TSH Levels as an Independent Risk Factor for NAFLD and Liver Fibrosis in the General Population

Thyroid hormones may be a risk factor for the development of non-alcoholic fatty liver disease (NAFLD) and its progression to liver fibrosis. The aim of this study is to investigate the relationship between thyroid stimulating hormone (TSH) levels, NAFLD, and liver fibrosis in the general population. A descriptive cross-sectional study was performed in subjects aged 18–75 years randomly selected from primary care centers between 2012 and 2016. Each subject underwent clinical evaluation, physical examination, blood tests and transient elastography. Descriptive and multivariate logistic regression analyses were used to identify factors associated with NAFLD and fibrosis. We included 2452 subjects (54 ± 12 years; 61% female). Subjects with TSH ≥ 2.5 μIU/mL were significantly associated with obesity, atherogenic dyslipidemia, metabolic syndrome (MetS), hypertransaminasemia and altered cholesterol and triglycerides. The prevalence of NAFLD and liver fibrosis was significantly higher in subjects with TSH ≥ 2.5 (μIU/mL). We found a 1.5 times increased risk of NAFLD, 1.8 and 2.3 times increased risk of liver fibrosis for cut-off points of ≥ 8.0 kPa and ≥ 9.2 kPa, respectively, in subjects with TSH ≥ 2.5 μIU/mL compared with TSH < 2.5 μIU/mL (control group), independent of the presence of MetS. These findings remained significant when stratifying TSH, with values ≥ 10 μIU/mL.

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Is Rheumatoid Arthritis a Risk Factor for Fractures: A Systematic Review of Observational Studies

Current Rheumatology Reviews ◽

10.2174/1573397115666190723160312 ◽

2020 ◽

Vol 16 (1) ◽

pp. 29-37

Author(s):

Ambika Gupta ◽

Stephanie G. Pipe ◽

Tanveer Towheed ◽

Tassos Anastassiades

Keyword(s):

Risk Factor ◽

General Population ◽

Disease Severity ◽

Functional Impairment ◽

Primary Objective ◽

Control Group ◽

Cross Sectional ◽

Risk Of Fracture ◽

Increased Risk ◽

Study Heterogeneity

Aim: The primary objective was to assess the risk of fractures in adults with RA compared with controls from the general population. The review also assessed an increased risk of fractures in RA patients when accounting for steroid use, RA disease severity or functional impairment. Method: Citations were screened from MEDLINE, EMBASE, Cochrane Database of Systematic Reviews and CINAHL. Included citations were written in English, including adult patients at least 18 years of age and compared fracture incidence or prevalence between RA patients and a control group. Case-control, cohort and cross-sectional studies were included. Results: There were a total of 3451 citations; after application of the inclusion criteria, 17 studies were selected. In 14 of the 17 studies, there was an increase in the risk of fracture in RA patients compared to controls. In studies that evaluated for glucocorticoid use, four of 13 demonstrated an increased risk of fracture with glucocorticoid use, however, only two of these four studies specifically assessed glucocorticoid use amongst patients with RA. In studies that analyzed RA severity or functional impairment, two of seven demonstrated disease severity or impairment as a risk factor for fracture. There was marked study heterogeneity in terms of patient and fracture characteristics, which was a limitation of the analysis that impeded the ability to make direct comparisons. Conclusion: The risk of fracture in RA patients is elevated when compared to the general population, although the etiology of the increased risk remains to be elucidated.

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Abstract P015: Serum Thrombospondin-2 Of Cardiovascular Risk Factor Is Strongly Associated With Liver Fibrosis In A General Population

Circulation ◽

10.1161/circ.143.suppl_1.p015 ◽

2021 ◽

Vol 143 (Suppl_1) ◽

Author(s):

Nagisa Morikawa ◽

Hisashi Adachi ◽

Mika Enomoto ◽

Ako Fukami ◽

Akiko Sakaue ◽

...

