Severity of fatty liver is highly correlated with the risk of hypertension and diabetes: a cross-sectional and longitudinal cohort study.

BACKGROUND AND AIMS: Fatty liver disease (FLD) is associated with several metabolic derangements. We conducted a retrospective cross-sectional and longitudinal study to evaluate the role of FL severity in the risk of new-onset and co-existing hypertension (HTN) and diabetes mellitus (DM). METHODS: The cross-sectional cohort consisted of 41,888 adults who received health checkups in a tertiary hospital of Taiwan from 1999 to 2013. Of them, 34,865 without HTN and/or DM at baseline and within 1 year after enrollment were included as a longitudinal cohort (mean, 6.45 years for HTN; 6.75 years for DM). FL severity based on the degree of hepatic steatosis was assessed by ultrasound sonography. RESULTS: In cross-sectional cohort, 22,852 (54.6%) subjects had FL (18,203 [43.46%] mild FL and 4,649 [11.10%] moderate/severe FL); 13.5% (n = 5668) had HTN; and 3.4% (n = 1411) had DM. Moderate/severe FL and mild FL had significantly higher risks of existing HTN (adjusted odds ratio/95% confidence interval [CI] 1.59/1.43-1.77 and 1.22/1.13-1.32, respectively). In longitudinal cohort, 3,209 and 822 subjects developed new-onset HTN and DM, respectively (annual incidence, 14.3 and 3.5 per 1000 person-years; 10-year cumulative incidence, 14.35% and 3.89%, respectively). Moderate/severe and mild FL had significantly higher risks of new-onset HTN (adjusted hazard ratio [aHR]/CI 1.54/1.34-1.77 and 1.26/1.16-1.37, respectively) and DM (aHR/CI 5.88/4.44-7.81 and 3.22/2.56-4.07, respectively). Resolved FL during follow-up decreased the risk of HTN and/or DM. CONCLUSIONS: Patients with FL are at high risk of prevalent and incident HTN and/or DM. The risk increases with the severity of FL.

The Efficacy of Anthropometric Indicators in Predicting Non-Alcoholic Fatty Liver Disease Using FibroScan® CAP Values among the Taiwanese Population.

The controlled attenuation parameter (CAP) measurement obtained from FibroScan® is a low-risk method of assessing fatty liver. This study investigated the association between the FibroScan® CAP values and nine anthropometric indicators, including the abdominal volume index (AVI), body fat percentage (BFP), body mass index (BMI), conicity index (CI), ponderal index (PI), relative fat mass (RFM), waist circumference (WC), waist-hip ratio (WHR), and waist-to-height ratio (WHtR), and risk of non-alcoholic fatty liver disease (fatty liver). We analyzed the medical records of adult patients who had FibroScan® CAP results. CAP values <238 dB/m were coded as 0 (non- fatty liver) and ≥238 dB/m as 1 (fatty liver). An individual is considered to have class 1 obesity when their body mass index (BMI) ranges from 30 kg/m2 to 34.9 kg/m2. Class 2 obesity is defined by a BMI ranging from 35 kg/m2 to 39.9 kg/m2, while class 3 obesity is designated by a BMI of 40 kg/m2 or higher. Out of 1763 subjects, 908 (51.5%) had fatty liver. The BMI, WHtR, and PI were found to be more strongly correlated with the CAP by the cluster dendrogram with correlation coefficients of 0.58, 0.54, and 0.54, respectively (all p < 0.0001). We found that 28.3% of the individuals without obesity had fatty liver, and 28.2% of the individuals with obesity did not have fatty liver. The BMI, CI, and PI were significant predictors of fatty liver. The BMI, PI, and WHtR demonstrated better predictive ability, indicated by AUC values of 0.72, 0.68, and 0.68, respectively, a finding that was echoed in our cluster group analysis that showed interconnected clustering with the CAP. Therefore, of the nine anthropometric indicators we studied, the BMI, CI, PI, and WHtR were found to be more effective in predicting the CAP score, i.e., fatty liver.

Epidemiology of Chronic Hepatitis B Infection in the Cohort of College Students with Vaccination in Taiwan.

