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Clinics and Research in Hepatology and... Apr 2022Non-Alcoholic Fatty Liver Disease (NAFLD) is one of the most common causes of chronic liver disease worldwide. There is no universally accepted effective treatment for... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Non-Alcoholic Fatty Liver Disease (NAFLD) is one of the most common causes of chronic liver disease worldwide. There is no universally accepted effective treatment for NAFLD. Although various studies propose statins effective in lowering liver enzymes and in improving liver histology, their potency in the treatment and development of NAFLD remains unknown.
PURPOSE
We conducted this meta-analysis to evaluate the efficacy of statins in the treatment and the development of NAFLD.
METHODS
Electronic databases (MEDLINE and Cochrane CENTRAL) were searched from their inception until May 2021 for observational studies and randomized controlled trials (RCTs) that assessed the efficacy of statins for the treatment of NAFLD and its development. Studies were included irrespective of the dosage or duration, and their risk of bias was assessed. The outcomes of interest for our study were the effect of statins on liver histology (steatosis, fibrosis and necroinflammation, NAFLD activity score [NAS]) and liver enzymes (Alanine transaminase [ALT], Aspartate transaminase [AST], and Gamma-glutamyl transferase [GGT] levels). To pool continuous outcomes, a random-effects model was used to derive weighted mean difference (WMD) or standardized mean difference (SMD) and their corresponding 95% confidence intervals (CIs). Generic inverse variance was then used for different measurement units reported by the studies. For studies investigating the effects of statins on the development of NAFLD, generic inverse variance along with random effects model was used to derive odds ratio (ORs) and its corresponding 95% confidence interval (CI).
RESULTS
A total of 14 studies including 1,247,503 participants were short-listed for our analysis. All the studies included in our analysis had a low to moderate risk of bias. The results of our analysis suggest that statins may significantly reduce the risk of developing NAFLD (OR:0.69, 95% CI [0.57,0.84]; p = 0.0002; I² =36%). Statin use significantly reduced ALT levels (WMD: -27.28, 95% CI [-43.06, -11.51]; p = 0.0007; I² =90%), AST levels (WMD: -10.99, 95% CI [-18.17, -3.81]; p = 0.003; I² =79%) and GGT levels (WMD: -23.40, 95% CI [-31.82, -14.98]; p < 0.00001; I² = 21%) in patients presenting with NAFLD at baseline. In liver histology outcomes, steatosis grade (SMD: -2.59, 95% CI [-4.61, -0.56]; p = 0.01; I² = 95%), NAS (WMD: -1.03, 95% CI [-1.33, -0.74]; p < 0.00001; I² = 33%), necro-inflammatory stage (WMD: -0.19, 95% CI [-0.26, -0.13]; p < 0.00001; I² = 0%) and significant fibrosis (OR:0.20, 95% CI [0.04, 0.95]; p = 0.04; I² = 97%) underwent notable reduction. However, fibrosis stage outcome (WMD: 0.07, 95% CI [-0.05, 0.20]; p = 0.27; I² = 0%) was non-significant.
CONCLUSION
There was a significant decrease in transaminase and transferase levels. Marked improvement in liver histology of NAFLD patients was observed. Statin use also remarkably reduced the risk of developing NAFLD. Future large-scale trials can further aid in identifying the positive impact of statins in treatment for NAFLD and those at risk of developing it.
Topics: Alanine Transaminase; Aspartate Aminotransferases; Fatty Liver; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Non-alcoholic Fatty Liver Disease; Observational Studies as Topic; Randomized Controlled Trials as Topic; gamma-Glutamyltransferase
PubMed: 34607067
DOI: 10.1016/j.clinre.2021.101816 -
British Journal of Clinical Pharmacology Feb 2022Statin liver safety in non-alcoholic fatty liver disease (NAFLD) patients is not well defined. We analysed differences in liver function tests, including alanine... (Meta-Analysis)
Meta-Analysis Review
AIMS
Statin liver safety in non-alcoholic fatty liver disease (NAFLD) patients is not well defined. We analysed differences in liver function tests, including alanine transaminase aminotransferase (ALT), aspartate transaminase (AST) and gamma-glutamyl transpeptidase (GGT) in NAFLD patients treated or not treated with statins.
METHODS
We performed a systematic review of MEDLINE via PubMed and EMBASE databases and metanalysis of clinical studies investigating levels of ALT, AST and GGT in NAFLD according to statin treatment. Mean difference (MD) and percentage MD were calculated between the two groups.
