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Growing evidence supports that nonalcoholic fatty liver disease (NAFLD) is associated with extrahepatic cancers. Nonalcoholic fatty liver disease (NAFLD) and breast cancer share similar risk factors, including obesity. The aim of this case-control study was to investigate the association between NAFLD and breast cancer. Subjects who received health screening, including mammography and breast and hepatic ultrasonography simultaneously, were included. Subjects diagnosed with breast cancer were matched with controls. Conditional logistic regression analyses were performed. Among 270 breast cancer patients and 270 controls, 81 cancer patients (30.0%) and 54 controls (20.0%) had NAFLD (P = 0.008). NAFLD was significantly associated with breast cancer in multivariate analysis (P = 0.046). When the interaction between obesity (BMI < 25 kg/m2 vs. ≥25 kg/m2) and NAFLD in breast cancer patients was examined, a significant effect modification between obesity and NAFLD in breast cancer was noted (P = 0.021). The subgroup analysis showed that NAFLD was significantly associated with breast cancer in the nonobese subgroup (odds ratio 3.04, 95% confidence interval 1.37–4.32, P = 0.002) but not in the obese group (P = 0.163). NAFLD was significantly associated with breast cancer independent of traditional risk factors, and this association existed in the nonobese subgroup but not in the obese subgroup. [ABSTRACT FROM AUTHOR]

Abstract Background Liver fibroscan has recently been suggested as an alternative method to measure liver steatosis noninvasively. In this study, we evaluated usefulness of controlled attenuation parameter (CAP) for detecting increased arterial stiffness in general population. Methods A total of 515 asymptomatic patients without potential cause of liver disease who had liver fibroscan and cardio-ankle vascular index (CAVI) during their health check-up exams were included. A cut off of CAP ≥222 dB/m was used to define fatty liver and CAVI ≥ 8 for increased arterial stiffness. Results Both unadjusted and adjusted regression analyses showed significant association between fatty liver and increased arterial stiffness [unadjusted Odds ratio (OR) 1.896, 95% CI 1.305–2.754, p =.001 for CAP ≥ 222 dB/m alone]. With all traditional cardiovascular risk factors such as age, gender, body mass index, hypertension, diabetes mellitus, hypercholesterolemia and smoking adjusted, CAP ≥ 222 dB/m still showed significant association with increased arterial stiffness (OR 2.309, 95% CI 1.419–3.756, p =.001). The correlation between CAP-defined fatty liver and arterial stiffness was especially strong in subjects without diabetes (OR 2.959, 95% CI 1.709–5.122, p < 0.001). Conclusion CAP ≥ 222 dB/m is independently associated with increased arterial stiffness. As increased arterial stiffness is a surrogate and prognosticator for cardiovascular disease, surveillance using liver fibroscan may help screen and further stratify risk of patients. [ABSTRACT FROM AUTHOR]

Aims To investigate the longitudinal association between changes in body fat amount and the incidence and regression of nonalcoholic fatty liver disease (NAFLD). Methods We performed a cohort study of 2017 subjects without liver disease or significant alcohol consumption from 2007 to 2008 and participated in a voluntary follow-up between 2011 and 2013. Of the 2017 subjects, we enrolled 956 (47.4%) subjects who had available abdominal fat data in both 2007–2008 and 2011–2013. NAFLD was diagnosed on the basis of ultrasonographic findings. Adipose tissue area was evaluated by computed tomography. Results We observed 145 incident cases of NAFLD (22.6% of 642), and 79 subjects experienced a regression of NAFLD (25.2% of 314) during a median of 4.64 years. An increasing change in visceral adipose tissue (VAT) area was associated with a higher incidence of NAFLD (highest tertile vs. lowest tertile of VAT hazard ratio [HR] 2.45, 95% confidence interval [CI] 1.56–3.85, P for trend <0.001) in the multivariable analysis. An increasing change in VAT area was inversely associated with the regression of NAFLD (highest tertile vs. lowest tertile of VAT HR 0.40, 95% CI 0.20–0.80, P for trend = 0.008). Conclusions An increasing change in VAT area was longitudinally associated with a higher risk of incident NAFLD and inversely associated with the regression of NAFLD. [ABSTRACT FROM AUTHOR]

