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BACKGROUND & AIMS Evaluation of the controlled attenuation parameter (CAP) is a promising noninvasive method for assessing hepatic steatosis. Despite the increasing reliability of the CAP for assessing steatosis in subjects with chronic liver disease, few studies have evaluated the CAP in asymptomatic subjects without overt liver disease. Therefore, we aimed to evaluate the usefulness of the CAP for a health check-up population. METHODS We enrolled subjects who underwent abdominal ultrasonography (US), FibroScan (Echosens, France) and blood sampling during medical health check-ups. The CAP was measured using FibroScan, and increased CAP was defined as CAP ≥ 222 dB/m. RESULTS A total of 1133 subjects were included; 589 subjects (52.0%) had fatty liver based on US, and 604 subjects (53.3%) had increased CAP. Increased CAP was significantly associated with metabolic abnormalities, including higher body mass index (BMI)[odds ratio (OR) = 1.33;95% confidence interval (CI),1.24-1.43; P

BACKGROUND AND OBJECTIVE Although both non-alcoholic fatty liver disease (NAFLD) and lung function are known to be associated with metabolic syndromes, few studies have evaluated the relationship between NAFLD and lung function. Our population-based study was conducted to investigate whether NAFLD, diagnosed by elevation of liver enzymes without other chronic liver disease or heavy alcohol drinking, is associated with lung function. METHODS A survey design analysis was performed using national representative data of health and nutritional status of civilians in Korea (Korean National Health and Nutrition Examination Survey, KNHANES) between 2010 and 2012. The criteria for NAFLD diagnosis was elevated serum alanine aminotransferase (ALT) without other chronic liver disease or heavy alcohol drinking. Covariate-adjusted linear regression analyses and post-stratification adjustments to the survey weights based on the propensity scores (PS) were conducted to evaluate the association of NAFLD and lung function, including the forced expiratory volume in 1 s (FEV1 ) and forced vital capacity (FVC). RESULTS A total of 7417 subjects were included in this analysis. NAFLD was significantly associated with a lower FVC among males as determined by both the covariate-adjusted linear regression analysis (P

Background Nonalcoholic fatty liver disease (NAFLD) is associated with a wide spectrum of metabolic abnormalities. This study aimed to evaluate whether NAFLD is associated with benign prostatic hyperplasia (BPH) independent of other risk factors. Methods A total of 3,508 subjects who underwent prostate and hepatic ultrasonography were enrolled. NAFLD was diagnosed and graded by ultrasonographic findings. BPH was defined by total prostate volume. Results The prevalence of BPH was significantly increased according to NAFLD severity (P < 0.001). The multivariate analysis showed that NAFLD was associated with a 22% increase in the risk of BPH (odds ratio [OR], 1.22; 95% confidence interval [CI], 1.02–1.45). In non-obese subjects, NAFLD was associated with a 41% increase in the risk of BPH (OR, 1.41; 95% CI, 1.14–1.73), and an incremental increase in the risk of BPH according to NAFLD severity was pronounced (adjusted OR [95% CI], 1.32 [1.05–1.68] for mild NAFLD, 1.55 [1.15–2.10] for moderate to severe NAFLD vs. no NAFLD, P for trend = 0.004). However, in the obese population, the association of NAFLD in the risk of BPH was insignificant (P = 0.208). Conclusion NAFLD is associated with an increased risk of BPH regardless of metabolic syndrome, especially in non-obese subjects. An incrementally increased risk of BPH according to NAFLD severity is prominent in non-obese subjects with NAFLD. Thus, physicians caring for non-obese patients with NAFLD may consider assessing the risk of BPH and associated urologic conditions., Graphical Abstract

The coexistence of HBsAg and anti-HBs has been reported in some chronic hepatitis B patients; however, the long-term outcomes of this serological profile have not been elucidated. We aimed to evaluate the long-term outcomes of HBsAg/anti-HBs double-positive chronic hepatitis B patients. Chronic hepatitis B patients who underwent baseline abdominal ultrasonography and follow-up (HBsAg/anti-HBs assessment and abdominal ultrasonography) at our healthcare center were included. The “coexistence group” included patients positive for both HBsAg and anti-HBs and the “control group” included patients positive for only HBsAg during follow-up. The outcomes were hepatocellular carcinoma (HCC) incidence, HBsAg seroclearance and overall mortality. Kaplan-Meier and Cox proportional hazard regression analyses were performed. Of the 2,341 eligible patients, 166 (7.1%) were in the coexistence group. The total follow-up duration was 5.4 years. The coexistence group had a 3.08-fold higher risk of HCC than the control group [hazard ratio (HR) 3.08, 95% confidence interval(CI) 1.26–7.55, P = 0.014] in multivariate analysis. The coexistence group had more HBsAg seroclearance than the control group (HR 1.43, 95% CI 1.01–2.03, P = 0.046). However, overall mortality did not significantly differ between the 2 groups. The coexistence group is heterogeneous and includes subjects with unfavorable outcomes (incidence of HCC) and favorable outcomes (more HBsAg seroclearance).

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.

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.

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 1,373 subjects enrolled, 288 (21.0%) developed NAFLD. Both total and leisure-time PA at baseline were inversely associated with incident NAFLD (p for trend=0.005 and 0.003, 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=0.028]. 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. This article is protected by copyright. All rights reserved.