After the mass vaccination project in Taiwan, the prevalence of the hepatitis B virus (HBV) infection for the college-aged population of 18 to 21 years is uncertain. We aimed to investigate the prevalence of hepatitis B markers in different birth cohorts. A total of 38,075 students in universities in Kaohsiung area undergoing entrance examinations between July 2006 to September 2020 were included. Seroprevalence of the hepatitis B surface antigen (HBsAg) and hepatitis B surface antibody (anti-HBs) status and laboratory data were collected. The seropositive rate of HBsAg was less than 1% for students born after 1991. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST), were significantly higher, and body mass index (BMI) was significantly lower in HBV carriers compared to those who were not carriers (all p < 0.001). Multivariate logistic regression showed that age, male, higher BMI, and positive HBsAg were risk factors of abnormal ALT value. A decrease in the positive rate of anti-HBs which was significantly higher in the cohort of plasma-derived vaccines than recombinant vaccines was found. We concluded that there were decreasing trends in seropositive rates of HBsAg and anti-HBs for students of the college-aged population in the Kaohsiung area. The status of HBsAg was a predictive factor of abnormal ALT levels. The period effect on anti-HBs seropositivity for DNA recombinant vaccine somehow existed.

Cardiac Autonomic and Cardiac Vagal Control During and After Depressive and Happiness Autobiographical Memories in Patients With Major Depressive Disorder.

Background: Heart rate variability (HRV) and respiratory sinus arrhythmia (RSA) are indices of cardiac autonomic and cardiac vagal control (CVC), both of which are markers of emotional regulation and physical health. This study examined (1) the differences in cardiac autonomic regulation and CVC during baseline, depressive, and happiness autobiographical memory tasks between participants with major depressive disorder (MDD group) and healthy controls (HC group); (2) the associations between depressive symptoms and cardiac autonomic and CVC; and (3) the reactivity and recovery of cardiac autonomic and CVC between the MDD and HC groups. Methods: A total of 168 and 178 participants were included in the MDD and HC groups, respectively. Demographic data and the Beck Depression Inventory-II were collected before the experimental procedure. Lead II electrocardiograph (ECG) was measured during baseline, depressive, and happiness autobiographical memory tasks, and then interbeat intervals from ECG were converted to the time and frequency domains of HRV and RSA. Results: The participants in the MDD group showed lower HRV (including standard deviation of normal to normal intervals, low frequency, the natural logarithm of low frequency, and the natural logarithm of high frequency) and CVC (RSA and lnRSA) than those in the HC group. Depressive symptoms were positively correlated with heart rate and negatively correlated with the indices of cardiac autonomic and CVC. There was significantly increased reactivity and recovery of cardiac autonomic and CVC during and after depressive and happiness autobiographical memory tasks in the HC group, but not in the MDD group. Discussion: Participants with MDD had cardiac autonomic and CVC dysregulation, decreased reactivity, and did not recover to baseline after emotional provocations. These results can be the theoretical basis for clinical intervention by using HRV biofeedback to restore cardiac autonomic regulation and CVC during and after emotional events in the future.

Prefrontal Lobe and Posterior Cingulate Cortex Activations in Patients with Major Depressive Disorder by Using Standardized Weighted Low-Resolution Electromagnetic Tomography.