RESULTS
We included 22 studies with 2345 NAFLD patients. Overall, 16 were before-after interventional, five were cross-sectional and one was combined cross-sectional/interventional study. In all interventional studies, except one, patients had raised ALT, AST and GGT at baseline. Interventional studies showed reduced ALT values with an MD reduction of -27.2 U/L (95% CI -35.25/-19.15) and a percentage MD reduction of -35.41% (95% CI -44.78/-26.04). Also, AST values were reduced after statin treatment in interventional studies with an MD of -18.82 U/L (95% CI -25.63/-12.02) (percentage -31.78%, 95% CI -41.45/-22.11). Similarly, GGT levels were reduced after statin treatment with an MD of -19.93 U/L (95% CI -27.10/-12.77) (percentage -25.57%, 95% CI -35.18/-15.97). Cross-sectional studies showed no difference in AST and GGT values between patients treated with and without statins.
CONCLUSION
In interventional studies, ALT, AST and GGT were reduced after statin treatment with a percentage mean difference of -35.41%, -31.78% and -25.57%, respectively, while observational studies showed a null effect, suggesting liver safety of statins in NAFLD patients.
Topics: Alanine Transaminase; Aspartate Aminotransferases; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Liver; Non-alcoholic Fatty Liver Disease; gamma-Glutamyltransferase
PubMed: 34133035
DOI: 10.1111/bcp.14943 -
Indian Journal of Dental Research :... 2021The aim of this study is to review studies evaluating the role of genetics in skeletal class II malocclusion. (Review)
Review
AIM
The aim of this study is to review studies evaluating the role of genetics in skeletal class II malocclusion.
OBJECTIVE
To assess the scientific evidence associating the role of genes in skeletal class II malocclusion. Materials and Methods: A complete search across the electronic database through PubMed, Cochrane, LILACS, BMC and manual hand search of orthodontic journals were done till May 2019. The keywords for the search included: "Genetics", "class II malocclusion", "maxillary prognathism", "mandibular retrognathism".
DATA COLLECTION AND ANALYSIS
Studies were selected based on PRISMA guidelines.
RESULTS
Articles were selected based on the inclusion and exclusion criteria. A total of 11 cross-sectional studies satisfied the inclusion criteria and were analyzed for the role of genes in skeletal class II malocclusion. Almost all the studies except for one revealed a positive correlation of genes with skeletal class II malocclusion.
CONCLUSIONS
Out of the 11 studies included, a positive correlation of the genes with the skeletal II malocclusion was found in 10 studies. Genes FGFR2, MSX1, MATN1, MYOH1, ACTN3, GHR, KAT6B, HDAC4, AJUBA were found to be positively linked to skeletal class II malocclusion.
Topics: Actinin; Cephalometry; Cross-Sectional Studies; Histone Acetyltransferases; Humans; LIM Domain Proteins; Malocclusion; Malocclusion, Angle Class II; Malocclusion, Angle Class III
PubMed: 35229783
DOI: 10.4103/ijdr.IJDR_59_20 -
Biochemical Pharmacology Feb 2022Cholesterol esterification proteins Sterol-O acyltransferases (SOAT) 1 and 2 are emerging prognostic markers in many cancers. These enzymes utilise fatty acids... (Meta-Analysis)
Meta-Analysis
Cholesterol esterification proteins Sterol-O acyltransferases (SOAT) 1 and 2 are emerging prognostic markers in many cancers. These enzymes utilise fatty acids conjugated to coenzyme A to esterify cholesterol. Cholesterol esterification is tightly regulated and enables formation of lipid droplets that act as storage organelles for lipid soluble vitamins and minerals, and as cholesterol reservoirs. In cancer, this provides rapid access to cholesterol to maintain continual synthesis of the plasma membrane. In this systematic review and meta-analysis, we summarise the current depth of understanding of the role of this metabolic pathway in pan-cancer development. A systematic search of PubMed, Scopus, Web of Science, and Cochrane Library for preclinical studies identified eight studies where cholesteryl ester concentrations were compared between tumour and adjacent-normal tissue, and 24 studies where cholesterol esterification was blocked by pharmacological or genetic approaches. Tumour tissue had a significantly greater concentration of cholesteryl esters than non-tumour tissue (p < 0.0001). Pharmacological or genetic inhibition of SOAT was associated with significantly smaller tumours of all types (p ≤ 0.002). SOAT inhibition increased tumour apoptosis (p = 0.007), CD8 + lymphocyte infiltration and cytotoxicity (p ≤ 0.05), and reduced proliferation (p = 0.0003) and metastasis (p < 0.0001). Significant risk of publication bias was found and may have contributed to a 32% overestimation of the meta-analysed effect size. Avasimibe, the most frequently used SOAT inhibitor, was effective at doses equivalent to those previously reported to be safe and tolerable in humans. This work indicates that SOAT inhibition should be explored in clinical trials as an adjunct to existing anti-neoplastic agents.
