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1.
Epigenomics ; 2021 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-33876652

RESUMO

Aims: To determine the association of the methylation age (Horvath epigenetic clock) of gastric cancer (GC) tissues with molecular subtypes and patient survival. Materials & methods: Multivariate regression models were used to determine the association of methylation age acceleration (AA) with the clinical and molecular characteristics of 333 GC patients. Results: Relative to the chromosomal instability (CIN) subtype, the epigenetic AA was 49.8 (95% CI: 42.7-56.9) years for Epstein-Barr virus, 16.1 (10.6-21.6) years for microsatellite instability (MSI), and 6.05 (0.1-11.1) years for genomic stability (GS) subtype. GC patients with accelerated aging of tumor tissues had better outcomes (adjusted hazard ratio: 3.13; p = 0.03). Differentially methylated probes in patients with accelerated and decelerated methylation aging enriched in pathways including BMP signaling, HMGB1 signaling, STAT3 signaling and human embryonic stem cell pluripotency. Conclusions: Our results highlight the prognostic value of epigenetic AA in GC and suggest that epigenetic AA is also an indicator of molecular subtype in GC.

2.
Artigo em Inglês | MEDLINE | ID: mdl-33908180

RESUMO

BACKGROUND: The presence of significant liver fibrosis is a key determinant of long-term prognosis in non-alcoholic fatty liver disease (NAFLD). We aimed to develop a novel machine learning algorithm (MLA) to predict fibrosis severity in NAFLD and compared it with the most widely used non-invasive fibrosis biomarkers. METHODS: We used a cohort of 553 adults with biopsy-proven NAFLD, who were randomly divided into a training cohort (n=278) for the development of both logistic regression model (LRM) and MLA, and a validation cohort (n=275). Significant fibrosis was defined as fibrosis stage F≥2. MLA and LRM were derived from variables that were selected using a least absolute shrinkage and selection operator (LASSO) logistic regression algorithm. RESULTS: In the training cohort, the variables selected by LASSO algorithm were body mass index, pro-collagen type III, collagen type IV, aspartate aminotransferase and albumin-to-globulin ratio. The diagnostic accuracy of MLA showed the highest values of area under the receiver operator characteristic curve (AUROC: 0.902, 95%CI 0.869-0.904) for identifying fibrosis F≥2. The LRM AUROC was 0.764, 95%CI 0.710-0.816) and significantly better than the AST-to-Platelet ratio (AUROC 0.684, 95%CI 0.605-0.762), FIB-4 score (AUROC 0.594, 95%CI 0.503-0.685) and NAFLD Fibrosis Score (AUROC 0.557, 95%CI 0.470-0.644). In the validation cohort, MLA also showed the highest AUROC (0.893, 95%CI 0.864-0.901). The diagnostic accuracy of MLA outperformed that of LRM in all subgroups considered. CONCLUSIONS: Our newly developed MLA algorithm has excellent diagnostic performance for predicting fibrosis F≥2 in patients with biopsy-confirmed NAFLD.

3.
Artigo em Inglês | MEDLINE | ID: mdl-33853719

RESUMO

BACKGROUND AND AIMS: Several susceptibility gene variants predisposing to nonalcoholic fatty liver disease (NAFLD) have been identified in chronic kidney disease (CKD). Evidence supports that 17-beta hydroxysteroid dehydrogenase 13 (HSD17B13) rs72613567 plays a role in NAFLD development by affecting lipid homeostasis. Since lipid droplets may accumulate in the kidneys and contribute to renal injury, we investigated the association between the HSD17B13 rs72613567 variant and markers of renal function/injury in NAFLD. METHODS AND RESULTS: We measured estimated glomerular filtration rate (eGFR), urinary/serum neutrophil gelatinase-associated lipocalin (NGAL), and urinary albumin-to-creatinine ratio (u-ACR) in individuals with biopsy-proven NAFLD. Multivariable regression analyses were undertaken to examine the associations between the HSD17B13 rs72613567 variant and markers of renal function/injury. Individuals were stratified by HSD17B13 rs72613567 genotypes into -/-, A/- and A/A groups. HSD17B13 rs72613567 genotypes were not significantly associated with eGFR and urinary/serum NGAL levels. Conversely, the prevalence of abnormal albuminuria in the A/- + A/A group was lower than in the -/- group (4.92% vs. 19.35%, p = 0.001). Additionally, the mean u-ACR levels were lower among carriers of the A/- or A/A genotypes with coexisting hypertension or diabetes, than among those with the -/- genotype. The risk of abnormal albuminuria (adjusted-odds ratio 0.16, p = 0.001) remained significantly lower in the A/- + A/A group after adjustment for established renal risk factors and histologic severity of NAFLD. CONCLUSION: HSD17B13 rs72613567: A allele is associated with a lower risk of having abnormal albuminuria, but not with lower eGFR or urinary/serum NGAL levels, in patients with biopsy-proven NAFLD.

