• DOI:10.7326/0003-4819-143-10-200511150-00009
• Corpus ID: 22475943

The Metabolic Syndrome as a Predictor of Nonalcoholic Fatty Liver Disease

@article{Hamaguchi2006TheMS,
  title={The Metabolic Syndrome as a Predictor of Nonalcoholic Fatty Liver Disease},
  author={Masahide Hamaguchi and Takao Kojima and Noriyuki Takeda and Takayuki Nakagawa and Hiroya Taniguchi and Kota Fujii and Tatsushi Omatsu and Tomoaki Nakajima and Hiroshi Sarui and Makoto Shimazaki and Takahiro A. Kato and Junichi Okuda and Kazunori Ida},
  journal={Annals of Internal Medicine},
  year={2006},
  volume={143},
  pages={722-728}
}

• M. Hamaguchi, T. Kojima, +10 authors K. Ida
• Published 7 March 2006
• Medicine
• Annals of Internal Medicine

Context The metabolic syndrome is often present in patients with nonalcoholic fatty liver disease (NAFLD), but no one knows whether it precedes NAFLD. Content At baseline, 812 members of a cohort of 4401 apparently healthy Japanese adults had NAFLD on abdominal ultrasonography. In 1 year, the authors identified 308 new cases, and NAFLD had resolved in 113 participants. Participants with the metabolic syndrome were much more likely to develop NAFLD and were less likely to experience disease resolution. Limitations Abdominal ultrasonography is not a perfect gold standard test for NAFLD. Implication The metabolic syndrome appears to predispose people to develop NAFLD. The Editors Nonalcoholic fatty liver disease is increasingly recognized as a major cause of liver-related morbidity and mortality (1-3). Because of its potential to progress to cirrhosis and liver failure (4), interest in this disease is increasing among researchers and clinicians in the relevant basic and clinical science fields. The pathologic picture of nonalcoholic fatty liver disease, ranging from simple steatosis to steatohepatitis, advanced fibrosis, and cirrhosis, resembles that of alcohol-induced liver disease, but it occurs in patients who do not abuse alcohol (3). Nonalcoholic steatohepatitis that is characterized by hepatic steatosis and liver cell injury, hepatic inflammation, and fibrosis and necrosis is believed to be an intermediate stage of nonalcoholic fatty liver disease. (1) This disease is often associated with obesity (5), type 2 diabetes mellitus (6, 7), dyslipidemia (8), and hypertension (9). Each of these abnormalities carries a cardiovascular disease risk, and together they are often categorized as the insulin resistance syndrome or the metabolic syndrome (10). The third report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III [ATP III]) (11) recommended the use of 5 variables for diagnosing the metabolic syndrome, namely waist circumference, serum triglyceride level, serum high-density lipoprotein (HDL) cholesterol level, blood pressure, and fasting plasma glucose level. As stated above, the frequent association of nonalcoholic fatty liver disease with individual components of the metabolic syndrome is now well known. However, it is unknown whether the risk for this disease is increased in patients with the metabolic syndrome. This is important because the metabolic syndrome is an emerging problem worldwide and its prevalence is likely increasing (12). The current study was designed first to evaluate the cross-sectional relationship between the metabolic syndrome, defined by the modified ATP III criteria, and the prevalence of nonalcoholic fatty liver disease in Japanese persons. Second, and more important, we addressed longitudinal aspects of the disease and its development and regression and tried to clarify the role of the metabolic syndrome in its pathogenesis. Despite serious concern about a possible future epidemic of this disease in the Asia-Pacific region (13), information regarding a possible association with the metabolic syndrome in Asia is very limited; our study may have special clinical relevance for people who live in this part of the world. Methods Study Participants We designed a prospective cohort study to investigate the role of the metabolic syndrome in the pathogenesis of nonalcoholic fatty liver disease in participants in a medical health checkup program at Murakami Memorial Hospital, Gifu, Japan. Each participant had abdominal ultrasonography. The purpose of the medical health checkup program is to promote public health through early detection of chronic diseases and their risk factors. Medical service of this kind, known as a human dock, is very popular in Japan. The center at which the checkups were performed was founded in 1994 and currently evaluates more than 8000 examinees annually. Of these examinees, 60% repeatedly have annual or biannual examinations and 40% are newly registered examinees. Most of the participants were employees of various companies and local governmental organizations in Gifu, Japan, and their spouses. These companies and organizations recruit employees each year according to a contract with our center. The cost of the medical examination was largely paid for by the employers. Fewer than 10% of the participants individually registered for the program and paid for it themselves, and they are citizens of local communities. Because many participants were expected to have repeated examinations, we took advantage of this opportunity to conduct a follow-up study