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Medicine May 2019Many studies explored the prognostic and clinicopathological significance of pretreatment serum Gamma-Glutamyltransferase (GGT) level in hepatocellular carcinoma (HCC).... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Many studies explored the prognostic and clinicopathological significance of pretreatment serum Gamma-Glutamyltransferase (GGT) level in hepatocellular carcinoma (HCC). However, there are inconsistent results in the prognostic and clinicopathological significance of pretreatment serum GGT level in HCC. Thus, we conducted this meta-analysis to comprehensively assess the prognostic and clinicopathological significance of pretreatment serum GGT level in HCC patients.
METHODS
We systematically searched PubMed, EMBASE and Web of Science for relevant studies (up to June 14, 2018). The estimated hazard ratios (HRs) were used to assess the association between pretreatment serum GGT level and survival in HCC patients. The estimated odds ratios (ORs) were applied to evaluate the correlation between pretreatment serum GGT and clinicopathological features in HCC.
RESULTS
Our results showed that high pretreatment serum GGT level was significantly correlated with poor overall survival (OS) (HR = 1.70, 95% CI: 1.54-1.87; P < .01) and disease-free survival/relapse-free survival (DFS/RFS) (HR = 1.56, 95% CI: 1.42-1.71; P < .01). Additionally, our results also revealed that there was a close correlation between GGT level and several clinicopathological features in HCC patients, including vascular invasion, tumor size, tumor number and Alpha-fetoprotein (AFP) level.
CONCLUSIONS
This meta-analysis shows that high pretreatment serum GGT level is significantly correlated with poor survival and unfavorable clinicopathological features in HCC patients, suggesting that pretreatment serum GGT may be an economical and effective prognostic biomarker for HCC patients. However, more high-quality studies are still warranted to further validate our findings, considering there are several limitations in this meta-analysis.
Topics: Biomarkers, Tumor; Carcinoma, Hepatocellular; Humans; Liver Neoplasms; Prognosis; gamma-Glutamyltransferase
PubMed: 31083251
DOI: 10.1097/MD.0000000000015603 -
The Cochrane Database of Systematic... Apr 2019Survival rates have greatly improved as a result of more effective treatments for childhood cancer. Unfortunately, the improved prognosis has been accompanied by the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Survival rates have greatly improved as a result of more effective treatments for childhood cancer. Unfortunately, the improved prognosis has been accompanied by the occurrence of late, treatment-related complications. Liver complications are common during and soon after treatment for childhood cancer. However, among long-term childhood cancer survivors, the risk of hepatic late adverse effects is largely unknown. To make informed decisions about future cancer treatment and follow-up policies, it is important to know the risk of, and associated risk factors for, hepatic late adverse effects. This review is an update of a previously published Cochrane review.
OBJECTIVES
To evaluate all the existing evidence on the association between antineoplastic treatment (that is, chemotherapy, radiotherapy involving the liver, surgery involving the liver and BMT) for childhood cancer and hepatic late adverse effects.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2018, Issue 1), MEDLINE (1966 to January 2018) and Embase (1980 to January 2018). In addition, we searched reference lists of relevant articles and scanned the conference proceedings of the International Society of Paediatric Oncology (SIOP) (from 2005 to 2017) and American Society of Pediatric Hematology/Oncology (ASPHO) (from 2013 to 2018) electronically.
SELECTION CRITERIA
All studies, except case reports, case series, and studies including fewer than 10 patients that examined the association between antineoplastic treatment for childhood cancer (aged 18 years or less at diagnosis) and hepatic late adverse effects (one year or more after the end of treatment).
DATA COLLECTION AND ANALYSIS
Two review authors independently performed the study selection and 'risk of bias' assessment. The 'risk of bias' assessment was based on earlier checklists for observational studies. For the original version of the review, two review authors independently performed data extraction. For the update of the review, the data extraction was performed by one reviewer and checked by another reviewer.
