-
Clinical Gastroenterology and... Sep 2019A higher proportion of female vs male patients receive a diagnosis of celiac disease. Little is known about sex-based differences in the prevalence of celiac disease in... (Meta-Analysis)
Meta-Analysis
BACKGROUND & AIMS
A higher proportion of female vs male patients receive a diagnosis of celiac disease. Little is known about sex-based differences in the prevalence of celiac disease in undiagnosed populations. We aimed to address this knowledge gap with a systematic review and meta-analysis.
METHODS
We searched MEDLINE, Embase, Cochrane, and Scopus databases through 2017 for studies of screen-detected or undiagnosed celiac disease. Our final analysis included studies that included screening and confirmatory tests (either second serologic analysis or a small intestine biopsy) and provided information on the sex of participants. Studies were excluded if they were performed with specific, high-risk, or referral populations. The primary outcome was the percentage of undetected celiac disease among female and male patients.
RESULTS
We identified 4070 articles and analyzed data from 87. Our meta-analysis comprised data from 291,969 study participants. The pooled prevalence of undetected celiac disease in female participants was 0.589% (95% CI, 0.549%-0.629%) and in male participants was 0.415% (95% CI, 0.343%-0.487%). The risk of undetected celiac disease was higher among female than male participants (relative risk [RR], 1.42; 95% CI, 1.27-1.57; P < .00001). The I was 5% (low heterogeneity among studies). In subgroup analyses, the RR of celiac disease for girls vs boys was 1.79 (95% CI, 1.44-2.22; P < .00001; I = 18%), the RR for female vs male blood donors was 1.13 (95% CI, 0.76-1.69; P = .54; I = 0), and the RR for women vs men with villous atrophy was 1.38 (95% CI, 1.07-1.79; P = .01; I = 0).
CONCLUSIONS
In a systematic review and meta-analysis, we found a higher risk for celiac disease in women than men in an undiagnosed populations (identified through general population screening). The increased risk for celiac disease among girls and women should be considered for screening, diagnosis, and management strategies.
Topics: Autoantibodies; Celiac Disease; Female; GTP-Binding Proteins; Gliadin; Humans; Male; Mass Screening; Prevalence; Protein Glutamine gamma Glutamyltransferase 2; Sex Distribution; Transglutaminases; Undiagnosed Diseases
PubMed: 30448593
DOI: 10.1016/j.cgh.2018.11.013 -
Scientific Reports Feb 2020N-acetyltransferase 2 (NAT2) acetylator status can be classified into three groups depending on the number of rapid alleles (e.g., NAT2*4): rapid, intermediate, and slow... (Meta-Analysis)
Meta-Analysis
N-acetyltransferase 2 (NAT2) acetylator status can be classified into three groups depending on the number of rapid alleles (e.g., NAT2*4): rapid, intermediate, and slow acetylators. Such acetylator status may influence the occurrence of adverse drug reactions (ADRs) during sulfasalazine treatment. This systematic review and meta-analysis aimed to evaluate the association between NAT2 acetylator status and ADRs of sulfasalazine. We searched for qualified studies in PubMed, Web of Science, Embase, and the Cochrane Library. Odds ratio (OR) and 95% confidence intervals (CIs) were calculated to evaluate the strength of the association between NAT2 acetylator status and ADRs of sulfasalazine. Nine cohort studies involving 1,077 patients were included in the meta-analysis. NAT2 slow acetylators were associated with an increase in overall ADRs (OR 3.37, 95% CI: 1.43 to 7.93; p = 0.005), discontinuation due to overall ADRs (OR 2.89, 95% CI: 1.72 to 4.86; p < 0.0001), and dose-related ADRs (OR 5.20, 95% CI: 2.44 to 11.08; p < 0.0001), compared with rapid and intermediate acetylators. In conclusion, NAT2 slow acetylators are at risk of ADRs during sulfasalazine treatment. Based on our findings, NAT2 genotyping may be useful to predict the occurrence of ADRs during sulfasalazine treatment.
Topics: Arylamine N-Acetyltransferase; Humans; Polymorphism, Genetic; Sulfasalazine
PubMed: 32107440
DOI: 10.1038/s41598-020-60467-8 -
European Journal of Clinical... Oct 2022Significant pharmacokinetic variabilities have been reported for isoniazid across various populations. We aimed to summarize population pharmacokinetic studies of... (Review)
Review
Influence of N-acetyltransferase 2 (NAT2) genotype/single nucleotide polymorphisms on clearance of isoniazid in tuberculosis patients: a systematic review of population pharmacokinetic models.