Keyword(s):

Risk Factor ◽

Liver Fibrosis ◽

General Population ◽

Cross Sectional Study ◽

High Serum ◽

Cvd Risk ◽

Cross Sectional ◽

Alcoholic Fatty Liver ◽

Log Odds ◽

Restricted Cubic Splines

Background: Non-alcoholic fatty liver disease is increasing in decades and has been recently reported to be associated with cardiovascular disease (CVD). However, the underlying pathophysiology has not been elucidated. Thrombospondin(TSP)-2 is a cardio-protective extracellular matrix, while some clinical studies showed that high serum TSP-2 is a good predictor for adverse events in patients with heart failure. We previously found that in healthy people, serum TSP-2 was associated with insulin resistance, N-terminal pro-brain natriuretic peptide and atrial fibrillation, which suggested a potential CVD risk factor. Therefore, serum thrombospondin-2 can affect on the association between liver fibrosis and CVD. Hypotheses: Serum TSP-2 levels were associated with liver fibrosis in a general population. Methods: We performed a cross-sectional study with a health-check up in 224 participants (mean age: 69.0±7.8 years, men: 42.0%) in Uku, Japan in 2019. Serum TSP was measured by ELISA. Liver fibrosis was defined by the Fibrosis-4 (FIB-4) index ≥2.67, where FIB-4 was calculated as {(ageхaspartate aminotransferase)/(plateletх(alanine aminotransferase) 0.5 )}/10. Continuous serum TSP-2 was modeled using restricted cubic splines with 3 knots (5 th , 50 th , 95th) to allow a nonlinear association with the log odds ratio of liver fibrosis. Results: Mean FIB-4 was 1.92±0.89 and 14.3% of total had liver fibrosis. Age and sex adjusted log odds ratios (ORs) for liver fibrosis was associated with serum TSP-2 non-linearly and the risk accelerate when serum TSP-2 ≥29.5ng/mL(Figure 1). ORs(95% CI) for 29.5 and 31.0 of serum TSP-2 compared to 23.0(median) were 1.57(1.11-2.21) and 1.86(1.25-2.78), respectively. Conclusion: Serum TSP-2, which is a CVD biomarker, was strongly associated with liver fibrosis in the pathological range in a general population. This finding provides a new insight into the pathology in the link between liver fibrosis and CVD.

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Early kidney dysfunction in non-alcoholic fatty liver disease - is transient elastography useful as a screening method?

Digestive Diseases ◽

10.1159/000514811 ◽

2021 ◽

Author(s):

Marta Freitas ◽

Vítor Macedo Silva ◽

Sofia Xavier ◽

Joana Magalhes ◽

Carla Marinho ◽

...

Keyword(s):

Liver Disease ◽

Liver Fibrosis ◽

Fatty Liver ◽

Fatty Liver Disease ◽

Transient Elastography ◽

Screening Method ◽

Kidney Dysfunction ◽

Alcoholic Fatty Liver ◽

Increased Risk ◽

Significant Liver Fibrosis

Introduction: Increasing evidence suggests an association between metabolic associated fatty liver disease (MAFLD) and chronic kidney disease (CKD). Timely prediction of early kidney dysfunction (EKD) is thus essential in this population, although a screening method is not stablished. We aimed to evaluate the role of transient elastography (TE) in predicting EKD in patients with MAFLD. Methods: Prospective cohort study that included patients with MAFLD scheduled for evaluation, between May/2019 and January/2020. Demographic, clinical and laboratory data, and TE parameters were obtained. EKD was defined as microalbuminuria (urinary albumin-to-creatinine ratio 30-300mg/g) and estimated glomerular filtration rate≥60mL/min/1.73m2. Significant liver fibrosis was defined as liver stiffness measurement (LSM)≥8.2kPa. Results: Included 45 patients with MALFD, 53.3% female gender, mean age of 53.5±10.9years. EKD was found in 17.8% of patients. MAFLD patients with EKD were significantly more obese (body mass index≥30) (75.0% vs 32.4%,p=0.045) and had significantly higher LSM (8.5±4.1 vs 5.8±2.2kPa,p=0.01). After adjustment of potential confounders for EKD the presence of liver fibrosis, remained a significant predictor of EKD, being associated with a 14.3-fold increased risk of EKD (p=0.04). The optimal cutoff value of LSM to predict EKD was 6.1kPa (sensitivity:85.7%; specificity:67.6%). Conclusion: Significant liver fibrosis is associated with a significant increased risk of EKD in patients with MAFLD, regardless of other comorbidities. Higher levels of LSM, particularly >6.1kPa, alert for timely identification of EKD and associated comorbidities, as well as their control, in order to prevent the development of CKD in the long term.

