (T2DM) are at increased risk of non-alcoholic fatty liver disease (NAFLD) and might eventually progress to advanced fibrosis, cirrhosis and hepatocellular carcinoma (HCC). Recommendations on whether to screen for NAFLD in diabetic patients remains conflicted between major [...] Read more.
Patients with type 2 diabetes mellitus (T2DM) are at increased risk of non-alcoholic fatty liver disease (NAFLD) and might eventually progress to advanced fibrosis, cirrhosis and hepatocellular carcinoma (HCC). Recommendations on whether to screen for NAFLD in diabetic patients remains conflicted between major guidelines. Transient elastography using FibroScan with CAP (controlled attenuation parameter) can assess both liver steatosis and fibrosis simultaneously. This paper took a new look at the prevalence of NAFLD and the severity of fibrosis among T2DM patients in Vietnam. The study was conducted using a cross-sectional design in T2DM adults who attended Dai Phuoc Ho Chi Minh Polyclinic and Polyclinic of Pham Ngoc Thach University of Medicine. Liver steatosis and fibrosis was assessed by FibroScan. NAFLD was diagnosed if CAP > 233 dB/m (steatosis > 5%). Data were analyzed using STATA 12 software program. We found that a total of 307 type 2 diabetic patients qualified for the study’s criteria. The prevalence of NAFLD in T2DM patients based on FibroScan was 73.3%. Rates of mild, moderate and severe steatosis were 20.5%, 21.8% and 30.9%, respectively. The prevalence of significant fibrosis (≥ F2), advanced fibrosis (≥ F3) and cirrhosis (F4) was 13.0%, 5.9% and 3.6%, respectively. On multivariate analysis, aspartate aminotransferase (AST) (OR: 1.067; 95% CI: 1.017–1.119; p = 0.008) and platelet levels (OR: 0.985; 95% CI: 0.972–0.999; p = 0.034) were independent of risk factors of advanced fibrosis. Thus, our study supports screening for NAFLD and for evaluating the severity of liver fibrosis in T2DM patients. Full article
(This article belongs to the Special Issue Diagnosing NAFLD: Which Tool, Where, When and Why to Use It)
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