Aims Hemoglobin (Hb) is known to be associated with both nonalcoholic fatty liver disease (NAFLD) and metabolic syndrome (MS). We evaluated the relationship between serum Hb levels and the development of MS or NAFLD. Methods A retrospective cohort study was conducted. We recruited participants who underwent abdominal ultrasonography and blood samplings in both 2005 and 2010. Results Graded independent relationships were observed between higher Hb levels and the incidence of MS and NAFLD. After adjusting for age, body mass index, and fasting glucose, high-density lipoprotein cholesterol and triglyceride levels, the risk of developing MS was significantly higher according to the Hb quartiles in men ( P for trend = 0.027). The adjusted odds ratio (OR) and 95% confidence intervals (CIs) for the highest Hb quartile was 1.81 (1.06–3.10) for women and 1.43 (1.00–2.05) for men. The risk of developing NAFLD was also significantly higher according to the Hb quartiles in men ( P for trend = 0.03). The adjusted OR and 95% CI for the highest Hb quartile was 1.18 (0.73–1.91) in women and 1.76 (1.16–2.66) in men. Conclusions The risk of developing either MS or NAFLD was significantly associated with serum Hb levels in men. These findings have implications in the clinical availability of serum Hb as a predictor of MS and NAFLD. [ABSTRACT FROM AUTHOR]

Population-based data regarding the prognostic implications of hepatic steatosis have been inconsistent. We examined the association between the fatty liver index (FLI) with all-cause and disease-specific mortality in the general population. We included subjects who underwent a health examination in 2009 using the Korean nationwide health screening database. Death and cause of death data were provided by Statistics Korea. The causes of death were classified using 10th Revision of the International Classification of Diseases codes. Among the included 10,585,844 participants, there were 418,296 deaths during a median follow-up period of 8.3 years. When adjusting for possible confounding factors, the risk of all-cause mortality linearly increased with a higher FLI score (hazard ratio [HR], 95% confidence interval [CI]: FLI 30–59, 1.19, 1.18–1.20; FLI ≥ 60, 1.67, 1.65–1.69, P for trend <0.001). The risk of disease-specific mortality including cardiovascular disease (CVD), cancer, respiratory disease and liver disease, linearly increased as the FLI score became higher (HR, 95% CI: FLI 30–59, 1.18, 1.16–1.20, FLI ≥ 60: 1.61, 1.56–1.65 for CVD; FLI 30–59, 1.13, 1.11–1.14, FLI ≥ 60, 1.41, 1.38–1.44 for cancer; FLI 30–59, 1.26, 1.22–1.29, FLI ≥ 60, 1.96, 1.88–2.05 for respiratory disease, FLI 30–59, 2.29, 2.21–2.38, FLI ≥ 60, 5.57, 5.31–5.85 for liver disease). The risk of all-cause mortality increased as the FLI score became higher across all the body mass index groups, and the greatest risk was observed in those who were underweight (HR, 95% CI = 2.43, 2.09–2.82 in FLI ≥ 60). FLI may serve as a prognostic indicator of death and a high FLI is associated with a poor prognosis particularly in the underweight group. • The risk of all-cause and disease-specific mortality linearly increased with a higher fatty liver index (FLI) score. • Those who were underweight showed the greatest risk of all-cause mortality with high FLI scores compared to other BMI groups. • FLI may serve as a prognostic indicator of death and a high FLI is associated with a poor prognosis. [ABSTRACT FROM AUTHOR]