PURPOSE
Significant pharmacokinetic variabilities have been reported for isoniazid across various populations. We aimed to summarize population pharmacokinetic studies of isoniazid in tuberculosis (TB) patients with a specific focus on the influence of N-acetyltransferase 2 (NAT2) genotype/single-nucleotide polymorphism (SNP) on clearance of isoniazid.
METHODS
A systematic search was conducted in PubMed and Embase for articles published in the English language from inception till February 2022 to identify population pharmacokinetic (PopPK) studies of isoniazid. Studies were included if patient population had TB and received isoniazid therapy, non-linear mixed effects modelling, and parametric approach was used for building isoniazid PopPK model and NAT2 genotype/SNP was tested as a covariate for model development.
RESULTS
A total of 12 articles were identified from PubMed, Embase, and hand searching of articles. Isoniazid disposition was described using a two-compartment model with first-order absorption and linear elimination in most of the studies. Significant covariates influencing the pharmacokinetics of isoniazid were NAT2 genotype, body weight, lean body weight, body mass index, fat-free mass, efavirenz, formulation, CD4 cell count, and gender. Majority of studies conducted in adult TB population have reported a twofold or threefold increase in isoniazid clearance for NAT2 rapid acetylators compared to slow acetylators.
CONCLUSION
The variability in disposition of isoniazid can be majorly attributed to NAT2 genotype. This results in a trimodal clearance pattern with a multi-fold increase in clearance of NAT2 rapid acetylators compared to slow acetylators. Further studies exploring the generalizability/adaptability of developed PopPK models in different clinical settings are required.
Topics: Adult; Humans; Antitubercular Agents; Arylamine N-Acetyltransferase; Body Weight; Genotype; Isoniazid; Polymorphism, Single Nucleotide; Tuberculosis
PubMed: 35852584
DOI: 10.1007/s00228-022-03362-7 -
Liver International : Official Journal... Nov 2021Previous studies investigating the prevalence of celiac disease (CD) in individuals with autoimmune hepatitis (AIH) have shown highly variable results. We therefore... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Previous studies investigating the prevalence of celiac disease (CD) in individuals with autoimmune hepatitis (AIH) have shown highly variable results. We therefore aimed to examine the prevalence of CD in individuals with AIH.
METHODS
Two professional librarians searched PubMed, EMBASE, Cochrane and Web of Science Core Collection up until 7 February 2020. The search terms included 'celiac disease', 'celiac', 'transglutaminases', 'gluten', 'gliadin', 'EMA', 'TTG' and 'villous' combined with 'autoimmune', 'hepatitis', 'ANA', 'SMA' and 'LKM'. This search yielded 2419 unique publications. A systematic review based on the PRISMA guidelines resulted in 31 articles eligible for full text review. Fifteen articles were deemed relevant, with 8 being included in our main analysis. A fixed-effect inverse variance-weighted model was used, and heterogeneity was calculated.
RESULTS
Our main analysis included 567 individuals with AIH from eight studies, where biopsy-verified CD (equivalent to Marsh III) was seen in 23 individuals (4.1%). The pooled prevalence of CD in AIH was 3.5% (95% CI = 1.6%-5.3%) (heterogeneity: P = .874; I = 0.0%), which is clearly higher than the 1% CD seen in most general populations. When also including studies where CD had been diagnosed through positive serology without biopsy (15 studies: n = 1817 individuals with AIH), the pooled prevalence of CD was 2.9% (95% CI = 2.1%-3.8%) (heterogeneity: P < .001; I = 66.8%).
CONCLUSION
Our results demonstrate a higher prevalence of CD in individuals with AIH compared to the general population. CD screening may be considered in patients with AIH.
Topics: Biopsy; Celiac Disease; Hepatitis, Autoimmune; Humans; Prevalence; Transglutaminases
PubMed: 34219350
DOI: 10.1111/liv.15000 -
Journal of Clinical Gastroenterology Apr 2021The goal of this study was to estimate the impact of verification bias on the diagnostic accuracy of immunoglobulin A tissue transglutaminase (IgA tTG) in detecting... (Meta-Analysis)
Meta-Analysis
GOAL
The goal of this study was to estimate the impact of verification bias on the diagnostic accuracy of immunoglobulin A tissue transglutaminase (IgA tTG) in detecting celiac disease as reported by an authoritative meta-analysis, the 2016 Comparative Effectiveness Review (CER).
