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Clinical Otolaryngology : Official... Nov 2022A large proportion of patients with infectious mononucleosis (IM) have abnormal liver function tests (LFT) at presentation. There is no guideline regarding the... (Review)
Review
INTRODUCTION
A large proportion of patients with infectious mononucleosis (IM) have abnormal liver function tests (LFT) at presentation. There is no guideline regarding the management and follow-up of these patients. Some patients also have abdominal ultrasound (US) due to deranged LFT, the need for this practice is unclear. The aim of this systematic review was to evaluate the evidence base on LFT assessment in IM, time to resolution of derangement, and the role of abdominal US.
METHODS
A systematic search of PubMed, EMBASE and the Cochrane library was done. Two authors independently screened records for eligibility using pre-defined criteria. We included both adult and paediatric populations. Quality assessment of included studies was done.
RESULTS
A total of 3924 patients were included from 32 studies, of which LFT values were reported on 2779 patients. A combination of typical clinical features, heterophile antibodies and Epstein-Barr virus-specific antibodies were used to ascertain diagnosis. The following proportion of patients had abnormal LFT: aspartate transaminase (57%); alanine transaminase (62%); alkaline phosphatase (65%); bilirubin (16%); gamma-glutamyltransferase (41%). Reported median (interquartile range) time to resolution of LFT was 8 (6-12) weeks (n = 438). Maximum time to resolution was >6 months. Clinical hepatomegaly and splenomegaly were found in 35% and 44% of patients, respectively. Enlarged liver and spleen on US were seen in 16 of 29 and 38 of 38 of patients, respectively. There were no reports of decompensated liver disease.
CONCLUSION
Current evidence questions the need for routine assessment of LFT in immunocompetent patients presenting with IM; serial LFT assessments following initial abnormalities are not required in immunocompetent patients with subclinical derangement of LFT; routine US abdomen in IM to evaluate for derangement of LFT is not required.
Topics: Adult; Alanine Transaminase; Alkaline Phosphatase; Antibodies, Heterophile; Aspartate Aminotransferases; Bilirubin; Child; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Humans; Infectious Mononucleosis; Liver Diseases; Liver Function Tests; gamma-Glutamyltransferase
PubMed: 35834363
DOI: 10.1111/coa.13965 -
Nutrition Research (New York, N.Y.) Oct 2022Nonalcoholic fatty liver disease has become the most common liver disorder worldwide, reaching a prevalence of 60% and 24% in patients with chronic liver disease and the... (Meta-Analysis)
Meta-Analysis Review
Coffee consumption has no effect on circulating markers of liver function but increases adiponectin concentrations: A systematic review and meta-analysis of randomized controlled trials.
Nonalcoholic fatty liver disease has become the most common liver disorder worldwide, reaching a prevalence of 60% and 24% in patients with chronic liver disease and the general population, respectively. Liver function is often assessed using standard liver tests such as alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, and alkaline phosphatase. Randomized controlled trials (RCTs) investigating the potential beneficial effects of coffee consumption on liver function are scarce and their results are inconclusive. Some clinical trials have shown a significant increase in adiponectin concentrations following coffee consumption; however, there are few studies in this field. Hence, the hypothesis of this meta-analysis of RCTs is that coffee consumption decreases blood markers of liver function and increases adiponectin concentrations. A systematic search was conducted in PubMed-MEDLINE, Scopus, Web of Science, ClinicalTrials.gov, and Google Scholar databases. Meta-analysis was performed using a random-effects model followed by sensitivity analysis. Meta-analysis of 14 RCTs, including a total of 897 subjects, showed that coffee consumption has no significant effect on alanine aminotransferase (weighted mean difference [WMD], -0.89 mg/mL; 95% CI, -2.90 to 1.12; P = .39), aspartate aminotransferase (WMD, -0.29 mg/mL; 95% CI, -1.25 to 0.66; P = .55), gamma-glutamyl transferase (WMD, .10 mg/mL; 95% CI, -3.94 to 4.15; P = .96), alkaline phosphatase (WMD, -4.60 mg/mL; 95% CI, -9.26 to 0.07; P = .05), and lactate dehydrogenase (WMD, -0.65 mg/mL; 95% CI, -10.80 to 9.49; P = .90). However, coffee administration significantly increased adiponectin concentrations (WMD, 1.19 mg/mL; 95% CI, 0.08-2.31; P = .04). The results of this meta-analysis of RCTs suggest that coffee consumption may improve liver dysfunction through the elevation of adiponectin levels; however, further clinical trials are needed to corroborate our findings.