BACKGROUND: The differences in brain activity between patients with major depressive disorder (MDD) and healthy adults have been confirmed by functional magnetic resonance imaging (fMRI), positron emission tomography (PET), and electroencephalography (EEG). The prefrontal lobe and posterior cingulate cortex (PCC) are related to emotional regulation in patients with MDD. However, the high cost and poor time resolution of fMRI and PET limit their clinical application. Recently, researchers have used high time resolution of standardized weighted low-resolution electromagnetic tomography (swLORETA) to investigate deep brain activity. This study aimed to convert raw EEG signals into swLORETA images and explore deep brain activity in patients with MDD and healthy adults. METHODS: BrainMaster EEG equipment with a 19-channel EEG cap was used to collect resting EEG data with eyes closed for 5 min. NeuroGuide software was used to remove the EEG artifacts, and the swLORETA software was used to analyze 12,700 voxels of current source density (CSD) for 139 patients with MDD and co-morbid anxiety symptoms (mean age = 43.08, SD = 13.76; 28.78% were male) and 134 healthy adults (mean age = 40.60, SD = 13.52; 34.33% were male). Deep brain activity in the frontal lobe and PCC at different frequency bands was analyzed, including delta (1-4 Hz), theta (5-7 Hz), alpha (8-11 Hz), beta (12-24 Hz), beta1 (12-14 Hz), beta2 (15-17 Hz), beta3 (18-24 Hz), and high beta (25-29 Hz). RESULTS: There was lower delta and theta and higher beta, beta1, beta2, beta3, and high-beta activity at the prefrontal lobe (dorsal medial prefrontal cortex [dmPFC], ventral medial prefrontal cortex [vmPFC], and dorsal lateral prefrontal cortex [dlPFC], ventral lateral prefrontal cortex [vlPFC], orbital frontal cortex [OFC]) and PCC in MDD patients compared with healthy adults. There was no significant difference in alpha activity between the two groups. CONCLUSION: This study indicates brain hyperactivity in the right prefrontal lobe (dlPFC and vmPFC) and PCC in patients with MDD with co-morbid anxiety symptoms, and the dlPFC and PCC were also related to emotion regulation in MDD. Inhibiting high-beta activity or restoring delta and theta activity to the normal range in the right frontal lobe and PCC may be possible in z-score neurofeedback protocols for patients with MDD in future studies.

Higher NAFLD fibrosis score is associated with impaired eGFR.

BACKGROUND/PURPOSE: Chronic kidney disease (CKD) has become a worldwide health problem, leading to high morbidity and mortality, and non-alcoholic fatty liver disease (NAFLD) is considered a risk factor for CKD. The aim of this study was to explore the relationship between NAFLD fibrosis score (NFS) and the estimated glomerular filtration rate (eGFR), and identify possible risk factors related to the NFS among Taiwanese subjects. METHODS: Subjects were enrolled from the database of the Department of Preventive Medicine of Kaohsiung Municipal Hsiao-Kang Hospital. The eGFR was calculated according to the Taiwanese Modification of Diet in Renal Disease (TMDRD) equation, and the NFS was employed to evaluate the fibrotic level. RESULTS: In total, 11,376 subjects were enrolled in this study, with a mean age of 52.0 ± 6.81 years, including 4529 (39.8%) males. A fasting sugar level ≥100 mg/dL (OR = 1.70, 95% CI = 1.52-1.87) and an abnormal waist circumference (OR = 1.81, 95% CI = 1.65-1.99) were significant factors associated with NFS (p < 0.05). Trends of a decreasing TMDRD score and an increasing NFS with increasing age were noted (p < 0.05). The NFS was significantly negatively correlated with the TMDRD score (standard coefficients: -0.067, p < 0.001). CONCLUSION: A higher NFS is associated with an impaired eGFR in Taiwanese subjects. Controlling risk factors, especially fasting sugar level and waist circumference, may be useful in preventing NFS deterioration, which is negatively correlated with the eGFR.

Effect of music on level of anxiety in patients undergoing colonoscopy without sedation.

BACKGROUND: Listening to music can be a noninvasive method for reducing the anxiety level without any adverse effects. The aim of this study was to explore whether music can reduce anxiety and to compare two different styles of music, informal classical music and light music, to ascertain the more effective style of music in reducing anxiety in patients undergoing colonoscopy without sedation. METHODS: This study enrolled 138 patients who underwent colonoscopy without sedation during a general health examination from February 2009 to January 2015. The patients were randomly assigned to a group that did not listen to music, a group that listened to music by David Tolley, or a group that listened to music by Kevin Kern. The State-Trait Anxiety Inventory was used to evaluate the status of anxiety. RESULTS: A trend test for mild anxiety was performed on the patients in the three groups, and a significant trend was noted (p=0.017 for all patients; p=0.014 for analysis by sex). Multivariate analysis for mild anxiety on the patients in each group was also performed in this study, and music by Kevin Kern was found to have the lowest odds ratio (Odds ratio=0.34, p=0.045). CONCLUSION: Listening to music, especially music by Kevin Kern, reduced the level of anxiety in patients undergoing colonoscopy examination without sedation.