4.
Front Endocrinol (Lausanne) ; 12: 604100, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33763027

RESUMO

Background and Aim: Circulating levels of interleukin (IL)-6, a well-known inflammatory cytokine, are often elevated in coronavirus disease-2019 (COVID-19). Elevated IL-6 levels are also observed in patients with metabolic dysfunction-associated fatty liver disease (MAFLD). Our study aimed to describe the association between circulating IL-6 levels and MAFLD at hospital admission with risk of severe COVID-19. Methods: A total of 167 patients with laboratory-confirmed COVID-19 from three Chinese hospitals were enrolled. Circulating levels of IL-2, IL-4, IL-6, IL-10, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ were measured at admission. All patients were screened for fatty liver by computed tomography. Forty-six patients were diagnosed as MAFLD. Results: Patients with MAFLD (n = 46) had higher serum IL-6 levels (median 7.1 [interquartile range, 4.3-20.0] vs. 4.8 [2.6-11.6] pg/mL, p = 0.030) compared to their counterparts without MAFLD (n = 121). After adjustment for age and sex, patients with MAFLD had a ~2.6-fold higher risk of having severe COVID-19 than those without MAFLD. After adjustment for age, sex and metabolic co-morbidities, increased serum IL-6 levels remained associated with higher risk of severe COVID-19, especially among infected patients with MAFLD (adjusted-odds ratio 1.14, 95% CI 1.05-1.23; p = 0.002). There was a significant interaction effect between serum IL-6 levels and MAFLD for risk of severe COVID-19 (p for interaction = 0.008). Conclusions: Patients with MAFLD and elevated serum IL-6 levels at admission are at higher risk for severe illness from COVID-19.


Assuntos
/complicações , Fígado Gorduroso/epidemiologia , Interleucina-6/sangue , Doenças Metabólicas/fisiopatologia , Índice de Gravidade de Doença , Adolescente , Adulto , Idoso , /virologia , China/epidemiologia , Fígado Gorduroso/sangue , Fígado Gorduroso/patologia , Fígado Gorduroso/virologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
5.
Clin Transl Gastroenterol ; 12(3): e00321, 2021 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-33704100

RESUMO

INTRODUCTION: Strong evidence indicates that multiple genetic and environmental risk factors play a role in the pathogenesis of nonalcoholic steatohepatitis (NASH). We aimed to develop and validate a novel nomogram, incorporating both genetic and clinical factors, for predicting NASH. METHODS: A total of 1,070 Asian individuals with biopsy-confirmed nonalcoholic fatty liver disease (NAFLD) from 2 countries (China and South Korea) were recruited. The histological spectrum of NAFLD was classified according to the NASH clinical research network scoring system. The nomogram was developed in the Chinese training set (n = 402), and then, it was validated in both the Chinese internal validation set (n = 136) and the external Korean validation cohort (n = 532), respectively. RESULTS: Sex, metabolic syndrome, insulin resistance, serum aspartate aminotransferase levels, and PNPLA3 (rs738409) and HSD17B13 (rs72613567) genetic variants were strongly associated with NASH. Based on their regression coefficients, we developed a nomogram with good discriminatory ability (area under the receiver operating characteristic curve: 0.81, 95% confidence interval [CI] 0.77-0.85) and good calibration (Hosmer-Lemeshow test, P = 0.794) for identifying NASH. In the 2 validation cohorts, the nomogram showed high area under the receiver operating characteristic curves (internal validation set: 0.80, 95% CI 0.72-0.88; external validation cohort: 0.76, 95% CI 0.72-0.80) and good calibration. DISCUSSION: Our newly developed and externally validated nomogram, incorporating both genetic and clinical risk factors, may be conveniently used to predict NASH. Further validation studies in other ethnic groups are warranted to confirm its diagnostic utility to identify NASH, among patients with biopsy-proven NAFLD.

