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Canadian Liver Journal May 2024Curcumin is an anti-inflammatory that is proposed to have a positive impact on patients with non-alcoholic fatty liver disease (NAFLD). We aim to assess the effects of...
BACKGROUND
Curcumin is an anti-inflammatory that is proposed to have a positive impact on patients with non-alcoholic fatty liver disease (NAFLD). We aim to assess the effects of curcumin in patients with NAFLD.
METHODS
Clinical trials from PubMed, Scopus, the Web of Science, and Cochrane CENTRAL with variables alanine transferase, aspartate transaminase, alkaline phosphatase, glycated hemoglobin (HBA1c), BMI, waist circumference, total cholesterol, total glycerides, high-density lipoproteins, and low-density lipoproteins were included. Homogeneous and heterogeneous were analyzed under a fixed-effects model and the random-effects model, respectively.
RESULTS
Fourteen clinical trials found that curcumin has no statistically significant effect on alanine transferase (MD = -2.20 [-6.03, 1.63], = 0.26], aspartate transaminase (MD = 1.37 [-4.56, 1.81], = 0.4), alkaline phosphatase (MD = 3.06 [-15.85, 9.73], = 0.64), glycated hemoglobin (HBA1c), (MD = -0.06 [-0.13, 0.02], = 0.16], and BMI (MD = 0.04 [-0.38, 0.46], = 0.86). Curcumin reduced the waist circumference (MD = -4.87 [-8.50, -1.25], = 0.008). Lipid profile parameters were not significant, except the total glycerides (MD = -13.22 [-24.19, -2.24], = 0.02).
CONCLUSIONS
Curcumin significantly reduces total glycerides and waist circumference in NAFLD.
PubMed: 38746865
DOI: 10.3138/canlivj-2023-0022 -
Photodiagnosis and Photodynamic Therapy Jun 2024Protoporphyrin IX (PPIX) is the final precursor of heme, forming heme when iron is inserted. Individuals with erythropoietic protoporphyrias (EPP) have accumulation of... (Review)
Review
BACKGROUND
Protoporphyrin IX (PPIX) is the final precursor of heme, forming heme when iron is inserted. Individuals with erythropoietic protoporphyrias (EPP) have accumulation of PPIX, causing photosensitivity and increased liver disease risk. Many also have iron deficiency and anemia. We investigated outcomes of oral iron supplements in individuals with EPP.
METHODS
A systematic review identified literature on oral iron supplements in EPP patients. Subsequently, we administered iron supplements to EPP patients with iron deficiency. The primary outcome was impact on PPIX level. Secondary outcomes were adverse events and relative differences in hemoglobin and iron parameters.
RESULTS
The systematic review found 13 case reports and one uncontrolled clinical trial with uncertain results. From our department 10 patients with EPP and iron deficiency took daily dosages of 330 mg of ferrous fumarate for two months. Five of our patients had anemia at baseline. After 2 months of supplementation seven patients had increased PPIX level compared to baseline, two had decrease, one remained unchanged. The administration of iron led to a rise in ferritin, and in four of the anemic patients also to an improvement in blood hemoglobin. A small transiently elevation in plasma alanine transaminase concentration was observed during supplementation.
CONCLUSIONS
Overall, iron supplementation in EPP patients replenished iron stores and elevated erythrocyte PPIX and plasma alanine transaminase. For anemic patients, there was some degree of normalization of the hemoglobin level. If iron therapy is needed for EPP patients, monitoring of photosensitivity, PPIX, hemoglobin, and plasma liver enzymes is advisable.
Topics: Humans; Protoporphyria, Erythropoietic; Protoporphyrins; Dietary Supplements; Male; Female; Adult; Iron; Anemia, Iron-Deficiency; Middle Aged; Treatment Outcome
PubMed: 38734198
DOI: 10.1016/j.pdpdt.2024.104211 -
Translational Gastroenterology and... 2024Local ischemic preconditioning (LIPC) has been proven to be a protective strategy against hepatic ischemia-reperfusion injury (HIRI) during hepatectomy. Growing evidence...
Comparing the protective effects of local and remote ischemic preconditioning against ischemia-reperfusion injury in hepatectomy: a systematic review and network meta-analysis.
BACKGROUND
Local ischemic preconditioning (LIPC) has been proven to be a protective strategy against hepatic ischemia-reperfusion injury (HIRI) during hepatectomy. Growing evidence suggests remote ischemic preconditioning (RIPC) has the potential to reduce liver injury in hepatectomy. Few studies have directly compared the protective effects of these two mechanical preconditioning strategies. Therefore, we performed a network meta-analysis to compare the efficacy of LIPC and RIPC for hepatic injury during liver resection.
