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Medicina
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Non-alcoholic Fatty Liver Disease – from Bench to the Bedside
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Non-alcoholic Fatty Liver Disease – from Bench to the Bedside

A special issue of Medicina (ISSN 1648-9144). This special issue belongs to the section "Gastroenterology & Hepatology".

Deadline for manuscript submissions: closed (31 December 2021) | Viewed by 24567

Special Issue Editors

Prof. Sandra Milić

E-Mail Website
Guest Editor
Department of Gastroenterology, University Hospital Rijeka, Faculty of Medicine, Rijeka, Croatia
Interests: nonalcoholic fatty liver disease and complications; metabolic liver diseases; chronic viral hepatitis; endoscopic ultrasound
Prof. Bojan Tepeš

E-Mail Website
Guest Editor
AM DC Rogaška, Rogaška Slatina, Faculty of Medicine, Ljubljana, Slovenia
Interests: alcohol liver disease; colorectal cancer screening; Helicobacter pylori infection; chronic pancreatitis

Special Issue Information

Nonalcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease in the world, parallel to the increasing prevalence of diabetes mellitus type 2 (T2DM) and obesity and exhibiting a close relationship with insulin resistance (IR) and metabolic risk factors, with an estimated prevalence of 10–40%. Presentation of the disease ranges from simple steatosis to nonalcoholic steatohepatitis (NASH). NAFLD is a hepatic manifestation of metabolic syndrome (MetS). Up to 80% of patients with NAFLD are obese, defined as a body mass index (BMI) >30 kg/m. The distribution of fat tissue plays a greater role in IR than BMI. The presence of inflammation is relevant for predicting the progression of the liver disease and the development of complications (cirrhosis and hepatocellular carcinoma), as well as in the context of the presence and development of extrahepatic manifestations of NAFLD. Due to the increased incidence of metabolic syndrome (MetS) and its components, NASH cirrhosis and hepatocellular carcinoma will soon become a major indication for liver transplantation. Since there are currently no medications directly used for the treatment of more advanced NAFLD stages, the central focus is on the ongoing and recently completed clinical trials testing promising drugs for NASH resolution. This Special Issue welcomes manuscripts addressing any aspects of NAFLD research and treatment.

Prof. Sandra Milić
Prof. Bojan Tepeš
Guest Editors

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Keywords

  • nonalcoholic fatty liver disease
  • nonalcoholic steatohepatitis
  • pathogenesis
  • complications
  • treatment
  • diagnostic tests

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Published Papers (7 papers)