MAIN RESULTS
Thirteen new studies were identified for the update of this review. In total, we included 33 cohort studies including 7876 participants investigating hepatic late adverse effects after antineoplastic treatment (especially chemotherapy and radiotherapy) for different types of childhood cancer, both haematological and solid malignancies. All studies had methodological limitations. The prevalence of hepatic late adverse effects, all defined in a biochemical way, varied widely, between 0% and 84.2%. Selecting studies where the outcome of hepatic late adverse effects was well-defined as alanine aminotransferase (ALT) above the upper limit of normal, indicating cellular liver injury, resulted in eight studies. In this subgroup, the prevalence of hepatic late adverse effects ranged from 5.8% to 52.8%, with median follow-up durations varying from three to 23 years since cancer diagnosis in studies that reported the median follow-up duration. A more stringent selection process using the outcome definition of ALT as above twice the upper limit of normal, resulted in five studies, with a prevalence ranging from 0.9% to 44.8%. One study investigated biliary tract injury, defined as gamma-glutamyltransferase (γGT) above the upper limit of normal and above twice the upper limit of normal and reported a prevalence of 5.3% and 0.9%, respectively. Three studies investigated disturbance in biliary function, defined as bilirubin above the upper limit of normal and reported prevalences ranging from 0% to 8.7%. Two studies showed that treatment with radiotherapy involving the liver (especially after a high percentage of the liver irradiated), higher BMI, and longer follow-up time or older age at evaluation increased the risk of cellular liver injury in multivariable analyses. In addition, there was some suggestion that busulfan, thioguanine, hepatic surgery, chronic viral hepatitis C, metabolic syndrome, use of statins, non-Hispanic white ethnicity, and higher alcohol intake (> 14 units per week) increase the risk of cellular liver injury in multivariable analyses. Chronic viral hepatitis was shown to increase the risk of cellular liver injury in six univariable analyses as well. Moreover, one study showed that treatment with radiotherapy involving the liver, higher BMI, higher alcohol intake (> 14 units per week), longer follow-up time, and older age at cancer diagnosis increased the risk of biliary tract injury in a multivariable analysis.
AUTHORS' CONCLUSIONS
The prevalence of hepatic late adverse effects among studies with an adequate outcome definition varied considerably from 1% to 53%. Evidence suggests that radiotherapy involving the liver, higher BMI, chronic viral hepatitis and longer follow-up time or older age at follow-up increase the risk of hepatic late adverse effects. In addition, there may be a suggestion that busulfan, thioguanine, hepatic surgery, higher alcohol intake (>14 units per week), metabolic syndrome, use of statins, non-Hispanic white ethnicity, and older age at cancer diagnosis increase the risk of hepatic late adverse effects. High-quality studies are needed to evaluate the effects of different therapy doses, time trends, and associated risk factors after antineoplastic treatment for childhood cancer.