Topics: Animals; Anticholesteremic Agents; Antineoplastic Agents; Cholesterol; Clinical Trials as Topic; Esterification; Humans; Organic Anion Transporters; Tumor Burden; Urea; Xenograft Model Antitumor Assays
PubMed: 34407453
DOI: 10.1016/j.bcp.2021.114731 -
Complementary Therapies in Medicine Jun 2023Liver conditions are major burdens upon health systems around the world. Turmeric /curcumin is believed to possess therapeutic features in ameliorating various metabolic... (Meta-Analysis)
Meta-Analysis Review
Effects of curcumin/turmeric supplementation on liver function in adults: A GRADE-assessed systematic review and dose-response meta-analysis of randomized controlled trials.
INTRODUCTION
Liver conditions are major burdens upon health systems around the world. Turmeric /curcumin is believed to possess therapeutic features in ameliorating various metabolic disorders. In this systematic review and meta-analysis of the randomized controlled trials (RCTs), we examined the effect of turmeric/curcumin supplementation on some liver function tests (LFTs).
METHODS
We comprehensively searched online databases (i.e. PubMed, Scopus, Web of Science, Cochrane Library, and Google Scholar) from inception up to October 2022. Final outcomes included aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma-glutamyl transferase (GGT). Weighted mean differences (WMDs) were reported. In case of between-study heterogeneity, subgroup analysis was conducted. Non-linear dose-response analysis was carried out to detect the potential effect of dosage and duration. The registration code is CRD42022374871.
RESULTS
Thirty-one RCTs were included in the meta-analysis. Turmeric/curcumin supplementation significantly reduced blood levels of ALT (WMD = -4.09 U/L; 95 % CI = -6.49, -1.70) and AST (WMD = -3.81 U/L; 95 % CI = -5.71, -1.91), but not GGT (WMD: -12.78 U/L; 95 % CI: -28.20, 2.64). These improvements, though statistically significant, do not ensure clinical effectiveness.
CONCLUSION
It seems that turmeric/curcumin supplementation might be effective in improving AST and ALT levels. However, further clinical trials are needed to examine its effect on GGT. Quality of the evidence across the studies was low for AST and ALT and very low for GGT. Therefore, more studies with high quality are needed to assess this intervention on hepatic health.
Topics: Humans; Adult; Curcumin; Curcuma; Randomized Controlled Trials as Topic; Liver; gamma-Glutamyltransferase; Dietary Supplements
PubMed: 37178581
DOI: 10.1016/j.ctim.2023.102952 -
Annals of Human Genetics Jul 2022The circadian locomotor output cycles kaput (CLOCK) gene and the alcohol dehydrogenase 4 (ADH4) gene are promising candidates for susceptibility to cluster headaches... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The circadian locomotor output cycles kaput (CLOCK) gene and the alcohol dehydrogenase 4 (ADH4) gene are promising candidates for susceptibility to cluster headaches (CH). Associations of the three single nucleotide polymorphisms (SNPs)-CLOCK SNP rs1801260 and ADH4 SNPs rs1800759, and rs1126671-with CH were studied previously, but the results were inconsistent.
METHODS
Associations between the three SNPs (rs1801260, rs1126671, and rs1800759) and CH risk were separately assessed by pooled odds ratios (ORs) along with 95% confidence intervals (95% CIs) based on five different genetic models. Methodological quality was assessed using the Newcastle-Ottawa Quality Assessment Scale (NOS). All statistical analyses were carried out with RevMan 5.3 software.
RESULTS
Eight studies involving 1437 CH patients and 2541 healthy controls were selected for quantitative synthesis, from five studies on CLOCK rs1801260, five on ADH4 rs1800759, and three on ADH4 rs1126671. Our pooled data did not support associations between the three SNPs (rs1801260 in the CLOCK gene, rs1800759 and rs1126671 in the ADH4 gene) and susceptibility to CH (rs1801260: OR 1.10, 95% CI: 0.95-1.28; p = 0.19; rs1800759: OR 1.06, 95% CI: 0.93-1.22; p = 0.37; and rs1126671: OR 1.09, 95% CI: 0.92-1.28; p = 0.32).
CONCLUSION
We found no significant associations between the three SNPs (rs1801260 in the CLOCK gene and rs1800759 and rs1126671 in the ADH4 gene) and the susceptibility to CH across both Caucasian and Asian ethnicities in our meta-analysis.
