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Journal of Gastroenterology and... May 2021Artificial liver systems are used to bridge between transplantation or to allow a patient's liver to recover. They are used in patients with acute liver failure (ALF)...
Artificial liver systems are used to bridge between transplantation or to allow a patient's liver to recover. They are used in patients with acute liver failure (ALF) and acute-on-chronic liver failure. There are five artificial systems currently in use: molecular adsorbent recirculating system (MARS), single-pass albumin dialysis (SPAD), Prometheus, selective plasma filtration therapy, and hemodiafiltration. The aim is to compare existing data on the efficiency of these devices. A literature search was conducted using online libraries. Inclusion criteria included randomized control trials or comparative human studies published after the year 2000. A systematic review was conducted for the five individual devices with a more detailed comparison of the biochemistry for the SPAD and MARS systems. Eighty-nine patients were involved in the review comparing SPAD and MARS. Results showed that there was an average reduction in bilirubin (-53 μmol/L in MARS and -50 μmol/L in SPAD), creatinine (-19.5 μmol/L in MARS and -7.5 μmol/L in SPAD), urea (-0.9 mmol/L in MARS and -0.75 mmol/L in SPAD), and gamma-glutamyl transferase (-0.215 μmol/L·s in MARS and -0.295 μmol/L·s in SPAD) in both SPAD and MARS. However, there was no significant difference between the changes in the two systems. This review demonstrated that both MARS and SPAD aid recovery of ALF. There is no difference between the efficiency of MARS and SPAD. Because of the limited data, there is a need for more randomized control trials. Evaluating cost and patient preference would aid in differentiating the systems.
Topics: Acute-On-Chronic Liver Failure; Bilirubin; Creatinine; Dialysis; Female; Hemodiafiltration; Humans; Liver Failure, Acute; Liver, Artificial; Male; Sorption Detoxification; Treatment Outcome; Urea; gamma-Glutamyltransferase
PubMed: 32918840
DOI: 10.1111/jgh.15255 -
International Journal of Molecular... May 2023Heart failure (HF) is a progressive chronic disease that remains a primary cause of death worldwide, affecting over 64 million patients. HF can be caused by... (Review)
Review
Heart failure (HF) is a progressive chronic disease that remains a primary cause of death worldwide, affecting over 64 million patients. HF can be caused by cardiomyopathies and congenital cardiac defects with monogenic etiology. The number of genes and monogenic disorders linked to development of cardiac defects is constantly growing and includes inherited metabolic disorders (IMDs). Several IMDs affecting various metabolic pathways have been reported presenting cardiomyopathies and cardiac defects. Considering the pivotal role of sugar metabolism in cardiac tissue, including energy production, nucleic acid synthesis and glycosylation, it is not surprising that an increasing number of IMDs linked to carbohydrate metabolism are described with cardiac manifestations. In this systematic review, we offer a comprehensive overview of IMDs linked to carbohydrate metabolism presenting that present with cardiomyopathies, arrhythmogenic disorders and/or structural cardiac defects. We identified 58 IMDs presenting with cardiac complications: 3 defects of sugar/sugar-linked transporters (GLUT3, GLUT10, THTR1); 2 disorders of the pentose phosphate pathway (G6PDH, TALDO); 9 diseases of glycogen metabolism (GAA, GBE1, GDE, GYG1, GYS1, LAMP2, RBCK1, PRKAG2, G6PT1); 29 congenital disorders of glycosylation (ALG3, ALG6, ALG9, ALG12, ATP6V1A, ATP6V1E1, B3GALTL, B3GAT3, COG1, COG7, DOLK, DPM3, FKRP, FKTN, GMPPB, MPDU1, NPL, PGM1, PIGA, PIGL, PIGN, PIGO, PIGT, PIGV, PMM2, POMT1, POMT2, SRD5A3, XYLT2); 15 carbohydrate-linked lysosomal storage diseases (CTSA, GBA1, GLA, GLB1, HEXB, IDUA, IDS, SGSH, NAGLU, HGSNAT, GNS, GALNS, ARSB, GUSB, ARSK). With this systematic review we aim to raise awareness about the cardiac presentations in carbohydrate-linked IMDs and draw attention to carbohydrate-linked pathogenic mechanisms that may underlie cardiac complications.
