The application of liver stiffness measurement (LSM) by transient elastography (TE) in general population remains to clarify. This cohort study aimed to examine the usefulness of TE and to identify factors associated with significant liver fibrosis in community-based population.We conducted a hepatitis screening program in 2 remote villages of Southern Taiwan. All residents participated voluntarily and received questionnaire evaluation, blood tests, abdominal sonography, and LSM by TE. Residents with any one of following criteria including hepatitis B virus infection, hepatitis C virus infection, more than moderate alcohol drinking, and failure to obtain valid or reliable LSM were excluded.There were 831 residents participated in program. The valid and reliable LSM were obtained in 98.3% and 96.3% of residents, respectively. Finally, a total of 559 residents including 283 residents with nonalcoholic steatotic fatty liver disease (NAFLD) were enrolled for analysis. The mean liver stiffness was 4.9 ± 1.9 kPa. The liver stiffness increased in residents with diabetes mellitus (DM), higher body mass index (BMI), hypertension, abnormal waist–hip circumference ration (WHR), higher waist circumference (WC), and presence of fatty liver. Higher body weight, higher BMI, higher WC, abnormal WHR, abnormal aspartate aminotransferase (AST), abnormal alanine aminotransferase (ALT), and DM were the factors associated with significant fibrosis (liver stiffness ≥7 kPa) in either all participants or NAFLD residents. As determined by multivariate analysis, abnormal AST values and DM were the 2 independent factors in all participants (abnormal AST: OR 3.648, 95% CI 1.134–11.740, P = .03; DM: OR 2.882, 95% CI 1.282–6.478, P = .01) and in residents with NAFLD (abnormal AST: OR 4.197, 95% CI 1.154–15.262, P = .03; DM: OR 3.254, 95% CI 1.258–8.413, P = .02).LSM by TE is a useful screening tool in community. In residents, who were absence of chronic hepatitis virus infection or consumed less than moderate alcohol drinking, exhibited DM or abnormal AST values may consider a substantial group with significant fibrosis in community.

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Chronic hepatitis C (CHC) is strongly associated with risks of cardiovascular diseases. The impact of direct acting antiviral (DAA) therapy on central blood pressure remains unclear. This investigation evaluates changes in central blood pressure following DAA therapy. One hundred and two DAA-treated patients were prospectively enrolled. Lipid profiles and pulse wave analysis of brachial artery by cuff sphygmomanometry including augmentation index (AIx), a parameter of central artery stiffness, were evaluated. All of the 102 patients achieved sustained virological response (SVR12). Cholesterol and LDL significantly increased following SVR12. Along with lipid changes, significantly higher central diastolic pressure (78.2 ± 14.2 mm Hg at baseline vs. 83.3 ± 13.9 mm Hg at SVR12, p = 0.011) and AIx (33.0 ± 12.7% at baseline vs. 36.9 ± 12.9% at SVR12, p = 0.012) were only observed in the advanced fibrosis patients. Co-morbid diseases, including hypertension (33.4 ± 13.0% vs. 39.7 ± 12.6%, p = 0.003), abnormal waist circumference (33.8 ± 12.2% vs. 38.0 ± 13.2%, p = 0.027), and metabolic syndrome (34.5 ± 12.1% vs. 39.0 ± 11.2%, p = 0.043) were associated with augmented AIx upon SVR12. The augmented central artery stiffness following viral eradication by DAA therapy may raise the concern of short-term cardiovascular risk in CHC patients.

Galectin-1 (Gal-1) is a secretory lectin with pro-tumor activities and is associated strongly with hepatocellular carcinoma (HCC) development. Although Gal-1 is a well-known soluble pro-tumor factor in the tumor microenvironment (TME), the secretion mode of Gal-1 is not clearly defined. On the other hand, in addition to cancer cells, Gal-1 is widely expressed in tumor stromal cells, including tumor-associated macrophages (TAMs). TAMs are a significant component of stromal cells in TME; however, their contributions in producing Gal-1 to TME are still not explored. Here we reveal that TAMs can actively secrete Gal-1 in response to stimuli of HCC cells. Gal-1 produced by TAMs leads to an increase of the systemic level of Gal-1 and HCC tumor growth in mice. Mechanistically, TLR2-dependent secretory autophagy is found to be responsible for Gal-1 secretion from TAMs. Gal-1 acts as a cargo of autophagosomes to fuse with multivesicular bodies via Rab11 and VAMP7-mediated vesicle trafficking before being secreted. This autophagy-regulated Gal-1 secretion in TAMs correlates to poor overall survival and progression-free survival rates of HCC patients. Our findings uncover the secretion mode of Gal-1 via secretory autophagy and highlight the pathological role of TAM-produced Gal-1 in HCC progression.