Topics: Adiponectin; Alanine; Alanine Transaminase; Alkaline Phosphatase; Aspartate Aminotransferases; Biomarkers; Coffee; Humans; Lactate Dehydrogenases; Liver; Randomized Controlled Trials as Topic; gamma-Glutamyltransferase
PubMed: 36126527
DOI: 10.1016/j.nutres.2022.07.010 -
Thyroid : Official Journal of the... Jun 2021Abnormal liver blood tests (LBTs) in hyperthyroid patients are not uncommonly encountered. One major adverse event of antithyroid drug (ATD) therapy is drug-induced... (Meta-Analysis)
Meta-Analysis
Abnormal liver blood tests (LBTs) in hyperthyroid patients are not uncommonly encountered. One major adverse event of antithyroid drug (ATD) therapy is drug-induced hepatotoxicity. Abnormal LBT in the hyperthyroidism scenario is a main diagnostic and therapeutic dilemma. We aimed to assess the prevalence and the response to ATD therapy of LBT abnormalities in newly diagnosed and uncomplicated hyperthyroidism through a systematic review and meta-analysis. A literature search was performed reporting LBTs at presentation and after ATD therapy in hyperthyroid patients. A proportion meta-analysis was performed with random-effects model. Pooled data were presented with 95% confidence intervals (CI). I statistic index was used to quantify the heterogeneity. Sensitivity analyses for prevalence of hyperthyroid patients with at least one abnormal LBT were performed. -Value of <0.05 was regarded as significant. The literature search yielded 2286 studies, of which 25 were included for systematic review and meta-analysis. The prevalence of untreated hyperthyroid and Graves' disease patients with at least one abnormal LBT was 55% ([CI 46-63%], I 96%) and 60% ([CI 53-67%], I 92%), respectively. The prevalence of alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), total bilirubin (BIL), and γ-glutamyltransferase (GGT) abnormalities in hyperthyroid patients were 33% ([CI 24-44%], I 95%), 23% ([CI 17-29%], I 89%), 44% ([CI 35-52%], I 93%), 12% ([CI 7-20%], I 92%), and 24% ([CI 16-36%], I 95%), respectively. ATD therapy, along with euthyroidism restoration, was accompanied by normalization of LBT abnormalities in the following percentage of cases: ALT 83% ([CI 72-90%], I 46%), AST 87% ([CI 74-94%], I 2%), ALP 53% ([CI 32-73%], I 76%), BIL 50% (CI cannot be calculated), and GGT 70% ([CI 47-87%], I 74%). The sensitivity analyses showed similar results as those of the main analyses. The publication bias was not statistically significant for all outcomes, except for the prevalence of resolved BIL abnormalities that was not calculable. LBT abnormalities are common in newly diagnosed and untreated hyperthyroidism setting. A high chance of safely normalizing elevated transaminases, up to fivefold above the upper limit of normal, accompanies the use of ATDs in the treatment of hyperthyroidism.
Topics: Alanine Transaminase; Alkaline Phosphatase; Antithyroid Agents; Aspartate Aminotransferases; Bilirubin; Graves Disease; Humans; Hyperthyroidism; Liver Diseases; Liver Function Tests; Prevalence; gamma-Glutamyltransferase
PubMed: 33327837
DOI: 10.1089/thy.2020.0715 -
PloS One 2023Arylamine N-acetyltransferase 2 has been related to drug side effects and cancer susceptibility; its protein structure and acetylation capacity results from the...
