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Aims Continuing physical activity (PA) and maintaining body weight are tightly intertwined; however, no study investigated whether these two factors have interactions in terms of the mortality. The aim of this study is to elucidate whether continuing regular PA and maintaining body weight have interactions in terms of all-cause mortality risk. Methods and results Participants with health screening from both 2009 and 2011 without underlying cancer or cardiovascular disease were included. Physical activity change was grouped as remained active, inactive-to-active, active-to-inactive, or remained inactive. Body weight change was categorized as stable (weight change Conclusions Continuing regular PA as recommended and maintaining body weight have multiplicative and additive interactions on reducing all-cause mortality. Healthcare providers should emphasize the importance of both regular PA and body weight maintenance for the general public.

There is still controversy about the association between nonalcoholic fatty liver disease (NAFLD) and bone mineral density (BMD). The aim of this study was to clarify the association between NAFLD and the decline in BMD in healthcare examinees. Participants who underwent regular health check-ups with BMD and hepatic ultrasonography from 2006 to 2015 with more than one follow-up until 2020 were included. Propensity score matching was performed between the NAFLD group and the control group, and mixed linear regression models were used for the longitudinal analysis. Of 2623 eligible participants (mean age 58.7 ± 7.3 years; males 31.3%), 888 (33.9%) had NAFLD. At baseline, the NAFLD group had a higher total hip BMD than the non-NAFLD group in men (0.988 vs. 1.015 g/cm2, p = 0.007); however, there was no difference in baseline BMD in women (p = 0.253). In longitudinal analysis during a follow-up period of 7.1 years, there was no significant difference in the BMD decline rate between the two groups in the PS-matched cohort (p = 0.816 in men and p = 0.827 in women). However, among men with NAFLD, those with a high and intermediate probability of advanced fibrosis by the FIB-4 showed a significantly increased rate of decline in total hip BMD compared to those with low scores (0.01 vs. − 0.19% change/year, p = 0.011). NAFLD was not associated with the total hip BMD decline rate. However, hepatic fibrosis was significantly associated with an increased rate of decline in total hip BMD in men with NAFLD. This study is a retrospective observational study and is not a drug trial. There was no need for clinical trial registration.

OBJECTIVE Hypertension, diabetes mellitus and physical inactivity can cause cardiovascular complications or premature death. However, it has not been clarified whether those major comorbidities and physical activity interact in affecting health outcomes. The aim of this study is to evaluate the potential interaction between temporal physical activity profiles and hypertension or diabetes mellitus on the risk for all-cause mortality. METHODS This study used Korea National Health Insurance Service (KNHIS) database and included about 6.5 million participants who underwent health screening in 2009 and 2011. Physical activity was evaluated as 2-year change based on self-reported survey using 7-day recall method, and grouped as remained active, inactive-to-active, active-to-inactive, or remained inactive. Participants were categorized into groups according to the presence of hypertension/diabetes mellitus. Outcome included all-cause mortality. RESULTS In total, 6 554 082 participants (48.4 ± 13.3 years; 56.7% men) were included. During a median 6.4-year follow-up, 83 241 deaths occurred. Compared with the 'remained active' group, other groups had a higher mortality risk after adjustment for covariates [adjusted hazard ratio (aHR) 1.17, 95% CI 1.13-1.21 in the 'inactive-to-active' group, aHR 1.28, 95% CI 1.24-1.32 in the 'active-to-inactive' group, aHR 1.52, 95% CI 1.48-1.57 in the 'remained inactive' group). Hypertension and diabetes mellitus were significant effect modifiers in the association between physical activity and the risk of all-cause mortality (P for interaction