Topics: Humans; Cardiomyopathies; Metabolic Diseases; Heart Defects, Congenital; Glycosylation; Carbohydrates; Sugars; Chondroitinsulfatases; Pentosyltransferases; Mannosyltransferases; Acetyltransferases
PubMed: 37239976
DOI: 10.3390/ijms24108632 -
Annals of Hepatology 2022We performed a systematic review and meta-analysis to evaluate the prevalence of concomitant Sjögren's syndrome (SS) with primary biliary cholangitis (PBC) in adults... (Meta-Analysis)
Meta-Analysis
INTRODUCTION AND OBJECTIVES
We performed a systematic review and meta-analysis to evaluate the prevalence of concomitant Sjögren's syndrome (SS) with primary biliary cholangitis (PBC) in adults and quantify the impact of SS on PBC.
METHODS
PubMed, Web of Science and Cochrane library were searched using subject terms and predefined inclusion and exclusion criteria.
RESULTS
Seventeen articles were included. The prevalence of SS in PBC patients ranged from 3.5 to 73% (35% pooled) (95% CI: 28-41%; p < 0.01). Seven studies included various biochemical indicators, including alanine transaminase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), γ-glutamyltransferase (γ-GT), total bilirubin (TBiL), albumin (ALB) and platelet (PLT), and immunological indexes including IgG, IgM, antinuclear antibody (ANA), anti-mitochondrial antibody (AMA), AMA-M2 and anti-Ro/Sjögren's syndrome antigen A (SSA) antibodies. Meta-analysis showed that there were no significant differences in ALT, AST, ALP, γ-GT, TBiL and IgM levels between PBS and PBC with SS. Pooled analysis showed that ALB (MD=0.82; 95% CI: 0.08-1.56) and PLT (MD=30.41; 95% CI: 10.16-50.66) levels were lower, IgG levels (MD=-1.55; 95% CI: -2.39 to -0.72) were higher, and the positive ratios of ANA (RR=0.92; 95% CI: 0.87-0.98), AMA (RR=0.94; 95% CI: 0.89-0.98), AMA-M2 (RR=0.77; 95% CI: 0.70-0.85) and anti-Ro/SSA antibodies (RR=0.29; 95% CI: 0.08-1.01) were significantly higher in PBC patients with SS than in PBC patients.
CONCLUSIONS
Our study confirms that SS is common in PBC. Comorbid SS appears to influence the clinical phenotype of PBC and may therefore influence the management of PBC.
Topics: Humans; Sjogren's Syndrome; Liver Cirrhosis, Biliary; Autoantibodies; Prevalence; Antibodies, Antinuclear; gamma-Glutamyltransferase; Alkaline Phosphatase; Alanine Transaminase; Immunoglobulin M; Immunoglobulin G
PubMed: 35970319
DOI: 10.1016/j.aohep.2022.100746 -
Pathology, Research and Practice Jan 2023LncRNAs have the potential to play a regulatory role in different processes of cancer development and progression. We conducted a systematic review and meta-analysis of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
LncRNAs have the potential to play a regulatory role in different processes of cancer development and progression. We conducted a systematic review and meta-analysis of evidence on the clinical significance and prognostic value of lncRNA CERS6-AS1 in cancer.
METHODS
This systematic review was conducted following PRISMA guidelines. Medline and Embase databases were searched using the relevant key terms covering lncRNA CERS6-AS1 and cancer. We pooled the estimated effect sizes and their 95 % confidence interval (CI) using random-effects models in STATA 16.0 (StataCorp, College Station, TX, USA).