Nonalcoholic fatty liver disease (NAFLD) is associated with coronary artery calcification (CAC) in cross-sectional studies. However, whether NAFLD itself affects CAC development or progression remains unknown.This study investigated the longitudinal association between NAFLD and CAC score.This study is a longitudinal cohort study performed in a healthcare center.Among 1732 subjects who underwent serial CAC evaluation, we evaluated 846 subjects with NAFLD and 886 subjects without NAFLD, as diagnosed via ultrasonography.CAC score was compared at baseline and follow-up. In subjects without calcification (CAC score = 0) at baseline, any incidental calcification (CAC score0) at follow-up was defined as development of CAC. In subjects with CAC (CAC score0) at baseline, confirmed CAC aggravation was defined as progression. Logistic regression analysis was performed.More subjects with NAFLD than without showed CAC development or progression (48.8 vs 38.4%; P.001). The impact of NAFLD on a change in CAC score significantly differed according to the CAC score at baseline. In subjects without calcification at baseline, NAFLD significantly affected the development of calcification (odds ratio, 1.49; 95% confidence interval, 1.01-2.21; P = .045) after adjusting for traditional metabolic risk factors. However, in subjects with baseline CAC, NAFLD did not significantly affect progression (P = .734). Additionally, the severity of NAFLD was important. The severity of NAFLD was dose-dependently associated with the development of CAC (P for trend = .043).NAFLD plays a role in the early development of CAC, but not the progression. Ultrasonographic severity of NAFLD is dose-dependently associated with CAC development in subjects with a CAC score of 0 at baseline, independent of traditional risk factors.

INTRODUCTION: Spontaneous hepatitis B surface antigen (HBsAg) seroclearance, the functional cure of hepatitis B infection, occurs rarely. Prior original studies are limited by insufficient sample size and/or follow-up, and recent meta-analyses are limited by inclusion of only study-level data and lack of adjustment for confounders to investigate HBsAg seroclearance rates in most relevant subgroups. Using a cohort with detailed individual patient data, we estimated spontaneous HBsAg seroclearance rates through patient and virologic characteristics. METHODS: We analyzed 11,264 untreated patients with chronic hepatitis B with serial HBsAg data from 4 North American and 8 Asian Pacific centers, with 1,393 patients with HBsAg seroclearance (≥2 undetectable HBsAg ≥6 months apart) during 106,192 person-years. The annual seroclearance rate with detailed categorization by infection phase, further stratified by hepatitis B e antigen (HBeAg) status, sex, age, and quantitative HBsAg (qHBsAg), was performed. RESULTS: The annual seroclearance rate was 1.31% (95% confidence interval: 1.25–1.38) and over 7% in immune inactive patients aged ≥55 years and with qHBsAg 55 years: aHR = 1.21), negative HBeAg (aHR = 6.34), and genotype C (aHR = 1.82) predicted higher seroclearance rates, as did lower hepatitis B virus DNA and lower qHBsAg (P < 0.05 for all), and inactive carrier state. DISCUSSION: The spontaneous annual HBsAg seroclearance rate was 1.31%, but varied from close to zero to about 5% among most chronic hepatitis B subgroups, with older, male, HBeAg-negative, and genotype C patients with lower alanine aminotransferase and hepatitis B virus DNA, and qHBsAg independently associated with higher rates (see Visual Abstract, Supplementary Digital Content 2, http://links.lww.com/CTG/A367).

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.

Purpose The Health and Prevention Enhancement (H-PEACE) study was designed to investigate the association of diagnostic imaging results, biomarkers and the predisease stage of non-communicable diseases (NCDs), such as malignancies and metabolic diseases, in an average-risk population in Korea. Participants This study enrolled a large-scale retrospective cohort at the Healthcare System Gangnam Center, Seoul National University Hospital, from October 2003 to December 2014. Findings to date The baseline and follow-up information collected in the predisease stage of NCDs allows for evaluation of an individual’s potential NCD risk, which is necessary for establishing personalised prevention strategies. A total of 91 336 health examinees were included in the cohort, and we repeatedly measured and collected information for 50.9% (n=46 484) of the cohort members. All participants completed structured questionnaires (lifestyle, medical history, mini-dietary assessment index, sex-specific variables and psychiatric assessment), doctors’ physical examinations, laboratory blood and urine tests and digital chest X-ray imaging. For participants with available data, we also obtained information on specific diagnostic variables using advanced diagnostic tests, including coronary CT for coronary calcium scores, colonoscopy and brain MRI. Furthermore, 17 455 of the participants who provided informed consent and donated blood samples were enrolled into the Gene-environmental interaction and phenotype study, a subcohort of the H-PEACE, from October 2013, and we analysed genome-wide single-nucleotide polymorphism array data for 6579 of these blood samples. Future plans The data obtained from this cohort will be used to facilitate advanced and accurate diagnostic techniques related to NCDs while considering various phenotypes. Potential collaborators can access the dataset after receiving approval from our institutional review board. Applications can be submitted on the study homepage (http://en-healthcare.snuh.org/HPEACEstudy).

Min-Sun Kwak,1 Eunyoung Kim,2 Eun Jin Jang,3 Hyun Jung Kim,4 Chang-Hoon Lee5 1Department of Internal Medicine, Healthcare Research Institute, Healthcare System Gangnam Center, Seoul National University Hospital, Seoul, Republic of Korea; 2Department of Statistics, Kyungpook National University, Daegu, Republic of Korea; 3Department of Information Statistics, Andong National University, Andong, Republic of Korea; 4Department of Preventive Medicine, College of Medicine, Korea University, Seoul, Republic of Korea; 5Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Republic of Korea Purpose: Although tiotropium (TIO) and inhaled corticosteroid (ICS)/long-acting β-agonists are frequently prescribed together, the efficacy of “triple therapy” has not been scientifically demonstrated. We conducted a systematic review and meta-analysis using Bayesian methods to compare triple therapy and TIO monotherapy.Methods: We searched the MEDLINE, EMBASE, and Cochrane Library databases for randomized controlled trials comparing the efficacy and safety of triple therapy and TIO monotherapy in patients with chronic obstructive pulmonary disease (COPD). We conducted a meta-analysis to compare the effectiveness and safety of triple therapy and TIO monotherapy using Bayesian random effects models.Results: Seven trials were included, and the risk of bias in the majority of the studies was acceptable. There were no statistically significant differences in the incidence of death and acute exacerbation of disease in the triple therapy and TIO monotherapy groups. Triple therapy improved the prebronchodilator forced expiratory volume in 1 second (mean difference [MD], 63.68 mL; 95% credible interval [CrI], 45.29–82.73), and patients receiving triple therapy showed more improvement in St George Respiratory Questionnaire scores (MD, -3.11 points; 95% CrI, -6.00 to -0.80) than patients receiving TIO monotherapy. However, both of these differences were lower than the minimal clinically important difference (MCID). No excessive adverse effects were reported in triple therapy group.Conclusion: Triple therapy with TIO and ICSs/long-acting β-agonists was only slightly more efficacious than TIO monotherapy in treating patients with COPD. Further investigations into the efficacy of new inhaled drugs are needed. Keywords: inhaled long-acting muscarinic antagonists (LAMAs), inhaled corticosteroids (ICSs), inhaled long-acting β2-agonists (LABAs), chronic obstructive pulmonary disease (COPD)

