scholarly journals Association between circulating alpha-1 antitrypsin polymers and lung and liver disease

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Alexa Núñez ◽  
Irene Belmonte ◽  
Elena Miranda ◽  
Miriam Barrecheguren ◽  
Georgina Farago ◽  
...  
Keyword(s):  
Liver Disease ◽  
Genetic Diseases ◽  
Sandwich Elisa ◽  
Liver Stiffness ◽  
Cross Sectional Study ◽  
Control Group ◽  
Cross Sectional ◽  
Impaired Lung Function ◽  
Alpha 1 Antitrypsin Deficiency ◽  
Alpha 1 Antitrypsin

Abstract Background Alpha-1 antitrypsin deficiency (AATD) is considered one of the most common genetic diseases and is characterised by the misfolding and polymerisation of the alpha-1 antitrypsin (AAT) protein within hepatocytes. The relevance of circulating polymers (CP) of AAT in the pathogenesis of lung and liver disease is not completely understood. Therefore, the main objective of our study was to determine whether there is an association between the levels of CP of AAT and the severity of lung and liver disease. Method This was a cross-sectional study in patients with different phenotypes of AATD and controls. To quantify CP, a sandwich ELISA was performed using the 2C1 monoclonal antibody against AAT polymers. Sociodemographic data, clinical characteristics, and liver and lung parameters were collected. Results A cohort of 70 patients was recruited: 32 Pi*ZZ (11 on augmentation therapy); 29 Z-heterozygous; 9 with other genotypes. CP were compared with a control group of 47 individuals (35 Pi*MM and 12 Pi*MS). ZZ patients had the highest concentrations of CP (p < 0.001) followed by Z heterozygous. The control group and patients with Pi*SS and Pi*SI had the lowest CP concentrations. Pi*ZZ also had higher levels of liver stiffness measurements (LSM) than the remaining AATD patients. Among patients with one or two Z alleles, two patients with lung and liver impairment showed the highest concentrations of CP (47.5 µg/mL), followed by those with only liver abnormality (n = 6, CP = 34 µg/mL), only lung (n = 18, CP = 26.5 µg/mL) and no abnormalities (n = 23, CP = 14.3 µg/mL). Differences were highly significant (p = 0.004). Conclusions Non-augmented Pi*ZZ and Z-patients with impaired lung function and increased liver stiffness presented higher levels of CP than other clinical phenotypes. Therefore, CP may help to identify patients more at risk of developing lung and liver disease and may provide some insight into the mechanisms of disease.

scholarly journals Capitalizing on the Autophagic Response for Treatment of Liver Disease Caused by Alpha-1-Antitrypsin Deficiency and Other Genetic Diseases

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Andrew S. Chu ◽  
David H. Perlmutter ◽  
Yan Wang
Keyword(s):  
Liver Disease ◽  
Liver Diseases ◽  
Storage Disease ◽  
Genetic Diseases ◽  
Clinical Manifestations ◽  
Definitive Therapy ◽  
Antitrypsin Deficiency ◽  
Exciting Potential ◽  
Alpha 1 Antitrypsin Deficiency ◽  
Alpha 1 Antitrypsin

Alpha-1-antitrypsin deficiency (ATD) is one of the most common genetic causes of liver disease and is a prototype of liver diseases caused by the pathologic accumulation of aggregated mutant alpha-1-antitrypsin Z (ATZ) within liver cells. In the case of ATD-associated liver disease, the resulting “gain-of-function” toxicity can lead to serious clinical manifestations, including cirrhosis and hepatocellular carcinoma. Currently, the only definitive therapy for ATD-associated liver disease is liver transplantation, but recent efforts have demonstrated the exciting potential for novel therapies that target disposal of the mutant protein aggregates by harnessing a cellular homeostasis mechanism called autophagy. In this review, we will summarize research advances on autophagy and genetic liver diseases. We will discuss autophagy enhancer strategies for liver disease due to ATD and another genetic liver disease, inherited hypofibrinogenemia, caused by the proteotoxic effects of a misfolded protein. On the basis of recent evidence that autophagy plays a role in cellular lipid degradation, we also speculate about autophagy enhancer strategies for treatment of hepatic lipid storage diseases such as cholesterol ester storage disease.