Increasing hepatitis-related mortality has reignited interest to fulfill the World Health Organization’s goal of viral hepatitis elimination by 2030. However, economic barriers have enabled only 28% of countries to implement countermeasures. Given the high disease burden among Asians, we aimed to present age, sex, disease activity and treatment-specific annual progression rates among Asian chronic hepatitis B (CHB) patients to inform health economic modeling efforts and cost-effective public health interventions. We analyzed 18,056 CHB patients from 36 centers across the U.S. and seven countries/regions of Asia Pacific (9530 treated; 8526 untreated). We used Kaplan–Meier methods to estimate annual incidence of cirrhosis and hepatocellular carcinoma (HCC). Active disease was defined by meeting the APASL treatment guideline criteria. Over a median follow-up of 8.55 years, there were 1178 incidences of cirrhosis and 1212 incidences of HCC (297 without cirrhosis, 915 with cirrhosis). Among the 8526 untreated patients (7977 inactive, 549 active), the annual cirrhosis and HCC incidence ranged from 0.26% to 1.30% and 0.04% to 3.80% in inactive patients, and 0.55 to 4.05% and 0.19 to 6.03% in active patients, respectively. Of the 9530 treated patients, the annual HCC rates ranged 0.03–1.57% among noncirrhotic males and 2.57–6.93% among cirrhotic males, with lower rates for females. Generally, transition rates increased with age, male sex, the presence of fibrosis/cirrhosis, and active disease and/or antiviral treatment. Using data from a large and diverse real-world cohort of Asian CHB patients, the study provided detailed annual transition rates to inform practice, research and public health planning.

Background Several genetic variants are known to be associated with nonalcoholic fatty liver disease (NAFLD). We aimed to evaluate the longitudinal associations between genetic variants and NAFLD. Methods We performed a genome-wide association study (GWAS) in Korean individuals who underwent repeated health check-ups. NAFLD was defined by ultrasonography and exclusion of secondary causes. Results The subjects had a median age of 50.0 years, and 54.8% were male. The median follow-up duration was 39 months. Among the 3905 subjects without NAFLD at baseline, 874 (22.4%) subjects developed NAFLD, and among the 1818 subjects with NAFLD at baseline, NAFLD regressed in 336 (18.5%) subjects during the follow-up period. After adjusting for age, sex and body mass index, no single-nucleotide polymorphism (SNP) passed Bonferroni correction for genome-wide significance in the development or regression of NAFLD. Among the SNPs that passed the genome-wide suggestiveness threshold (p = 1E-04) in the discovery set in the GWAS, only 1 SNP (rs4906353) showed an association with the development of NAFLD, with marginal significance in the validation set (p-value, discovery set = 9.68E-5 and validation set = 0.00531). Conclusions This exploratory study suggests that longitudinal changes in NAFLD are not associated with genetic variants in the Korean population. These findings provide new insight into genetic mechanisms in the pathogenesis of NAFLD.

Nonalcoholic fatty liver disease (NAFLD) is increasing worldwide, highlighting the importance of early and accurate detection and the appropriate management of NAFLD. However, ultrasonography (US) is not included in many mass screening programs, and people have limited access to it. The aim of this study is to validate the fatty liver index (FLI) and investigate the optimal cutoff value for predicting NAFLD in an asymptomatic population. We conducted a retrospective cohort study in Korea. All subjects who underwent health checkup exams, including abdominal US, controlled attenuation parameter (CAP) and blood testing, were enrolled. Analyses of the area under the receiver operating characteristic curve (AUROC) were used to evaluate the diagnostic accuracy and to calculate the optimal FLI cutoff for US-NAFLD. Among the 4009 subjects (mean age 54.9 years, 83.5% male), the prevalence of US-diagnosed NAFLD and CAP-defined hepatic steatosis was 61.4% and 55.4%. The previously used cutoff of FLI = 60 showed poor performance in predicting US-diagnosed NAFLD, with an AUROC of 0.63 (0.62–0.64), and CAP-defined NAFLD, with an AUROC 0.63 (0.62–0.64). The optimal FLI cutoff values to discriminate fatty liver detected by US were 29 for the entire population, with an AUROC of 0.82 (0.81–0.84). The sex-specific values were 31 for males and 18 for females (sensitivity 72.8% and 73.4%; specificity 74.2% and 85.0%, respectively). The FLI cutoff for US-diagnosed NAFLD can be set as 29 for the entire Korean population. Considering the sex dimorphism in NAFLD, different cutoff values are suggested to predict US-diagnosed NAFLD. These results may be helpful in the accurate non-invasive diagnosis of NAFLD.