The objective of the present study is to systematically evaluate and compare the rheological behaviors of body cream and body lotion in actual usage situations. Using a strain-controlled rheometer, the steady shear flow properties of commercially available body cream and body lotion were measured over a wide range of shear rates, and the linear viscoelastic properties of these two materials in small amplitude oscillatory shear flow fields were measured over a broad range of angular frequencies. The temperature dependency of the linear viscoelastic behaviors was additionally investigated over a temperature range most relevant to usual human life. The main findings obtained from this study are summarized as follows: (1) Body cream and body lotion exhibit a finite magnitude of yield stress. This feature is directly related to the primary (initial) skin feel that consumers usually experience during actual usage. (2) Body cream and body lotion exhibit a pronounced shear-thinning behavior. This feature is closely connected with the spreadability when cosmetics are applied onto the human skin. (3) The linear viscoelastic behaviors of body cream and body lotion are dominated by an elastic nature. These solid-like properties become a criterion to assess the selfstorage stability of cosmetic products. (4) A modified form of the Cox-Merz rule provides a good ability to predict the relationship between steady shear flow and dynamic viscoelastic properties for body cream and body lotion. (5) The storage modulus and loss modulus of body cream show a qualitatively similar tendency to gradually decrease with an increase in temperature. In the case of body lotion, with an increase in temperature, the storage modulus is progressively decreased while the loss modulus is slightly increased and then decreased. This information gives us a criterion to judge how the characteristics of cosmetic products are changed by the usual human environments.

Nonalcoholic fatty liver disease (NAFLD) is a prevalent disease with 20–30 % of the population affected in many developed and developing countries. Studies assessing the prognosis of NAFLD have shown that simple steatosis has a benign long-term outcome without excess mortality compared to the general population but that patients with NASH or with fibrosis have increased long-term mortality with standardized mortality ratio of 1.34–2.6 and hazard ratio of 1.004–1.05. The excess mortality of NAFLD patients is mainly due to cardiovascular disease. Liver-related mortality is also elevated in patients with NAFLD, especially in those patients with NASH or advanced fibrosis. A simple noninvasive fibrosis marker such as the NAFLD fibrosis score might be useful for predicting overall mortality and cause-specific mortality in these patients. A proportion of NAFLD develop concomitant or subsequent NASH at a rate of 10–20 %, and about 10 % of NASH cases progress to cirrhosis. NAFLD can progress to HCC, especially in patients with cirrhosis or advanced liver fibrosis. In addition to these liver-related complications, metabolic complications can also occur. The incidence of newly developed diabetes is elevated in NAFLD patients, and nonfatal and fatal cardiovascular diseases occur more frequently in patients with NAFLD. Therefore, cardiovascular assessment and liver-related surveillance might be considered in patients with NAFLD. In summary, we should pay more attention to patients with NAFLD, especially those with advanced forms of the disease because these individuals have increased morbidity and mortality.

Incidental, small rectal neuroendocrine tumors during colonoscopy screening are sometimes removed using biopsy forceps. Few studies have examined the clinical course of rectal neuroendocrine tumors removed by simple excisional biopsy.We investigated the long-term outcome of rectal neuroendocrine tumors removed by simple excisional biopsy compared with standard endoscopic resection.This was a cohort study.This study was performed at a healthcare center in Korea.We enrolled patients with rectal neuroendocrine tumors detected during a screening colonoscopy between 2003 and 2015.The clinical characteristics and long-term outcomes (overall survival and disease-free survival) of small neuroendocrine tumors10 mm were compared between the simple excisional biopsy group and advanced endoscopic resection group.In total, 166 patients were diagnosed with rectal neuroendocrine tumors (≤5 mm, n = 100; 6-9 mm, n = 50; 10-19 mm, n = 15; ≥20 mm, n = 1). Among the 150 patients with neuroendocrine tumors10 mm, follow-up endoscopy was performed on 99 (59.6%). All of the tumors were confined to the mucosa or submucosa. Thirty-one and 68 patients were included in the simple excisional biopsy and advanced endoscopic resection groups. The overall follow-up duration was 6.5 years (range, 1.0-12.8 y). Neither overall nor disease-related death occurred. Two patients exhibited local recurrence (6.5%, at 8 and 11 y) in the simple excisional biopsy group and 1 patient (1.5%, at 7 y) in the advanced endoscopic resection group, resulting in no significant difference (p = 0.37). All of the recurrences were diagnosed5 years from initial diagnosis and successfully treated endoscopically.More long-term data should be warranted.The long-term outcome of small rectal neuroendocrine tumors10 mm removed by simple excisional biopsy was excellent. Neither overall survival nor disease-free survival significantly differed between the simple excisional biopsy group and the advanced endoscopic resection group. Thus, simple excisional biopsy and long-term follow-up can be cautiously applied for small rectal neuroendocrine tumors in clinical practice. See Video Abstract at http://links.lww.com/DCR/A406.