METHODS
We searched Cochrane, PubMed, Embase, and China National Knowledge Infrastructure (CNKI) from the database inception to January 2023. We included studies directly comparing the effectiveness of LIPC and RIPC and those comparing LIPC or RIPC with no-preconditioning in liver resection. Postoperative liver function and surgical events were analyzed. Data were expressed as standardized mean differences (SMDs) or odds ratios (ORs) and analyzed using network meta-analysis with random effects model.
RESULTS
Following the screening of 268 citations, we identified 26 eligible randomized clinical trials (RCTs) involving 1,476 participants (LIPC arm: 789, RIPC arm: 859, no-preconditioning arm: 1,072). LIPC and RIPC were superior to no-preconditioning in reducing postoperative serum transaminase levels [aspartate aminotransferase (AST): SMD RIPC versus no-preconditioning: -2.05, 95% confidence interval (CI): -3.39, -0.71; SMD LIPC versus no-preconditioning: -1.10, 95% CI: -2.07, -0.12; alanine aminotransferase (ALT): SMD RIPC versus no-preconditioning: -2.24, 95% CI: -4.15, -0.32; SMD LIPC versus no-preconditioning: -1.32, 95% CI: -2.63, -0.01]. No significant difference was observed between RIPC and LIPC in postoperative liver function and surgical outcomes (AST: SMD RIPC versus LIPC: -0.95, 95% CI: -2.52, 0.62; ALT: SMD RIPC versus LIPC: -0.91, 95% CI: -3.11, 1.28). In addition, the subgroup analysis revealed the potential benefits of RIPC in improving liver function, especially in patients who diagnosed with cirrhosis or underwent major resection.
CONCLUSIONS
RIPC and LIPC could serve as effective strategies in relieving HIRI during hepatectomy. No significant differences were observed between LIPC and RIPC, however, RIPC may be an easily applicable strategy to relieve liver injury in hepatectomy.
PubMed: 38716220
DOI: 10.21037/tgh-23-95 -
Neurobiology of Disease Jul 2024Autism spectrum disorder (ASD) is a neurodevelopmental disorder affecting 1 in 36 children and is associated with physiological abnormalities, most notably mitochondrial... (Meta-Analysis)
Meta-Analysis
Autism spectrum disorder (ASD) is a neurodevelopmental disorder affecting 1 in 36 children and is associated with physiological abnormalities, most notably mitochondrial dysfunction, at least in a subset of individuals. This systematic review and meta-analysis discovered 204 relevant articles which evaluated biomarkers of mitochondrial dysfunction in ASD individuals. Significant elevations (all p < 0.01) in the prevalence of lactate (17%), pyruvate (41%), alanine (15%) and creatine kinase (9%) were found in ASD. Individuals with ASD had significant differences (all p < 0.01) with moderate to large effect sizes (Cohen's d' ≥ 0.6) compared to controls in mean pyruvate, lactate-to-pyruvate ratio, ATP, and creatine kinase. Some studies found abnormal TCA cycle metabolites associated with ASD. Thirteen controlled studies reported mitochondrial DNA (mtDNA) deletions or variations in the ASD group in blood, peripheral blood mononuclear cells, lymphocytes, leucocytes, granulocytes, and brain. Meta-analyses discovered significant differences (p < 0.01) in copy number of mtDNA overall and in ND1, ND4 and CytB genes. Four studies linked specific mtDNA haplogroups to ASD. A series of studies found a subgroup of ASD with elevated mitochondrial respiration which was associated with increased sensitivity of the mitochondria to physiological stressors and neurodevelopmental regression. Lactate, pyruvate, lactate-to-pyruvate ratio, carnitine, and acyl-carnitines were associated with clinical features such as delays in language, social interaction, cognition, motor skills, and with repetitive behaviors and gastrointestinal symptoms, although not all studies found an association. Lactate, carnitine, acyl-carnitines, ATP, CoQ10, as well as mtDNA variants, heteroplasmy, haplogroups and copy number were associated with ASD severity. Variability was found across biomarker studies primarily due to differences in collection and processing techniques as well as the intrinsic heterogeneity of the ASD population. Several studies reported alterations in mitochondrial metabolism in mothers of children with ASD and in neonates who develop ASD. Treatments targeting mitochondria, particularly carnitine and ubiquinol, appear beneficial in ASD. The link between mitochondrial dysfunction in ASD and common physiological abnormalities in individuals with ASD including gastrointestinal disorders, oxidative stress, and immune dysfunction is outlined. Several subtypes of mitochondrial dysfunction in ASD are discussed, including one related to neurodevelopmental regression, another related to alterations in microbiome metabolites, and another related to elevations in acyl-carnitines. Mechanisms linking abnormal mitochondrial function with alterations in prenatal brain development and postnatal brain function are outlined. Given the multisystem complexity of some individuals with ASD, this review presents evidence for the mitochondria being central to ASD by contributing to abnormalities in brain development, cognition, and comorbidities such as immune and gastrointestinal dysfunction as well as neurodevelopmental regression. A diagnostic approach to identify mitochondrial dysfunction in ASD is outlined. From this evidence, it is clear that many individuals with ASD have alterations in mitochondrial function which may need to be addressed in order to achieve optimal clinical outcomes. The fact that alterations in mitochondrial metabolism may be found during pregnancy and early in the life of individuals who eventually develop ASD provides promise for early life predictive biomarkers of ASD. Further studies may improve the understanding of the role of the mitochondria in ASD by better defining subgroups and understanding the molecular mechanisms driving some of the unique changes found in mitochondrial function in those with ASD.