BACKGROUND
Verification bias is introduced to diagnostic accuracy studies when screening test results impact the decision to verify disease status.
MATERIALS AND METHODS
We adjusted the sensitivity and specificity of IgA tTG reported by the 2016 CER with the proportion of IgA tTG positive and negative individuals who are referred for confirmatory small bowel biopsy. We performed a systematic review from January 1, 2007, to July 19, 2017, to determine these referral rates.
RESULTS
The systematic review identified 793 articles of which 9 met inclusion criteria (n=36,477). Overall, 3.6% [95% confidence interval (CI): 1.1%-10.9%] of IgA tTG negative and 79.2.2% (95% CI: 65.0%-88.7%) of IgA tTG positive individuals were referred for biopsy. Adjusting for these referral rates the 2016 CER reported sensitivity of IgA tTG dropped from 92.6% (95% CI: 90.2%-94.5%) to 57.1% (95% CI: 35.4%-76.4%) and the specificity increased from 97.6% (95% CI: 96.3%-98.5%) to 99.6% (95% CI: 98.4%-99.9%).
CONCLUSIONS
The CER may have largely overestimated the sensitivity of IgA tTG due to a failure to account for verification bias. These findings suggest caution in the interpretation of a negative IgA tTG to rule out celiac disease in clinical practice. More broadly, they highlight the impact of verification bias on diagnostic accuracy estimates and suggest that studies at risk for this bias be excluded from systematic reviews.
Topics: Autoantibodies; Biopsy; Celiac Disease; Humans; Immunoglobulin A; Sensitivity and Specificity; Transglutaminases
PubMed: 32433257
DOI: 10.1097/MCG.0000000000001361 -
European Journal of Clinical... Oct 2020Despite the demonstrated increased cardiovascular (CV) risk associated with metabolic-dysfunction-associated fatty liver disease (MAFLD), genetic variants predisposing...
BACKGROUND
Despite the demonstrated increased cardiovascular (CV) risk associated with metabolic-dysfunction-associated fatty liver disease (MAFLD), genetic variants predisposing to MAFLD were not constantly associated with CV events. Recently, rs641738C > T near membrane-bound O-acyltransferase domain-containing 7 (MBOAT7) has been studied in MAFLD and CV outcomes. Therefore, we aimed to evaluate the association between rs641738C > T in the presence and severity of hepatic steatosis, fibrosis, biochemical markers and progression to hepatocellular carcinoma (HCC), in addition to CV outcomes in MAFLD.
MATERIALS AND METHODS
An electronic search on PubMed, Embase and Cochrane Library for articles published till 23 March 2020 was systematically performed. Articles were screened, and data extracted from eligible studies by two reviewers independently.
RESULTS
Studies conducted on adults with MAFLD involving European, Hispanic and African American populations evaluating rs641738 reported reduced hepatic expression of MBOAT7, increased hepatic fat content, severity of MAFLD, susceptibility to develop NASH, advanced fibrosis and HCC in adults. However, most articles involving Asian individuals contradicted these findings. Studies involving obese children associated rs641738 with increased plasma alanine aminotransferase (ALT) levels, while its association with MAFLD remains inconsistent. The rs641738 variant was assessed as a MAFLD susceptibility gene in coronary artery disease (CAD) reporting neutral effects.
CONCLUSIONS
Despite inconclusive results in Asian populations, rs641738C > T near MBOAT7 is associated with increased hepatic fat, MAFLD severity, susceptibility to develop NASH, advanced fibrosis and HCC in adults from Caucasian, Hispanic and African American ethnicities with MAFLD, as well as elevated ALT levels in children, while exerting neutral effects in CAD.
Topics: Acyltransferases; Black or African American; Alanine Transaminase; Asian People; Carcinoma, Hepatocellular; Cardiovascular Diseases; Coronary Artery Disease; Disease Progression; Genetic Predisposition to Disease; Heart Disease Risk Factors; Hispanic or Latino; Humans; Liver Cirrhosis; Liver Neoplasms; Membrane Proteins; Non-alcoholic Fatty Liver Disease; Severity of Illness Index; White People
PubMed: 32589269
DOI: 10.1111/eci.13331 -
Sports Medicine (Auckland, N.Z.) Jun 2022The maximal rate of oxygen consumption (VO) is an important measure in exercise science as it is an indicator of cardiorespiratory fitness. Individual studies have... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The maximal rate of oxygen consumption (VO) is an important measure in exercise science as it is an indicator of cardiorespiratory fitness. Individual studies have identified central and peripheral adaptions to interval training that may underlie improvements in VO, but there is no compilation of results.