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, and the prevalence of non-alcoholic steatohepatitis (NASH) with fibrosis is increasing as the population with NAFLD ages. To date, lifestyle modifications including weight loss, increased physical activity, and dietary changes remain the treatment of choice for NAFLD because there are no approved effective pharmacologic agents. Increased physical activity has therapeutic effects on NAFLD by reducing hepatic fat independent of weight reduction. Indeed, even minimal physical activity below the recommended threshold may have a beneficial impact on NAFLD. Aerobic activity and resistance training have similar effects on NAFLD. Universal recommendations for the optimal intensity and dose of physical activity have not been established. Therefore, physical activity should be tailored based on a patient's clinical characteristics, comorbidities, and fitness capacity. Physical activity also prevents the development of NAFLD and may represent a valuable strategy for reducing the public health burden. However, there are insufficient data supporting the effects of physical activity on the progression of non-alcoholic fatty liver to NASH with advanced fibrosis, and on extrahepatic disease-related morbidity and mortality. In this paper, we review the role of physical activity in the management of NAFLD.

BACKGROUND/AIMS Lacunar infarct, a small subcortical ischaemic lesion, is a known risk factor for future cognitive impairment, dementia and stroke. We evaluated the relationship between fatty liver disease (FLD) and lacunar infarct in a healthy general population. METHODS Subjects who underwent brain magnetic resonance imaging (MRI) and abdominal ultrasonography (US) during health check-ups from 2007 to 2009 were included. FLD was diagnosed by US. Subjects with a history of cerebrovascular disease, radiological findings consistent with cerebrovascular stenosis or cerebral small vessel disease were excluded. RESULTS Of the 1277 subjects, 54 (4.2%) exhibited lacunar infarct, and 514 (40.3%) had FLD. Subjects with lacunar infarct had a higher prevalence of FLD (59.3% vs 39.4%, P = .004). There was significant interaction between obesity (BMI

We conducted this study to explore the extent of occult helminth infection identified by fecal parasitological examinations or organ-specific examinations such as colonoscopy and abdominal ultrasonography (US) during health checkups. We analyzed 197,422 fecal samples from 99,451 subjects who received health checkups at a single center over 10 years. We found that 3,472 (1.8%) samples from 3,342 (3.4%) subjects tested positive for parasitic ova, including clonorchiasis, metagonimiasis, trichuriasis, ascariasis, trichostrongylosis, taeniasis, and enterobiasis. The detection rate for clonorchiasis was higher in those who were taking their first examination than in those who had been examined previously. The detection rate for clonorchiasis decreased gradually over the 10 years. Only 2.5% of the patients with clonorchiasis showed US or computed tomography (CT) images that were compatible with the disease. Clonorchiasis patients who had abdominal US or CT images that suggested clonorchiasis were older and had lower body mass indices and higher eosinophil counts than did those whose US or CT images did not suggest the disease. We observed worms in 9% of the patients with trichuriasis who had received a colonoscopy. Colonoscopy also uncovered adult worms in 0.03% of subjects who were not identified as having Trichuris trichiura ova in their fecal helminth examinations. In summary, our study shows that occult helminth infection is fairly frequently identified by a variety of methods during health checkups, which suggests that doctors need to make greater effort to identify and treat occult helminth infections in Korea.

To investigate the longitudinal association between changes in body fat amount and the incidence and regression of nonalcoholic fatty liver disease (NAFLD).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.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 trend0.001) 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).An increasing change in VAT area was longitudinally associated with a higher risk of incident NAFLD and inversely associated with the regression of NAFLD.

Endoplasmic reticulum (ER) stress has been implicated in the development of nonalcoholic steatohepatitis. A methionine–choline-deficient (MCD) diet induces robust ER stress response and steatohepatitis, but the effects of ER stress modulation on the course of steatohepatitis remain uncertain. The present study evaluated whether reducing ER stress using the chemical chaperone tauroursodeoxycholic acid (TUDCA) could limit hepatocyte lipoapoptosis and progression of MCD diet-induced steatohepatitis. HuH7 cells stably transfected with sodium taurocholate cotransporting polypeptide (HuH-Ntcp cells) and palmitate (PA) were used. Experimental steatohepatitis was induced in male C57BL/6 mice using an MCD diet, and three different doses of TUDCA (500, or 1,000 mg/kg, once daily; or 500 mg/kg twice daily) were administered by gavage from the start of the MCD diet regimen or after 4 weeks. TUDCA reduced PA-induced ER stress as manifested by decreased eIF2α phosphorylation, XBP1 splicing and expression of BiP, ATF4, and CHOP in HuH-Ntcp cells. TUDCA also decreased PA-induced JNK phosphorylation, Puma up-regulation and Bax activation, which in turn suppressed caspase-dependent hepatocyte lipoapoptosis. Mice given TUDCA did not show a significant decrease in the intrahepatic triglyceride contents and steatosis. However, TUDCA treatment significantly reduced hepatic damage compared to controls for both early and late treatment groups. TUDCA treatment reduced the expression of ER stress markers and pro-apoptotic proteins, leading to decreased apoptosis and oxidative stress. Finally, TUDCA reduced histological fibrosis along with the down-regulation of pro-fibrotic gene expression in both early and late treatment groups. These results show that TUDCA attenuates the progression of MCD diet-induced steatohepatitis by reducing ER stress.

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

Background & Aims 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. Methods 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. Results 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. Conclusion 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.

Seroclearance of hepatitis B surface antigen (HBsAg) is a marker for clearance of chronic hepatitis B virus (HBV) infection, but reported annual incidence rates of HBsAg seroclearance vary. We performed a systematic review and meta-analysis to provide more precise estimates of HBsAg seroclearance rates among subgroups and populations.We searched PubMed, Embase, and the Cochrane library for cohort studies that reported HBsAg seroclearance in adults with chronic HBV infection with more than 1 year of follow-up and at least 1 repeat test for HBsAg. Annual and 5-, 10-, and 15-year cumulative incidence rates were pooled using a random effects model.We analyzed 34 published studies (with 42,588 patients, 303,754 person-years of follow-up, and 3194 HBsAg seroclearance events), including additional and updated aggregated data from 19 studies. The pooled annual rate of HBsAg seroclearance was 1.02% (95% CI, 0.79-1.27). Cumulative incidence rates were 4.03% at 5 years (95% CI, 2.49-5.93), 8.16% at 10 years (95% CI, 5.24-11.72), and 17.99% at 15 years (95% CI, 6.18-23.24). There were no significant differences between the sexes. A higher proportion of patients who tested negative for HBeAg at baseline had seroclearance (1.33%; 95% CI, 0.76-2.05) than those who tested positive for HBeAg (0.40%; 95% CI, 0.25-0.59) (P.01). Having HBsAg seroclearance was also associated with a lower baseline HBV DNA level (6.61 logIn a systematic review and meta-analysis, we found a low rate of HBsAg seroclearance in untreated and treated patients (pooled annual rate, approximately 1%). Seroclearance occurred mainly in patients with less active disease. Patients with chronic HBV infection should therefore be counseled on the need for lifelong treatment, and curative therapies are needed.