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Research

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8 pages, 996 KiB  
Article
Nash Up, Virus Down: How the Waiting List Is Changing for Liver Transplantation: A Single Center Experience from Italy
by Alberto Ferrarese, Sara Battistella, Giacomo Germani, Francesco Paolo Russo, Marco Senzolo, Martina Gambato, Alessandro Vitale, Umberto Cillo and Patrizia Burra
Medicina 2022, 58(2), 290; https://doi.org/10.3390/medicina58020290 - 14 Feb 2022
Cited by 9 | Viewed by 2518
Abstract
Background and Objectives: Non-alcoholic steatohepatitis (NASH) has become the leading indication for liver transplantation in many countries, with a growing rate in the Western world. NASH patients are older and share a higher risk of comorbidities and cancer than patients with viral [...] Read more.
Background and Objectives: Non-alcoholic steatohepatitis (NASH) has become the leading indication for liver transplantation in many countries, with a growing rate in the Western world. NASH patients are older and share a higher risk of comorbidities and cancer than patients with viral and/or alcoholic etiologies. The aims of this study were to evaluate waiting list (WL) registration and liver transplantation rates in patients with NASH-related cirrhosis at Padua University Hospital in the last fifteen years (1.2006–6.2020) and to compare clinical characteristics and indications for liver transplantation between patients with and without NASH, as well as the WL survival and post-transplant outcome. Materials and Methods: All adult patients with cirrhosis listed for liver transplantation at Padua University Hospital between 1.2006 and 6.2020 were retrospectively collected using a prospectively updated database; patients with NASH-related cirrhosis were divided by indication for liver transplantation (Dec-NASH vs. hepatocellular carcinoma (HCC)-NASH) and compared with patients with other etiologies of liver disease. The outcomes in terms of waiting list survival and post-transplant outcome were assessed. Results: One thousand four hundred and ninety-one adult cirrhotic patients were waitlisted during the study period. NASH patients accounted for 12% of all WL registrations, showing an increasing trend over time (from 2.5% in 2006 to 23% in 2020). In the last five years, NASH was the third, but most rapidly growing, indication for liver transplantation at our center. This trend was confirmed both for patients with decompensated cirrhosis (from 1.8% to 18%) and HCC as leading indication for transplantation (from 4% to 30%). NASH patients were older than non-NASH ones (mean ± SD age 59 ± 9 vs. 56 ± 9 years; p < 0.01), whereas no difference was found in gender or Child-Pugh of the model for end-stage liver disease score at WL registration. A majority (60.9%) of NASH patients underwent liver transplantation, showing 1-, 5- and 10-y post-transplant survivals of 86%, 73% and 60%, respectively. Conclusion: NASH cirrhosis has become a rapidly growing indication for liver transplantation at our center, both for HCC and decompensated disease, with good post-transplant survival. Full article
(This article belongs to the Special Issue Non-alcoholic Fatty Liver Disease – from Bench to the Bedside)
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14 pages, 620 KiB  
Article
The Accuracy of Serum Biomarkers in the Diagnosis of Steatosis, Fibrosis, and Inflammation in Patients with Nonalcoholic Fatty Liver Disease in Comparison to a Liver Biopsy
by Ivana Mikolasevic, Viktor Domislovic, Irena Krznaric-Zrnic, Zeljko Krznaric, Lucija Virovic-Jukic, Sanja Stojsavljevic, Ivica Grgurevic, Sandra Milic, Ivan Vukoja, Petra Puz, Merica Aralica and Goran Hauser
Medicina 2022, 58(2), 252; https://doi.org/10.3390/medicina58020252 - 8 Feb 2022
Cited by 5 | Viewed by 3028
Abstract
Background and Objective: This study was conducted to evaluate the diagnostic performance of various biomarkers for steatosis, fibrosis, and inflammation in comparison to a liver biopsy (LB) in patients with nonalcoholic fatty liver disease (NAFLD). Materials and Methods: This was a cross-sectional [...] Read more.
Background and Objective: This study was conducted to evaluate the diagnostic performance of various biomarkers for steatosis, fibrosis, and inflammation in comparison to a liver biopsy (LB) in patients with nonalcoholic fatty liver disease (NAFLD). Materials and Methods: This was a cross-sectional study that included 135 patients with biopsy-proven NAFLD. Fatty liver index (FLI), hepatic steatosis index (HSI), cell death markers (CK-18 M30 and CK-18 M65), FIB-4 index, NAFLD fibrosis score (NFS), BARD, and AST to platelet ratio index (APRI) were calculated and analysed. Results: FLI, HSI scores, and the cell death biomarkers showed poor diagnostic accuracy for steatosis detection and quantification, with an area under the curve (AUC) of <0.70. The cell death biomarkers likewise did not perform well for the detection of nonalcoholic steatohepatitis (NASH) (AUC < 0.7). As for the fibrosis staging, only APRI and the cell death biomarkers had moderate accuracy (AUC > 0.7) for advanced fibrosis, whereas FIB-4, BARD, and NFS scores demonstrated poor performance (AUC < 0.70). However, a combination of FIB-4 and NFS with the cell death biomarkers had moderate accuracy for advanced (≥F3) fibrosis detection, with an AUC of >0.70. Conclusions: In this first study on Croatian patients with NAFLD, serum biomarkers demonstrated poor diagnostic performance for the noninvasive diagnosis of liver steatosis and NASH. APRI and the cell death biomarkers had only moderate accuracy for diagnosing advanced fibrosis, as did the combination of FIB-4 and NFS with the cell death biomarkers. Further studies regarding serum biomarkers for all NAFLD stages are needed. Full article
