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Background & Aims: Nonalcoholic fatty liver disease (NAFLD) has become the most common liver disease in Western countries. Smoking and diabetes mellitus (DM) have been shown to increase mortality; however, whether NAFLD adds to the detrimental effect of smoking in DM and non‐DM patients is unknown. We evaluated the possible interactive effect of NAFLD and smoking on mortality risk in a US population‐based sample. Methods: Cross‐sectional data from 11 205 participants in the third National Health and Nutrition Examination Survey were analysed. NAFLD was defined as ultrasonographic hepatic steatosis without evidence of other liver diseases. Proportional hazards regression modelling was used to test for the multiplicative interaction of NAFLD and smoking on overall mortality, controlling for DM. Results: 36.5% of the participants had NAFLD of whom 21.1% were current smokers, while among non‐NAFLD subjects, 26.2% reported current smoking. Smoking was associated with a hazard ratio (HR) of 2.23 (95% confidence interval (CI): 1.87‐2.65) among non‐NAFLD subjects, and 2.31 (95% CI: 1.33‐2.92, P < 0.01) among NAFLD patients. In contrast, the HR for NAFLD was 1.01 (95% CI: 0.78‐1.31, P = 0.96) among smokers and 0.98 (95% CI: 0.87‐1.10, P = 0.73) among non‐smokers. There was no evidence of interaction between NAFLD and smoking (HR = 1.01, 95% CI: 0.74‐1.38, P = 0.94) in the combined model. Conclusion: We found that smoking increased mortality by two‐fold among the US population. Although the magnitude of the increase in mortality did not differ from that in non‐NAFLD subjects, smoking represents a modifiable determinant of long‐term outcomes in NAFLD patients. [ABSTRACT FROM AUTHOR]

Background and Aim: We investigated the effects of PNPLA3 rs738409, TM6SF2 rs58542926, and MBOAT7-TMC4 rs641738 variants on metabolic phenotypes and their combined effects on the histological severity of non-alcoholic fatty liver disease (NAFLD). Methods: We genotyped rs738409, rs58542926, and rs641738 in biopsy-proven NAFLD patients (n = 416) and healthy controls (n = 109). Homeostasis model assessment of insulin resistance and adipose tissue insulin resistance were calculated. Results: The rs738409 and rs58542926 variants, but not rs641738, were associated not only with non-alcoholic steatohepatitis (NASH) (odds ratio [OR], 2.00; 95% confidence interval [CI], 1.46-2.73 and OR, 1.91; 95% CI, 1.04-3.51) but also with significant fibrosis (≥ F2) (OR, 1.53; 95% CI, 1.11-2.11 and OR, 1.88; 95% CI, 1.02-3.46) in NAFLD, even after adjustment for metabolic risk factors. Of both variants, only rs738409 was associated with homeostasis model assessment of insulin resistance and adipose tissue insulin resistance even in healthy controls (P = 0.046 and 0.002, respectively) as well as in the entire study cohort (P = 0.016 and 0.048, respectively). PNPLA3 and TM6SF2 risk variants additively increased the risk of NASH and significant fibrosis (OR per risk allele, 2.03; 95% CI, 1.50-2.73 and 1.61; 95% CI, 1.19-2.17). Even in subjects with low insulin resistance, the risk of NASH or significant fibrosis increased as the number of risk alleles increased (P = 0.008 and 0.020, respectively). Conclusions: PNPLA3 and TM6SF2 determine the risk of NASH and significant fibrosis, even after adjustment for insulin resistance, and exert an additive effect on NASH and significant fibrosis. [ABSTRACT FROM AUTHOR]