To determine the relationship between hepatitis B virus (HBV) DNA level and the survival of patients with hepatocellular carcinoma treated by means of transarterial chemoembolization (TACE).This study was approved by the institutional review board, and the requirement to obtain informed consent was waived. From January 2005 to March 2007, 183 patients with HBV-related hepatocellular carcinoma who underwent TACE but never received antiviral therapy were consecutively enrolled in our cohort. All patients were tested for pre-TACE serum level of HBV DNA, and overall survival was measured from date of enrollment until death from any cause. Radiologic progression was evaluated by using the modified response evaluation criteria in solid tumors by means of independent radiologic assessment.The median overall survival was 19 months (95% confidence interval: 13.7, 24.3) and median time to progression was 4 months (95% confidence interval: 3.03, 4.97). Multivariate analysis revealed that a high pre-TACE serum level of HBV DNA (2000 IU/L) was an independent risk factor for reduced overall survival (P = .021; hazard ratio [HR], 1.725), high cancer progression-related mortality (P = .014; HR, 1.936), and hepatic failure-related mortality associated with cancer progression (P = .005, HR, 3.908). Pre-TACE level of HBV DNA did not significantly affect hepatic failure-related mortality that was not caused by cancer progression.A high pre-TACE serum level of HBV DNA was associated with poor overall survival and rapid progression of hepatocellular carcinoma after TACE, and the cause of mortality was not hepatitis exacerbation but cancer progression.

Background & aims The impact of marijuana on nonalcoholic fatty liver disease (NAFLD) is largely unknown. We studied the association between marijuana and NAFLD utilizing cross-sectional data from the National Health and Nutrition Examination Survey (NHANES) from 2005–2014 and NHANES III (1988–1994). Methods Suspected NAFLD was diagnosed if serum alanine aminotransferase (ALT) was > 30 IU/L for men and > 19 IU/L for women in the absence of other liver diseases (NHANES 2005–2014). In NHANES III cohort, NAFLD was defined based on ultrasonography. Results Of the 14,080 (NHANES 2005–2014) and 8,286 (NHANES III) participants, prevalence of suspected NAFLD and ultrasonographically-diagnosed NAFLD were inversely associated with marijuana use (p < 0.001). Compared to marijuana-naive participants, marijuana users were less likely to have suspected NAFLD (odds ratio [OR]: 0.90, 95% confidence interval [CI]: 0.82–0.99 for past user; OR: 0.68, 95% CI: 0.58–0.80 for current user) and ultrasonographically-diagnosed NAFLD (OR: 0.75, 95% CI: 0.57–0.98 for current user) in the age, gender, ethnicity-adjusted model. On multivariate analysis, the ORs for suspected NAFLD comparing current light or heavy users to non-users were 0.76 (95% CI 0.58–0.98) and 0.70 (95% CI 0.56–0.89), respectively (P for trend = 0.001) with similar trends in ultrasonographically-diagnosed NAFLD (OR: 0.77, 95% CI: 0.59–1.00 for current user; OR: 0.71, 95% CI: 0.51–0.97 for current light user). In insulin resistance-adjusted model, marijuana use remained an independent predictor of lower risk of suspected NAFLD. Conclusions In this nationally representative sample, active marijuana use provided a protective effect against NAFLD independent of known metabolic risk factors. The pathophysiology is unclear and warrants further investigation.

Background: Polymorphisms near the IL28B gene have been proposed to be strongly associated with treatment response and the rate of spontaneous clearance of hepatitis C virus infection, and treatment response of hepatitis B virus (HBV) infection. In this study, we aimed to determine whether these polymorphisms could affect natural courses of HBV infection. Methods: Genetic variations were identified through direct DNA sequencing using TaqMan assay in 1,439 patients with past or present HBV infection. Subjects included 404 spontaneously recovered patients, 313 chronic hepatitis B (CHB) patients, 305 liver cirrhosis (LC) patients and 417 hepatocellular carcinoma (HCC) patients. Three polymorphisms near the IL28B gene, rs8099917T>G, rs12979860C>T and rs12980275A>G, were identified. Associations between these polymorphisms and HBV clearance, hepatitis B e antigen (HBeAg) clearance as well as HCC occurrence among patients were analyzed using logistic regression analyses adjusted for age and gender. Results: There were no significant associations between these polymorphisms and the HBV clearance both in CHB and LC groups. Similarly, these polymorphisms showed no significant associations with HBeAg clearance and the occurrence of HCC either. Discussion: No significant association was identified between polymorphisms near the IL28B gene and the natural courses of chronic HBV infection, including the HBV clearance and HCC occurrence.

