Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Sep 28, 2017; 23(36): 6571-6592
Published online Sep 28, 2017. doi: 10.3748/wjg.v23.i36.6571
Nonalcoholic fatty liver disease: Evolving paradigms
Amedeo Lonardo, Fabio Nascimbeni, Mauro Maurantonio, Alessandra Marrazzo, Luca Rinaldi, Luigi Elio Adinolfi
Amedeo Lonardo, Fabio Nascimbeni, Mauro Maurantonio, Alessandra Marrazzo, Azienda Ospedaliero-Universitaria di Modena, Ospedale Civile di Baggiovara, 41126 Modena, Italy
Fabio Nascimbeni, Alessandra Marrazzo, University of Modena and Reggio Emilia, 41126 Modena, Italy
Luca Rinaldi, Luigi Elio Adinolfi, Department of Medical, Surgical, Neurological, Geriatric, and Metabolic Sciences, University of Campania “Luigi Vanvitelli”, 80100 Naples, Italy
Author contributions: Lonardo A, Nascimbeni F and Adinolfi LE contributed to conception, designed the study, partially wrote the manuscript and made critical revision of the manuscript; Maurantonio M, Marrazzo A and Rinaldi L partially wrote the manuscript; all the authors approved the final version of the manuscript; Lonardo A and Nascimbeni F contributed equally.
Conflict-of-interest statement: There are no conflicts of interest to report.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Correspondence to: Luigi Elio Adinolfi, MD, Professor, Department of Medical, Surgical, Neurological, Metabolic, and Geriatric Sciences, University of Campania, “L. Vanvitelli”, Piazza Miraglia, 80100 Naples, Italy.
Telephone: +39-81-5665081 Fax: +39-81-5665081
Received: July 14, 2017
Peer-review started: July 15, 2017
First decision: August 10, 2017
Revised: August 21, 2017
Accepted: September 5, 2017
Article in press: September 5, 2017
Published online: September 28, 2017

In the last years new evidence has accumulated on nonalcoholic fatty liver disease (NAFLD) challenging the paradigms that had been holding the scene over the previous 30 years. NAFLD has such an epidemic prevalence as to make it impossible to screen general population looking for NAFLD cases. Conversely, focusing on those cohorts of individuals exposed to the highest risk of NAFLD could be a more rational approach. NAFLD, which can be diagnosed with either non-invasive strategies or through liver biopsy, is a pathogenically complex and clinically heterogeneous disease. The existence of metabolic as opposed to genetic-associated disease, notably including ”lean NAFLD” has recently been recognized. Moreover, NAFLD is a systemic condition, featuring metabolic, cardiovascular and (hepatic/extra-hepatic) cancer risk. Among the clinico-laboratory features of NAFLD we discuss hyperuricemia, insulin resistance, atherosclerosis, gallstones, psoriasis and selected endocrine derangements. NAFLD is a precursor of type 2 diabetes (T2D) and metabolic syndrome and progressive liver disease develops in T2D patients in whom the course of disease is worsened by NAFLD. Finally, lifestyle changes and drug treatment options to be implemented in the individual patient are also critically discussed. In conclusion, this review emphasizes the new concepts on clinical and pathogenic heterogeneity of NAFLD, a systemic disorder with a multifactorial pathogenesis and protean clinical manifestations. It is highly prevalent in certain cohorts of individuals who are thus potentially amenable to selective screening strategies, intensive follow-up schedules for early identification of liver-related and extrahepatic complications and in whom earlier and more aggressive treatment schedules should be carried out whenever possible.

Keywords: Nonalcoholic fatty liver disease, Biomarkers, Clinical correlates, Diagnosis, Epidemiology, Genetics, Liver histology, Management, Metabolic Syndrome, Pathogenesis, Screening, Type 2 diabetes

Core tip: Nonalcoholic fatty liver disease (NAFLD) is a pandemic disease. Recent evidence highlights new concepts in clinical and pathogenic heterogeneity of NAFLD, a systemic disorder with a multifactorial pathogenesis and protean clinical manifestations. Other than the classical obese phenotype of NAFLD, a lean though metabolically abnormal variant has been recognized. Simple steatosis is no more considered a benign condition; insulin resistance is necessary but not sufficient for the disease progression, and NAFLD is not only a mere hepatic manifestation of metabolic syndrome, but may forerun the development of metabolic syndrome and cardio-renal complications. Several non-invasive diagnostic tests are now available and new drug treatment options are coming.