Topics: Alcohol Dehydrogenase; CLOCK Proteins; Case-Control Studies; Cluster Headache; Genetic Predisposition to Disease; Genotype; Humans; Polymorphism, Single Nucleotide
PubMed: 35437765
DOI: 10.1111/ahg.12467 -
Nutrients Dec 2021The need of adding the determination of anti-deamidated gliadin peptide (DGP) IgG to anti-transglutaminase (TTG) IgA antibodies for diagnosis of celiac disease (CD) in... (Meta-Analysis)
Meta-Analysis
Diagnostic Accuracy of IgA Anti-Transglutaminase and IgG Anti-Deamidated Gliadin for Diagnosis of Celiac Disease in Children under Two Years of Age: A Systematic Review and Meta-Analysis.
The need of adding the determination of anti-deamidated gliadin peptide (DGP) IgG to anti-transglutaminase (TTG) IgA antibodies for diagnosis of celiac disease (CD) in children <2 years of age is controversial. We performed a systematic review and meta-analysis to evaluate, by head-to-head comparison, the diagnostic accuracy of TTG IgA and DGP IgG antibodies. We searched PubMed, MEDLINE, and Embase databases up to January 2021. The diagnostic reference was intestinal biopsy. We calculated the sensitivity and specificity of these tests and the odds ratio (OR) between the tests. Fifteen articles were eligible for the systematic review and ten were eligible for the meta-analysis. Sensitivity and specificity were 0.96 (95% confidence interval (CI), 0.91-0.98) and 0.96 (95% CI, 0.85-0.99) for DGP IgG and 0.93 (95% CI, 0.88-0.97) and 0.98 (95% CI, 0.96-0.99) for TTG IgA, respectively. TTG IgA specificity was significantly higher (OR 9.3 (95% CI, 2.3-37.49); < 0.001) while the sensitivity of DGP IgG was higher without reaching statistical significance (OR: 0.6 (95% CI, 0.24-1.51); = 0.28). Both the meta-analysis and the systematic review showed that some children with early CD are missed without the DGP IgG test. In children <2 years of age, TTG IgA is the best CD screening test; however, the addition of DGP IgG may increase the diagnostic sensitivity.
Topics: Autoantibodies; Celiac Disease; Child, Preschool; Gliadin; Humans; Immunoglobulin A; Immunoglobulin G; Infant; Infant, Newborn; Sensitivity and Specificity; Transglutaminases
PubMed: 35010880
DOI: 10.3390/nu14010007 -
Complementary Therapies in Clinical... May 2020Existing evidence on the possible effects of ginseng on liver function has not been fully established. Therefore, the present review was undertaken to evaluate the... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Existing evidence on the possible effects of ginseng on liver function has not been fully established. Therefore, the present review was undertaken to evaluate the overall effects of ginseng supplementation on liver enzymes in adults.
METHODS
A systematic computerized literature search of PubMed, Scopus, Web of Science, Cochrane Library and Google scholar databases was conducted up to May 2019. All RCTs using ginseng supplements in adults were included in this systematic review and meta-analysis.
RESULTS
Overall, 14 randomized trials (with 20 arms) including 992 subjects were identified. Pooled analysis did not illustrate any significant changes in alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), and albumin (ALB) levels, however, it showed a minor significant increase in bilirubin (BIL) levels. Subgroup analysis by dosage and study population revealed significant increase of bilirubin after ginseng supplementation ≥3 g/day or in unhealthy individuals.
CONCLUSION
Ginseng appears to have neither hepatoprotective nor hepatotoxic effects in conventional doses and duration. It is noteworthy that this seems applicable only for individuals with healthy liver function. Further largescale studies are warranted to confirm present findings.
Topics: Adult; Aged; Aged, 80 and over; Alanine Transaminase; Alkaline Phosphatase; Aspartate Aminotransferases; Bilirubin; Complementary Therapies; Dietary Supplements; Female; Humans; Liver; Liver Function Tests; Male; Middle Aged; Panax; Plant Exudates; gamma-Glutamyltransferase
PubMed: 32379697
DOI: 10.1016/j.ctcp.2020.101173 -
Gastroenterology Apr 2024Current international guidelines recommend duodenal biopsies to confirm the diagnosis of celiac disease in adult patients. However, growing evidence suggests that... (Meta-Analysis)
Meta-Analysis
BACKGROUND & AIMS
Current international guidelines recommend duodenal biopsies to confirm the diagnosis of celiac disease in adult patients. However, growing evidence suggests that immunoglobulin A (IgA) anti-tissue transglutaminase (tTg) antibody levels ≥10 times the upper limit of normal (ULN) can accurately predict celiac disease, eliminating the need for biopsy. We performed a systematic review and meta-analysis to evaluate the accuracy of the no-biopsy approach to confirm the diagnosis of celiac disease in adults.