Background The presence of white matter hyperintensity (WMH) and lacunar infarct are recognized as risk factors of dementia, stroke and mortality. It is undetermined whether visceral adipose tissue (VAT) area is associated with an increased risk of cerebral small vessel disease. We explored whether VAT area was responsible for cerebral small vessel disease through the identification of WMH and lacunar infarct. Subjects A total of 2046 subjects free of cerebrovascular disease who underwent brain magnetic resonance imaging and abdominal fat computed tomography during a general health check-up were enrolled. Results The prevalence of cerebral WMH was 37.7%. Subjects with WMH had greater VAT area and higher BMI and waist circumference than those without WMH, although significant differences in subcutaneous adipose tissue (SAT) area were not shown. Subjects with lacunar infarct also had significantly greater VAT area and higher waist circumference and BMI than those without lacunar infarct. Multivariate analyses adjusted for age, sex, diabetes, hypertension, smoking and alcohol, showed VAT area was an independent risk factor of cerebral WMH (odds ratio (OR): 1.13, 95% confidence interval (CI): 1.02-1.24, P=0.016), whereas waist circumference and SAT area were not significantly associated with the risk of WMH. Likewise, VAT area was also independently associated with lacunar infarct (OR: 1.38, 95% CI: 1.06-1.81, P=0.018), whereas the other anthropometric measures were not related with lacunar infarct. Conclusions VAT has a significant association with cerebral small vessel disease, which was defined as WMH or lacunar infarct. Visceral obesity can be a potential therapeutic target for the prevention of cerebral small vessel disease.

3-bromopyruvate (3-BP), a hexokinase (HK) II inhibitor, promotes tumor cell death by inducing endoplasmic reticulum (ER) stress in human hepatocellular carcinoma (HCC) cell lines. Protein disulfide isomerase (PDI) is an essential folding catalyst and attenuates ER stress by folding the misfolded proteins. We examined if PDI is expressed in hypoxic HCC cells, and evaluated its inhibition potentiated HK II inhibitor-induced ER stress in hypoxic HCC cells. HCC apoptotic cell death was assessed by DAPI staining and apoptotic signaling pathways were explored by immunoblot analysis. An in vivo model of HCC was established in C3H mice intradermally with implanted MH134 cells. 3-BP with/without a PDI inhibitor (bacitracin) was subsequently administered. The anti-tumor efficacies were evaluated by measuring tumor volumes and quantifying apoptotic cells and microvessel densities (MVDs). HCC cells were found to express PDI in a hypoxia-inducible manner. The simultaneous treatment of bacitracin and 3-BP enhanced 3-BP-induced apoptosis. This enhancement was attributed to increased ER stress and JNK activation compared to the cells treated with just 3-BP. In an in vivo model of HCC, tumor growth was significantly suppressed in mice co-treated with bacitracin and 3-BP, and the percentages of apoptotic cells significantly increased and MVDs significantly decreased. These results demonstrated that PDI was induced in hypoxic HCC tissue and that PDI inhibition enhanced HK II inhibitor-induced anti-tumor efficacy synergistically via augmenting ER stress and anti-angiogenesis in vivo. Thus, blockage of PDI activity in combination with HK II inhibitor may be therapeutically useful in HCCs.

The hypoxic condition within large or infiltrative hypovascular tumors produces intracellular acidification, which could activate many signaling pathways and augment cancer cell growth and invasion. Carbonic anhydrase-IX (CA-IX) is an enzyme lowering pH. This study is to examine whether hypoxia induces CA-IX in hepatocellular carcinoma (HCC) cells, and to evaluate its clinical implication in HCC patients. Human HCC cell lines (Huh-7 and HepG2 cells) were used, and cell growth was assessed using MTS assay. CA-IX expression and apoptotic/kinase signaling were evaluated using immunoblotting. The cells were transfected with CA-IX-specific siRNA, or treated with its inhibitor 4-(2-aminoethyl) benzenesulfonamide (CAI#1), and/or the hexokinase II inhibitor, 3-bromopyruvate (3-BP). A clinic pathological analysis of 69 patients who underwent an HCC resection was performed using a tissue array. Incubation of HCC cells under hypoxia (1% O2, 5% CO2, 94% N2) for 36 h significantly increased CA-IX expression level. CAI#1 (400 μmol/L) or CA-IX siRNA (100 μmol/L) did not influence HCC cell growth and induce apoptosis. However, CAI#1 or CA-IX siRNA at these concentrations enhanced the apoptosis induced by 3-BP (100 μmol/L). This enhancement was attributed to increased ER stress and JNK activation, as compared with 3-BP alone. Furthermore, a clinic pathological analysis of 69 HCC patients revealed that tumor CA-IX intensity was inversely related to E-cadherin intensity. Inhibition of hypoxia-induced CA-IX enhances hexokinase II inhibitor-induced HCC apoptosis. Furthermore, CA-IX expression profiles may have prognostic implications in HCC patients. Thus, the inhibition of CA-IX, in combination with a hexokinase II inhibitor, may be therapeutically useful in patients with HCCs that are aggressively growing in a hypoxic environment.

Aim: Hepatic stellate cells (HSCs) have immune regulatory functions. Mesalamine is an effective immune regulatory drug for inflammatory bowel disease. Thus, we hypothesized that mesalamine may also modulate the immune regulatory functions of HSCs. Since B7-H1 plays a crucial role in regulating T-cell apoptosis, we evaluated if mesalamine induces B7-H1 expression on HSCs, and if so, whether mesalamine attenuates autoimmune liver injury in vivo. Methods: LX-2 cells, an immortalized human HSC cell line, and human peripheral T-cells were used in this study. B7-H1 expression on LX-2 cells following mesalamine treatment was examined by using flow cytometry. Cell viability was analyzed by MTS assay. Concanavalin-A (ConA) mice hepatitis model was used for in vivo study. Results: Flow cytometry showed that mesalamine treatment increased the B7-H1-expressing LX-2 cell fraction from 45.4% to 88.2%, of which increment is equivalent to that of positive control (29.9%, interferon γ-treated cells). Human T-cells incubated with LX-2 cells showed significantly less cell viability in the presence of mesalamine than cells without mesalamine treatment (P

The selection of a high-risk group of gastric cancer is important. This study was performed to compare the efficacy of non-invasive gastric cancer screening through the measurement of pepsinogen (PG) I/II ratio and endoscopic screening using histologic criteria (Meining’s risk index for gastric cancer) in Korean patients. Included in the study were 460 gastric cancer patients and 460 control cases who underwent upper endoscopy between June 2003 and July 2008 at Seoul National University Bundang Hospital. Serum PG I/II ratio and histologic characteristics were evaluated for each participant. Multivariate logistic regression was performed to compare the predictive power for gastric cancer of both the PG II/I ratio (the inverse form of PG I/II ratio) and the histologic gastric cancer risk index. A higher PG II/I ratio was significantly associated with a higher risk for gastric cancer (odds ratio of highest quartile for cancer vs. lowest quartile, 3.51; 95% confidence interval, 2.29–5.36) in the multivariate logistic model. The validity (in terms of calibration and discrimination) of the PG-including multivariate logistic model was comparable to the histologic gastric cancer risk index model. The results were similar regardless of the staging of the cancer, Lauren’s histologic classification, and the location of the cancer. These results suggest that non-invasive measurement of serum PG I/II ratio is as effective as Meining’s histologic gastric cancer risk index in predicting gastric cancer occurrence.