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of liver disease associated with various metabolic disorders. Metabolic dysfunction-associated fatty liver disease (MAFLD) emphasizes metabolic dysfunction in NAFLD. Although the relationship between NAFLD and colorectal adenomas has been suggested, the effect of MAFLD on colorectal adenoma has yet to be investigated. In this study, we examined the relationship between NAFLD/MAFLD and colorectal adenoma in comparison with other metabolic factors. Methods: Examinees who underwent colonoscopy and abdominal ultrasonography on the same day from January 2012 to December 2012 were included. NAFLD was diagnosed according to the findings of ultrasonography. The Fibrosis-4 (FIB-4) index was used as a surrogate marker for advanced hepatic fibrosis. A logistic regression model was used to analyze the risk of NAFLD/MAFLD for colorectal adenoma. Results: The prevalence of NAFLD and MAFLD was 37.5% and 32.8%, respectively. In the multivariate analysis, male sex, older age, diabetes, and smoking increased the risk of colorectal adenoma. NAFLD and MAFLD were the most important risk factors for colorectal adenoma only in females [adjusted odds ratio (OR) 1.43 and 95% confidence interval (CI) 1.01–2.03, and OR 1.55, 95% CI 1.09–2.20, respectively]. NAFLD and MAFLD with an advanced fibrosis index were significantly associated with an increased risk of colorectal adenoma. (NAFLD: OR 1.38, 95% CI, 1.04–1.83, p = 0.027; MAFLD: OR 1.45, 95% CI, 1.13–1.96, p = 0.004, respectively). Conclusion: NAFLD and MAFLD were significantly associated with a higher risk of colorectal adenomas, especially in females. NAFLD and MAFLD with advanced fibrosis were associated with an increased risk of colorectal adenoma. Colonoscopic examinations may be emphasized for patients with NAFLD/MAFLD, for women, or patients with the presence of hepatic fibrosis.

BACKGROUND Studies on association between fatty liver disease and overall mortality have yielded conflicting results. We evaluated the impact of fatty liver disease and advanced fibrosis on overall morality with a focus on body size and abdominal fat distribution measured by computed tomography. METHODS We performed a prospective cohort study including 34 080 subjects (mean age, 51.4 years; 58.6% men) who underwent abdominal ultrasonography and fat computed tomography, from 2007 to 2015. Fatty liver was diagnosed by ultrasonography, and advanced fibrosis was defined as high probability of advanced fibrosis based on three noninvasive methods, aspartate aminotransferase-to-platelet ratio index, non-alcoholic fatty liver disease fibrosis score, and fibrosis-4 score. Body size was categorized by body mass index into obese (≥ 25 kg/m2 ) or nonobese (

Background 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. Aim The aim of this case-control study was to investigate the association between NAFLD and breast cancer. Methods 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. Results 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 Conclusions 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.

Weight loss, the most established therapy for nonalcoholic fatty liver disease (NAFLD), is frequently followed by weight regain and fluctuation. The aim of this study was to investigate whether body weight change and variability were independent risk factors for incident NAFLD. We conducted a longitudinal cohort study. Among the 1907 participants, incident NAFLD occurred in 420 (22.0%) cases during median follow-up of 5.6 years. In the multivariate analysis, there was no significant association between weight variability and the risk of incident NAFLD. The risk of incident NAFLD was significantly higher in subjects with weight gain ≥ 10% and 7%

Background: An association between nonalcoholic fatty liver disease (NAFLD) and low vitamin D levels has been suggested. We investigated the relationship between vitamin D and NAFLD assessed by controlled attenuation parameter (CAP). Methods: We conducted a retrospective cohort study of apparently healthy subjects who underwent Fibroscan during health screening tests. NAFLD was diagnosed using CAP values. Results: Among the 1202 subjects (mean age 57.2 years, 60.6% male), 630 (52.4%) subjects had NAFLD with CAP ≥ 248 dB/m. Multivariable analysis was conducted after adjusting for metabolic risk factors including diabetes, hypertension, hypercholesterolemia, body mass index, high-density lipoprotein cholesterol, triglyceride and smoking. Higher vitamin D levels showed a lower risk of NAFLD compared to the lowest quartile of vitamin D in a dose-dependent manner (OR 0.68, 95% CI 0.47–1.00 in Q2 vs. Q1, OR 0.65, 95% CI 0.44–0.94 in Q3 vs. Q1, and OR 0.64, 95% CI 0.44–0.94 in Q4 vs. Q1). The highest quartile of vitamin D showed a decreased risk of a severe grade of steatosis (CAP ≥ 302 dB/m) compared to the lowest quartile (OR 0.52, 95% CI 0.31–0.87 in Q4 vs. Q1). Conclusions: Higher levels of serum vitamin D were associated with a decreased risk of CAP-defined NAFLD, compared to low levels of serum vitamin D. The association between NAFLD and vitamin D suggests that vitamin D may exert a protective role against NAFLD.