METHODS
We systematically searched MEDLINE, EMBASE, Cochrane Library, and Web of Science from January 1998 to October 2023 for studies reporting the sensitivity and specificity of IgA-tTG ≥10×ULN against duodenal biopsies (Marsh grade ≥2) in adults with suspected celiac disease. We used a bivariate random effects model to calculate the summary estimates of sensitivity, specificity, and positive and negative likelihood ratios. The positive and negative likelihood ratios were used to calculate the positive predictive value of the no-biopsy approach across different pretest probabilities of celiac disease. The methodological quality of the included studies was evaluated using the QUADAS-2 tool. This study was registered with PROSPERO, number CRD42023398812.
RESULTS
A total of 18 studies comprising 12,103 participants from 15 countries were included. The pooled prevalence of biopsy-proven celiac disease in the included studies was 62% (95% confidence interval [CI], 40%-83%). The proportion of patients with IgA-tTG ≥10×ULN was 32% (95% CI, 24%-40%). The summary sensitivity of IgA-tTG ≥10×ULN was 51% (95% CI, 42%-60%), and the summary specificity was 100% (95% CI, 98%-100%). The area under the summary receiver operating characteristic curve was 0.83 (95% CI, 0.77 - 0.89). The positive predictive value of the no-biopsy approach to identify patients with celiac disease was 65%, 88%, 95%, and 99% if celiac disease prevalence was 1%, 4%, 10%, and 40%, respectively. Between-study heterogeneity was moderate (I =30.3%), and additional sensitivity analyses did not significantly alter our findings. Only 1 study had a low risk of bias across all domains.
CONCLUSION
The results of this meta-analysis suggest that selected adult patients with IgA-tTG ≥10×ULN and a moderate to high pretest probability of celiac disease could be diagnosed without undergoing invasive endoscopy and duodenal biopsy.
Topics: Adult; Humans; Celiac Disease; Transglutaminases; Protein Glutamine gamma Glutamyltransferase 2; Immunoglobulin A; GTP-Binding Proteins; Biopsy; Sensitivity and Specificity; Autoantibodies
PubMed: 38176661
DOI: 10.1053/j.gastro.2023.12.023 -
Acta Diabetologica Jun 2020Relationship between liver enzymes such as gamma-glutamyl transferase (GGT), alanine aminotransferase (ALT), aspartate transaminase (AST) and alkaline phosphatase and... (Meta-Analysis)
Meta-Analysis
AIMS
Relationship between liver enzymes such as gamma-glutamyl transferase (GGT), alanine aminotransferase (ALT), aspartate transaminase (AST) and alkaline phosphatase and risk of gestational diabetes mellitus (GDM) is a controversial issue. The aim of this systematic review and dose-response meta-analysis was to investigate the association between liver enzymes and risk of GDM in observational studies.
METHODS
A comprehensive systematic literature search was conducted in MEDLINE/PubMed, SCOPUS and Web of Science databases up to September 2019. Combined odds ratios (ORs) with 95% confidence intervals (CIs) were evaluated by DerSimonian and Laird random-effects models. Dose-response analyses of these relationships were also carried out.
RESULTS
Eight studies with 25,451 participants containing 2549 cases were included in this study. Pooled results showed a significant association between GGT levels and risk of GDM (OR 2.10, 95% CI 1.14-3.86, I 84%). In addition, random-effects model indicated a dramatic and direct significant association between GGT and risk of GDM in nonlinear (p < 0.001) and linear (p < 0.001) dose-response analysis. Associations between ALT and AST with risk of GDM were found to be non-significant (OR 1.32, 95% CI 0.91-1.90, I 65% and OR 0.76, 95% CI 0.52-1.10, I 16%, respectively).
CONCLUSION
This systematic review and dose-response meta-analysis highlights GGT as a significant and robust predictor of the incidence of GDM in pregnant women.
Topics: Alanine Transaminase; Alkaline Phosphatase; Aspartate Aminotransferases; Blood Chemical Analysis; Diabetes, Gestational; Female; Humans; Incidence; Liver; Liver Function Tests; Observational Studies as Topic; Pregnancy; Prenatal Diagnosis; Risk Factors; gamma-Glutamyltransferase
PubMed: 31781958
DOI: 10.1007/s00592-019-01458-8