Cigarette smoking is a risk factor for the onset of fatty liver disease in nondrinkers: A longitudinal cohort study.

BACKGROUND: The effect of cigarette smoking on the onset of nonalcoholic fatty liver disease (NAFLD) is unclear, especially that associated with drinking small amounts of alcohol. We conducted a longitudinal study to investigate the relationship between cigarette smoking and NAFLD onset, which was stratified according to the amount of alcohol consumed. METHODS: We enrolled 7,905 Japanese subjects who had received annual health checkups more than twice between April 2003 and August 2013, 4,045 of whom met at least one of the following exclusion criteria and were excluded: (a) fatty liver at baseline; (b) hepatitis B or hepatitis C; (c) alcohol consumption (men: ≥210 g/wk; women: ≥140 g/wk); (d) change in alcohol drinking status between baseline and the study's endpoint; (e) change in cigarette smoking habits between baseline and the study's endpoint; or (f) current treatment with antidiabetic agents, antihypertensive agents, and/or lipid-lowering agents. The remaining 3,860 subjects (1,512 men, 2,348 women) were divided into two groups based on average alcohol consumption. RESULTS: After adjusting for the variables associated with metabolic disease, smoking was associated with fatty liver disease onset compared with nonsmokers in nondrinkers (adjusted hazard ratio = 1.988, 95% confidence interval 1.057-3.595; p = 0.034). No association was found between smoking and fatty liver disease onset in the low alcohol consumption group (men: <210 g alcohol/week; women: <140 g alcohol/week). The fatty liver disease incidence increased significantly among the nondrinkers as the number of cigarettes smoked increased (p = 0.001). CONCLUSIONS: Cigarette smoking may be a significant risk factor associated with NAFLD onset in nondrinkers. These results may help clinicians to identify patients who are at a high risk of developing NAFLD and to prevent the progression of NAFLD by promoting earlier interventions that help people discontinue unhealthy lifestyle habits.

Differences in the risk of fatty liver for onset of impaired fasting glucose according to baseline plasma glucose levels.

BACKGROUND: It remains unclear whether fatty liver is a risk factor for the onset of abnormal glucose tolerance in any patient. The objective of this study was to clarify the relationship between fatty liver and the onset of impaired fasting glucose according to baseline fasting plasma glucose (FPG) levels. METHODS: This community-based longitudinal cohort study included 7,905 adults (3,863 men, 4,042 women; age range, 18-80 years) who had at least two annual checkups between 2003 and 2013. Those with FPG levels ≥110 mg/dl, taking anti-diabetic agents, and/or testing positive for hepatitis B surface antigen or anti-hepatitis C virus antibody were excluded, leaving 7,203 participants eligible for inclusion. All participants were divided into quartiles derived from their FPG levels at baseline. FPG ≥110 mg/dl during the observation period was defined as onset of IFG. RESULTS: Onset of IFG was found in 7.7 % of men and 2.1 % of women (p < 0.001). After adjusting for age, body mass index, systolic blood pressure, triacylglycerol, high-density lipoprotein cholesterol, uric acid, creatinine, family history of diabetes, alcohol consumption, and current smoking, a positive association was found between fatty liver and the onset of IFG in both sexes with the highest quartile of FPG levels [men: adjusted hazard ratio (aHR) 1.823, 95 % confidence interval (CI) 1.316-2.534, p < 0.001; women: aHR 2.016, 95 % CI 1.117-3.6, p = 0.02]. CONCLUSIONS: Our results suggest that fatty liver is independently associated with an increased risk of developing IFG in individuals with high FPG.

