Contents
Special Issue Topic

Exploring NAFLD/NASH

Guest Editors

Dr. Amedeo Lonardo E-Mail

Director of Simple Operating Unit, Ospedale Civile di Baggiovara, Azienda Ospedaliero-Universitaria di Modena, Modena, Italy

Research Keywords: NAFLD, NASH, cirrhosis, HCC

Dr. Giovanni Targher E-Mail

Section of Endocrinology and Metabolism, Department of Medicine, University of Verona, Verona, Italy

Research Keywords: Role of NAFLD in cardiovascular morbidity/mortality, role of NAFLD in microvascular complications of diabetes

About the Special lssue

Exploration of Medicine (EM) is a novel peer-reviewed, open access, online journal. It publishes articles that provide substantial and novel insights into medicine spanning molecular and cell biology through research of all human diseases. The journal adopts a single-blind peer review. Those authors who publish for EM hold the copyright of their works, make their original works completely available and free to use as long as the authors and the original source are properly cited.

EM has charged two Associate Editors, Dr. Lonardo (Gastroenterology & Hepatology) and Professor Targher (Endocrinology & Metabolism) to edit a special issue dedicated to nonalcoholic fatty liver disease (NAFLD). Why has this topic been chosen? NAFLD defines a spectrum of hepatic (steatosis, nonalcoholic steatohepatitis [NASH], cirrhosis and hepatocellular carcinoma) and extra-hepatic manifestations (nephro-cardio-metabolic diseases and extra-hepatic cancers) that occur in individuals free of any competing causes of hepatic steatosis (e.g., alcohol, virus, drugs and others) but who often have concurrent dysmetabolic features. NAFLD is the most common chronic liver disease worldwide, causes considerable health care expenses, requests a heavy toll in terms of morbidity and premature mortality and has, therefore, gained considerable scientific interest. Areas of ongoing research include epidemiological features and risk factors, (molecular) pathogenesis, (non-invasive) diagnosis, government of the patients fluxes from primary to specialist care as well as management of this burdensome liver disease with lifestyle modifications and innovative drugs that are being evaluated.

In order to provide a virtual forum for exchange of ideas and data in Academic as well as in Translational and Clinical research, Dr. Lindsay Farrer, the Editor-in-Chief of EM, has invited Doctors Lonardo and Targher to edit this single-topic issue.