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Increased prevalence of liver fibrosis in people living with HIV without viral hepatitis compared to population controls

The Journal of Infectious Diseases ◽

10.1093/infdis/jiaa763 ◽

2020 ◽

Author(s):

Ditte Marie Kirkegaard-Klitbo ◽

Flemming Bendtsen ◽

Jens Lundgren ◽

Robert J de Knegt ◽

Klaus Fuglsang Kofoed ◽

...

Keyword(s):

Liver Fibrosis ◽

Transient Elastography ◽

Liver Stiffness ◽

People Living With Hiv ◽

Previous Exposure ◽

Hiv Status ◽

Cross Sectional ◽

Increased Risk ◽

Living With Hiv ◽

Population Controls

Abstract Background Liver fibrosis is associated with poor liver related outcomes and mortality. People living with HIV (PWH) may be at increased risk. We aimed to estimate the prevalence and factors associated with liver fibrosis in PWH compared to population controls. Methods Cross-sectional cohort study. We compared 342 PWH with 2,190 population controls aged 50-70 years. Transient elastography was performed and elevated liver stiffness measurement (LSM) defined as 7.6kPa as a proxy for significant liver fibrosis. Adjusted odds ratios (aOR) and 95% confidence intervals (95% CI) were computed by logistic regression. Results The prevalence of elevated LSM was higher in PWH than in uninfected controls (12% vs 7%), p<0.01). HIV infection was independently associated with elevated LSM. In multivariate analysis, elevated LSM was associated with HIV (aOR:1.84 (1.17;2.88), p<0.01); higher age (per decade, aOR:3.34 (1.81;6.18), p<0.01); ALT (per 10 IU/L, aOR:1.25 (1.05;1.49), p<0.01); BMI (per 1 kg/m 2, aOR:1.17 (1.05;1.29), p<0.01) and previous exposure to didanosine (per year aOR:2.26 (1,01;5.06), p=0.05). Conclusions The prevalence of elevated LSM was higher in PWH compared to population controls. Higher age, BMI, ALT, previous exposure to didanosine and a positive HIV status was independently associated with higher odds of elevated LSM.

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Association of prehypertension and hyperhomocysteinemia with subclinical atherosclerosis in asymptomatic Chinese: a cross-sectional study

BMJ Open ◽

10.1136/bmjopen-2017-019829 ◽

2018 ◽

Vol 8 (3) ◽

pp. e019829 ◽

Cited By ~ 7

Author(s):

Bo Liu ◽

Zhihao Chen ◽

Xiaoqi Dong ◽

Guangming Qin

Keyword(s):

Risk Factor ◽

Subclinical Atherosclerosis ◽

Multiple Logistic Regression Analysis ◽

Fasting Blood Glucose ◽

Intima Media Thickness ◽

Carotid Intima Media Thickness ◽

Control Group ◽

Cross Sectional ◽

Increased Risk ◽

Significant Difference

ObjectivesComorbid hypertension and hyperhomocysteinemia is an important risk factor for carotid atherosclerotic plaque formation. We put forward the hypothesis that the subjects with comorbid prehypertension and hyperhomocysteinemia also had an increased risk of subclinical atherosclerosis, using carotid intima–media thickness (CIMT) as the marker of the atherosclerotic process.MethodsA total of 4102 asymptomatic Chinese subjects aged 18–60 years were divided into four groups according to blood pressure (BP) and homocysteine (HCY) level: the control group without prehypertension or hyperhomocysteinemia, isolated prehypertension group, simple hyperhomocysteinemia group and prehypertension with hyperhomocysteinemia group. Serum lipids, fasting blood glucose (FBG), HCY and CIMT were measured.ResultsThere was significant difference in the positive rates of increased CIMT among four groups. Compared with the controls, the subjects in the other three groups had a higher risk of increased CIMT (isolated prehypertension group, OR 2.049, 95% CI 1.525 to 2.754; simple hyperhomocysteinemia group, OR 2.145, 95% CI 1.472 to 3.125; prehypertension and hyperhomocysteinemia group, OR 3.199, 95% CI 2.362 to 4.332). However, by multiple logistic regression analysis, only comorbid prehypertension and hyperhomocysteinemia was independently associated with increased CIMT (OR 1.485, 95% CI 1.047 to 2.108, P<0.05).ConclusionsComorbid prehypertension and hyperhomocysteinemia was an independent risk factor of subclinical atherosclerosis in asymptomatic Chinese, but isolated prehypertension or hyperhomocysteinemia was not. Therefore, combined intervention for prehypertension and hyperhomocysteinemia may contribute to decrease the incident of cardiovascular disease.