Topics: Humans; Autism Spectrum Disorder; Biomarkers; DNA, Mitochondrial; Mitochondria; Mitochondrial Diseases
PubMed: 38703861
DOI: 10.1016/j.nbd.2024.106520 -
Clinics and Research in Hepatology and... Jun 2024Non-alcoholic steatohepatitis (NASH) is an advanced subtype of non-alcoholic fatty liver disease (NAFLD). NASH prevalence is increasing exponentially and carries a high... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Non-alcoholic steatohepatitis (NASH) is an advanced subtype of non-alcoholic fatty liver disease (NAFLD). NASH prevalence is increasing exponentially and carries a high risk for disease progression, cirrhosis, and liver-related mortality. Aldafermin, a fibroblast growth factor 19 (FGF19) analog, is one of the evolving therapeutic agents with the potential to regulate multiple pathways involved in the pathogenesis of NASH. We aimed to investigate the efficacy and safety of aldafermin in patients with NASH.
METHODS
PubMed, Scopus, Cochrane Library, and Web of Science were searched till November 2023 to identify eligible randomized controlled trials (RCTs). Continuous data were pooled as mean difference (MD), while dichotomous data were pooled as risk ratios (RR) with a 95 % confidence interval. A subgroup meta-analysis was conducted to evaluate the efficacy of the two doses (1 mg and 3 mg) of aldafermin.
RESULTS
Four RCTs with a total of 491 patients were included. Aldafermin showed a dose-dependent improvement in the ≥30 % reduction in the liver fat content (RR: 2.16, 95 % CI [1.41 to 3.32]) and (RR: 5.00, 95 % CI [1.34 to 18.64]), alanine aminotransferase levels (MD: -19.79, 95 % CI [-30.28 to -9.3]) and (MD: -21.91, 95 % CI [-29.62 to -14.21]), aspartate aminotransferase levels (MD: -11.79, 95 % CI [-18.06 to -5.51]) and (MD: -13.9, 95 % CI [-18.59 to -9.21]), and enhanced liver fibrosis score (ELF) (MD: -0.13, 95 % CI [-0.29 to 0.02]) and (MD: -0.33, 95 % CI [-0.50 to -0.17]), in the 1 mg and 3 mg subgroups respectively. No significant differences were detected in the aldafermin group regarding histologic endpoints, lipid profile, metabolic parameters, and overall adverse effects, except for the increased occurrence of diarrhea in the aldafermin 3 mg subgroup.
CONCLUSION
Aldafermin is a promising well-tolerated therapeutic agent for NASH with evidence supporting its ability to reduce liver fat content, fibrosis serum biomarkers, and liver enzymes. However, its effectiveness in improving histologic fibrosis, while showing numerical trends, still lacks statistical significance. Larger and longer NASH trials are warranted to enhance the robustness of the evidence.
Topics: Humans; Non-alcoholic Fatty Liver Disease; Randomized Controlled Trials as Topic; Treatment Outcome; Fibroblast Growth Factors; Propionates; Chalcones
PubMed: 38688423
DOI: 10.1016/j.clinre.2024.102357 -
Obesity Science & Practice Jun 2024Overall, there is conflicting evidence regarding the beneficial effects of optimal lifestyle modification, particularly weight loss interventions, with nonalcoholic... (Review)
Review
BACKGROUND
Overall, there is conflicting evidence regarding the beneficial effects of optimal lifestyle modification, particularly weight loss interventions, with nonalcoholic fatty liver disease (non-alcoholic fatty liver disease (NAFLD)). Therefore, this study investigated the effects of weight loss interventions on laboratory and clinical parameters in children and adolescents with NAFLD.