Topics: Adolescent; Alanine Transaminase; Antineoplastic Agents; Chemical and Drug Induced Liver Injury; Child; Child, Preschool; Humans; Infant; Liver Diseases; Neoplasms; Radiotherapy; gamma-Glutamyltransferase
PubMed: 30985922
DOI: 10.1002/14651858.CD008205.pub3 -
Medicina (Kaunas, Lithuania) Apr 2019Numerous studies examined the association between factors FV, FVII, FXII, and FXIII-A gene polymorphisms and ischemic stroke, but conclusive evidence is yet to be... (Review)
Review
Numerous studies examined the association between factors FV, FVII, FXII, and FXIII-A gene polymorphisms and ischemic stroke, but conclusive evidence is yet to be obtained. Thus, this meta-analysis aimed to investigate the novel association of FV rs1800595, FVII rs5742910, FXII rs1801020, and FXIII-A rs5982 and rs3024477 polymorphisms with ischemic stroke risk. A systematic review was performed on articles retrieved before June 2018. Relevant data were extracted from eligible studies and meta-analyzed using RevMan version 5.3. The strength of association between studied polymorphisms and ischemic stroke risk was calculated as odds ratios and 95% confidence intervals, by applying both fixed- and random-effect models. A total of 25 studies involving 6100 ischemic stroke patients and 9249 healthy controls were incorporated in the final meta-analysis model. Specifically, rs1800595, rs5742910, rs1801020, rs5982, and rs3024477 consisted of 673, 3668, 922, 433, and 404 cases, as well as 995, 4331, 1285, 1321, and 1317 controls, respectively. The pooled analysis indicated that there was no significant association of FV rs1800595, FVII rs5742910, FXII rs1801020, FXIII-A rs5982, and rs3024477 polymorphisms with ischemic stroke risk, under any genetic models (dominant, recessive, over-dominant, and allelic). The present meta-analysis concluded that FV rs1800595, FVII rs5742910, FXII rs1801020, and FXIII-A rs5982 and rs3024477 polymorphisms are not associated with ischemic stroke risk.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Brain Infarction; Chi-Square Distribution; Factor V; Factor VII; Factor XII; Factor XIIIa; Female; Humans; Male; Middle Aged; Polymorphism, Genetic; Risk; Young Adult
PubMed: 30979054
DOI: 10.3390/medicina55040101 -
The International Journal of... Mar 2019Tuberculosis (TB) patients receiving anti-tuberculosis treatment may experience serious adverse drug reactions (ADRs) such as hepatotoxicity. Variants of the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Tuberculosis (TB) patients receiving anti-tuberculosis treatment may experience serious adverse drug reactions (ADRs) such as hepatotoxicity. Variants of the -acetyltransferase 2 () gene may increase the risk of experiencing such toxicity events.
OBJECTIVE
To provide a comprehensive evaluation of the evidence base for associations between variants and anti-tuberculosis drug-related toxicity.
METHOD
This was a systematic review and meta-analysis. We searched for studies in Medline, PubMed, EMBASE, BIOSIS and Web of Science. We included data from 41 articles (39 distinct cohorts of patients). We pooled effect estimates for each genotype on each outcome using meta-analyses stratified by country.
RESULTS
We assessed the quality of the included studies, which was variable, with many areas of concern. Slow/intermediate acetylators were statistically significantly more likely to experience hepatotoxicity than rapid acetylators (OR 1.59, 95%CI 1.26-2.01). Heterogeneity was not detected in the overall pooled analysis (² = 0%). acetylator status was significantly associated with the likelihood of experiencing anti-tuberculosis drug-related hepatotoxicity.
CONCLUSION
We encountered several challenges in performing robust syntheses of data from pharmacogenetic studies, and we outline recommendations for the future reporting of pharmacogenetic studies to enable high-quality systematic reviews and meta-analyses to be performed.
Topics: Antitubercular Agents; Arylamine N-Acetyltransferase; Chemical and Drug Induced Liver Injury; Genotype; Humans; Tuberculosis
PubMed: 30871660
DOI: 10.5588/ijtld.18.0324 -
Bioscience Reports Dec 2018To assess the prognostic value of the pretreatment serum γ-glutamyltranspeptidase (GGT) level in patients with primary liver cancer (PLC). Relevant studies were... (Meta-Analysis)
Meta-Analysis
To assess the prognostic value of the pretreatment serum γ-glutamyltranspeptidase (GGT) level in patients with primary liver cancer (PLC). Relevant studies were systematically searched online on Web of Science, PubMed, and Embase databases published until 9 October 2018. The end points were overall survival (OS), recurrence-free survival (RFS), and disease-free survival (DFS). Meta-analysis was conducted using hazard ratio (HR), and its 95% confidence interval (CI) as effect measure. A total of 33 eligible studies with 9238 patients with PLC were included in this meta-analysis. The synthesized analysis showed that that higher serum GGT level was significantly related to poorer OS (HR: 1.79, 95% CI: 1.66-1.93, <0.01), RFS (HR: 1.60, 95% CI: 1.46-1.77, <0.01), and DFS (HR: 1.52, 95% CI: 1.33-1.73, <0.01) of patients with PLC. Subgroup analyses demonstrated that the negative prognostic impact of higher serum GGT level on OS and RFS was still of significance regardless of ethnicity, pathological type, sample size, cut-off value, first-line treatment, and analysis type. The pretreatment serum GGT might be a predictive factor of poor prognosis for PLC patients.