Objectives Many interventions have been attempted to improve adenoma detection rate (ADR) and sessile serrated lesion detection rate (SDR), and one of these interventions is educational training to recognize polyp characteristics. This study aimed to investigate the change in polyp detection rates of endoscopists before and after comprehensive training through the Gangnam-Real Time Optical Diagnosis (Gangnam-READI) program. Methods Fifteen gastroenterologists participated in a 1-year comprehensive training program that consisted of ex vivo and in vivo training that encompasses knowledge and skills in endoscopic characterization of colonic polyps using the Workgroup serrAted polypS and Polyposis (WASP) classification. We evaluated the impact of the training program by comparing the overall and individual ADR and SDR 6 months before and after the training. Results Overall, 18,280 polyps (9337 adenomas and 855 sessile serrated lesion) were collected. The optical diagnosis training had no significant impact on the difference in ADR after training compared to before training (47.7% vs. 46.5%, P = 0.608). A tendency for a decrease in ADR variance was noted among the endoscopists after training (74.9 vs. 32.7, P = 0.121). The overall pre-training period SDR was 4.5% and showed a statistically significant increase to 5.6%, 8.0%, and 7.1% in the first and second half of the training period, and post-training period, respectively (P = 0.003). The optical diagnosis training did not decrease variance in SDR (8.9 vs. 8.8, P = 0.985). Conclusion Comprehensive optical diagnosis training with WASP classification has a significant impact on increasing the overall SDR of expert endoscopists.

AimsNon-alcoholic fatty liver disease (NAFLD) has a dynamic disease course, therefore repeated measurements of NAFLD status could have benefits rather than single one. The aim of this study was to investigate the effects of persistent NAFLD on the incidence of myocardial infarction (MI) and stroke and all-cause mortality by using repeated measurement of fatty liver index (FLI).MethodsAbout 3 million subjects who had undergone the health screening four times from 2009 until 2013 were included. NAFLD was defined as an FLI ≥60. FLI points were defined as the number of times participants meeting the criteria of NAFLD (0–4). Outcomes included all-cause mortality, MI, and stroke.ResultsThe higher the FLI points, the higher the risk of all-cause mortality, MI, and stroke (P for trend P < 0.001), incidence of MI (aHR, 1.3; 95% CI, 1.21–1.40; P < 0.001), and stroke (aHR, 1.27; 95% CI, 1.19–1.37; P < 0.001) after adjustment for age, sex, smoking, alcohol consumption, income, hypertension, dyslipidemia, diabetes, body mass index, and physical activity. When the 1st and the last FLI were compared, the “incident NAFLD” group had a higher risk for death compared to the “no NAFLD” group (aHR, 1.46; 95% CI, 1.37–1.55), and the “regression of NAFLD” group had a decreased risk for death compared to the “persistent NAFLD” group (aHR, 0.83; 95% CI, 0.77–0.89).ConclusionRepeated evaluations of NAFLD status based on FLI measurements could help physicians identify higher-risk groups in terms of mortality, MI, and stroke. The association between FLI worsening or improvement and outcomes also suggests clinical benefits of the prevention and treatment of NAFLD.

Background & AIMS Antiviral treatment criteria are based on disease progression risk, and hepatocellular carcinoma (HCC) surveillance recommendations for patients with chronic hepatitis B (CHB) without cirrhosis is based on an annual incidence threshold of 0.2%. However, accurate and precise disease progression estimate data are limited. Thus, we aimed to determine rates of cirrhosis and HCC development stratified by age, sex, treatment status, and disease activity based on the 2018 American Association for the Study of Liver Diseases and 2017 European Association for the Study of the Liver guidelines. Methods We analyzed 18,338 patients (8914 treated, 9424 untreated) from 6 centers from the United States and 27 centers from Asia-Pacific countries. The Kaplan-Meier method was used to estimate annual progression rates to cirrhosis or HCC in person-years. Results The cohort was 63% male, with a mean age of 46.19 years, with baseline cirrhosis of 14.3% and median follow up of 9.60 years. By American Association for the Study of Liver Diseases criteria, depending on age, sex, and disease activity, annual incidence rates ranged from 0.07% to 3.94% for cirrhosis, from 0.04% to 2.19% for HCC in patients without cirrhosis, and from 0.40% to 8.83% for HCC in patients with cirrhosis. Several subgroups of patients without cirrhosis including males younger than 40 years of age and females younger than 50 years of age had annual HCC risk near or exceeding 0.2%. Similar results were found using European Association for the Study of the Liver criteria. Conclusion There is great variability in CHB disease progression rates even among “lower-risk” populations. Future CHB modeling studies, public health planning, and HCC surveillance recommendation should be based on more precise disease progression rates based on sex, age, and disease activity, plus treatment status.