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Risk of Liver Fibrosis According to TSH Levels in Euthyroid Subjects

Journal of Clinical Medicine ◽

10.3390/jcm10071350 ◽

2021 ◽

Vol 10 (7) ◽

pp. 1350

Author(s):

Alba Martínez-Escudé ◽

Guillem Pera ◽

Lluís Rodríguez ◽

Ingrid Arteaga ◽

Carmen Expósito-Martínez ◽

...

Keyword(s):

Liver Fibrosis ◽

General Population ◽

Thyroid Function ◽

Liver Stiffness ◽

Cross Sectional Study ◽

Blood Analysis ◽

Cross Sectional ◽

Alcoholic Fatty Liver ◽

Normal Thyroid ◽

Normal Thyroid Function

Alterations in thyroid function may contribute to the development of liver fibrosis especially in subjects with non-alcoholic fatty liver disease. This study aimed to investigate the risk of liver fibrosis according to low-normal thyroid function in the general population. We performed a descriptive cross-sectional study in subjects from 18–75 years randomly selected from 16 primary health care centers from 2017–2019. Each subject underwent clinical evaluation, physical examination, blood analysis and transient hepatic elastography. Descriptive and multivariate logistic regression analyses were used to identify factors associated with fibrosis. We included 1096 subjects (60 ± 11 years; 61% women); 70% had strict-normal thyroid function and 30% had low-normal thyroid function. Low-normal thyroid function was associated with a higher liver stiffness (LS) values: 5.2 vs. 4.8 kPa (p = 0.001) and a greater prevalence of fibrosis: 6.1 vs. 3% (p = 0.016) and 4.3 vs. 2.1% (p = 0.044) for the cut-off points of ≥8.0 kPa and ≥9.2 kPa, respectively. After adjustment for potential confounding factors, the risk of fibrosis in subjects with low-normal thyroid function was OR 1.54 (p = 0.213). In conclusion, low-normal thyroid function is associated with higher LS values and a greater risk of liver fibrosis in the general population, being dependent on other metabolic factors.

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Liver Stiffness, Albuminuria and Chronic Kidney Disease in Patients with NAFLD: A Systematic Review and Meta-Analysis

Biomolecules ◽

10.3390/biom12010105 ◽

2022 ◽

Vol 12 (1) ◽

pp. 105

Author(s):