Arylamine N-acetyltransferase 2 has been related to drug side effects and cancer susceptibility; its protein structure and acetylation capacity results from the polymorphism's arrays on the NAT2 gene. Absorption, distribution, metabolism, and excretion, cornerstones of the pharmacological effects, have shown diversity patterns across populations, ethnic groups, and even interethnic variation. Although the 1000 Genomes Project database has portrayed the global diversity of the NAT2 polymorphisms, several populations and ethnicities remain underrepresented, limiting the comprehensive picture of its variation. The NAT2 clinical entails require a detailed landscape of its striking diversity. This systematic review spans the genetic and acetylation patterns from 164 articles from October 1992 to October 2020. Descriptive studies and controls from observational studies expanded the NAT2 diversity landscape. Our study included 243 different populations and 101 ethnic minorities, and, for the first time, we presented the global patterns in the Middle Eastern populations. Europeans, including its derived populations, and East Asians have been the most studied genetic backgrounds. Contrary to the popular perception, Africans, Latinos and Native Americans have been significantly represented in recent years. NAT2*4, *5B, and *6A were the most frequent haplotypes globally. Nonetheless, the distribution of *5B and *7B were less and more frequent in Asians, respectively. Regarding the acetylator status, East Asians and Native Americans harboured the highest frequencies of the fast phenotype, followed by South Europeans. Central Asia, the Middle East, and West European populations were the major carriers of the slow acetylator status. The detailed panorama presented herein, expands the knowledge about the diversity patterns to genetic and acetylation levels. These data could help clarify the controversial findings between acetylator states and the susceptibility to diseases and reinforce the utility of NAT2 in precision medicine.
Topics: Arylamine N-Acetyltransferase; Acetylation; Polymorphism, Genetic; Haplotypes; Phenotype; Genotype
PubMed: 37023111
DOI: 10.1371/journal.pone.0283726 -
Reviews in Endocrine & Metabolic... Aug 2023Circadian clocks can be traced in nearly all life kingdoms, with the male reproductive system no exception. However, our understanding of the circadian clock in... (Review)
Review
Circadian clocks can be traced in nearly all life kingdoms, with the male reproductive system no exception. However, our understanding of the circadian clock in spermatogenesis seems to fall behind other scenarios. The present review aims to summarize the current knowledge about the role and especially the potential mechanisms of clock genes in spermatogenesis regulation. Accumulating studies have revealed rhythmic oscillation in semen parameters and some physiological events of spermatogenesis. Disturbing the clock gene expression by genetic mutations or environmental changes will also notably damage spermatogenesis. On the other hand, the mechanisms of spermatogenetic regulation by clock genes remain largely unclear. Some recent studies, although not revealing the entire mechanisms, indeed attempted to shed light on this issue. Emerging clues hinted that gonadal hormones, retinoic acid signaling, homologous recombination, and the chromatoid body might be involved in the regulation of spermatogenesis by clock genes. Then we highlight the challenges and the promising directions for future studies so as to stimulate attention to this critical field which has not gained adequate concern.
Topics: Animals; Humans; Male; Spermatogenesis; CLOCK Proteins; Circadian Clocks
PubMed: 36792803
DOI: 10.1007/s11154-022-09783-0 -
International Journal For Vitamin and... Jun 2024According to previous studies, astaxanthin exerts various biological effects due to its anti-inflammatory and antioxidant capabilities; however, its effects on liver... (Meta-Analysis)
Meta-Analysis Review
According to previous studies, astaxanthin exerts various biological effects due to its anti-inflammatory and antioxidant capabilities; however, its effects on liver enzymes have not yet been well elucidated. Therefore, we conducted a meta-analysis to assess astaxanthin's effects on liver enzymes. A systematic literature search was conducted using scientific databases including PubMed, Scopus, Web of Science, the Cochrane databases, and Google Scholar up to February 2023 to find relevant randomized controlled trials (RCTs) examining the effects of astaxanthin supplementation on alanine transaminase (ALT), aspartate transaminase (AST), gamma-glutamyl transferase (GGT), and alkaline phosphatase (ALP). A random-effects model was used for the estimation of the pooled weighted mean difference (WMD). Overall, we included five trials involving 196 subjects. The duration of the intervention was between 4 and 48 weeks, and the dose was between 6 and 12 mg/day. ALT levels increased in the intervention group compared to the control group following astaxanthin supplementation (WMD: 1.92 U/L, 95% CI: 0.16 to 3.68, P=0.03), whereas supplementation with astaxanthin had a non-significant effect on AST (WMD: 0.72 U/L, 95% CI: -0.85 to 2.29, P=0.36), GGT (WMD: 0.48 U/L, 95% CI: -2.71 to 3.67, P=0.76), and ALP levels (WMD: 2.85 U/L, 95% CI: -7.94 to 13.63, P=0.60) compared to the placebo group. Our data showed that astaxanthin supplementation increases ALT concentrations in adults without affecting the levels of other liver enzymes. Further long-term and well-designed RCTs are necessary to assess and confirm these findings.