Topics: Biomarkers, Tumor; Disease-Free Survival; Humans; Liver Neoplasms; Prognosis; gamma-Glutamyltransferase
PubMed: 30389711
DOI: 10.1042/BSR20181058 -
British Journal of Clinical Pharmacology Dec 2018The aim of this study is to evaluate the potential association between N-acetyltransferase type 2 (NAT2) polymorphisms and drug-induced liver injury during anti-TB... (Meta-Analysis)
Meta-Analysis
AIMS
The aim of this study is to evaluate the potential association between N-acetyltransferase type 2 (NAT2) polymorphisms and drug-induced liver injury during anti-TB treatment (AT-DILI).
METHODS
We conducted a systematic review and performed a meta-analysis to clarify the role of NAT2 polymorphism in AT-DILI. PubMed, Medline and EMBASE databases were searched for studies published in English to December 31, 2017, on the association between the NAT2 polymorphism and AT-DILI risk. Outcomes were pooled with random-effects meta-analysis. Details were registered in the PROSPERO register (number: CRD42016051722).
RESULTS
Thirty-seven studies involving 1527 cases and 7184 controls were included in this meta-analysis. The overall odds ratio (OR) of AT-DILI associated with NAT2 slow acetylator phenotype was 3.15 (95% CI 2.58-3.84, I = 51.3%, P = 0.000). The OR varied between different ethnic populations, ranging from 6.42 (95% CI 2.41-17.10, I = 2.3%) for the West Asian population to 2.32 (95% CI 0.58-9.24, I = 80.3%) for the European population. Within the slow NAT2 genotype, variation was also observed; NAT2*6/*7 was associated with the highest risk of AT-DILI (OR = 1.68, 95% CI 1.09-2.59) compared to the other slow NAT2 acetylators combined.
CONCLUSIONS
NAT2 slow acetylation was observed to increase the risk of AT-DILI in tuberculosis patients. Our results support the hypothesis that the slow NAT2 genotype is a risk factor for AT-DILI.
Topics: Antitubercular Agents; Arylamine N-Acetyltransferase; Chemical and Drug Induced Liver Injury; Genetic Predisposition to Disease; Genotype; Humans; Polymorphism, Genetic
PubMed: 30047605
DOI: 10.1111/bcp.13722 -
Nutrients Sep 2017In developed countries which are at the epicenter of the obesity pandemic, pulse crop consumption is well below recommended levels. In a recent systematic review and... (Review)
Review
In developed countries which are at the epicenter of the obesity pandemic, pulse crop consumption is well below recommended levels. In a recent systematic review and meta-analysis of 21 randomized controlled clinical trials, pulse consumption was associated with improved weight control and reduced adiposity, although the underlying mechanisms were a matter of speculation. Common bean ( L.) is the most widely consumed pulse crop and was the focus of this investigation. Using outbred genetic models of dietary induced obesity resistance and of dietary induced obesity sensitivity in the rat, the impact of bean consumption was investigated on the efficiency with which consumed food was converted to body mass (food efficiency ratio), body fat accumulation, adipocyte morphometrics, and patterns of protein expression associated with lipid metabolism. Cooked whole bean as well as a commercially prepared cooked bean powders were evaluated. While bean consumption did not affect food efficiency ratio, bean reduced visceral adiposity and adipocyte size in both obesity sensitive and resistant rats. In liver, bean consumption increased carnitine palmitoyl transferase 1, which is the rate limiting step in long chain fatty acid oxidation and also resulted in lower levels of circulating triglycerides. Collectively, our results are consistent with the clinical finding that pulse consumption is anti-obesogenic and indicate that one mechanism by which cooked bean exerts its bioactivity is oxidation of long chain fatty acids.