OBJECTIVE
We aimed to systematically review the adaptive responses to high-intensity interval training (HIIT) and sprint interval training (SIT) on the central and peripheral factors influencing VO in healthy individuals.
DATA SOURCES
SPORTDiscus and MEDLINE (up to and including 13 June, 2020) were explored to conduct the literature search.
STUDY SELECTION
Reviewed studies met the following criteria: (1) were in the English language; (2) prospective in nature; (3) included at least three interval sessions or were at least 1 week in duration; (4) contained HIIT or SIT; (5) involved participants between the ages of 18 and 65 years; and (6) included at least one of the following central (blood volume, plasma volume, hemoglobin mass, left ventricular mass, maximal stroke volume, maximal cardiac output) or peripheral factors (capillary density, maximal citrate synthase activity, mitochondrial respiration associated with VO).
RESULTS
Thirty-two studies (369 participants, 49 were female) were included in the quantitative analyses, consisting of both HIIT (n = 18) and SIT (n = 17) interventions. There were only statistically significant changes in hematological measures (plasma volume) following HIIT. There was a significant increase in left ventricular mass following HIIT (7.4%, p < 0.001) and SIT (5.3%, p = 0.007) in inactive individuals, though the change following SIT may be misleading. There was only a significant increase in maximal stroke volume (14.1%, p = 0.015) and maximal cardiac output (12.6%, p = 0.002) following HIIT. In addition to central factors, there was a significant increase in capillary density (13.8%, p < 0.001) following SIT in active individuals. With respect to maximal citrate synthase activity, there were improvements following HIIT (20.8%, p < 0.001) and SIT (15.7%, p < 0.001, I = 97%) in active individuals. The results for mitochondrial respiration suggested that there was no statistically significant improvement following HIIT (5.0%, p = 0.585).
CONCLUSIONS
Improvements in the central and peripheral factors influencing VO were dependent on the interval type. Only HIIT led to a statistically significant improvement in cardiac function. Both HIIT and SIT increased maximal citrate synthase activity, while changes in other peripheral measures (capillary density, mitochondrial respiration) only occurred with SIT.
Topics: Adolescent; Adult; Aged; Cardiorespiratory Fitness; Citrate (si)-Synthase; Female; High-Intensity Interval Training; Humans; Male; Middle Aged; Oxygen Consumption; Prospective Studies; Young Adult
PubMed: 35041180
DOI: 10.1007/s40279-021-01624-5 -
The Efficacy of Vitamin D Supplementation against Nonalcoholic Fatty Liver Disease: A Meta-Analysis.Journal of Dietary Supplements 2020Nonalcoholic fatty liver disease (NAFLD) is the most common cause of liver disease worldwide. If this disease is not appropriately controlled, it can eventually cause... (Meta-Analysis)
Meta-Analysis
Nonalcoholic fatty liver disease (NAFLD) is the most common cause of liver disease worldwide. If this disease is not appropriately controlled, it can eventually cause chronic liver damage, including cirrhosis and hepatocellular carcinoma. Accordingly, the adoption of appropriate interventions to control NAFLD is important for any healthcare system. The aim of the present systematic review and meta-analysis was to clarify the effect of vitamin D supplementation on NAFLD. PubMed, Scopus, Science Direct, ISI Web of Science, and Google Scholar were systematically searched up to March 2019 to find clinical trials that examined the effects of vitamin D supplementation on liver enzyme levels in NAFLD patients. Means for liver enzymes and potential sources of heterogeneity were extracted. A subgroup analysis was performed to detect potential sources of interstudy heterogeneity. Nine trials (10 arms) comprising 467 participants were eligible for meta-analysis. The results from a pooled analysis did not reveal a significant effect of vitamin D intake on alanine aminotransferase (-2.88 U/L; 95% CI, -6.03 to 0.27; = 85%), aspartate aminotransferase (-0.10 U/L; 95% CI, -1.18 to 0.97; = 26%), and γ-glutamyltransferase levels (0.12 U/L; 95% CI, -5.94 to 6.18; = 38%). The meta-analysis suggested a significant reduction in alkaline phosphatase (-13.79 U/L; 95% CI, -22.13 to -5.45; = 72%) following vitamin D supplementation. This effect was robust in the subgroup in which > 3,000 IU/day vitamin D was administered (-19.74 U/L; 95% CI, -25.36 to -14.12; = 0.0%). The present meta-analysis does not suggest the efficacy of vitamin D supplementation on NAFLD treatment.