RESULTS
Eleven articles on pancreatic, colorectal, gastric, papillary thyroid, breast, and hepatocellular cancers fulfilled our eligibility criteria. Studies consistently found that lncRNA CERS6-AS1 expression is upregulated in all assessed cancers. Based on our meta-analysis, its aberrant expression was directly associated with unfavorable clinical outcomes, including higher stage (pooled Odds ratios (95 % CI): 3.15 (2.01-4.93; I = 0.0 %), tumor size (1.97 (1.27-3.05; I = 37.8 %), lymph node metastasis (6.48 (4.01-10.45; I = 0.40 %), and poor survival (Pooled log-rank test P-value < 0.001) in patients. Regarding potential mechanisms, functional studies revealed that LncRNA CERS6-AS1 is involved in cancer growth mainly by sponging miRNAs and regulating their downstream targets.
CONCLUSION
Available evidence suggests that LncRNA CERS6-AS1 is upregulated in different cancers and has an oncogenic role. LncRNA CERS6-AS1 expression level might predict cancer prognosis, highlighting its potential application as a prognostic biomarker for cancer.
Topics: Humans; RNA, Long Noncoding; MicroRNAs; Prognosis; Liver Neoplasms; Lymphatic Metastasis; Gene Expression Regulation, Neoplastic; Membrane Proteins; Sphingosine N-Acyltransferase
PubMed: 36580796
DOI: 10.1016/j.prp.2022.154245 -
Clinical Therapeutics Nov 2020This systematic review and meta-analysis assesses the pharmacokinetic (PK) summary estimates of isoniazid (INH) between healthy volunteers and patients with tuberculosis... (Meta-Analysis)
Meta-Analysis
PURPOSE
This systematic review and meta-analysis assesses the pharmacokinetic (PK) summary estimates of isoniazid (INH) between healthy volunteers and patients with tuberculosis (TB), evaluates whether the current INH dose regimen is appropriate in patients with TB, and evaluates the impact of N-acetyl-transferase-2 (NAT2) status on the PK properties of INH.
METHODS
A systematic approach was conducted to find studies with relevant INH PK data published in the English language up to February 2018. The PK properties of INH were extracted with their respective INH dosages and were dose normalized to allow a fair comparison between healthy volunteers and patients with TB. Meta-analysis was then performed for the C and AUC estimates for all INH dosages.
FINDINGS
Ninety studies were included in this systematic review. TB status significantly affected the INH C and AUC estimates. In healthy volunteers, the dose-normalized INH C and AUC were statistically higher than those of patients with TB. No significant differences were found in dose-normalized C and AUC between adults with TB and adults with TB/HIV; however, the AUC in pediatric patients was significantly different between patients with TB and patients with TB/HIV. In addition, no significance was observed comparing the dose-normalized C and AUC of pediatric patients with TB and TB/HIV with their respective adult counterparts. Dose-normalized INH C and AUC in patients with fast and intermediate NAT2 were significantly lower than in patients with slow NAT2.
IMPLICATIONS
The current recommended dosages of INH were found to produce less drug exposure in patients with TB when compared with healthy volunteers. NAT2 polymorphism greatly impacts the PK properties of INH; hence, testing for acetylator status is highly recommended, and therapeutic drug monitoring would help reduce INH toxicity.
Topics: Adult; Antitubercular Agents; Arylamine N-Acetyltransferase; Drug Monitoring; Humans; Isoniazid; Tuberculosis
PubMed: 33032843
DOI: 10.1016/j.clinthera.2020.09.009 -
Journal of Lipid Research Mar 2022Syndromes associated with LCAT deficiency, a rare autosomal recessive condition, include fish-eye disease (FED) and familial LCAT deficiency (FLD). FLD is more severe... (Review)
Review
Syndromes associated with LCAT deficiency, a rare autosomal recessive condition, include fish-eye disease (FED) and familial LCAT deficiency (FLD). FLD is more severe and characterized by early and progressive chronic kidney disease (CKD). No treatment is currently available for FLD, but novel therapeutics are under development. Furthermore, although biomarkers of LCAT deficiency have been identified, their suitability to monitor disease progression and therapeutic efficacy is unclear, as little data exist on the rate of progression of renal disease. Here, we systematically review observational studies of FLD, FED, and heterozygous subjects, which summarize available evidence on the natural history and biomarkers of LCAT deficiency, in order to guide the development of novel therapeutics. We identified 146 FLD and 53 FED patients from 219 publications, showing that both syndromes are characterized by early corneal opacity and markedly reduced HDL-C levels. Proteinuria/hematuria were the first signs of renal impairment in FLD, followed by rapid decline of renal function. Furthermore, LCAT activity toward endogenous substrates and the percentage of circulating esterified cholesterol (EC%) were the best discriminators between these two syndromes. In FLD, higher levels of total, non-HDL, and unesterified cholesterol were associated with severe CKD. We reveal a nonlinear association between LCAT activity and EC% levels, in which subnormal levels of LCAT activity were associated with normal EC%. This review provides the first step toward the identification of disease biomarkers to be used in clinical trials and suggests that restoring LCAT activity to subnormal levels may be sufficient to prevent renal disease progression.