on nonalcoholic fatty liver disease by using abdominal ultrasonography. The ethics committee of Murakami Memorial Hospital approved the study. All participants who were examined in the health checkup programs between January and December 2001 were invited to enroll in the study. Data Collection and Measurements The health checkup programs included the following: urinalysis, blood cell counts, blood chemistry, measurements of hepatitis B antigen and hepatitis C antibody, electrocardiography, chest radiography, barium examination of the upper gastrointestinal tract, and abdominal ultrasonography. Medical history and lifestyle factors, including physical activity, habits regarding smoking, and habits regarding alcohol consumption, were surveyed by using a self-administered questionnaire. When the participants had difficulty completing the questionnaire, trained nurses provided assistance. Smoking status was expressed by using the Brinkman index, which is calculated as the number of cigarettes smoked per day multiplied by the number of years that the participant smoked. Habits regarding alcohol consumption were evaluated by asking the participants about the amount and type of alcoholic beverages consumed per week, then estimating the mean ethanol intake per day. The diagnosis of fatty liver was based on the results of abdominal ultrasonography, which was done by trained technicians. All ultrasonographic images were stored in the image server. One gastroenterologist reviewed the images and made the diagnosis of fatty liver without reference to any of the participant's other individual data. Of 4 known criteria (hepatorenal echo contrast, liver brightness, deep attenuation, and vascular blurring) (14), the participants were required to have hepatorenal contrast and liver brightness to be given a diagnosis of nonalcoholic fatty liver disease. Body mass index (BMI) was calculated as body weight in kilograms divided by the square of the participant's height in meters. The ATP III proposed the following 5 abnormalities to define the metabolic syndrome: 1) abdominal obesity (abdominal circumference> 102 cm for men and> 88 cm for women); 2) elevated serum triglyceride level (1.70 mmol/L [150 mg/dL]); 3) decreased HDL cholesterol level (<1.04 mmol/L [<40 mg/dL] for men and <1.30 mmol/L [<50 mg/dL] for women); 4) elevated blood pressure (systolic and diastolic blood pressure 130/85 mm Hg); and 5) an elevated fasting glucose level (6.11 mmol/L (110 mg/dL]). Because waist measurements were not available for the entire study sample, we substituted a BMI of 25 kg/m2 or greater for all participants as an index of obesity. A BMI of 25 kg/m2 or greater has been proposed as a cutoff for the diagnosis of obesity in Asian people (15). Individuals with 3 or more of the 5 abnormalities were considered to have the metabolic syndrome. Exclusion criteria were an alcohol intake of more than 20 g/d, known liver disease, or current use of medication. Regarding liver disease, participants who tested positive for hepatitis B antigen or hepatitis C antibody and those who reported a history of known liver disease, including viral, genetic, autoimmune, and drug-induced liver disease, were also excluded (16). Statistical Analysis The SPSS statistical package, version 11.0.1 J (SPSS, Inc., Chicago, Illinois) was used for all statistical analyses, and a P value less than 0.05 was considered statistically significant. Because the incidence rate of nonalcoholic fatty liver disease was unknown, a formal sample size estimate was not made a priori. Participants with and without follow-up visits were compared to determine the appropriateness of an analysis based on participants with complete data only. Two groups of participants were compared by using the unpaired t-test and the chi-square test. Logistic regression was used to analyze associations between the development and regression of nonalcoholic fatty liver disease and the metabolic syndrome while controlling for potential confounders. The potential confounders were selected from clinical variables, which were different between participants with and without the disease at baseline. As will be described later, weight change was also selected as a confounder because the development and regression of nonalcoholic fatty liver disease generally occurred with weight changes. Unadjusted and adjusted odds ratios and 95% CIs were calculated. Data are expressed as means and SDs for continuous variables. Role of the Funding Source No funding was received for this study. Results Between January and December 2001, we invited 8056 participants in the health checkup program to enroll in the study. A total of 6654 Japanese participants (4601 men and 2053 women) gave informed consent to be included in the study. We excluded 290 participants (216 men and 74 women) who had known liver disease. In addition, 1657 participants (1577 men and 80 women) who consumed more than 20 g of ethanol per day and 306 participants (236 men and 70 women) who were currently receiving medication were excluded. As a result, there were 4401 participants (2572 men and 1829 women). Mean age and BMI were 47.6 years (SD, 8.8) (range, 21 to 80 years) and 22.6 kg/m2 (SD, 3.0) (range, 14.2 to 38.1 kg/m2), respectively. By the end of June 2003, 387