Topics: Adipocytes; Adiposity; Animals; Carnitine O-Palmitoyltransferase; Cholesterol; Diet; Disease Models, Animal; Fabaceae; Fatty Acids; Humans; Lipid Metabolism; Liver; Meta-Analysis as Topic; Obesity; Oxidation-Reduction; Randomized Controlled Trials as Topic; Triglycerides
PubMed: 28891931
DOI: 10.3390/nu9090998 -
Reumatologia Clinica 2019To assess the efficacy and side effects of methotrexate and leflunomide in patients with rheumatoid arthritis (RA) as the first disease-modifying antirheumatic drug... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To assess the efficacy and side effects of methotrexate and leflunomide in patients with rheumatoid arthritis (RA) as the first disease-modifying antirheumatic drug (DMARD).
METHODS
We performed a systematic review and meta-analysis of clinical studies that included patients who took methotrexate, leflunomide, placebo or another DMARD for RA treatment. A systematic review yielded 1971 articles from databases; once completely reviewed, 73 trials that completed inclusion criteria were selected. In structured workshops for discussion and assessment of each article, 6 could be meta-analyzed for the primary and secondary outcomes: achievement of American College of Rheumatology (ACR) 20 and its core set components; and change of serum C-reactive protein (CRP) levels, Health Assessment Questionnaire Disability Index (HAQ-Di), liver enzyme aspartate transaminase/alanine transaminase ratio, new gastrointestinal (GI) side effects and infections.
RESULTS
A total of 1984 patients were included: 986 took leflunomide and 998 methotrexate. The probability of achieving ACR 20 had an odds ratio (OR) of 0.88 (95% confidence interval [CI] 0.74, 1.06) with a trend toward favoring methotrexate; reduction of the swollen joint count was greater for methotrexate: mean difference=0.82 (95%CI 0.24, 1.39); tender joint count, physician global assessment, HAQ-Di, and serum CRP levels revealed no significant difference between groups. Increased liver enzymes were more frequent in the leflunomide group, OR=0.38 (95%CI 0.27, 0.53), and new GI complaints were more common with methotrexate (OR=1.44; 95%CI 1.17, 1.79). There was no difference in the incidence of non-severe infections.
CONCLUSION
Leflunomide used as the first DMARD in RA seemed to be as efficacious as methotrexate; only the reduction of swollen joint count was more marked for methotrexate. Leflunomide was linked to a greater increase in liver enzymes, but there were fewer GI complaints.
Topics: Alanine Transaminase; Anti-Inflammatory Agents, Non-Steroidal; Antirheumatic Agents; Arthritis, Rheumatoid; Aspartate Aminotransferases; C-Reactive Protein; Chemical and Drug Induced Liver Injury; Clinical Trials as Topic; Disability Evaluation; Drug Therapy, Combination; Gastrointestinal Diseases; Humans; Immunosuppressive Agents; Leflunomide; Methotrexate; Treatment Outcome; gamma-Glutamyltransferase
PubMed: 28867467
DOI: 10.1016/j.reuma.2017.07.020 -
World Journal of Gastroenterology Jul 2017To evaluate the effect of silymarin on the serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma glutamyl transpeptidase (γGT) in... (Meta-Analysis)
Meta-Analysis Review
AIM
To evaluate the effect of silymarin on the serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma glutamyl transpeptidase (γGT) in patients with liver diseases.
METHODS
A systematic review with meta-analysis of ramdomized and controlled clinical trials was performed, evaluating the effects of sylimarin in patients with hepatic diseases, published by January 31, 2016. Clinical trials were sought on the basis of The Cochrane Central Register of Controlled Trials in the Cochrane Library, PubMed/Medline, Scopus, Web of Science, Lilacs and Clinical Trials. The trials with adult and elderly patients of both sexes, with Liver Diseases who took oral silymarin supplementation, as extract or isolated, as well as Silymarin combined with other nutrients, were included. The trials should provide information about the intervention, such as dosages and detailing of the product used, besides the mean and standard deviation of serum levels of ALT, AST and γGT of the baseline and at the end of the intervention.