6.
Int J Cardiol ; 330: 245-250, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33577908

RESUMO

BACKGROUND: Spontaneous echo contrast (SEC) is a known precursor to thrombus formation and thromboembolic events. This study aims to demonstrate the clinical characteristics and outcomes of patients with left ventricular spontaneous echo contrast (LV-SEC). METHODS: Patients with consecutive echocardiogram performed from October 2009 to September 2019 were enrolled in this retrospective, single-center study. Those with LV-SEC were included, while patients complicated by left ventricular thrombus, with history of infective endocarditis, prosthetic valves, or lost to follow-up were excluded. The clinical endpoint was 1-year thromboembolic events (i.e. stroke and peripheral embolism). RESULTS: Among 417 patients (mean age 63.5 ± 14.7 years; 86.8% men) with LV-SEC, the incidence of 1-year embolism was 12.9%. In multivariate Cox proportional hazard model, significant risk factors for thromboembolic event were age [hazard ratio (HR) = 1.022, 95% confidence interval (CI): 1.000-1.045], atrial fibrillation (AF) (HR = 2.292, 95% CI: 1.237-4.244), hemoglobin (HR = 1.032, 95% CI: 1.017-1.047), left ventricular ejection fraction (LVEF) (HR = 1.021, 95% CI: 1.002-1.041), and anticoagulant therapy (HR = 0.310, 95% CI: 0.168-0.572). For patients with repeated measurements for echocardiography, D-dimer (HR = 1.137, 95% CI: 1.051-1.231), and △LVEF (HR = 0.961, 95% CI: 0.928-0.996) were independently associated with the persistent LV-SEC. CONCLUSION: The present study reported a high incidence of 1-year thromboembolic event in patients with LV-SEC. Age, AF, hemoglobin, LVEF were independent risk factors for 1-year embolism and a reduced risk of embolism was observed among patients with anticoagulation therapy. Additionally, D-dimer and △LVEF are independently associated with the persistent LV-SEC.

7.
Int J Med Sci ; 18(5): 1137-1142, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33526973

RESUMO

Background: It's reported SARS-CoV-2 could transmit via gastrointestinal tract, with or without pulmonary symptoms. However, as far as we know, there is no effective marker to predict the virus discharge in stool and initial gastrointestinal involvement of COVID-19 patients. Aims: We aimed to investigate the likely biomarker predicting virus discharge in stool and initial gastrointestinal involvement of COVID-19, which may assist the clinicians in better preventing COVID-19 spread. Methods: The patients complained of gastrointestinal symptoms, including vomiting, diarrhea, with or without respiratory symptoms, attending the Sixth People's Hospital of Wenzhou, and the Second Affiliated Hospital of Wenzhou Medical University, were screened by qRT-PCR for SARS-CoV-2. The confirmed COVID-19 patients, without any history of intaking contaminated food or water, were all enrolled to investigate the association between circulating lymphocyte count and virus discharge, initial gastrointestinal involvement. Results: Seventy-six COVID-19 patients were included in the final analysis (mean age of 44.5 years, male 44.7%), with 24 (31.5%) complained of initial gastrointestinal symptoms. Significantly lower circulating lymphocyte count was found in the patients with positive results of qRT-PCR on stool (p = 0.012). Patients were divided into tertile groups by circulating lymphocyte count: lymphocyte ≤0.88*10^9/l ( n = 25 ), 0.88*10^9/l -1.2*10^9/l ( n = 28 ), and >1.2*10^9/l ( n = 23 ), respectively. When circulating lymphocyte count increased from 1st tertile to the 2nd and 3rd tertiles, the risk of initial gastrointestinal symptoms decreased by nearly 75% (OR = 0.25, 95% CI: 0.07, 0.98, p = 0.047), 83% (OR = 0.17, 95% CI: 0.05, 0.63, p = 0.008), after adjusting for likely confounders. Conclusions: The circulating lymphocyte count is inversely associated with virus discharge in stool, and the risk of initial gastrointestinal involvement in COVID-19 patients.