Heart rhythm complexity analysis has been shown to have good prognostic power in patients with cardiovascular disease. The aim of this study was to analyze serial changes in heart rhythm complexity from the acute to chronic phase of acute myocardial infarction (MI). We prospectively enrolled 27 patients with anterior wall ST segment elevation myocardial infarction (STEMI) and 42 control subjects. In detrended fluctuation analysis (DFA), the patients had significantly lower DFAα2 in the acute stage (within 72 hours) and lower DFAα1 at 3 months and 12 months after MI. In multiscale entropy (MSE) analysis, the patients had a lower slope 5 in the acute stage, which then gradually increased during the follow-up period. The areas under the MSE curves for scale 1 to 5 (area 1–5) and 6 to 20 (area 6–20) were lower throughout the chronic stage. Area 6–20 had the greatest discriminatory power to differentiate the post-MI patients (at 1 year) from the controls. In both the net reclassification improvement and integrated discrimination improvement models, MSE parameters significantly improved the discriminatory power of the linear parameters to differentiate the post-MI patients from the controls. In conclusion, the patients with STEMI had serial changes in cardiac complexity.

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The hierarchical interaction between electrical signals of the brain and heart is not fully understood. We hypothesized that the complexity of cardiac electrical activity can be used to predict changes in encephalic electricity after stress. Most methods for analyzing the interaction between the heart rate variability (HRV) and electroencephalography (EEG) require a computation-intensive mathematical model. To overcome these limitations and increase the predictive accuracy of human relaxing states, we developed a method to test our hypothesis. In addition to routine linear analysis, multiscale entropy and detrended fluctuation analysis of the HRV were used to quantify nonstationary and nonlinear dynamic changes in the heart rate time series. Short-time Fourier transform was applied to quantify the power of EEG. The clinical, HRV, and EEG parameters of postcatheterization EEG alpha waves were analyzed using change-score analysis and generalized additive models. In conclusion, the complexity of cardiac electrical signals can be used to predict EEG changes after stress.

Background and aimThe role of non-invasive methods to evaluate fibrosis severity of chronic hepatitis C (CHC) subjects in community needs to be explored. This study investigated FIB-4 and transient elastography (TE) in staging liver fibrosis of CHC subjects in community.MethodsA total of 905 subjects who were positive for anti-HCV antibody from five districts of Tainan City of Taiwan were invited to participate in surveillance activities for CHC. FIB-4 and TE were measured for each participant.ResultsA total of 502 subjects with detectable HCV RNA and valid TE were enrolled. The distribution of FIB-4 and TE values differed markedly. Both methods exhibited a strongest correlation in subjects with at age 50~60 years (r = 0.655, p <0.001). FIB-4 score increased proportionally with age (p <0.001), but TE did not (p = 0.142). The intraclass correlation efficient of both methods was 0.255 (p <0.001). Subjects with TE defined advanced fibrosis exhibited younger age, higher BMI, higher platelet count, lower FIB-4 score, higher incidence of fatty liver and splenomegaly, and higher controlled attenuation parameter value than those defined by FIB-4. By multivariate logistic regression analysis, higher ALT levels, higher incidence of fatty liver, and presence of splenomegaly were the independent factors associated with advanced fibrosis defined by TE rather than defined by FIB-4.ConclusionsFIB-4 and TE defined different distribution of fibrosis stages in same HCV population. FIB-4 was deeply influenced by age whereas TE was not. TE had the advantages over than FIB-4 in strong association with splenomegaly and in detecting the role of non-alcoholic fatty liver disease in advanced fibrosis.