Stefano Ciardullo ◽

Cinzia Ballabeni ◽

Roberto Trevisan ◽

Gianluca Perseghin

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

Liver Fibrosis ◽

Statistical Power ◽

Transient Elastography ◽

Meta Analysis ◽

Liver Stiffness ◽

Significant Heterogeneity ◽

Cross Sectional ◽

Increased Risk

An association between liver stiffness, a surrogate measure of liver fibrosis, and chronic kidney disease (CKD) in patients with nonalcoholic fatty liver disease (NAFLD) has been proposed. However, most studies were small and had low statistical power. We systematically searched PubMed-MEDLINE and Scopus from inception to August 2021 for cross-sectional or cohort studies reporting the association between liver stiffness diagnosed by vibration controlled transient elastography (VCTE) and renal dysfunction. The primary outcome was CKD, defined as a composite of urinary albumin to creatinine ratio (UACR) ≥ 30 mg/g and estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2. Measures of association from individual studies were meta-analyzed using random effects models. Of the 526 titles initially scrutinized, 7 cross-sectional studies fulfilled the criteria and were included. For CKD, risk was higher in patients with liver fibrosis assessed by VCTE, compared with patients without (n = 5 studies: OR 2.49, 95% CI 1.89–3.29; test for overall effect z = 6.475, p < 0.001). When increased UACR was considered as an outcome, elevated liver stiffness was associated with a significantly increased risk as well (n = 3 studies: OR 1. 98 95% CI 1.29–3.05; test for overall effect z = 3.113, p = 0.002). Neither analysis showed significant heterogeneity (I2 = 0% and I2 = 46.5%, respectively for the two outcomes). This meta-analysis indicates that elevated liver stiffness is associated with increased odds of kidney outcomes among patients with NAFLD. Wider use of VCTE to screen for advanced fibrosis might help identify patients at risk of end-stage renal disease.

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Dyslipidemia as a risk factor for liver fibrosis progression in a multicentric population with non-alcoholic steatohepatitis

F1000Research ◽

10.12688/f1000research.21918.1 ◽

2020 ◽

Vol 9 ◽

pp. 56 ◽

Cited By ~ 2

Author(s):

Nahum Méndez-Sánchez ◽

Eira Cerda-Reyes ◽

Fátima Higuera-de-la-Tijera ◽

Ana K. Salas-García ◽

Samantha Cabrera-Palma ◽

...

Keyword(s):

Risk Factor ◽

Liver Fibrosis ◽

Metabolic Diseases ◽

Cross Sectional ◽

Nonalcoholic Fatty Liver ◽

Fibrosis Progression ◽

Increased Risk ◽

Advanced Liver Fibrosis ◽

The Impact ◽

Significant Liver Fibrosis

Background: Nonalcoholic fatty liver disease (NAFLD) is a serious worldwide health problem, with an estimated global prevalence of 24%; it has a notable relationship with other metabolic disorders, like obesity and type 2 diabetes mellitus (T2DM). Nonalcoholic steatohepatitis (NASH) is one of the most important clinical entities of NAFLD, which is associated with an increased risk of progression to liver cirrhosis and hepatocellular carcinoma (HCC). Mexico is one of the countries with the highest prevalence of metabolic diseases; therefore, we sought to investigate the impact that these clinical entities have in the progression to advanced fibrosis in Mexican patients with NASH. Methods: We performed a multicenter retrospective cross-sectional study, from January 2012 to December 2017. A total of 215 patients with biopsy-proven NASH and fibrosis were enrolled. NASH was diagnosed according NAS score and liver fibrosis was staged by the Kleiner scoring system. For comparing the risk of liver fibrosis progression, we divided our sample into two groups. Those patients with stage F0-F2 liver fibrosis were included in the group with non-significant liver fibrosis (n=178) and those individuals with F3-F4 fibrosis were included in the significant fibrosis group (n=37). We carried out a multivariate analysis to find risk factors associated with liver fibrosis progression. Results: From the 215 patients included, 37 had significant liver fibrosis (F3-4). After logistic regression analysis T2DM (p=0.044), systemic arterial hypertension (p=0.014), cholesterol (p=0.041) and triglycerides (p=0.015) were the main predictor of advanced liver fibrosis. Conclusions: In a Mexican population, dyslipidemia was the most important risk factor associated with advanced liver fibrosis and cirrhosis.

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The VITA Project: Prothrombin G20210A Mutation and Venous Thromboembolism in the General Population

Thrombosis and Haemostasis ◽

10.1055/s-0037-1614842 ◽

1999 ◽

Vol 82 (11) ◽

pp. 1395-1398 ◽

Cited By ~ 29

Author(s):

Alberto Tosetto ◽

Edoardo Missiaglia ◽

Maurizio Frezzato ◽

Francesco Rodeghiero

Keyword(s):