Assuntos
/imunologia , Gastroenteropatias/virologia , Adulto , Fezes/virologia , Feminino , Gastroenteropatias/imunologia , Humanos , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
8.
J Hepatol ; 74(4): 989-991, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33347953
12.
Artigo em Inglês | MEDLINE | ID: mdl-33250371

RESUMO

BACKGROUND AND AIMS: Some previous studies reported serum autoantibody positivity in patients with nonalcoholic fatty liver disease (NAFLD). The clinical significance of these findings remains uncertain. We aimed to investigate the association between the presence of serum autoantibodies and liver disease severity in NAFLD. METHODS AND RESULTS: A total of 388 consecutive patients with biopsy-proven NAFLD were included in the study. Various serum autoantibodies (including also anti-nuclear antibodies [ANA]) were detected by indirect immunofluorescent or immunoblotting assays. Overall, 84 (21.6%) patients with biopsy-confirmed NAFLD had positivity for at least one of the measured serum autoantibodies. ANA positivity was present in 50 (12.9%) patients, whereas anti-U1RNP or pANCA antibodies were detectable in 9 (2.3%) and 6 (1.5%) patients, respectively. Multivariate logistic regression analysis showed that ANA positivity (adjusted-odds ratio: 4.51, 95%CI: 1.77-11.5; P = 0.002) or positivity of any serum autoantibodies (adjusted-odds ratio: 3.14, 95%CI: 1.30-7.62; P = 0.01) were independently associated with advanced liver fibrosis (stages F3-F4). In serum autoantibody/ANA-positive patients, the proportion of those with advanced fibrosis was also greater among carriers of PNPLA3 rs738409 GG or CG than among those carrying PNPLA3 rs738409 CC genotype. CONCLUSIONS: Serum autoantibody positivity was independently associated with advanced liver fibrosis in patients with biopsy-proven NAFLD. The presence of serum autoantibodies in patients with advanced fibrosis occurred more frequently amongst those carrying PNPLA3 rs738409 GG or CG genotypes.

13.
Br J Nutr ; : 1-39, 2020 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-33198849

RESUMO

BACKGROUND: The FNDC5 gene encodes the fibronectin type III domain-containing protein 5 that is a membrane protein mainly expressed in skeletal muscle and the FNDC5 rs3480 polymorphism may be associated with liver disease severity in nonalcoholic fatty liver disease (NAFLD). We investigated the influence of the FNDC5 rs3480 polymorphism on the relationship between sarcopenia and the histological severity of NAFLD. METHODS: 370 adult individuals with biopsy-proven NAFLD were studied. Appendicular skeletal muscle mass was measured by bioelectrical impedance. The association between the key exposure sarcopenia, and the outcome liver histological severity, was investigated by binary logistic regression. Stratified analyses were undertaken to examine the impact of FNDC5 rs3480 polymorphism on the association between sarcopenia and the severity of NAFLD histology. RESULTS: Patients with sarcopenia had more severe histological grades of steatosis and a higher prevalence of significant fibrosis and definite NASH than those without sarcopenia. There was a significant association between sarcopenia and significant fibrosis (adjusted odds ratio 2.79, 95%CI 1.31-5.95, p=0.008), independent of established risk factors and potential confounders. Among patients with sarcopenia, significant fibrosis occurred more frequently in the rs3480 AA genotype carriers than in those carrying the FNDC5 rs3480 G genotype (43.8% vs. 17.2%, p=0.031). In the association between sarcopenia and liver fibrosis, there was a significant interaction between the FNDC5 genotype and sarcopenia status (p-value for interaction=0.006). CONCLUSION: Sarcopenia is independently associated with significant liver fibrosis, and the FNDC5 rs3480 G variant influences the association between sarcopenia and liver fibrosis in patients with biopsy-proven NAFLD.