Topics: Xanthophylls; Humans; Dietary Supplements; Liver; Alanine Transaminase; gamma-Glutamyltransferase; Aspartate Aminotransferases; Alkaline Phosphatase; Randomized Controlled Trials as Topic; Antioxidants
PubMed: 38407143
DOI: 10.1024/0300-9831/a000804 -
Pharmacology & Therapeutics Jun 2021Chronic kidney disease (CKD) is a global health problem with a prevalence of 10-15%. Progressive fibrosis of the renal tissue is a main feature of CKD, but current... (Review)
Review
Chronic kidney disease (CKD) is a global health problem with a prevalence of 10-15%. Progressive fibrosis of the renal tissue is a main feature of CKD, but current treatment strategies are relatively unspecific and delay, but do not prevent, CKD. Exploration of novel pharmacological targets to inhibit fibrosis development are therefore important. Transglutaminase 2 (TG2) is known to be central for extracellular collagenous matrix formation, but TG2 is a multifunctional enzyme and novel research has broadened our view on its extra- and intracellular actions. TG2 exists in two conformational states with different catalytic properties as determined by substrate availability and local calcium concentrations. The open conformation of TG2 depends on calcium and has transamidase activity, central for protein modification and cross-linking of extracellular protein components, while the closed conformation is a GTPase involved in transmembrane signaling processes. We first describe different methodologies to assess TG2 activity in renal tissue and cell cultures such as biotin cadaverine incorporation. Then we systematically review animal CKD models and preliminary studies in humans (with diabetic, IgA- and chronic allograft nephropathy) to reveal the role of TG2 in renal fibrosis. Mechanisms behind TG2 activation, TG2 externalization dependent on Syndecan-4 and interactions between TG and profibrotic molecules including transforming growth factor β and the angiotensin II receptor are discussed. Pharmacological TG2 inhibition shows antifibrotic effects in CKD. However, the translation of TG2 inhibition to treat CKD in patients is a challenge as clinical information is limited, and further studies on pharmacokinetics and efficacy of the individual compounds are required.
Topics: Animals; Fibrosis; Humans; Protein Glutamine gamma Glutamyltransferase 2; Renal Insufficiency, Chronic
PubMed: 33307141
DOI: 10.1016/j.pharmthera.2020.107787 -
European Review For Medical and... Nov 2019This meta-analysis aims to clarify the correlation between N-acetyltransferases 2 (NAT2) polymorphisms and susceptibility of acute leukemia. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
This meta-analysis aims to clarify the correlation between N-acetyltransferases 2 (NAT2) polymorphisms and susceptibility of acute leukemia.
MATERIALS AND METHODS
Articles reporting the correlation between NAT2 polymorphisms and susceptibility of acute leukemia were searched from PubMed, Embase, and Cochrane. Citations in eligible articles were manually reviewed. Only cohort studies and case-control studies which provided odds ratio (OR) and 95% confidence interval (CI) of the correlation between NAT2 polymorphisms and susceptibility of acute leukemia up to December 1st, 2018 were enrolled. The included data were weighted by an inverse variance and analyzed using the fixed-effects or random-effects model. The data acquisition and the heterogeneity test were conducted. STATA 12.0 was used for statistical analysis.
RESULTS
This meta-analysis enrolled 10 independent case-control studies with 1,874 leukemia patients and 2,789 healthy volunteers. No significant difference was found between the fast-acetylator incidence of NAT2 haplotype and the onset risk of acute lymphoblastic leukemia (ALL, OR=0.70, 95% CI=0.45-1.08) or acute myeloid leukemia (AML, OR=0.79, 95% CI=0.46-1.47). The subgroup analysis was conducted based on the sources of controls (SOCs). We did not find statistical difference in population-based (PB) group (OR=0.82, 95% CI=0.47-1.42) and hospital-based (HB) group (OR=0.54, 95% CI=0.27-1.08). In addition, the fast-acetylator incidence of NAT2 haplotype was only observed to be higher in ALL patients compared with HB group (OR=0.52, 95% CI=0.33-0.83), rather than the PB group (OR=0.82, 95% CI=0.47-1.44).