Significance of exercise in nonalcoholic fatty liver disease in men: a community-based large cross-sectional study.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a risk factor for diabetes and cardiovascular disease that could progress to nonalcoholic steatohepatitis, cirrhosis, and liver failure. We aimed to assess the relationship between NAFLD and lifestyle habits. METHODS: Using a community-based, cross-sectional design, the records of 11,094 Japanese subjects who had undergone at least 1 annual health checkup were reviewed. RESULTS: Of the 6,370 subjects who qualified for enrolment, 1,346 met the diagnostic criteria for NAFLD. The prevalence rate (PR) of NAFLD increased significantly to 36.6, 41.5, and 41.1 % with no snacking, snacking less than once/day, and snacking ≥2 times/day, respectively, in men (P = 0.0495) and to 10.8, 11.7, and 15.3 %, respectively, in women (P = 0.002). In men, the NAFLD PR decreased significantly to 48.8, 36.9, and 29.9 % with no exercise, exercise consciousness, and periodical exercise, respectively (P < 0.001). In women, the NAFLD PR decreased significantly to 19.3, 13.5, 11, and 8 % with sleep durations of ≤4, 5-6, 7-8, and ≥9 h, respectively (P = 0.003). Periodical exercise was identified as an independent factor associated with NAFLD in men (odds ratio 0.707, 95 % confidence interval 0.546-0.914; P = 0.008). CONCLUSIONS: Performing regular exercise was associated with a reduced risk for NAFLD in men. Men with a high risk for NAFLD can be identified using questionnaires on exercise in an outpatient setting. Disease progression and further complications may be prevented by educating high-risk NAFLD patients about the importance of exercise.

Hyperuricemia is a risk factor for the onset of impaired fasting glucose in men with a high plasma glucose level: a community-based study.

BACKGROUND: It is not clear whether elevated uric acid is a risk factor for the onset of impaired fasting glucose after stratifying by baseline fasting plasma glucose levels. We conducted a community-based retrospective longitudinal cohort study to clarify the relationship between uric acid levels and the onset of impaired fasting glucose, according to baseline fasting plasma glucose levels. METHODS: We enrolled 6,403 persons (3,194 men and 3,209 women), each of whom was 18-80 years old and had > 2 annual check-ups during 2003-2010. After excluding persons who had fasting plasma glucose levels ≥ 6.11 mM and/or were currently taking anti-diabetic agents, the remaining 5,924 subjects were classified into quartiles according to baseline fasting plasma glucose levels. The onset of impaired fasting glucose was defined as fasting plasma glucose ≥ 6.11 mM during the observation period. RESULTS: In the quartile groups, 0.9%, 2.1%, 3.4%, and 20.2% of the men developed impaired fasting glucose, respectively, and 0.1%, 0.3%, 0.5%, and 5.6% of the women developed impaired fasting glucose, respectively (P trend <0.001). After adjusting for age, body mass index, systolic blood pressure, triacylglycerols, high density lipoprotein-cholesterol, creatinine, fatty liver, family history of diabetes, alcohol consumption, and current smoking, uric acid levels were positively associated with onset of impaired fasting glucose in men with highest-quartile fasting plasma glucose levels (adjusted hazard ratio, 1.003; 95% confidence interval, 1.0001-1.005, P = 0.041). CONCLUSIONS: Among men with high fasting plasma glucose, hyperuricemia may be independently associated with an elevated risk of developing impaired fasting glucose.

Metabolic markers and ALT cutoff level for diagnosing nonalcoholic fatty liver disease: a community-based cross-sectional study.

BACKGROUND: Untreated nonalcoholic fatty liver disease (NAFLD) may progress to liver cirrhosis or failure and is associated with the development of hepatocellular carcinoma, diabetes, and cardiovascular disease. It is therefore essential to diagnose and treat NAFLD at an early stage. To assist in this effort, this retrospective study explored the risk factors for NAFLD, and derived new surrogates, a revised alanine aminotransferase (ALT) cutoff level and a novel NAFLD index, to identify previously undiagnosed cases of NAFLD. METHODS: Using a community-based, cross-sectional design, the records of 6,370 Japanese subjects who had undergone at least 1 annual health check-up were reviewed for the identification of subjects meeting the diagnostic criteria for NAFLD and the variables associated with NAFLD for the estimation of ideal ALT cutoff levels. RESULTS: The results of multivariate analysis of the 1,346 subjects who met the diagnostic criteria for NAFLD confirmed that metabolic disease markers and a novel NAFLD index, using the variables derived from multivariate analysis, were also markers of NAFLD. The ALT cutoff levels for NAFLD diagnosis were estimated at 25 U/L for males and 17 U/L for females. CONCLUSIONS: ALT level and the novel NAFLD index were confirmed to be surrogate markers for NAFLD in addition to metabolic disease markers. The ALT cutoff level used in NAFLD diagnosis should be revised downward to identify subjects at risk of NAFLD to prevent NAFLD progression and the development of associated diseases.