December 5, 2013

Non-alcoholic fatty liver disease: Factors associated with its presence and onset

Journal of Gastroenterology and Hepatology

Special Issue: Third Asian-Pacific Topic Conference (APTC2012): Nutrition-related disorders and digestive system. Organized by Japanese Society of Gastroenterology (JSGE) and Asian-Pacific Association of Gastroenterology (APAGE), Tokyo, Japan, November 2–3, 2012. Guest Editor: Soichiro Miura

Volume 28, Issue Supplement S4, pages 71–78, December 2013

Nutrition-Related Liver Disorders: NAFLD

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Teruki Miyake, Teru Kumagi*, Shinya Furukawa, Yoshio Tokumoto, Masashi Hirooka, Masanori Abe, Yoichi Hiasa,  Bunzo Matsuura, Morikazu Onji

Article first published online: 19 NOV 2013

DOI: 10.1111/jgh.12251

© 2013 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd

Keywords: blood tests;  non-alcoholic fatty liver disease;  risk factors;  physical measurements;  predictive factors


Non-alcoholic fatty liver disease (NAFLD) may progress to cirrhosis, liver failure, and complicated hepatocellular carcinoma. In addition, NAFLD is a risk factor for the development of other serious diseases, such as diabetes or cardiovascular disease. Therefore, the detection of early-stage NAFLD is important. Many studies have described the factors that predict the presence of NAFLD and its onset, and several markers have been identified. These markers have enabled the identification of high-risk patients and have improved routine medical practice. To prevent advanced disease, clinicians need to have simple markers that predict the onset of NAFLD so that interventions can be started at much earlier stages of disease. This review summarizes the current state of knowledge regarding independent factors, as reported in large studies, that predict the presence of NAFLD and its onset, especially markers that can be used in daily medical practice, such as physical measurements and blood tests.


Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver diseases worldwide and is a manifestation of metabolic syndrome in the liver.[1, 2] Pathologically, NAFLD represents a wide spectrum of liver conditions from simple steatosis to non-alcoholic steatohepatitis (NASH). NASH may progress to cirrhosis, liver failure, or hepatocellular carcinoma[1-5] and thus requires periodic follow-up. NAFLD is also an independent risk factor for the onset of cardiovascular disease (CVD)[6] and diabetes,[7] making the prevention of NAFLD as important as the management of the condition.

In contrast, NAFLD has not been shown to be associated with an increased risk of death from all causes, CVD, cancer, or liver disease.[8]In large studies, approximately 5% of patients showing evidence of NAFLD are ultimately diagnosed with advanced NASH,[9] which is associated with a mortality rate similar to that of advanced liver fibrosis due to hepatitis C virus infection.[10] Considering the financial burden of the increasing number of individuals with metabolic syndrome, the identification of simple markers that can identify patients with NAFLD or those who might progress to NAFLD is desired. In this regard, this review provides an overview of the independent factors that predict NAFLD onset in individuals who do not have any other known liver disease, as previously reported in large studies.

Body mass index

A risk factor for the presence of NAFLD

Body mass index (BMI) is a simple marker that reveals an individual's degree of obesity. In Japan, a BMI of 22 is used to indicate the ideal body weight, and obesity-related diseases are associated with higher BMIs.[11] Previously, we reported a community-based, cross-sectional study involving the records of 6370 Japanese subjects, and confirmed that BMI was an independent marker for the presence of NAFLD (men: odds ratio [OR] 1.257; 95% confidence interval [CI] 1.20–1.319; P < 0.001; women: OR 1.291; 95% CI 1.245–1.340; P < 0.001)[12, 13] (Table 1). The BMI cut-off levels for identifying the presence of NAFLD were identified in men and women using the area under the receiver operating characteristic (ROC) curve (AUC) (95% CI). Using these techniques, the AUC (95% CI) (men, 0.809 [0.791–0.825]; women, 0.831 [0.82–0.843]), cut-off level (men, 24.1 kg/m2; women, 22.5 kg/m2), sensitivity (men, 71.6%; women, 77.9%), specificity (men, 76.5%; women, 75.4%), positive predictive value (PPV; men, 66.3%; women, 31.2%), negative predictive value (NPV; men, 80.6%; women, 96%), and diagnostic accuracy (men, 74.6%; women, 75.7%) for predicting NAFLD were identified (Table 1).[13] Eguchi et al. also carried out a large, multicenter, retrospective study examining 5075 subjects who underwent health checkups at three health centers, and identified BMI as a useful marker for determining the presence of NAFLD. They showed that BMI (> 25 kg/m2) was an independent risk factor for NAFLD (men: OR 3.81; 95% CI 3.11–4.67; P < 0.01; women: OR 7.23; 95% CI 5.5–9.5; P < 0.01) by multiple regression analysis, and the prevalence of NAFLD showed a linear increase with increasing BMI (BMI < 23 kg/m2, 10.5%; 23 ≤ BMI < 25 kg/m2, 37.9%; 25 ≤ BMI < 28 kg/m2, 58.4%; BMI ≥ 28 kg/m2, 84.2%)[14] (Table 1).

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