Backgrounds: Depression and anxiety disorder are frequently seen in patients with nonalcoholic fatty liver disease (NAFLD). However, the associations between mood disorders and NAFLD have not been fully evaluated. In this study, we investigated the relationship between NAFLD and depression or anxiety in a Korean population.Methods: We conducted a retrospective cross-sectional study that included subjects who underwent abdominal ultrasonography and completed a symptom questionnaire for a routine health check-up. NAFLD was diagnosed and graded according to the ultrasonography findings. Depression and anxiety were assessed using the Beck Depression Inventory and State-Trait Anxiety Inventory, respectively.Results: Among the total of 25,333 subjects, the mean age was 47 years (men, 56.2%), and the prevalence rate of NAFLD was 30.9%. In the multivariate analysis, NAFLD showed a significant association with depression [adjusted odds ratio (OR) 1.43 and 95% confidence interval (CI) 1.14–1.80, p = 0.002] in women. Severe NAFLD significantly correlated with state anxiety and trait anxiety (adjusted OR 1.84 and 95% CI 1.01–3.37, p = 0.047 and adjusted OR 2.45 and 95% CI 1.08–4.85, p = 0.018, respectively) in women.Conclusions: There was a higher tendency of women with NAFLD to suffer from depression with increase in steatosis, and severe stage of steatosis was significantly associated with anxiety in the female compared to non-NAFLD. Understanding the association between NAFLD and mood disorders may have clinical implications for reducing the prevalence of comorbidities.

BACKGROUND The association between elevated γ-glutamyltransferase (GGT) at a certain point and incident cancer has been suggested; however, no study has evaluated the association between repeatedly elevated GGT and cancer incidence. AIM To investigate the effects of repeatedly elevated GGT on the incidence of digestive cancers. METHODS Participants who had undergone health screening from 2009 to 2012 and 4 consecutive previous examinations were enrolled. GGT points were calculated as the number of times participants met the criteria of quartile 4 of GGT in four serial measurements (0-4 points). Multivariable Cox proportional hazard regression models were applied. RESULTS In total, 3559109 participants were included; among them, 43574 digestive cancers developed during a median of 6.8 years of follow-up. The incidence of total digestive cancers increased in a dose-response manner in men [adjusted hazard ratio (aHR) compared with those with 0 GGT points = 1.28 and 95% confidence interval (CI) = 1.24-1.33 in those with 1 point; aHR = 1.40 and 95%CI = 1.35-1.46 in those with 2 points; aHR = 1.52 and 95%CI = 1.46-1.58 in those with 3 points; aHR = 1.88 and 95%CI = 1.83-1.94 in those with 4 points; P for trend < 0.001]. This trend was more prominent in men than in women and those with healthy habits (no smoking, no alcohol consumption, and a low body mass index) than in those with unhealthy habits. CONCLUSION Repeatedly elevated GGT levels were associated with an increased risk of incident digestive cancer in a dose-responsive manner, particularly in men and those with healthy habits. Repeated GGT measurements may be a good biomarker of incident digestive cancer and could help physicians identify high-risk populations.

Nonalcoholic fatty liver disease (NAFLD) plays a significant role in coronary atherosclerosis, independent of shared metabolic risk factors. The measurement of the controlled attenuation parameter (CAP) has shown to allow early and noninvasive detection of NAFLD at subclinical stage. We evaluated the significance of CAP-defined NAFLD in association with the presence of any type of coronary plaques and different plaque compositions. We conducted a retrospective cohort of apparently healthy subjects who had liver Fibroscan and coronary computed tomography during health screening exams. A greater number of subjects with CAP-defined NAFLD was found in group with coronary plaques (61.3% vs. 73.5%, p = 0.005 without vs. with any type of plaque). From multivariate regression model, CAP ≥ 222 dB/m was an independent and significant parameter associated with the presence of coronary plaques, after adjusting possible confounders (OR 1.624, 95% 1.047–2.518, p = 0.030). Interestingly, CAP ≥ 222 dB/m was significantly associated with non-calcified plaque (adjusted OR 3.528, 95% CI 1.463–8.511, p = 0.005), whereas it was not significant in calcified plaques (p = 0.171). CAP-defined NAFLD is independently associated with coronary plaques, especially non-calcified plaques. The association between NAFLD and non-calcified plaques suggests that particular attention should be given to the subjects with NAFLD for primary prevention.