Topics: Alanine Transaminase; Alkaline Phosphatase; Aspartate Aminotransferases; Clinical Trials as Topic; Humans; Liver; Liver Function Tests; Non-alcoholic Fatty Liver Disease; Vitamin D; gamma-Glutamyltransferase
PubMed: 31256692
DOI: 10.1080/19390211.2019.1624671 -
Angiology Oct 2019This meta-analysis assessed the prognostic value of serum γ-glutamyltransferase (GGT) level for cardiovascular (CV) and all-cause mortality in patients with coronary... (Meta-Analysis)
Meta-Analysis
Association Between γ-Glutamyltransferase Level and Cardiovascular or All-Cause Mortality in Patients With Coronary Artery Disease: A Systematic Review and Meta-Analysis.
This meta-analysis assessed the prognostic value of serum γ-glutamyltransferase (GGT) level for cardiovascular (CV) and all-cause mortality in patients with coronary artery disease (CAD). We conducted a systematic literature search of PubMed, Web of Science, Embase, China National Knowledge Infrastructure, Wanfang, and Weipu databases until December 2018. Observational studies investigating the prognostic role of serum GGT level for CV and all-cause mortality in patients with CAD were included. Pooled risk ratios (RR) with 95% confidence intervals (CI) for the highest versus the lowest GGT level were used to summarize the prognostic value. Twelve studies involving 12 531 patients with CAD were included. Meta-analysis showed that elevated GGT level was significantly associated with higher risk of CV mortality (RR: 2.04; 95% CI: 1.57-2.64) and all-cause mortality (RR: 1.49; 95% CI: 1.27-1.74) in patients with CAD. This meta-analysis suggests that elevated serum GGT levels are an independent predictor of CV and all-cause mortality in patients with CAD. Determination of GGT level may improve the prediction of CV and all-cause mortality in patients with CAD.
Topics: Cardiovascular Diseases; Cardiovascular System; Coronary Artery Disease; Humans; Prognosis; Risk Factors; gamma-Glutamyltransferase
PubMed: 31122026
DOI: 10.1177/0003319719850058 -
The British Journal of Nutrition Oct 2022Elevated levels of liver enzymes are the main markers of liver dysfunction. Liver enzymes are the important indicators of non-alcoholic fatty liver disease (NAFLD) in... (Meta-Analysis)
Meta-Analysis
Elevated levels of liver enzymes are the main markers of liver dysfunction. Liver enzymes are the important indicators of non-alcoholic fatty liver disease (NAFLD) in the general population. Previous randomised clinical trials (RCT) investigated the effects of Mediterranean diet (MedDiet) as a plant-based diet on features of NAFLD like liver enzymes, but their results are contradictory. This study aimed to systematically review and meta-analyse RCT investigating the effect of MedDiet on liver enzymes. PubMed, Web of Science, Scopus and Google Scholar were searched until December 2020. A total of ten RCT ( 705 participants) evaluating the effect of MedDiet on liver enzymes including aspartate aminotransferase (AST), alanine transaminase (ALT) and -glutamyltransferase (GGT) were included. A random effects model was used to estimate the pooled effect size. To evaluate the heterogeneity among the included studies, the Cochran's -test and I-squared test were used. The MedDiet significantly reduced AST (weighted mean difference (WMD) = -0·38 IU/l; 95 % CI - 0·73, -0·03 IU/l; = 0·03) and GGT (WMD = -0·16 IU/l; 95 % CI - 0·32, -0·006 IU/l; = 0·04) but had no significant effect on ALT (WMD = -0·55 IU/l; 95 % CI - 1·25, 0·13 IU/l; = 0·11). However, sensitivity analysis revealed that the overall effects of MedDiet on AST, GGT and ALT were significantly influenced by removing some studies. There was no publication bias based on Begg's and Egger's tests. Generally, MedDiet can improve liver enzymes. To better conclusion, further RCT investigating the effect of MedDiet on liver enzymes, especially in patients with NAFLD, are still required.
Topics: Humans; Non-alcoholic Fatty Liver Disease; Liver; Diet, Mediterranean; gamma-Glutamyltransferase; Alanine Transaminase; Aspartate Aminotransferases; Randomized Controlled Trials as Topic
PubMed: 34165054
DOI: 10.1017/S0007114521002270