Clinical strategy of diagnosing and following patients with nonalcoholic fatty liver disease based on invasive and noninvasive methods

J Gastroenterol https://doi.org/10.1007/s00535-017-1414-2 REVIEW Clinical strategy of diagnosing and following patients with nonalcoholic fatty liver disease based on invasive and noninvasive methods Masato Yoneda1 • Kento Imajo1 • Hirokazu Takahashi2 • Yuji Ogawa1 • Yuichiro Eguchi3 • Yoshio Sumida4 • Masashi Yoneda4 • Miwa Kawanaka5 • Satoru Saito1 • Katsutoshi Tokushige6 • Atsushi Nakajima1 Received: 27 September 2017 / Accepted: 13 November 2017 Ó The Author(s) 2017. This article is an open access publication Abstract Nonalcoholic fatty liver disease (NAFLD) is an important cause of chronic liver injury in many countries. The incidence of NAFLD is rising rapidly in both adults and children, because of the currently ongoing epidemics of obesity and type 2 diabetes. Notably, histological liver fibrosis is recognized as the main predictive factor for the overall long-term outcome of NAFLD, including cardiovascular disease and liver-related mortality. Thus, staging of liver fibrosis is essential in determining the prognosis and optimal treatment for patients with NAFLD and in guiding surveillance for the development of hepatocellular Contact for reagent and resource sharing Further information and requests for resources and reagents should be directed to and will be fulfilled by the lead contact, Atsushi Nakajima (). & Atsushi Nakajima 1 Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan 2 Division of Metabolism and Endocrinology, Faculty of Medicine, Saga University, 5-1-1 Nabeshima, Saga 849-8501, Japan 3 Liver Center, Saga University, 5-1-1 Nabeshima, Saga 849-8501, Japan 4 Division of Hepatology and Pancreatology, Department of Internal Medicine, Aichi Medical University School of Medicine, 1-1 Yazakokarimata, Nagakute, Aichi 480-1195, Japan 5 General Internal Medicine 2, General Medical Center, Kawasaki Medical School, 2-6-1 Nakasange, Kutaku, Okayama 700-8505, Japan 6 Department of Internal Medicine and Gastroenterology, Tokyo Women’s Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan carcinoma (HCC). Whereas liver biopsy remains the gold standard for staging liver fibrosis, it is impossible to enforce liver biopsy in all patients with NAFLD. Noninvasive biological markers, scoring systems and noninvasive modalities are increasingly being developed and investigated to evaluate fibrosis stage of NAFLD patients. This review will highlight recent studies on the diagnosis and staging of NAFLD based on invasive (liver biopsy) or noninvasive (biomarker, scoring systems, US-based elastography and MR elastography) methods. Keywords Nonalcoholic fatty liver disease
Scoring system
Elastography
Liver biopsy
MR elastography Abbreviations AAR Aspartate aminotransferase-to-alanine aminotransferase ratio AASLD American Association for the Study of Liver Diseases AGEs Advanced glycation end products ARFI Acoustic radiation force impulse BMI Body mass index FIB-4 Fibrosis-4 HCC Hepatocellular carcinoma ICC Intra-class correlation coefficient NAFL Nonalcoholic fatty liver NAFLD Nonalcoholic fatty liver disease NASH Nonalcoholic steatohepatitis MRI Magnetic resonance imaging NAS NAFLD activity score NFS NAFLD fibrosis score PLT Platelet PNPLA3 Patatin-like phospholipase domain-containing protein 3 gene 123 J Gastroenterol SWE US VCTE Shear wave elastography Ultrasound Vibration-controlled transient elastography Introduction Nonalcoholic fatty liver disease (NAFLD) is an important cause of chronic liver injury in many countries [1, 2]. NAFLD ranges from benign nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH). The latter condition includes progressive fibrosis, which is associated with high rates of overall and disease-specific mortality [3], hepatocellular carcinoma (HCC) [4, 5] and atherosclerotic diseases [6]. Liver biopsy is recommended as the gold standard method for the diagnosis of NASH and the staging of liver fibrosis in patients with NASH [7]. However, because of its increased cost, risk and healthcare resource use, an invasive liver biopsy is a poorly suited diagnostic test for such a prevalent condition [8]. Therefore, the development of reliable noninvasive methods for the assessment of liver fibrosis has become essential to estimate the potential progression of NASH to cirrhosis and HCC and to guide therapy. In this review, we highlight recent advances in biomarkers, scoring systems, ultrasound (US)-based elastography techniques and magnetic resonance imaging (MRI) techniques with which to evaluate the liver fibrosis stage and steatosis grade and discuss their usefulness for surveillance of the liver status, including the presence or absence of HCC, in patients with NAFLD. Liver biopsy Histological analysis of liver biopsy samples has played a central role in the management of NAFLD and NASH in terms of diagnosis, definition of severity, and prediction of prognosis. Hepatic steatosis is a histological hallmark of NAFLD. Hepatic steatosis independent from alcohol consumption in morbid obesity and diabetes had been reported in the decades after 1952 [9–11] and Ludwig et al. finally propounded NASH in 1980 [12]. Studies in the 1970s identified that most fatty liver did not progress to fibrosis and cirrhosis [13, 14]. Therefore, hepatic steastosis was considered as a benign or non-harmful findings; however, it was unknown whether the other concomitant findings including lobular inflammation, Mallory–Denk bodies, ballooning degeneration and fibrosis were associated with the disease progression of NAFLD/NASH. In 1999, Matteoni et al. confirmed the progressive course of patients who had NAFLD with ballooning degeneration 123 [15]. As a result of these differences, these authors classified NAFLD with hepatic steatosis and ballooning degeneration as type 3 and NAFLD with liver steatosis, ballooning degeneration, fibrosis, and Mallory–Denk bodies as type 4 (Table 1). Types 3 and 4 NAFLD are associated with higher liver-related mortality rates than type 1 (only liver steatosis) and type 2 (liver steatosis and lobular inflammation) [15]. NAFLD can be divided into NAFL without ballooning degeneration and NASH with ballooning degeneration [16, 17]. Matteoni’s classification, which is based on analysis of the liver-related prognosis, has been used as the standard classification system for the diagnosis of NASH. However, this study and classification by Matteoni et al. left three main issues for other researchers to resolve over the next decade: a too-small sample size of patients with type 2 and 3 NAFLD (n = 10 and 19, respectively) to confirm the impact of ballooning degeneration on prognosis, intraobserver and interobserver differences in the diagnosis of ballooning degeneration, and a missing classification for the disease severity of NAFLD [18, 19]. The classification published by Brunt et al. in 1999 enab (...truncated)