Background & Aims Physical activity ( PA) is inversely associated with nonalcoholic fatty liver disease ( NAFLD) prevalence. However, few studies evaluated the effect of PA on NAFLD incidence in regard to visceral adipose tissue ( VAT) and insulin resistance ( IR). We investigated whether PA at baseline and change in PA during follow-up have any effect on incident NAFLD. Methods We enrolled subjects who underwent health screenings between 2007 and 2008 and participated in voluntary follow-up between 2011 and 2013 (median 4.42 years). Incident NAFLD was defined as NAFLD absence at baseline and presence at follow-up by ultrasonography. PA was measured using a detailed questionnaire-based metabolic equivalent at baseline and follow-up; the difference during follow-up was calculated. Results Of the 1373 subjects enrolled, 288 (21.0%) developed NAFLD. Both total and leisure-time PA at baseline were inversely associated with incident NAFLD ( P for trend=.005 and .003 respectively). Decreased PA at follow-up was associated with increased incident NAFLD risk after adjusting for age, gender, body mass index, smoking, hypertension, diabetes and diet [hazard ratio ( HR) 1.45, 95% confidence interval ( CI) 1.04-2.02, 4th (most decreased PA) vs 1st quartile (increased PA), P=.028]. This relationship was attenuated but remained statistically significant after adjustment for VAT( HR 1.48, 95% CI 1.06-2.06, 4th vs 1st quartile) and IR( HR 1.59, 95% CI 1.11-2.27, 4th vs 1st quartile). Conclusions This study shows an independent protective effect of PA at baseline on incident NAFLD after 4-year follow-up. Furthermore, sustained or increased PA had a preventive effect on incident NAFLD independent of VAT and IR. [ABSTRACT FROM AUTHOR]

Background and Aim Gallbladder polyps ( GBPs) appear to be strongly associated with obesity and metabolic disease. To date, the relationship between GBPs and fatty liver has not been adequately evaluated. The aim of the present study was to investigate whether GBPs are associated with fatty liver, which is an ectopic regional fat deposit, independent of visceral adipose tissue ( VAT). Methods A cross-sectional study using 2643 health checkup subjects (961 patients with GBP and 1682 age- and sex-matched healthy controls) was conducted. The subjects underwent various laboratory tests, abdominal fat computed tomography ( CT), and hepatic ultrasonography. Results The mean age of the subjects was 51.4 ± 8.3 years, and 74.1% were male. GBPs were significantly associated with fatty liver. Multivariate regression analysis revealed that GBPs were significantly associated with the presence of fatty liver (odds ratio [ OR] 1.23, 95% confidence interval [ CI]: 1.02-1.48), and adjusting for the homeostatic metabolic assessment index had little effect on this association ( OR 1.23, 95% CI: 1.02-1.48). Additionally, GBPs remained significantly associated with the presence of fatty liver after adjustments for CT-measured VAT and subcutaneous adipose tissue ( OR 1.24, 95% CI: 1.03-1.50). The degree of fatty liver showed an independent ( OR 1.37 95% CI: 1.03-1.80) and dose-dependent relationship (moderate-severe fatty liver: OR 1.55 95% CI: 1.07-2.23, P for trend = 0.014) with large GBPs (≥ 5 mm). Conclusion Fatty liver, an ectopic regional fat deposit, was found to be closely associated with GBPs independent of known metabolic risk factors, insulin resistance, and CT-measured VAT, confirming a relevant clinical relationship between the two diseases. [ABSTRACT FROM AUTHOR]

Background & Aims Limited evidence supports a role for physical activity ( PA) in nonalcoholic fatty liver disease ( NAFLD) independent of visceral obesity or/and insulin resistance. We investigated the association between PA and NAFLD while considering visceral adipose tissue ( VAT) and insulin resistance in a large general population. Methods Nonalcoholic fatty liver disease was diagnosed based on typical ultrasonographic findings. A detailed PA questionnaire included type, frequency, duration and length of time that the subject engaged in PA. PA was determined by a metabolic equivalent. VAT was evaluated by computed tomography taken at the umbilicus level. Results A total of 3718 subjects were enrolled in the analysis. After adjusting for age, gender, body mass index, smoking, hypertension, diabetes, soft drink and coffee consumption, the total PA was inversely associated with NAFLD [4th quartile (highest activities), odds ratio ( OR) 0.68, 95% confidence interval ( CI) 0.54-0.85; 3rd quartile, OR 0.74, 95% CI 0.59-0.93 vs. 1st quartile (lowest activities), P for trend <0.001]. After further adjusting for VAT or insulin resistance or both ( P for trend = 0.027, 0.001 and 0.040 respectively), this relationship was slightly attenuated but remained statistically significant. The leisure-time PA and weighted PA also had inverse associations with NAFLD independent of the VAT or insulin resistance or both. Conclusions This study showed an inverse association between various types of PA and the prevalence of NAFLD in a dose-dependent manner that was independent of visceral obesity and insulin resistance. This finding suggests a beneficial association between PA and NAFLD. [ABSTRACT FROM AUTHOR]