We investigated the association between the patatin-like phospholipase domain-containing-3 (PNPLA3) rs738409 genotype and the risk of diabetes mellitus (DM) using a biopsy-confirmed nonalcoholic fatty liver disease (NAFLD) cohort and a longitudinal observational cohort. Associations between genotypes and the prevalence of DM were evaluated with stratification according to the histological severity of NAFLD in the Boramae cohort (n = 706). A longitudinal cohort consisting of nondiabetic individuals with ≥2 health checkups was then selected to investigate the risk of incident DM according to the genotype (the GENIE cohort; n = 4998). Among subjects with NAFLD in the Boramae cohort, the G allele was independently associated with a lower prevalence of DM in both NAFL (odds ratio [OR] per 1 allele, 0.66; 95% confidence interval [CI], 0.46–0.97) and nonalcoholic steatohepatitis (OR per 1 allele, 0.59; 95% CI, 0.38–0.92). This result was replicated in the longitudinal GENIE cohort. The G allele was associated with a lower risk of incident DM during the median follow-up of 60 months in subjects with NAFLD (hazard ratio, 0.65; 95% CI, 0.45–0.93). In contrast, G allele carriers without NAFLD showed higher odds for DM in the context of the Boramae cohort (OR, 2.44; 95% CI, 1.00–5.95). These findings clarify conflicting results regarding the association between the PNPLA3 rs738409 genotype and the risk of DM, demonstrating a clear difference between subjects with and without NAFLD; this difference might be explained by the low metabolic risk in genetic NAFLD. [Display omitted] [ABSTRACT FROM AUTHOR]

Nonalcoholic fatty liver disease (NAFLD) is associated with an increased risk of diabetes but has been rarely investigated in young adults. In this study, we investigated the relationship between NAFLD and incident diabetes risk in young adults using nationwide Korean population data. This population-based cohort study from the Korean National Health Insurance Service included adults aged 20 through 39 years who underwent a health examination from 2009 to 2012. NAFLD was defined as a fatty liver index (FLI) ≥60 in the absence of alcohol consumption of ≥30 g/day. Newly diagnosed diabetes during follow-up was identified using claims data. Cox regression was used to calculate the hazard ratio for incident diabetes after adjusting for classical confounders. Among the 5,254,786 participants, 9.3% had an FLI ≥60. During the median follow-up of 8.6 years, 91,885 cases of incident diabetes occurred. In multivariable analysis, the risk of incident diabetes was significantly higher in the NAFLD group than the control group (adjusted hazard ratio = 4.97, 95% confidence interval, 4.90–5.05). Stratified analyses showed higher associations in those who were ≥30 years, male, obese, smokers, alcohol consumers, and did not regularly exercise (all P < 0.001). NAFLD is associated with a five-fold increased risk of incident diabetes in young adults. These results suggest an independent high risk for incident diabetes in young adults and underscore the importance of paying early attention to patients who develop NAFLD before middle age. • The association between NAFLD and diabetes rarely has been studied in young adults. • NAFLD was associated with a 5-fold increased risk of diabetes in young adults. • There was a J-shaped relationship between the FLI and the risk of diabetes. • FLI can be a tool for identifying young NAFLD patients at higher risk for diabetes. [ABSTRACT FROM AUTHOR]

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide and a major cause of liver-related morbidity and mortality.1 Although our understanding of its classic risk factors has improved, the prevalence of NAFLD has increased rapidly; thus, further investigation of modifiable risk factors for NAFLD is needed. [ABSTRACT FROM AUTHOR]