Topics: Humans; Biomarkers; Heterozygote; Lecithin Cholesterol Acyltransferase Deficiency; Mutation; Phosphatidylcholine-Sterol O-Acyltransferase
PubMed: 35065092
DOI: 10.1016/j.jlr.2022.100169 -
Gastroenterology Sep 2020There is controversy over the association between celiac disease (CeD) and inflammatory bowel diseases (IBD). We performed a systematic review and meta-analysis to... (Meta-Analysis)
Meta-Analysis
BACKGROUND & AIMS
There is controversy over the association between celiac disease (CeD) and inflammatory bowel diseases (IBD). We performed a systematic review and meta-analysis to assess evidence for an association between CeD and IBD.
METHODS
We searched databases including MEDLINE, EMBASE, CENTRAL, Web of Science, CINAHL, DARE, and SIGLE through June 25, 2019 for studies assessing the risk of CeD in patients with IBD, and IBD in patients with CeD, compared with controls of any type. We used the Newcastle-Ottawa Scale to evaluate the risk of bias and GRADE to assess the certainty of the evidence.
RESULTS
We identified 9791 studies and included 65 studies in our analysis. Moderate certainty evidence found an increased risk of CeD in patients with IBD vs controls (risk ratio [RR] 3.96; 95% confidence interval [CI] 2.23-7.02) and increased risk of IBD in patients with CeD vs controls (RR 9.88; 95% CI 4.03-24.21). There was low-certainty evidence for the risk of anti-Saccharomyces antibodies, a serologic marker of IBD, in patients with CeD vs controls (RR 6.22; 95% CI 2.44-15.84). There was low-certainty evidence for no difference in risk of HLA-DQ2 or DQ8 in patients with IBD vs controls (RR 1.04; 95% CI 0.42-2.56), and very low-certainty evidence for an increased risk of anti-tissue transglutaminase in patients with IBD vs controls (RR 1.52; 95% CI 0.52-4.40). Patients with IBD had a slight decrease in risk of anti-endomysial antibodies vs controls (RR 0.70; 95% CI 0.18-2.74), but these results are uncertain.
CONCLUSIONS
In a systematic review and meta-analysis, we found an increased risk of IBD in patients with CeD and increased risk of CeD in patients with IBD, compared with other patient populations. High-quality prospective cohort studies are needed to assess the risk of CeD-specific and IBD-specific biomarkers in patients with IBD and CeD.
Topics: Autoantibodies; Case-Control Studies; Celiac Disease; Colitis, Ulcerative; Crohn Disease; GTP-Binding Proteins; Humans; Immunoglobulin A; Intestinal Mucosa; Prevalence; Protein Glutamine gamma Glutamyltransferase 2; Risk Factors; Saccharomyces; Transglutaminases
PubMed: 32416141
DOI: 10.1053/j.gastro.2020.05.016 -
Orphanet Journal of Rare Diseases Oct 2020N-Acetylglutamate synthase (NAGS) deficiency is an extremely rare autosomal recessive metabolic disorder affecting the urea cycle, leading to episodes of hyperammonemia... (Review)
Review
BACKGROUND
N-Acetylglutamate synthase (NAGS) deficiency is an extremely rare autosomal recessive metabolic disorder affecting the urea cycle, leading to episodes of hyperammonemia which can cause significant morbidity and mortality. Since its recognition in 1981, NAGS deficiency has been treated with carbamylglutamate with or without other measures (nutritional, ammonia scavengers, dialytic, etc.). We conducted a systematic literature review of NAGS deficiency to summarize current knowledge around presentation and management.