Risk Factor ◽

Venous Thromboembolism ◽

General Population ◽

Odds Ratio ◽

Genetic Variant ◽

Population Based ◽

Prothrombin G20210a ◽

Cross Sectional ◽

G20210a Mutation ◽

Increased Risk

SummaryRecently a new identified genetic variant in the 3’-untranslated region of the prothrombin gene (G20210A allele) associated with increased plasma prothrombin levels has been linked to an increased risk of venous thromboembolism (VTE). Most of our knowledge on the G20210A allele as a risk factor for VTE derives from a population-based case-control study and from studies on selected series of VTE patients. To determine the importance of the G20210A allele as a causative risk factor for VTE in the general population, we analyzed the cross-sectional data of the Vicenza Thrombophilia and Atherosclerosis (VITA) Project. One hundred sixteen cases of VTE, ascertained in a random fashion within the general population aged 18-65, were age and sex-matched with 232 healthy subjects. Heterozygosity for the G20210A allele was present in 4.3% of VTE cases and in 3.4% of controls, indicating a marginal increase of VTE risk in carriers of the allele (odds ratio: 1.26; 95% CI 0.4-3.9). However, the VTE risk was substantially higher in subjects with idiopathic VTE before age 45 or with recurrent, idiopathic VTE (odds ratio: 2.8; 95% CI 0.6-13.8) or in subjects with a family history of VTE (odds ratio: 7.6; 95% CI 1.8-32.8). Accordingly, our results suggest that the G20210A allele associates with VTE only in selected cases, and that screening for this genetic variant is not warranted for all patients with VTE.

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The relationship between leukocyte level and hypertension in elderly patients with hyperuricemia.

10.21203/rs.3.rs-31127/v1 ◽

2020 ◽

Author(s):

Lijin Shen ◽

Wei Zhao ◽

Mingzhen Li ◽

Bei Sun ◽

Zhichao Zhou ◽

...

Keyword(s):

Logistic Regression ◽

Risk Factor ◽

Elderly Patients ◽

Independent Risk Factor ◽

Serum Uric Acid Level ◽

Control Group ◽

Multiple Logistic Regression ◽

Cross Sectional ◽

Increased Risk ◽

The Relationship

Abstract Background : This study was to evaluate the change of leukocyte level caused by hyperuricemia and explore the relationship between leukocyte level and hypertension in elderly patients with hyperuricemia. Methods: A cross-sectional study of serum uric acid level was conducted in 1352 elderly people over 65 years old . The study samples were divided into three categories according to the tertiles of leukocyte: Tertile 1, leukocyte≤5.2 × 10 9 /L; Tertile 2, leukocyte=5.3~6.3 × 10 9 /L; and Tertile 3, leukocyte≥6.4 × 10 9 /L. Multiple logistic regression models were used for modeling relationships between leukocyte, hyperuricemia and hypertension. In vitro, human vascular endothelial cells (HUVECs) were treated by different concentrations of UA (0, 4, 8, 16 mg/dl) for 24 h, then cells were collected. Some cytokines were measured. Reactive oxygen species (ROS) were analyzed with a fluorescence microscope. Results: The levels of leukocyte were higher in elderly patients with hyperuricemia than without hyperuricemia( P <0.01). In multiple logistic regression, hyperuricemia was an independent risk factor of leukocyte in Tertile 3 (OR=1.657, 95%CI: 1.180～2.328, P =0.004). The prevalences of hypertension were higher in elderly patients with hyperuricemia than without hyperuricemia (77.0% vs 63.5%, χ 2 =11.447, P =0.001). In multiple logistic regression (Model 1), hyperuricemia was an independent risk factor of hypertension (OR=1.536, 95%CI: 1.026～2.302, P =0.037). Leukocyte in Tertile 3 was an independent risk factor of hypertension in Model 2 (OR= 1.333, 95%CI: 1.031~1.724, P =0.028). Expression levels of IL-1β, iNOS and TNF-α were obviously higher in the 8mg/dl UA group and 16mg/dl UA group than that in the control group ( P <0.05). Expression level of eNOS was obviously lower in the 8mg/dl UA group and 16mg/dl UA group than that in the control group ( P <0.05). The production of ROS in the 8mg/dl UA group and in the 16mg/dl UA group were obviously higher than that in the control group ( P <0.05). Conclusion: The present study demonstrated that hyperuricemia was associated with an increased risk for hypertension. The chronic inflammation caused by hyperuricemia maybe one of important pathogenesis of incident hypertension in patients with hyperuricemia.

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