scholarly journals Prevalence of Elevated Liver Stiffness Among Potential Candidates for Bariatric Surgery in the United States

2022 ◽  
Author(s):  
Stefano Ciardullo ◽  
Mattia Pizzi ◽  
Pietro Pizzi ◽  
Alice Oltolini ◽  
Emanuele Muraca ◽  
...  
Keyword(s):  
Bariatric Surgery ◽  
Liver Disease ◽  
Transient Elastography ◽  
Liver Stiffness ◽  
The United States ◽  
Cross Sectional Study ◽  
Metabolic Dysfunction ◽  
Cross Sectional ◽  
Logistic Regression Models ◽  
Using Data

Abstract Purpose Obesity represents a well-known risk factor for metabolic-dysfunction associated fatty liver disease (MAFLD) and its progression towards cirrhosis. The aim of this study is to estimate the proportion of potential candidates to a bariatric surgery intervention that has an elevated liver stiffness on vibration-controlled transient elastography (VCTE). Materials and Methods This is a cross-sectional study performed using data obtained during the 2017–2018 cycle of the National Health and Nutrition Examination Survey. Potential candidates for a bariatric surgery intervention from the general US population were identified by applying criteria from international guidelines. All included participants were evaluated by VCTE. A controlled attenuation parameter (CAP) value ≥ 288 dB/m was considered indicative of steatosis while liver stiffness measurement (LSM) was considered elevated if ≥ 9.7 kPa. Multivariable logistic regression models were fitted to identify independent predictors of both outcomes. Results A total of 434 participants were included (mean age 42.9 ± 0.6 years; 54.4% women). Among them, 76.7% (95% CI 71.7–81.0) had steatosis, while 23.1% (95% CI 17.8–29.3) had an elevated LSM. Male sex, older age, γ-glutamyltranspeptidase levels, and body mass index (BMI) were independent predictors of steatosis, while BMI was the only independent predictor of elevated LSM. Non-Hispanic black participants were protected from both outcomes, while other ethnicities were not. Conclusion The prevalence of elevated LSM is high in potential candidates for a bariatric surgery intervention. Accurate screening for occult advanced liver disease might be indicated in this patient population. Graphical abstract

Alpha-1 Antitrypsin Deficiency in COPD Patients: A Cross-Sectional Study

2015 ◽  
Vol 51 (11) ◽  
pp. 539-543 ◽  
Author(s):  
Patricia Beatriz Sorroche ◽  
Mariano Fernández Acquier ◽  
Orlando López Jove ◽  
Eduardo Giugno ◽  
Salvador Pace ◽  
...  
Keyword(s):  
Cross Sectional Study ◽  
Sectional Study ◽  
Cross Sectional ◽  
Copd Patients ◽  
Antitrypsin Deficiency ◽  
Alpha 1 Antitrypsin Deficiency ◽  
Alpha 1 Antitrypsin

scholarly journals Prevalence of alpha-1 antitrypsin deficiency and allele frequency in patients with COPD in Brazil

2016 ◽  
Vol 42 (5) ◽  
pp. 311-316 ◽  
Author(s):  
Rodrigo Russo ◽  
Laura Russo Zillmer ◽  
Oliver Augusto Nascimento ◽  
Beatriz Manzano ◽  
Ivan Teruaki Ivanaga ◽  
...  
Keyword(s):  
Allele Frequency ◽  
Cross Sectional Study ◽  
Genotype Distribution ◽  
Cross Sectional ◽  
Serpina1 Gene ◽  
Copd Patients ◽  
Antitrypsin Deficiency ◽  
Alpha 1 Antitrypsin Deficiency ◽  
Alpha 1 Antitrypsin