Distinct subpopulations of hepatitis C virus infectious cells with different levels of intracellular hepatitis C virus core protein.

Chronic infection by hepatitis C virus (HCV) is a major risk factor for the development of hepatocellular carcinoma (HCC). Despite the clear clinical importance of virus-associated HCC, the underlying molecular mechanisms remain largely unclarified. Oxidative stress, in particular, DNA lesions associated with oxidative damage, plays a major role in carcinogenesis, and is strongly linked to the development of many cancers, including HCC. However, in identifying hepatocytes with HCV viral RNA, estimates of the median proportion of HCV-infected hepatocytes have been found as high as 40% in patients with chronic HCV infection. In order to explore the gene alternation and association between different viral loads of HCV-infected cells, we established a method to dissect high and low viral load cells and examined the expression of DNA damage-related genes using a quantitative polymerase chain reaction array. We found distinct expression patterns of DNA damage-related genes between high and low viral load cells. This study provides a new method for future study on virus-associated gene expression research.

Nonalcoholic fatty liver disease severity is associated with the ratios of total cholesterol and triglycerides to high-density lipoprotein cholesterol.

BACKGROUND: Limited data support the notion that lipid ratios are risk factors for nonalcoholic fatty liver disease (NAFLD). We evaluated the association between lipid ratios and NAFLD. METHODS: This was a large population, cross-sectional, retrospective study. Data on NAFLD severity, blood pressure, fasting glucose, total cholesterol (TC), triglyceride (TG), and high-density lipoprotein cholesterol (HDL-C) levels were obtained from 44,767 examinees at single health checkup center. The enrollees were stratified into four subgroups based on their TC/HDL-C and TG/HDL-C ratios. We used multivariate analyses to evaluate the odds between lipid ratios and NAFLD. RESULTS: The prevalence rate of fatty liver in this study was 53.76%. In the baseline subgroup with the lowest TC/HDL-C and TG/HDL-C ratios, the prevalence of NAFLD, hypertension, and diabetes was lower than that of the other three subgroups. Patients with higher lipid ratios had a significantly greater risk for advanced NAFLD. CONCLUSIONS: Adults with high TC/HDL-C or TG/HDL-C ratios, or both, have a greater risk for NAFLD, especially advanced NAFLD.

Exploring the blood volume amplitude and pulse transit time during anger recall in patients with coronary artery disease.

BACKGROUND AND PURPOSE: One psychopathological mechanism that links anger to coronary artery disease (CAD) is cardiac autonomic imbalance. Blood volume amplitude (BVA) and pulse transit time (PTT) are related to peripheral arterial elasticity and cardiac conduction, which are used as indirect markers for autonomic activation. The purposes of this study were to examine the relationships between BVA and PTT, and the reactivity of BVA and PTT during the anger recall task in patients with CAD. METHODS AND SUBJECTS: A total of 112 patients with CAD and 93 healthy controls were recruited; BVA and PTT were collected during baseline, the neutral episode, the anger episode, and after recovery. RESULTS: There were significant positive correlations between BVA and PTT in all participants. BVA reactivity during the anger episode was greater in patients with CAD than in healthy controls, and there were also lower BVA recovery values after the neutral and anger episodes. However, there was no significant difference in BVA reactivity between the two groups in the neutral episode. PTT recovered to baseline levels after the neutral and anger episodes in healthy controls, but not in the patients with CAD. CONCLUSION: BVA and PTT were associated with peripheral vascular elasticity and cardiac conduction that were regulated by the cardiac autonomic system. Peripheral vasoconstriction and changes in travel time between left ventricular and peripheral vasculature during the anger episode, and impaired recovery to baseline levels may relate to the psychopathological mechanisms of CAD.