Background/Aims: A low vitamin D level has been associated with metabolic syndrome and diabetes. However, an association between a low vitamin D level and nonalcoholic fatty liver disease (NAFLD) has not yet been definitively established. This study aimed to characterize the relationship between a vitamin D level and NAFLD in Korea. Methods: A cross-sectional study involving 6,055 health check-up subjects was conducted. NAFLD was diagnosed on the basis of typical ultrasonographic findings and a history of alcohol consumption. Results: The subjects were aged 51.7±10.3 years (mean±SD) and 54.7% were female. NAFLD showed a significant inverse correlation with the vitamin D level after adjusting for age and sex [odds ratio (OR)=0.85, 95% confidence interval (CI)=0.75–0.96]. The age- and sex-adjusted prevalence of NAFLD decreased steadily with increasing vitamin D level [OR=0.74, 95% CI=0.60–0.90, lowest quintile (≤14.4 ng/mL) vs highest quintile (≥28.9 ng/mL), p for trend 20 ng/mL) [OR=0.86, 95% CI=0.75-0.99] and the quintiles of the vitamin D level in a dose-dependent manner (p for trend=0.001). Conclusions: The serum level of vitamin D, even when within the normal range, was found to be inversely correlated with NAFLD in a dose-dependent manner. Vitamin D was found to be inversely correlated with NAFLD independent of known metabolic risk factors. These findings suggest that vitamin D exerts protective effects against NAFLD.

Background/Aims. Women after menopause have increased insulin resistance and visceral fat, which may increase the prevalence of nonalcoholic fatty liver disease (NAFLD). However, the pathogenesis of NAFLD in women has not been clearly defined. In this study, we aimed to determine the risk factors for NAFLD in women.Methods. A retrospective cohort study was conducted. Women who underwent abdominal ultrasonography and blood sampling for routine health check-ups were recruited.Results. Among 1,423 subjects, 695 women (48.9%) were in a menopausal state. The prevalence of NAFLD was higher in postmenopausal women than in premenopausal women (27.2% versus 14.4%,P<0.001). In premenopausal women, low HDL-cholesterol, central obesity, and homeostasis model assessment-estimated insulin resistance showed a significant association with the increased risk of NAFLD in multivariate analysis. In postmenopausal women, the presence of diabetes, triglyceridemia, and central obesity showed a significant association with the risk of NAFLD. The presence of menopause and hormone replacement therapy in postmenopausal women were not risk factors for NAFLD.Conclusions. Our findings showed different metabolic factors for NAFLD in pre- and postmenopausal women. However, the key issues are the same: central obesity and insulin resistance. These results reemphasize the importance of metabolic factors irrespective of menopausal status in the pathogenesis of NAFLD in women.

A previous study showed that flavopiridol increased doxorubicin sensitivity in hypoxic hepatocellular carcinoma (HCC) cells by increasing apoptosis through suppressing hypoxia-inducible N-myc downstream-regulated gene-1 (NDRG1) expression. However, this has not been investigated in an in vivo HCC model. Therefore, we aimed to elucidate whether the combination of doxorubicin and flavopiridol has a synergistic anti-tumor effect in an in vivo HCC model. An HCC mouse model was established by implanting C3H/He mouse with MH134 cells. Then, doxorubicin with or without flavopiridol was injected. The anti-tumor efficacy was assessed by evaluating tumor volumes, and the underlying mechanism was investigated by quantifying apoptotic cells, the Ki-67 proliferation index, and microvessel densities (MVDs). Immunohistochemistry of NDRG1 was performed to determine the underlying mechanism. Tumor growth was significantly suppressed in the doxorubicin + flavopiridol combination group compared to the other three groups. The percentage of apoptotic cells was significantly higher, and Ki-67-positive proliferating cells were significantly lower in the combination group compared to the other groups; however, MVDs were not significantly different across the groups. Increased apoptosis by flavopiridol occurred by suppressing hypoxia-inducible NDRG1 expression. These results show that a combination of doxorubicin and flavopiridol has a synergistic anti-tumor effect in an in vivo HCC model. This synergistic effect of combination therapy was attributed to increased apoptosis and decreased proliferation of tumor cells rather than decreased angiogenesis. These findings suggest that flavopiridol might be an effective adjuvant therapy to doxorubicin-resistant HCC cells by inducing apoptosis through suppression of NDRG1 expression.

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.

Background In patients with diabetes, studies investigating the association between nonalcoholic fatty liver disease (NAFLD) and coronary artery calcium score (CACS) have shown conflicting results. The aim of this study was to evaluate the association between NAFLD and CACS in diabetic patients. Methods This is the cohort study performed in Seoul National University Hospital Gangnam Healthcare Center. NAFLD was defined as cases with the typical ultrasonographic findings without excessive alcohol consumption, medications causing hepatic steatosis or other chronic liver diseases. CACS was evaluated using the Agatston method. Diabetes was defined as cases with fasting serum glucose ≥ 126 mg/dl, glycated hemoglobin (HbA1c) ≥ 6.5%, or those taking anti-diabetic medications. Multivariate linear regression analyses were performed with use of the interaction term of NAFLD × glycemic level and other confounders of CACS such as age, sex, hypertension, body mass index, waist circumference, HDL cholesterol and triglyceride. Results A total of 213 participants with diabetes were included in the study. As 77 subjects (36.2%) had CACS 0, causing left sided skewness, CACS was analyzed after log transformation to Ln (CACS + 1). A statistically significant interaction was observed between NAFLD and HbA1c ≥ 7% (P for interaction = 0.014). While NAFLD was not associated with CACS in the group with HbA1c