ABSTRACT Objective: To determine the prevalence of alpha 1-antitrypsin (AAT) deficiency (AATD), as well as allele frequency, in COPD patients in Brazil. Methods: This was a cross-sectional study involving 926 COPD patients 40 years of age or older, from five Brazilian states. All patients underwent determination of AAT levels in dried blood spot (DBS) samples by nephelometry. Those with DBS AAT levels ≤ 2.64 mg/dL underwent determination of serum AAT levels. Those with serum AAT levels of < 113 mg/dL underwent genotyping. In case of conflicting results, SERPINA1 gene sequencing was performed. Results: Of the 926 COPD patients studied, 85 had DBS AAT levels ≤ 2.64 mg/dL, and 24 (2.6% of the study sample) had serum AAT levels of < 113 mg/dL. Genotype distribution in this subset of 24 patients was as follows: PI*MS, in 3 (12.5%); PI*MZ, in 13 (54.2%); PI*SZ, in 1 (4.2%); PI*SS, in 1 (4.2%); and PI*ZZ, in 6 (25.0%). In the sample as a whole, the overall prevalence of AATD was 2.8% and the prevalence of the PI*ZZ genotype (severe AATD) was 0.8% Conclusions: The prevalence of AATD in COPD patients in Brazil is similar to that found in most countries and reinforces the recommendation that AAT levels be measured in all COPD patients.

scholarly journals Comparison of COVID-19 outcomes with alpha-1-antitrypsin deficiency prevalence: A cross-sectional study.

2021 ◽  
Author(s):  
Yılmaz Sezgin ◽  
Sinan Becel
Keyword(s):  
Regression Analysis ◽  
Linear Regression ◽  
Significant Relationship ◽  
Linear Regression Analysis ◽  
Cross Sectional Study ◽  
Sectional Study ◽  
Cross Sectional ◽  
Antitrypsin Deficiency ◽  
Alpha 1 Antitrypsin Deficiency ◽  
Alpha 1 Antitrypsin

Background: We hypothesized that the geographic distributions of COVID-19 prevalence and risky alpha-1-antitrypsin allele prevalence are similar. We aimed to investigate whether there is a relationship between the geographical density of the COVID-19 pandemic and the distributions of risky alpha-1-antitrypsin alleles. Methods: This research is a cross-sectional study. Alpha-1-antitrypsin PI*SZ and PI*ZZ genotypes frequencies of European and American countries were compared with the case and death data related to the COVID-19 pandemic as of March 30, 2021. The relationship between the data was evaluated using Linear regression analysis. Results: According to the linear regression analysis results, a significant relationship was found between the number of COVID-19 cases in both European and American countries and the sum of PI*SZ and PI*ZZ genotypes. Similarly, according to the linear regression analysis results, a significant relationship was found between the COVID-19 death numbers in both European and American countries and the sum of PI*SZ and PI*ZZ genotypes. Conclusions: The findings showed that the prevalence distribution of the risky alleles of the gene defect that causes alpha-1-antitrypsin insufficiency is related to the prevalence of COVID-19 pandemic data.

DYSLIPIDEMIA IN THYROID DISORDERS

2020 ◽  
Vol 4 (7) ◽  
Author(s):  
Kashish Narula ◽  
Narendra Kumar Dara ◽  
Shyam Lal Meena
Keyword(s):  
Lipid Metabolism ◽  
Thyroid Dysfunction ◽  
Cross Sectional Study ◽  
Control Group ◽  
Thyroid Disorders ◽  
Cross Sectional ◽  
Carbohydrate And Lipid Metabolism ◽  
History Of ◽  
Thyroid Profile ◽  
Basal Energy Expenditure

Background: Thyroid hormones influence nearly all major metabolic pathways. Their most obvious and well-known action is the increase in basal energy expenditure obtained by acting on protein, carbohydrate and lipid metabolism. The lipid metabolism is more influenced by the thyroid hormone. Methods: A cross-sectional study was conducted on 100 patients with suspicion of thyroid disorders were taken as cases. One hundred patients with normal thyroid profile and no history of other chronic diseases were taken as control group. Results: The serum TC, TG and LDL levels in hypothyroid individuals (both overt and subclinical) were significantly higher than euthyroid subjects but the levels were comparable between hyperthyroid and euthyroid group. Conclusion: Dyslipidemias are associated with thyroid disorders, so biochemical screening for thyroid dysfunction in all dyslipidemic patients. Therefore, patients presenting with dyslipidemia are recommended for investigation to explore thyroid dysfunction. Keywords: Thyroid profile, Total cholesterol, Triglycerides and LDL

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