Narrow-band imaging (NBI) can be used to determine whether colorectal polyps are adenomatous or hyperplastic. We investigated whether an artificial intelligence (AI) system can increase the accuracy of characterizations of polyps by endoscopists of different skill levels. We developed convolutional neural networks (CNNs) for evaluation of diminutive colorectal polyps, based on efficient neural architecture searches via parameter sharing with augmentation using NBIs of diminutive (≤5 mm) polyps, collected from October 2015 through October 2017 at the Seoul National University Hospital, Healthcare System Gangnam Center (training set). We trained the CNN using images from 1100 adenomatous polyps and 1050 hyperplastic polyps from 1379 patients. We then tested the system using 300 images of 180 adenomatous polyps and 120 hyperplastic polyps, obtained from January 2018 to May 2019. We compared the accuracy of 22 endoscopists of different skill levels (7 novices, 4 experts, and 11 NBI-trained experts) vs the CNN in evaluation of images (adenomatous vs hyperplastic) from 180 adenomatous and 120 hyperplastic polyps. The endoscopists then evaluated the polyp images with knowledge of the CNN-processed results. We conducted mixed-effect logistic and linear regression analyses to determine the effects of AI assistance on the accuracy of analysis of diminutive colorectal polyps by endoscopists (primary outcome). The CNN distinguished adenomatous vs hyperplastic diminutive polyps with 86.7% accuracy, based on histologic analysis as the reference standard. Endoscopists distinguished adenomatous vs hyperplastic diminutive polyps with 82.5% overall accuracy (novices, 73.8% accuracy; experts, 83.8% accuracy; and NBI-trained experts, 87.6% accuracy). With knowledge of the CNN-processed results, the overall accuracy of the endoscopists increased to 88.5% (P <.05). With knowledge of the CNN-processed results, the accuracy of novice endoscopists increased to 85.6% (P <.05). The CNN-processed results significantly reduced endoscopist time of diagnosis (from 3.92 to 3.37 seconds per polyp, P =.042). We developed a CNN that significantly increases the accuracy of evaluation of diminutive colorectal polyps (as adenomatous vs hyperplastic) and reduces the time of diagnosis by endoscopists. This AI assistance system significantly increased the accuracy of analysis by novice endoscopists, who achieved near-expert levels of accuracy without extra training. The CNN assistance system can reduce the skill-level dependence of endoscopists and costs. [ABSTRACT FROM AUTHOR]

The optimal training method for endoscopic characterization of colorectal polyps using narrow-band imaging is uncertain, and sessile serrated lesions (SSLs) optical diagnosis data are lacking. We aimed to evaluate a comprehensive training program for real-time optical diagnosis of colorectal polyps, including SSLs. We performed a single-institution prospective study of 15 endoscopists trained with the Workgroup Serrated Polyps and Polyposis classification system. After the first phase of in vivo optical diagnosis, their performances were evaluated. After re-education for insufficient competency, they began the second phase. The learning curves and performance on 2 preservation and incorporation of valuable endoscopic innovations benchmarks were assessed. A total of 7294 polyps, including 486 SSLs, were diagnosed in real-time. The overall accuracy improved from 73.5% in the first phase to 77.1% in the second. The accuracy with high confidence was 79.4% and 85.1% in the first and second phases, respectively. In the first and second phases, the negative predictive values for diminutive neoplastic polyps were 82.1% and 92.5%, respectively, and concordances of the surveillance intervals were 80.7% and 89.7%, respectively. Eight endoscopists achieved the preservation and incorporation of valuable endoscopic innovations benchmarks after the second phase compared with none after the first. In contrast, the high confidence rate decreased from 74.6% to 70.2% as training progressed. A comprehensive training program for real-time optical diagnosis significantly improved performance and reduced individual variability in less-experienced endoscopists. ClinicalTrials.gov no: NCT 02516748. [ABSTRACT FROM AUTHOR]