(This article belongs to the Special Issue Non-alcoholic Fatty Liver Disease – from Bench to the Bedside)
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7 pages, 277 KiB  
Article
Colonic Diverticulosis and Non-Alcoholic Fatty Liver Disease: Is There a Connection?
by Ivana Pantic, Sofija Lugonja, Nina Rajovic, Igor Dumic and Tamara Milovanovic
Medicina 2022, 58(1), 38; https://doi.org/10.3390/medicina58010038 - 27 Dec 2021
Cited by 9 | Viewed by 4616
Abstract
Background and Objectives: The development and severity of colonic diverticulosis and non-alcoholic fatty liver disease (NAFLD) has been associated with several components of metabolic syndrome (MetS). Therefore, this study aimed to evaluate a possible connection between NAFLD, colonic diverticulosis, and MetS. Materials and [...] Read more.
Background and Objectives: The development and severity of colonic diverticulosis and non-alcoholic fatty liver disease (NAFLD) has been associated with several components of metabolic syndrome (MetS). Therefore, this study aimed to evaluate a possible connection between NAFLD, colonic diverticulosis, and MetS. Materials and Methods: This retrospective study included patients diagnosed with diverticulosis between January 2017 and December 2019. Data regarding the patient demographics, Diverticular Inflammation and Complication Assessment (DICA) score and category, disease localization, hepatic steatosis, blood pressure, comprehensive metabolic panel, need for colonic surgery, and co-morbidities were collected from medical records. Results: A total of 407 patients with a median age of 68 years (range, 34–89 years) were included (male: 53.81%). The majority was diagnosed with left-sided diverticulosis (n = 367, 90.17%) and an uncomplicated disease course (DICA category 1, n = 347, 85.3%). Concomitant hepatic steatosis was detected in 47.42% (n = 193) of patients. The systolic blood pressure, triglycerides, total cholesterol, C-reactive protein (CRP), and fasting glucose were higher in the NAFLD group (p < 0.001, p < 0.001, p < 0.001, p < 0.001, and p < 0.001, respectively). A higher prevalence of hypertension (HTA), type 2 diabetes mellitus (T2DM), and hypothyroidism was noted in the same group of patients (p < 0.001, p < 0.001, and p = 0.008, respectively). High-density lipoprotein cholesterol was lower in patients with more severe forms of diverticulosis (DICA category 2 and 3), while CRP levels were significantly higher (p = 0.006 and p = 0.015, respectively). HTA and NAFLD were more common in patients with more severe forms of colonic diverticulosis (p = 0.016 and p = 0.025, respectively). Using a multivariate logistic regression, the DICA score, CRP, total cholesterol, HTA, and hypothyroidism were identified as discriminating factors for the presence of hepatic steatosis. Conclusion: Components of metabolic dysregulation were prominent in patients diagnosed with colonic diverticulosis and concomitant hepatic steatosis. HTA, T2DM, and hypothyroidism were more frequently observed in this group. Hepatic steatosis was more commonly detected in more severe forms of colonic diverticulosis. Full article
(This article belongs to the Special Issue Non-alcoholic Fatty Liver Disease – from Bench to the Bedside)
13 pages, 502 KiB  
Article
Association between the Severity of Nonalcoholic Fatty Liver Disease and the Risk of Coronary Artery Calcification
by Chien-Chih Chen, Wei-Chien Hsu, Han-Ming Wu, Jiun-Yi Wang, Pei-Yu Yang and I-Ching Lin
Medicina 2021, 57(8), 807; https://doi.org/10.3390/medicina57080807 - 6 Aug 2021
Cited by 5 | Viewed by 2617
Abstract
Background and Objectives: There are limited data on the association between severity of non-alcoholic fatty liver disease (NAFLD) and coronary artery calcification. This study investigated sonographic diagnosed NAFLD and coronary artery calcium score (CAC) as detected by cardiac multidetector computed tomography in [...] Read more.
Background and Objectives: There are limited data on the association between severity of non-alcoholic fatty liver disease (NAFLD) and coronary artery calcification. This study investigated sonographic diagnosed NAFLD and coronary artery calcium score (CAC) as detected by cardiac multidetector computed tomography in general populations. Materials and Methods: A total of 545 patients were enrolled in this study. NAFLD was diagnosed by ultrasonography examination and CAC score were evaluated by cardiac multidetector computed tomography. The association between NAFLD and artery calcium score stage was determined by logistic regression analysis and Spearman correlation coefficient analysis. Results: Of all the participants, 437 (80.2%) had ultrasonography-diagnosed NAFLD and 242 (44%) had coronary artery calcification (CAC > 0). After adjustment for cardiovascular risk factors, the risk of developing coronary artery calcification was 1.36-fold greater in the patients with different severity of NAFLD compared to those without NAFLD (OR = 1.36, 95% CI = 1.07–1.77, p = 0.016). The highest OR for separate coronary artery calcification was 1.98 (OR = 1.98, 95% CI = 1.37–2.87, p < 0.001) in the left main artery, and the risk was still 1.71-fold greater after adjustments (OR = 1.71, 95% CI = 1.16–2.54, p = 0.007). Conclusions: This cross-sectional study demonstrated that the severity of NAFLD was associated with the presence of significant coronary artery calcification, especially in the left main coronary artery, suggesting increasing the cardiovascular risk. Full article
(This article belongs to the Special Issue Non-alcoholic Fatty Liver Disease – from Bench to the Bedside)
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Review