RESULTS
An amount of 10904 publications were identified. From those, only 17 were included in the systematic review and 6 in the meta-analysis, according to the used selection criteria. In this meta-analysis, the results indicated a reduction of 0.26 IU/mL (95%CI: -0.46-0.07, = 0.007) at the level of ALT and 0.53 IU/mL (95%CI: -0.74-0.32, = 0.000) at the serum levels of AST after using the silymarin, both, statistically significant, but with no clinical relevance. There was no significant change in the γGT levels. Subgroup analyzes were also performed for the biochemical markers in relation to the type of intervention, whether silymarin isolated or associated with other nutrients and the time of intervention (whether ≥ 6 mo or < 6 mo). Significant differences were not found. The evaluated studies presented a high degree of heterogeneity and low methodological quality in the carried out analysis.
CONCLUSION
Silymarin minimally reduced, but without clinical relevance, the serum levels of ALT and AST. It is necessary to carry out studies with more appropriate methodological designs.
Topics: Alanine Transaminase; Aspartate Aminotransferases; Humans; Liver; Liver Diseases; Protective Agents; Randomized Controlled Trials as Topic; Silymarin; gamma-Glutamyltransferase
PubMed: 28785154
DOI: 10.3748/wjg.v23.i27.5004 -
PloS One 2016Tat-interacting protein 30 (TIP30) is a tumor suppressor protein that has been found to be expressed in a wide variety of tumor tissues. TIP30 is involved in the control... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Tat-interacting protein 30 (TIP30) is a tumor suppressor protein that has been found to be expressed in a wide variety of tumor tissues. TIP30 is involved in the control of cell apoptosis, growth, metastasis, angiogenesis, DNA repair, and tumor cell metabolism. The methylation of the TIP30 promoter is also associated with tumor prognosis. To evaluate this topic further, we conducted a systematic meta-analysis to explore the clinicopathological and prognostic significance of TIP30 for tumor patients.
METHODS
We searched PubMed and EMBASE for eligible studies. We manually searched for printed journals and relevant textbooks. Subgroup analyses were performed based on the region, manuscript quality, methods of vasculogenic mimicry identification, pathology, and number of patients.
RESULTS
Fourteen studies with 1705 patients were included in this meta-analysis. A significant association was observed between high expression of TIP30 in patients with cancer with a good overall survival (hazard ratio = 0.53, 95% confidence interval: 0.41-0.69), and good recurrence-free survival or disease free survival (hazard ratio = 0.49, 95% confidence interval: 0.37-0.66). Lack of expression of TIP30 had an association with lymph node metastasis (odds ratio = 3.90, 95% confidence interval: 2.21-6.89) and high tumor node metastasis clinical stage (odds ratio = 2.10, 95% confidence interval: 1.68-2.62). The methylation of the TIP30 promoter did not significantly influence the overall survival (hazard ratio = 0.99, 95% confidence interval: 0.88-1.13) or disease free survival (hazard ratio = 0.62, 95% confidence interval: 0.19-2.02).
CONCLUSIONS
TIP30 expression is associated with a good prognosis in patients with tumors. Clinical studies with large samples are needed worldwide and standardized protocols should be adopted in the future to achieve a better understanding of the relationship between tumor prognosis and TIP30.
Topics: Acetyltransferases; Biomarkers, Tumor; Disease-Free Survival; Gene Expression Regulation, Neoplastic; Humans; Lymphatic Metastasis; Neoplasm Recurrence, Local; Neoplasms; Prognosis; Transcription Factors
PubMed: 28036326
DOI: 10.1371/journal.pone.0168408