METHODS
Case reports and case series were identified using the Medline database, as well as references from other articles and a general internet search. Clinical data related to presentation and management were abstracted by two reviewers.
RESULTS
In total, 98 cases of NAGS deficiency from 79 families, in 48 articles or abstracts were identified. Of these, 1 was diagnosed prenatally, 57 were neonatal cases, 34 were post-neonatal, and 6 did not specify age at presentation or were asymptomatic at diagnosis. Twenty-one cases had relevant family history. We summarize triggers of hyperammonemic episodes, diagnosis, clinical signs and symptoms, and management strategies. DNA testing is the preferred method of diagnosis, although therapeutic trials to assess response of ammonia levels to carbamylglutamate may also be helpful. Management usually consists of treatment with carbamylglutamate, although the reported maintenance dose varied across case reports. Protein restriction was sometimes used in conjunction with carbamylglutamate. Supplementation with citrulline, arginine, and sodium benzoate also were reported.
CONCLUSIONS
Presentation of NAGS deficiency varies by age and symptoms. In addition, both diagnosis and management have evolved over time and vary across clinics. Prompt recognition and appropriate treatment of NAGS deficiency with carbamylglutamate may improve outcomes of affected individuals. Further research is needed to assess the roles of protein restriction and supplements in the treatment of NAGS deficiency, especially during times of illness or lack of access to carbamylglutamate.
Topics: Amino-Acid N-Acetyltransferase; Ammonia; Humans; Hyperammonemia; Infant, Newborn; Urea Cycle Disorders, Inborn
PubMed: 33036647
DOI: 10.1186/s13023-020-01560-z -
International Journal For Vitamin and... Jun 2024To conduct a systematic review and dose-response meta-analysis of current findings from randomized controlled trials (RCTs) on the effect of soluble fiber... (Meta-Analysis)
Meta-Analysis Review
To conduct a systematic review and dose-response meta-analysis of current findings from randomized controlled trials (RCTs) on the effect of soluble fiber supplementation on liver function in both healthy individuals and people with specific health conditions, PubMed, Scopus, and ISI Web of Science were systematically searched for relevant RCTs published prior to April 2022. We estimated the change in liver function parameters for each 5 g/d increment in soluble fiber in each trial and then calculated the mean difference (MD) and 95%CI. A total of 25 RCTs with 27 treatment arms (1744 subjects; 884 cases, 860 controls) were included. A total of 25 RCTs with 27 treatment arms were included. The intervention duration of the included studies ranged from 3 to 52 weeks and the dose of soluble fiber supplementation varied from 0.0025 to 40 g/d. Soluble fiber supplementation could not significantly affect serum alanine transaminase (MD: -0.02 U/L, 95% CI: -1.06 to 1.01), aspartate transaminase (MD: -0.34 U/L, 95% CI: -0.84 to 0.15), alkaline phosphatase (MD: 0.29 U/L, -0.14 to 0.71), gamma-glutamyl transferase (MD: 0.12 U/L; 95% CI: -0.81 to 1.05), serum bilirubin (MD: 0.42μmol/L, 95% CI: -0.08 to 0.93) and albumin (MD: 0.64 g/dl, 95% CI: -0.42 to 1.70) levels. Findings from this study did not support the beneficial effects of soluble fiber supplementation on liver function biomarkers. There is a need for long-term high-quality interventions to examine the effects of different types and doses of soluble fibers on liver function as primary outcome.
Topics: Humans; Dietary Fiber; Liver; Aspartate Aminotransferases; Alanine Transaminase; Dietary Supplements; Randomized Controlled Trials as Topic; Alkaline Phosphatase; Liver Function Tests; gamma-Glutamyltransferase; Bilirubin
PubMed: 38044659
DOI: 10.1024/0300-9831/a000800 -
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