Acute hepatitis E virus infection in Taiwan 2002-2006 revisited: PCR shows frequent co-infection with multiple hepatitis viruses.

Sporadic cases of acute hepatitis E virus (HEV) infection with production of anti-HEV IgM have been reported occasionally in Taiwan despite no reported outbreaks in the past. This study was undertaken to determine whether serological markers correlated with virus detection. From 2002 to 2006, 72 reported cases of acute hepatitis E seropositive for anti-HEV IgM in Taiwan were enrolled for investigation. Acute phase serum samples were collected for detection of HEV RNA, HBV DNA, HCV RNA, and GBV-C RNA by PCR. The results showed that viral sequences of HEV, HBV, HCV and GBV-C were detected in 54 (75%), 21 (29.2%), 9 (12.5%), and 22 (30.6%) of cases, respectively. Acute hepatitis A co-infection was excluded in all patients because none were seropositive for anti-HAV IgM and, nine patients (12.5%) did not seroconvert to anti-HEV IgG. These results suggest that serum markers did not correlate completely with viremia in the diagnosis of acute HEV infection. Multiple viruses may co-infect with acute hepatitis E virus in Taiwan. Detection of hepatitis E viremia together with seropositivity for anti-HEV IgM and followed by seroconversion to anti-HEV IgG should be included in the diagnostic criteria for HEV infection.

Chronic autoimmune hepatitis with Epstein-Barr virus superinfection: a case report and review of literature.

A 66-year-old female presented with acute illness of severe hepatic dysfunction. She had a past history of chronic hepatitis of low disease activity. After admission and clinical investigation including liver biopsy, it showed an underlying chronic liver disease suggestive of autoimmune hepatitis (AIH) with early liver cirrhosis. Together with other clinical features, this patient was diagnosed as definite AIH type 1 by using the IAIHG (International Autoimmune Hepatitis Group) criteria. During this episode, superinfection by Epstein-Barr virus (EBV) was evidenced by positive PCR (polymerase chain reaction) test, and serial changes of EBV VCA IgM and IgG tests. Severe hepatic impairment was evidenced by markedly elevated AST level 3090 IU/L, high bilirubin level 26.4 mg/dL, and presence of ascites. The patient gradually recovered and liver function improved in agreement with the decline of EBV VCA titers. Immunosuppressive therapy resulted in further improvement of the aminotransferases levels. This is an unusual case of EBV superinfection on pre-existing AIH with early cirrhosis, which caused enhancement of the autoimmune disease process and resulted in severe hepatic decompensation and jaundice. We herein describe the case and briefly review the literature.

Anti-sense morpholino oligonucleotide assay shows critical involvement for NF-kappaB activation in the production of Wnt-1 protein by HepG2 cells: oncology implications.

The link of proto-oncogenic protein Wnt-1 production with NF-kappaB activation has been functionally demonstrated in PC12 cells, a rat pheochromocytoma cell line of neural crest lineage, while it is not yet verified in human cells. The link can be indirectly supported in our previous report that functional proteomics identifies enhanced expression of NF-kappaB-associated Wnt-1 production in human hepatocellular carcinoma tissues. This study aimed to further validate this link in human cells using anti-sense strategy. The effects of sequence-specific anti-sense morpholino oligonucleotides (ONs) targeting against pre-mRNA sequences of human p50 and p65 subunits of NF-kappaB as well as Wnt-1 genes were investigated. It revealed that all the three morpholino ONs inhibited NF-kappaB activation in human hepatoblastoma cell line HepG2 cells along with decreased Wnt-1 production. Chromatin immunoprecipitation assay ascertained the direct binding of NF-kappaB-p50 to the Wnt-1 promoter. Additionally, anti-P50 and anti-P65 morpholino ONs also repressed the phosphorylation of Ikappa Balpha which temporarily correlated with the inhibition of NF-kappaB activation accompanied by decreased Wnt-1 production by HepG2 cells. In summary, NF-kappaB activation is critically involved in the production of Wnt-1 by HepG2 cells. These results may have important oncology implications in treating patients with NF-kappaB-associated Wnt-1-producing cancers.