METHODS
Original databases (PubMed/MEDLINE, Web of Science, SCOPUS, and Embase) were searched using standard keywords to identify all controlled trials investigating the effects of weight loss interventions among NAFLD children and adolescents. Pooled weighted mean difference and 95% confidence intervals were achieved by random-effects model analysis.
RESULTS
Eighteen eligible clinical trials were included in this systematic review and meta-analysis. The pooled findings showed that especially more intense weight loss interventions significantly reduced the glucose ( = 0.007), insulin ( = 0.002), homeostatic model assessment-insulin resistance (HOMA-IR) ( = 0.003), weight ( = 0.025), body mass index (BMI) ( = 0.003), BMI -score ( < 0.001), waist circumference (WC) ( = 0.013), triglyceride (TG) ( = 0.001), and aspartate transaminase (AST) ( = 0.027). However, no significant changes were found in total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), alanine transaminase (ALT), and hepatic steatosis grades (all > 0.05) following weight loss interventions.
CONCLUSIONS
Weight loss interventions had significant effects on NAFLD-related parameters including glucose, insulin, HOMA-IR, weight, BMI, BMI z-score, WC, TG, and AST.
PubMed: 38682153
DOI: 10.1002/osp4.758 -
Nutrients Apr 2024Alcoholic Fatty Liver Disease (AFLD) is characterized by the accumulation of lipids in liver cells owing to the metabolism of ethanol. This process leads to a decrease... (Meta-Analysis)
Meta-Analysis
Alcoholic Fatty Liver Disease (AFLD) is characterized by the accumulation of lipids in liver cells owing to the metabolism of ethanol. This process leads to a decrease in the NAD/NADH ratio and the generation of reactive oxygen species. A systematic review and meta-analysis were conducted to investigate the role of oxidative stress in AFLD. A total of 201 eligible manuscripts were included, which revealed that animals with AFLD exhibited elevated expression of CYP2E1, decreased enzymatic activity of antioxidant enzymes, and reduced levels of the transcription factor Nrf2, which plays a pivotal role in the synthesis of antioxidant enzymes. Furthermore, animals with AFLD exhibited increased levels of lipid peroxidation markers and carbonylated proteins, collectively contributing to a weakened antioxidant defense and increased oxidative damage. The liver damage in AFLD was supported by significantly higher activity of alanine and aspartate aminotransferase enzymes. Moreover, animals with AFLD had increased levels of triacylglycerol in the serum and liver, likely due to reduced fatty acid metabolism caused by decreased PPAR-α expression, which is responsible for fatty acid oxidation, and increased expression of SREBP-1c, which is involved in fatty acid synthesis. With regard to inflammation, animals with AFLD exhibited elevated levels of pro-inflammatory cytokines, including TNF-a, IL-1β, and IL-6. The heightened oxidative stress, along with inflammation, led to an upregulation of cell death markers, such as caspase-3, and an increased Bax/Bcl-2 ratio. Overall, the findings of the review and meta-analysis indicate that ethanol metabolism reduces important markers of antioxidant defense while increasing inflammatory and apoptotic markers, thereby contributing to the development of AFLD.
Topics: Animals; Humans; Antioxidants; Cytochrome P-450 CYP2E1; Cytokines; Disease Models, Animal; Fatty Liver, Alcoholic; Lipid Peroxidation; Liver; NF-E2-Related Factor 2; Oxidative Stress; Reactive Oxygen Species
PubMed: 38674865
DOI: 10.3390/nu16081174 -
Cancer Medicine Apr 2024Thyroid cancer (TC) is the predominant malignancy within the endocrine system. However, the standard method for TC diagnosis lacks the capability to identify the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Thyroid cancer (TC) is the predominant malignancy within the endocrine system. However, the standard method for TC diagnosis lacks the capability to identify the pathological condition of all thyroid lesions. The metabolomics approach has the potential to manage this problem by identifying differential metabolites.
AIMS
This study conducted a systematic review and meta-analysis of the NMR-based metabolomics studies in order to identify significant altered metabolites associated with TC.
METHODS
A systematic search of published literature in any language in three databases including Embase, PubMed, and Scopus was conducted. Out of 353 primary articles, 12 studies met the criteria for inclusion in the systematic review. Among these, five reports belonging to three articles were eligible for meta-analysis. The correlation coefficient of the orthogonal partial least squares discriminant analysis, a popular model in the multivariate statistical analysis of metabolomic data, was chosen for meta-analysis. The altered metabolites were chosen based on the fact that they had been found in at least three studies.
RESULTS
In total, 49 compounds were identified, 40 of which were metabolites. The increased metabolites in thyroid lesions compared normal samples included lactate, taurine, alanine, glutamic acid, glutamine, leucine, lysine, phenylalanine, serine, tyrosine, valine, choline, glycine, and isoleucine. