Review
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jan 14, 2019; 25(2): 163-177
Published online Jan 14, 2019. doi: 10.3748/wjg.v25.i2.163
Current status, problems, and perspectives of non-alcoholic fatty liver disease research
Naoki Tanaka, Takefumi Kimura, Naoyuki Fujimori, Tadanobu Nagaya, Michiharu Komatsu, Eiji Tanaka
Naoki Tanaka, Department of Metabolic Regulation, Shinshu University School of Medicine, Matsumoto 390-8621, Japan
Naoki Tanaka, International Research Center for Agricultural Food Industry, Shinshu University, Matsumoto 390-8621, Japan
Takefumi Kimura, Naoyuki Fujimori, Tadanobu Nagaya, Michiharu Komatsu, Eiji Tanaka, Department of Internal Medicine, Shinshu University School of Medicine, Matsumoto 390-8621, Japan
Author contributions: All authors have approved the submission of this manuscript. Tanaka N wrote the manuscript; Tanaka N, Kimura T, Fujimori N, Nagaya T and Komatsu M have conducted long-term NAFLD/NASH research and discussed the perspectives; Tanaka E supervised the manuscript.
Conflict-of-interest statement: There is no conflict of interests.
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: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Naoki Tanaka, MD, PhD, Associate Professor, Doctor, Department of Metabolic Regulation, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto 390-8621, Japan. naopi@shinshu-u.ac.jp
Telephone: +81-263-372634 Fax: +81-263-329412
Received: October 5, 2018
Peer-review started: October 5, 2018
First decision: November 14, 2018
Revised: December 24, 2018
Accepted: December 27, 2018
Article in press: December 28, 2018
Published online: January 14, 2019
Abstract

Non-alcoholic fatty liver disease (NAFLD) is a major chronic liver disease that can lead to liver cirrhosis, liver cancer, and ultimately death. NAFLD is pathologically classified as non-alcoholic fatty liver (NAFL) or non-alcoholic steatohepatitis (NASH) based on the existence of ballooned hepatocytes, although the states have been known to transform into each other. Moreover, since the detection of ballooned hepatocytes may be difficult with limited biopsied specimens, its clinical significance needs reconsideration. Repeated liver biopsy to assess histological NAFLD activity for therapeutic response is also impractical, creating the need for body fluid biomarkers and less invasive imaging modalities. Recent longitudinal observational studies have emphasized the importance of advanced fibrosis as a determinant of NAFLD outcome. Thus, identifying predictors of fibrosis progression and developing better screening methods will enable clinicians to isolate high-risk NAFLD patients requiring early intensive intervention. Despite the considerable heterogeneity of NAFLD with regard to underlying disease, patient age, and fibrosis stage, several clinical trials are underway to develop a first-in-class drug. In this review, we summarize the present status and future direction of NAFLD/NASH research towards solving unmet medical needs.

Keywords: Non-alcoholic steatohepatitis, Fibrosis, Steatosis, Ballooning, Biomarker, Outcome, Treatment

Core tip: Recent trends in diet and lifestyle have increased the prevalence of non-alcoholic fatty liver disease/steatohepatitis (NAFLD/NASH) worldwide. Although advances in non-invasive biomarkers and imaging modalities have improved disease detection and follow-up, considerable work is needed to identify individuals with low fibrosis stages or at risk of rapid disease progression. In the future, earlier detection will enable prompt single or combination treatment with new-line drugs that have been optimized for maximum benefit and fewer adverse events. Only with a concerted effort across multi-disciplinary fields can clinicians begin to halt the rapid spread of NAFLD/NASH.