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 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.

Background.Helicobacter pylori (HP)and gastric atrophy are risk factors for gastric cancer. We evaluated whether the combination of serum HP antibody and pepsinogen (PG), which is indicative of gastric atrophy, could serve as a predictive marker for the development of gastric neoplasms in a Korean population.Methods. The subjects who had undergone health-screening examination with endoscopic follow-ups were classified into the following 4 groups according to serum PG status andHPantibody at baseline: group A (HP(−), normal PG), group B (HP(+), normal PG), group C (HP(+), atrophic PG), and group D (HP(−), atrophic PG). We compared the development of gastric neoplasms among the groups.Results. Of the 3297 subjects, 1239 (37.6%) were categorized as group A, 1484 (45.0%) as group B, 536 (16.3%) as group C, and 38 (1.2%) as group D. During the 5.6 years of mean follow-up period, the annual incidence of gastric neoplasms increased gradually by 0.06% in group A, 0.16% in group B, 0.38% in group C, and 0.49% in group D. A Cox proportional hazard model showed increased development of gastric neoplasms according to group (Pfor trend = 0.025). Compared to group A, the hazard ratio was 8.25 for group D (95% confidence interval 0.2–74.24), 5.35 for group C (1.68–17.05), and 2.65 for group B (0.86–8.14).Conclusion. The combination of serum PG andHPantibody is useful for predicting the development of gastric neoplasms, including cancer and adenoma, in a Korean population using endoscopic surveillance.

BACKGROUND & AIMS The association between nonalcoholic fatty liver disease and lung function has not been fully examined. The aim of this study was to clarify the association between nonalcoholic fatty liver disease and lung function in general population by performing cross-sectional and longitudinal analysis. METHODS Participants without hepatic and respiratory disease who underwent regular health exams including hepatic sonography and spirometry with at least 3 years' follow-up were included. In cross-sectional analysis, the association between nonalcoholic fatty liver disease and lung function at baseline was examined with multiple regression models. The longitudinal analysis was performed by mixed linear regression models with propensity score matching. RESULTS Of 11 892 eligible participants (mean age, 47.7 years; male, 47.2%), 3815(32.1%) had nonalcoholic fatty liver disease based on sonography. In cross-sectional analysis, the nonalcoholic fatty liver disease group had lower adjusted forced expiratory volume in 1-second (men, 3.52 vs 3.44 L, P

Background: An association between low muscle mass and nonalcoholic fatty liver disease (NAFLD) has been suggested. We investigated this relationship using controlled attenuation parameter (CAP). Methods: A retrospective cohort of subjects had liver FibroScan® (Echosens, Paris, France) and bioelectrical impedance analyses during health screening exams. Low muscle mass was defined based on appendicular skeletal muscle mass/body weight ratios of one (class I) or two (class II) standard deviations below the sex-specific mean for healthy young adults. Results: Among 960 subjects (58.1 years, 67.4% male), 344 (45.8%, class I) and 110 (11.5%, class II) had low muscle mass. After adjusting for traditional metabolic risk factors, hepatic steatosis, defined as a CAP ≥ 248 dB/m, was associated with low muscle mass (class I, odds ratio (OR): 1.96, 95% confidence interval (CI): 1.38–2.78, class II, OR: 3.33, 95% CI: 1.77–6.26). A dose-dependent association between the grade of steatosis and low muscle mass was also found (class I, OR: 1.88, for CAP ≥ 248, &lt, 302, OR: 2.19, in CAP ≥ 302, class II, OR: 2.33, for CAP ≥ 248, &lt, OR: 6.17, in CAP ≥ 302). High liver stiffness was also significantly associated with an increased risk of low muscle mass (class I, OR: 1.97, 95% CI: 1.31–2.95, class II, OR: 2.96, 95% CI: 1.51–5.78). Conclusion: Hepatic steatosis is independently associated with low muscle mass in a dose-dependent manner. The association between hepatic steatosis and low muscle mass suggests that particular attention should be given to subjects with NAFLD for an adequate assessment of muscle mass.