14.
Metabolism ; 115: 154433, 2020 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-33212070

RESUMO

BACKGROUND/AIMS: Whereas nonalcoholic fatty liver disease (NAFLD) is a multisystem disease, the association between metabolic dysfunction-associated fatty liver disease (MAFLD) and extra-hepatic diseases is not known. The aim of this cross-sectional study was to compare the prevalence of chronic kidney disease (CKD) in patients with either MAFLD or NAFLD, and then to examine the association between the presence and severity of MAFLD and CKD and abnormal albuminuria. METHODS: A total of 12,571 individuals with complete biochemical and liver ultrasonography data from the Third National Health and Nutrition Examination Survey (1988-1994) were included in the analysis. Multivariable logistic regression analyses were performed to test the independence of associations between MAFLD or MAFLD severity as the key exposures and CKD (defined as either CKD stage ≥1 or stage ≥3) or abnormal albuminuria (urinary albumin-to-creatinine ratio ≥ 3 mg/mmol) as the outcomes. RESULTS: The prevalence of MAFLD and NAFLD was 30.2% (n = 3794) and 36.2% (n = 4552), respectively. MAFLD individuals had a lower eGFR (74.96 ±â€¯18.21 vs. 76.46 ±â€¯18.24 ml/min/1.73 m2, P < 0.001) and a greater prevalence of CKD (29.60% vs. 26.56%, P < 0.05) than NAFLD individuals. Similarly, there was a higher prevalence CKD in MAFLD than in non-metabolic dysfunction-associated NAFLD (P < 0.05). Notably, after adjustment for sex, age, ethnicity, alcohol intake and diabetes, the severity of MAFLD (i.e. NAFLD fibrosis score ≥ 0.676) was associated with 1.34-fold higher risk of prevalent CKD (P < 0.05). CONCLUSIONS: MAFLD identifies patients with CKD better than NAFLD. MAFLD and MAFLD with increased liver fibrosis score are strongly and independently associated with CKD and abnormal albuminuria.

19.
MedComm (Beijing) ; 2020 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-32838396

RESUMO

Clinicians have been faced with the challenge of differentiating between severe acute respiratory syndrome associated coronavirus 2 (SARS-CoV-2) infected pneumonia (NCP) and influenza A infected pneumonia (IAP), a seasonal disease that coincided with the outbreak. We aim to develop a machine-learning algorithm based on radiomics to distinguish NCP from IAP by texture analysis based on computed tomography (CT) imaging. Forty-one NCP and 37 IAP patients admitted from January to February 6, 2019 admitted to two hospitals in Wenzhou, China. All patients had undergone chest CT examination and blood routine tests prior to receiving medical treatment. NCP was diagnosed by real-time RT-PCR assays. Eight of 56 radiomic features extracted by LIFEx were selected by least absolute shrinkage and selection operator regression to develop a radiomics score and subsequently constructed into a nomogram to predict NCP with area under the operating characteristics curve of 0.87 (95% confidence interval: 0.77-0.93). The nomogram also showed excellent calibration with Hosmer-Lemeshow test yielding a nonsignificant statistic (P = .904). The novel nomogram may efficiently distinguish between NCP and IAP patients. The nomogram may be incorporated to existing diagnostic algorithm to effectively stratify suspected patients for SARS-CoV-2 pneumonia.

20.
Expert Rev Gastroenterol Hepatol ; 14(12): 1125-1130, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32842793

RESUMO

INTRODUCTION: In light of the viral outbreak of SARS-CoV-2 that monopolized the focus of the scientific community and general public alike for the past 6 months, one of the greatest contributors in the battle against this pandemic was the international sharing of information. Whether regarding the viral genome, incubation periods, method of transmission, symptoms, dangerous behaviors, age groups at risk, all information was valuable, all data was shared as soon as possible. AREAS COVERED: Considering that the most severely impacted group of patients are already suffering from other conditions, accessing the impact that metabolic associated fatty liver disease (MAFLD), obesity, and diabetes has on patients by sharing information between different healthcare facilities is of vital importance. However, the value behind open information sharing would remain significant even without a viral outbreak and should there be a more efficient infrastructure in place, the global exchange of data can become more practical and less arduous. EXPERT OPINION: Since the sharing of data by individual researchers is often motivated by personal benefits, this observed international collaboration is conditional at best, and the widespread misinformation during this pandemic could be an indication of a certain lack of consensus within the scientific community itself.


Assuntos
Doenças Transmissíveis Emergentes/epidemiologia , Infecções por Coronavirus/epidemiologia , Disseminação de Informação/métodos , Pandemias/estatística & dados numéricos , Pneumonia Viral/epidemiologia , Síndrome Respiratória Aguda Grave/epidemiologia , Controle de Doenças Transmissíveis , Doenças Transmissíveis Emergentes/diagnóstico , Infecções por Coronavirus/diagnóstico , Feminino , Humanos , Masculino , Pandemias/prevenção & controle , Pneumonia Viral/diagnóstico , Sensibilidade e Especificidade , Síndrome Respiratória Aguda Grave/diagnóstico
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