CONCLUSIONS
Except for ALL patients and those hospital-based controls, no evidence has shown the relationship between NAT2 polymorphisms and the susceptibility of acute leukemia. This conclusion still needs to be further verified in multi-center hospital with a large sample size.
Topics: Arylamine N-Acetyltransferase; Genetic Predisposition to Disease; Humans; Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma
PubMed: 31773677
DOI: 10.26355/eurrev_201911_19418 -
Journal of Clinical Medicine Dec 2021High-density lipoprotein (HDL) functional traits have emerged as relevant elements that may explain HDL antiatherogenic capacity better than HDL cholesterol levels.... (Review)
Review
High-density lipoprotein (HDL) functional traits have emerged as relevant elements that may explain HDL antiatherogenic capacity better than HDL cholesterol levels. These properties have been improved in several lifestyle intervention trials. The aim of this systematic review is to summarize the results of such trials of the most commonly used dietary modifications (fatty acids, cholesterol, antioxidants, alcohol, and calorie restriction) and physical activity. Articles were screened from the Medline database until March 2021, and 118 randomized controlled trials were selected. Results from HDL functions and associated functional components were extracted, including cholesterol efflux capacity, cholesteryl ester transfer protein, lecithin-cholesterol acyltransferase, HDL antioxidant capacity, HDL oxidation status, paraoxonase-1 activity, HDL anti-inflammatory and endothelial protection capacity, HDL-associated phospholipase A2, HDL-associated serum amyloid A, and HDL-alpha-1-antitrypsin. In mainly short-term clinical trials, the consumption of monounsaturated and polyunsaturated fatty acids (particularly omega-3 in fish), and dietary antioxidants showed benefits to HDL functionality, especially in subjects with cardiovascular risk factors. In this regard, antioxidant-rich dietary patterns were able to improve HDL function in both healthy individuals and subjects at high cardiovascular risk. In addition, in randomized trial assays performed mainly in healthy individuals, reverse cholesterol transport with ethanol in moderate quantities enhanced HDL function. Nevertheless, the evidence summarized was of unclear quality and short-term nature and presented heterogeneity in lifestyle modifications, trial designs, and biochemical techniques for the assessment of HDL functions. Such findings should therefore be interpreted with caution. Large-scale, long-term, randomized, controlled trials in different populations and individuals with diverse pathologies are warranted.
PubMed: 34945193
DOI: 10.3390/jcm10245897 -
Expert Review of Clinical Pharmacology May 2023Isoniazid (INH) plays an important role in prevention and treatment of tuberculosis (TB). However, large pharmacokinetic (PK) variations are observed in patients...
INTRODUCTION
Isoniazid (INH) plays an important role in prevention and treatment of tuberculosis (TB). However, large pharmacokinetic (PK) variations are observed in patients receiving standard INH dosages. Considering the influence of PK variations on INH efficacy or adverse reactions, we reviewed the population PK studies of INH and explored significant covariates that influence INH PK.
METHODS
The PubMed and Embase databases were systematically searched from their inception to 30 January 2023. PPK studies on INH using a parametric nonlinear mixed-effect approach were included in this review. The characteristics and identified significant covariates of the included studies were summarized.
RESULTS
Twenty-one studies conducted in adults, and seven in pediatrics were included. A two-compartment model with first-order absorption and elimination was the frequently used structural model for INH. NAT2 genotype, body size, and age were identified as significant covariates affecting INH PK variation. The median clearance (CL) value in the fast metabolizers was 2.55-fold higher than that in the slow metabolizers. Infants and children had higher CL per weight values than adults with the same metabolic phenotype. In pediatric patients, CL value increased with postnatal age.
CONCLUSIONS
Compared with slow metabolizers, the daily dose of INH should be increased by 200-600 mg in fast metabolizers. To achieve effective treatment, pediatric patients need a higher dose per kilogram than adults. Further PPK studies of anti-tuberculosis drugs are needed to comprehensively understand the covariates that affect their PK characteristics and to achieve accurate dose adjustments.
Topics: Humans; Child; Isoniazid; Antitubercular Agents; Genotype; Phenotype; Area Under Curve; Arylamine N-Acetyltransferase
PubMed: 36971782
DOI: 10.1080/17512433.2023.2196401