Keywords: NAFLD, NASH, HCC, cirrhosis

Published Articles

Open Access Review
Pediatric vs. adult NAFLD to MAFLD transition: a welcome but tangled path
The term non-alcoholic fatty liver disease (NAFLD) appears unfitting both in adults and in children. As obesity and metabolic syndrome play a relevant pathogenic role, an international group of adults’ liver disease experts has proposed to rename this condition metabolic (dysfunction)-associated fatty liver disease (MAFLD). While this new more appropriate and useful definition has mostly been met with good reactions in adults, it may present a tangled path in pediatrics.
Published: August 31, 2021 Explor Med. 2021;2:333–342
3334 95 2
Open Access Review
Sex hormones abnormalities in non-alcoholic fatty liver disease: pathophysiological and clinical implications
Obesity and metabolic syndrome are conditions at high risk for the development of complications such as type 2 diabetes mellitus, atherosclerotic cardiovascular disease, and non-alcoholic fatty liver disease (NAFLD). The growing prevalence of NAFLD has recently raised attention in the clinical practice, due to the worsening prognosis observed in the affected patients. Sex hormones abnormalities, commonly found in subjects suffering from obesity and metabolic syndrome, have been recently hypothesized to be directly involved in the physiopathology of obesity-related comorbidites;
Published: August 31, 2021 Explor Med. 2021;2:311–323
5600 86 0
Open Access Review
Cardiovascular involvement after liver transplantation: role of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis
Patients submitted to liver transplantation (LT) are exposed to high risk of cardiovascular (CV) complications which are the main determinants of both short-term and long-term morbidity and mortality in LT. Non-alcoholic fatty liver disease (NAFLD) is a very frequent condition in general population and is associated with a high risk of cardiovascular disease (CVD) which represents the first cause of death of these patients. NAFLD is predicted to become the first indication to LT and nowadays is also frequently detected in patients submitted to LT for other indications.
Published: February 28, 2021 Explor Med 2021;2:20–38
3282 41 0
Open Access Review
The diagnostic conundrum in non-alcoholic fatty liver disease
Non-alcoholic fatty liver disease (NAFLD) has become the most common liver alteration worldwide. It encompasses a spectrum of disorders that range from simple steatosis to a progressive form, defined non-alcoholic steatohepatitis (NASH), that can lead to advanced fibrosis and eventually cirrhosis and hepatocellular carcinoma. On liver histology, NASH is characterized by the concomitant presence of significant fat accumulation and inflammatory reaction with hepatocellular injury.
Published: October 30, 2020 Explor Med. 2020;1:259–286
7832 188 6
Open Access Review
Nonalcoholic fatty liver disease and type 2 diabetes: pathophysiological mechanisms shared between the two faces of the same coin
The pathophysiological mechanisms underlying the close relationship between nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM) are multiple, complex and only partially known. The purpose of this paper was to review the current knowledge of these mechanisms in a unified manner. Subjects with NAFLD and T2DM have established insulin resistance (IR), which exacerbates the two comorbidities.
Published: October 30, 2020 Explor Med. 2020;1:287–306
9603 341 54
Open Access Review
Non-alcoholic fatty liver disease and transient elastography
Nonalcoholic fatty liver disease (NAFLD) is a serious condition that can lead to fibrosis, cirrhosis, and hepatocellular carcinoma. NAFLD is associated with metabolic syndrome (MetS) and all of its components. According to data, around 25–30% of population has NAFLD. Giving the growing incidence of MetS, obesity and diabetes mellitus type 2, NAFLD related terminal-stage liver disease is becoming prevailing indication for liver transplantation. In order to prevent terminal stage of this disease, it is crucial to determine those that are in risk group, to modify their risk factors and monitor their potential progression.
Published: August 31, 2020 Explor Med. 2020;1:205–217
6249 81 4
Open Access Review
Role of acetylation in nonalcoholic fatty liver disease: a focus on SIRT1 and SIRT3
Nonalcoholic fatty liver disease (NAFLD) has become the most prevalent liver chronic disease worldwide. The pathogenesis of NAFLD is complex and involves many metabolic enzymes and multiple pathways. Posttranslational modifications of proteins (PMPs) added another layer of complexity to the pathogenesis of NAFLD. PMPs change protein properties and regulate many biological functions, including cellular localization, stability, intracellular signaling, and protein function.
Published: August 31, 2020 Explor Med. 2020;1:248–258
5894 113 9
Open Access Review
Genetic and metabolic factors: the perfect combination to treat metabolic associated fatty liver disease
The prevalence of nonalcoholic or more recently re-defined metabolic associated fatty liver disease (MAFLD) is rapidly growing worldwide. It is characterized by hepatic fat accumulation exceeding 5% of liver weight not attributable to alcohol consumption. MAFLD refers to an umbrella of conditions ranging from simple steatosis to nonalcoholic steatohepatitis which may finally progress to cirrhosis and hepatocellular carcinoma. MAFLD is closely related to components of the metabolic syndrome and to environmental factors.
Published: August 31, 2020 Explor Med. 2020;1:218–243
5823 111 4
Open Access Review
The therapeutic potential of C-C chemokine receptor antagonists in nonalcoholic steatohepatitis
Pooled prevalence of nonalcoholic fatty liver disease (NAFLD) globally is about 25%. Nonalcoholic steatohepatitis (NASH) with advanced fibrosis has been linked with substantial morbidity and mortality, without having to-date any licensed treatment. C-C chemokine receptor (CCR) antagonists have been investigated as candidates for the treatment of NASH. Inhibition of CCR2 is expected to mitigate hepatic inflammation, through reducing the activation of Kupffer cells, as well as the infiltration of monocytes and macrophages into the liver.
Published: August 31, 2020 Explor Med. 2020;1:170–183
5283 72 5
Open Access Review
Perspectives of nonalcoholic fatty liver disease research: a personal point of view
Rational government of patient fluxes from primary care to hepatology clinic is a priority of nonalcoholic fatty liver disease (NAFLD) research. Estimating pre-test probability of disease, risk of fibrosis progression, and exclusion of competing causes of liver disease must be addressed. Here we propose a novel taxonomic classification of NAFLD based on hepatic, pathogenic and systemic features of disease in the individual patient. The variable course of disease in any given patient remains a clinical enigma.
Published: June 29, 2020 Explor Med. 2020;1:85–107
8754 130 25
Open Access Review
Nonalcoholic fatty liver disease and portal hypertension
Nonalcoholic fatty liver disease (NAFLD) is a substantial and growing problem worldwide and has become the second most common indication for liver transplantation as it may progress to cirrhosis and develop complications from portal hypertension primarily caused by advanced fibrosis and erratic tissue remodeling. However, elevated portal venous pressure has also been detected in experimental models of fatty liver and in human NAFLD when fibrosis is far less advanced and cirrhosis is absent.
Published: June 29, 2020 Explor Med. 2020;1:149–169
9359 139 29
Open Access Review
Sex differences in non-alcoholic fatty liver disease: hints for future management of the disease
Non-alcoholic fatty liver disease (NAFLD) remains a major cause of chronic liver disease worldwide. Despite extensive studies, the heterogeneity of the risk factors as well as different disease mechanisms complicate the goals toward effective diagnosis and management. Recently, it has been shown that sex differences play a role in the prevalence and progression of NAFLD.
Published: April 30, 2020 Explor Med. 2020;1:51–74
12415 252 20