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9 pages, 459 KiB  
Review
Non-Alcoholic Fatty Liver Disease and COVID-19–Two Pandemics Hitting at the Same Time
by Luka Vranić, Anja Radovan, Goran Poropat, Ivana Mikolašević and Sandra Milić
Medicina 2021, 57(10), 1057; https://doi.org/10.3390/medicina57101057 - 3 Oct 2021
Cited by 13 | Viewed by 3143
Abstract
The COVID-19 pandemic was and still is a global burden with more than 178,000,000 cases reported so far. Although it mainly affects respiratory organs, COVID-19 has many extrapulmonary manifestations, including, among other things, liver injury. Many hypotheses have been proposed to explain direct [...] Read more.
The COVID-19 pandemic was and still is a global burden with more than 178,000,000 cases reported so far. Although it mainly affects respiratory organs, COVID-19 has many extrapulmonary manifestations, including, among other things, liver injury. Many hypotheses have been proposed to explain direct and indirect impacts of the SARS-CoV-2 virus on the liver. Studies have shown that around 15–30% of patients with COVID-19 have underlying liver disease, and 20–35% of patients with COVID-19 had altered liver enzymes at admission. One of the hypotheses is reactivation of an underlying liver disease, such as non-alcoholic fatty liver disease (NAFLD). Some studies have shown that NAFLD is associated with severe COVID-19 and poor outcome; nevertheless, other studies showed no significant difference between groups in comparing complications and clinical outcomes. Patients with NAFLD may suffer severe COVID-19 due to other comorbidities, especially cardiovascular diseases. The link between NAFLD and COVID-19 is not clear yet, and further studies and research are needed. Full article
(This article belongs to the Special Issue Non-alcoholic Fatty Liver Disease – from Bench to the Bedside)
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15 pages, 769 KiB  
Review
Non-Alcoholic Fatty Liver Disease in Children
by Jernej Brecelj and Rok Orel
Medicina 2021, 57(7), 719; https://doi.org/10.3390/medicina57070719 - 16 Jul 2021
Cited by 11 | Viewed by 4646
Abstract
Background and Objectives: The prevalence of pediatric non-alcoholic fatty liver disease is increasing. A lot of new data are published regularly. Materials and Methods: Original clinical studies, review articles, and guidelines in children were searched for and the most relevant included [...] Read more.
Background and Objectives: The prevalence of pediatric non-alcoholic fatty liver disease is increasing. A lot of new data are published regularly. Materials and Methods: Original clinical studies, review articles, and guidelines in children were searched for and the most relevant included in this review. Results: A total of 138 retrieved papers were classified into pathogenesis, epidemiology, diagnosis, and treatment. Pathogenesis is currently explained with the “multi hit hypothesis”, with complex interactions of genetic and environmental factors which trigger inflammation in steatotic liver. The prevalence is rising. A diagnosis can be made with laboratory tests, imaging, and liver biopsy after the exclusion of other causes of liver steatosis. The mainstay of treatment is lifestyle modification consisting of dietary intervention and increased physical activity. The progression to liver cirrhosis can occur even in children. Conclusions: Non-alcoholic fatty liver disease in children is a part of a metabolic syndrome in the majority of patients. Due to its complex etiology and high prevalence, multidisciplinary teams, together with public health professionals, should be involved in its treatment. Full article
(This article belongs to the Special Issue Non-alcoholic Fatty Liver Disease – from Bench to the Bedside)
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13 pages, 1200 KiB  
Review
Ultrasound Elastography—Cornerstone of Non-Invasive Metabolic Dysfunction-Associated Fatty Liver Disease Assessment
by Andrej Hari
Medicina 2021, 57(6), 516; https://doi.org/10.3390/medicina57060516 - 21 May 2021
Cited by 1 | Viewed by 3040
Abstract
Metabolic dysfunction-associated fatty liver disease has become the most common chronic liver disease as well as the most common cause for liver transplantation. With its different methods types, elastography of the liver can be used for non-invasive evaluation of the liver fibrosis and [...] Read more.
Metabolic dysfunction-associated fatty liver disease has become the most common chronic liver disease as well as the most common cause for liver transplantation. With its different methods types, elastography of the liver can be used for non-invasive evaluation of the liver fibrosis and steatosis degree. The article focuses on the description, use, advantages, and limitations of the currently known elastographic techniques. It proposes a simple risk assessment algorithm for the liver fibrosis progress evaluation. The following is an overview of the use of liver and spleen elastography in the detection of clinically relevant portal hypertension. It concludes with research and technological possibilities that could be important to the field in the upcoming years. Full article
(This article belongs to the Special Issue Non-alcoholic Fatty Liver Disease – from Bench to the Bedside)
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