Background/Aims The development of nonalcoholic fatty liver disease (NAFLD) is associated with multiple genetic and environmental factors. Methods We performed a genome-wide association study to identify the genetic factors related to NAFLD in a Korean population-based sample of 1,593 subjects with NAFLD and 2,816 controls. We replicated the data in another sample that included 744 NAFLD patients and 1,137 controls. We investigated single-nucleotide polymorphisms (SNPs) that were related to NAFLD. Results After adjusting for age, sex and body mass index, rs738409, rs12483959 and rs2281135, located in the PNPLA3 gene, were validated in our population (p＜8.56×10-8) in the same linkage disequilibrium block. Additionally, rs2143571, rs3761472, and rs2073080 in the SAMM50 gene showed significant associations with NAFLD (p＜8.56×10-8). Furthermore, these six SNPs showed significant associations with the severity of fatty liver (all p＜2.0×10-10 in the discovery set and p＜2.0×10-6 in the validation set) and NAFLD, with elevated levels of alanine aminotransferase (all p＜2.0×10-10 in the discovery set and p＜2.0×10-6 in the validation set). Conclusions We demonstrated that the PNPLA3 and SAMM50 genes are significantly associated with the presence and severity of NAFLD in a Korean population. These findings confirm the important roles of genetic factors in the pathogenesis of NAFLD.

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).

Aims. Chronic low-grade inflammation is thought to be associated with the pathogenesis of nonalcoholic fatty liver disease (NAFLD). This study aimed to determine the association between serum white blood cell (WBC) counts and the development of incidental NAFLD.Methods. In this retrospective longitudinal cohort study, we recruited participants who underwent abdominal ultrasonography and blood samplings during medical checkups in both 2005 and 2010. A total of 2,216 subjects were included in our analyses.Results. The prevalence of NAFLD in 2010 increased steadily in conjunction with increasing WBC counts in 2005 after adjustment for body mass index (BMI) [odds ratio (OR) 2.44, 95% confidence interval (CI) = 1.49–4.00 for women and OR 2.42, 95% CI = 1.61–3.63 for men, lowest quartile versus highest quartile]. Multivariate regression analysis after adjusting for age, BMI, hypertension, smoking, triglycerides, HDL cholesterol, and glucose levels revealed that NAFLD was significantly associated with the highest WBC quartile compared to the lowest quartile [OR 1.85, 95% CI, 1.10−3.10 for women and OR 1.68, 95% CI, 1.08−2.61 for men].Conclusions. We demonstrated that the risk of developing NAFLD was significantly associated with WBC counts independently of metabolic factors. This finding provides novel evidence indicating that serum WBC counts may be potential surrogate markers of NAFLD.

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)

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.

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

BackgroundChronic systemic inflammation is an important causative factor in the pathogenesis of atherosclerosis. However, the effect of chronic Helicobacter pylori (Hp) infection on arterial stiffness, a predictor of cardiovascular events, remains unclear. We evaluated the association between Hp infection and arterial stiffness in asymptomatic healthy individuals.MethodsArterial stiffness was evaluated using the cardio-ankle vascular index (CAVI). We included subjects who underwent CAVI and anti-Hp IgG antibody evaluations, simultaneously, between March 2013 and July 2017. Demographic characteristics and metabolic and cardiovascular parameters were compared with respect to anti-Hp IgG antibody status. Multivariable logistic regression analyses were performed to determine the effect of Hp-seropositivity and conventional cardiovascular risk factors on arterial stiffness.ResultsOf 2,251 subjects, 1,326 (58.9%) were included in the Hp-seropositive group. Median age (P < 0.001) and systolic blood pressure (P = 0.027) were significantly higher in the Hp-seropositive than in the Hp-seronegative group. Levels of LDL-cholesterol were significantly higher in the Hp-seropositive than in the Hp-seronegative group (P = 0.016). Other serum metabolic parameters were not significantly different between the two groups. The median CAVI value and the proportion of subjects with a CAVI ≥ 8 were significantly higher in the Hp-seropositive than in the Hp-seronegative group (both P < 0.001). On multivariable logistic regression analyses, Hp-seropositivity, age, body mass index, waist circumference, smoking, hypertension, diabetes mellitus, and dyslipidemia were significantly associated with high CAVI values. In the subgroup analysis conducted according to age group, a tendency towards an increased association between Hp-seropositivity and CAVI was observed with increasing age, even though the difference did not reach the statistical significance.ConclusionsHp-seropositivity was significantly associated with arterial stiffness. Hp infection may contribute to the development of cardiovascular diseases.

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 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 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.