Occult hepatitis B virus (HBV) infection (OBI) refers to the presence of HBV DNA in the absence of detectable hepatitis B surface antigen. Since OBI was first described in the late 1970s, there has been increasing interest in this topic. The prevalence of OBI varies according to the different endemicity of HBV infection, cohort characteristics, and sensitivity and specificity of the methods used for detection. Although the exact mechanism of OBI has not been proved, intra-hepatic persistence of viral covalently closed circular DNA under the host’s strong immune suppression of HBV replication and gene expression seems to be a cause. OBI has important clinical significance in several conditions. First, OBI can be transmitted through transfusion, organ transplantation including orthotopic liver transplantation, or hemodialysis. Donor screening before blood transfusion, prophylaxis for high-risk organ transplantation recipients, and dialysis-specific infection-control programs should be considered to reduce the risk of transmission. Second, OBI may reactivate and cause acute hepatitis in immunocompromised patients or those receiving chemotherapy. Close HBV DNA monitoring and timely antiviral treatment can prevent HBV reactivation and consequent clinical deterioration. Third, OBI may contribute to the progression of hepatic fibrosis in patients with chronic liver disease including hepatitis C. Finally, OBI seems to be a risk factor for hepatocellular carcinoma by its direct proto-oncogenic effect and by indirectly causing persistent hepatic inflammation and fibrosis. However, this needs further investigation. We review published reports in the literature to gain an overview of the status of OBI and emphasize the clinical importance of OBI.

Polymorphisms near the IL28B gene have been proposed to be strongly associated with treatment response and the rate of spontaneous clearance of hepatitis C virus infection, and treatment response of hepatitis B virus (HBV) infection. In this study, we aimed to determine whether these polymorphisms could affect natural courses of HBV infection.Genetic variations were identified through direct DNA sequencing using TaqMan assay in 1,439 patients with past or present HBV infection. Subjects included 404 spontaneously recovered patients, 313 chronic hepatitis B (CHB) patients, 305 liver cirrhosis (LC) patients and 417 hepatocellular carcinoma (HCC) patients. Three polymorphisms near the IL28B gene, rs8099917TG, rs12979860CT and rs12980275AG, were identified. Associations between these polymorphisms and HBV clearance, hepatitis B e antigen (HBeAg) clearance as well as HCC occurrence among patients were analyzed using logistic regression analyses adjusted for age and gender.There were no significant associations between these polymorphisms and the HBV clearance both in CHB and LC groups. Similarly, these polymorphisms showed no significant associations with HBeAg clearance and the occurrence of HCC either.No significant association was identified between polymorphisms near the IL28B gene and the natural courses of chronic HBV infection, including the HBV clearance and HCC occurrence.

Background: Micro RNAs-371-372-373 (miRNAs-371-373), originating from the same pri-miRNA transcript, are reported to be upregulated in hepatocellular carcinoma (HCC) and to be related to the regulation of hepatitis B virus (HBV) infection. Our study investigated whether pri-miRNAs-371-373 polymorphisms are associated with the risk of HCC occurrence and HBV clearance. Methods: Genetic variations were identified through direct DNA sequencing using TaqMan assay. Three sequence variants of pri-miRNAs-371-373 were identified. Genetic associations of those with HCC occurrence and HBV clearance among patients with HBV infection were analyzed using logistic regression analyses with adjustment for age and gender (n = 1439). Results: For the occurrence of HCC, polymorphism rs3859501C > A acted as a protective factor both in chronic carriers (OR = 0.75, P = 0.005 in a codominant model; OR = 0.71, P = 0.02 in a dominant model; OR = 0.66, P = 0.03 in recessive model) and liver cirrhosis patients (OR = 0.69, P = 0.001 in a codominant model; OR = 0.60, P = 0.003 in a dominant model; OR = 0.63, P = 0.03 in a recessive model). The pri-miRNAs-371-373_ht2 [C-A-C] also showed a protective effect on HCC occurrence both in the chronic carrier and liver cirrhosis groups (P < 0.05 in both). However, there was no significant association between pri-miRNAs-371-373 polymorphisms and HBV clearance. Conclusions: In conclusion, among chronic carriers and liver cirrhosis patients, the A allele of rs3859501 and the haplotype pri-miRNAs-371-373_ht2 were more protective to HCC than other genotypes and haplotypes. Further studies into the roles of rs3859501 and pri-miRNAs-371-373_ht2 haplotype in hepatocarcinogenesis are needed.

Background and Aims: In chronic hepatitis B virus (HBV) infections, hepatitis B surface antigen (HBsAg) seroclearance reportedly occurs at a rate of 0.50–2.26%. Several factors were suggested to be associated with seroclearance including age and HBeAg negativity. However, there are few studies evaluating whether HBV DNA levels are an independent predictor of HBsAg seroclearance. The aim of this study was to evaluate the annual HBsAg seroclearance rate and its predictors including serum HBV DNA levels in HBeAg-negative chronic hepatitis B patients. Methods: We included 880 HBeAg-negative chronic hepatitis B patients who underwent an evaluation of baseline serum HBV DNA levels. We reviewed the electronic charts for baseline clinical, biochemical, and virological factors. Results: The median age was 50 years, and the follow-up duration was 31 months. The annual rate for the HBsAg seroclearance was 1.8%. In multivariable analysis, the probability of HBsAg seroclearance was positively associated with old age (p = 0.046), with a sustained inactive phase rather than the occurrence of HBeAg-negative hepatitis (p = 0.041), and with an initial HBV DNA level Conclusion: The annual rate for the HBsAg seroclearance in HBeAg-negative chronic hepatitis B patients was 1.8%. Old age, sustained inactive phase, and low levels of HBV DNA were independent predictors of HBsAg seroclearance.