Background & Aims Some studies have examined correlations between visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) with nonalcoholic fatty liver disease (NAFLD) or between VAT and NAFLD. We investigated the longitudinal association between body fat distribution (VAT vs SAT) and incidence and regression of NAFLD, adjusting for risk factors, in a large population-based cohort. Methods We collected data from adults who underwent abdominal ultrasonography (to identify liver fat), abdominal fat computed tomography scan, and blood tests from March 2007 through December 2008. Each patient underwent an anthropometric assessment and completed a questionnaire about their medical history, physical activity, and diet. Our final analysis involved 2017 subjects from the initial cohort who participated in a voluntary follow-up health screen performed in 2011 and 2013. The median follow-up time was 4.43 years. Results We found 288 incident cases of NAFLD; 159 patients had NAFLD regression during the follow-up period. An increasing area of VAT was associated with higher incidence of NAFLD in the multivariable analysis (highest quintile vs lowest quintile of VAT hazard ratio [HR], 2.23; 95% confidence interval [CI], 1.28−3.89; P for trend = .002; HR, 1.36 [per 1 standard deviation]; 95% CI, 1.16−1.59). An increased area of SAT was significantly associated with regression of NAFLD (highest quintile vs lowest quintile of SAT HR, 2.30; 95% CI, 1.28–4.12; P for trend = .002; HR, 1.36 [per 1 standard deviation]; 95% CI, 1.08−1.72). Conclusions In a large cohort study, larger areas of VAT were longitudinally associated with higher risk of incident NAFLD (during a period of approximately 4 years). In contrast, larger areas of SAT were longitudinally associated with regression of NAFLD. These data indicate that certain types of body fat are risk factors for NAFLD, whereas other types could reduce risk for NAFLD. [ABSTRACT FROM AUTHOR]

Abstract: Background: Inverse correlations of high serum bilirubin with metabolic and cardiovascular disease have been suggested. However, anti-atherogenic effects of bilirubin have not been well-established in terms of the presence of plaques and stenosis identified in coronary computed tomography (CT). Methods: A cross-sectional study was conducted on 2862 men who were free of cardiovascular disease and underwent coronary CT as part of a routine medical screening examination. Coronary stenotic lesions were considered to be incidences of coronary atherosclerosis, and stenosis was classified as stenosis <50% or ≥50%, according to degree of stenosis. Results: The prevalences of coronary atherosclerosis and stenosis ≥50% in subjects with elevated bilirubin levels (>1.2 mg/dL) were lower than those in subjects with normal bilirubin levels (≤1.2 mg/dL) (19.9% vs. 27.9%, p < 0.001, 8.5% vs. 10.3%, p = 0.044). Bilirubin was inversely associated with total plaques (odds ratio [OR] 0.59, 95% confidence interval [CI] 0.48–0.73 in the 4th quartile vs. 1st quartile) and calcified plaques (OR 0.60, 95% CI 0.49–0.75) in univariate analysis. After adjusting for traditional risk factors, it was found that coronary atherosclerosis (OR 0.73, 95% CI 0.56–0.94 in the 4th quartile vs. 1st quartile) and calcified plaque (OR 0.66, 95% CI 0.53–0.84) were inversely associated with the bilirubin grade in a dose-dependent manner. Conclusions: The serum bilirubin level was inversely associated with coronary atherosclerosis and calcified plaques in a dose-dependent manner. These results suggested that serum bilirubin could be used as a protective biomarker of coronary artery disease. [Copyright &y& Elsevier]

Abstract: Hypoxia induces survival signals in hepatocellular carcinoma (HCC). We attempted to find a hypoxia-induced signal that could be used for modulating HCC cell death. Cellular retinoic acid binding protein-II (CRABP-II) expression was significantly increased in hypoxic HCC cells. Treatment with retinoic acid (RA), a ligand for CRABP-II, induced HCC cell apoptosis more effectively in hypoxia than in normoxia, whereas hypoxia-induced CRABP-II expression attenuated RA-induced apoptosis. Inhibition of CRABP-II enhanced RA-induced apoptosis and sensitized RA-resistant HCC cells to RA cytotoxicity by attenuating p42/44 MAPK and Akt activation. Therefore, RA/CRABP-II signal modulation is therapeutically implicated in infiltrative HCCs exposed to hypoxia. [Copyright &y& Elsevier]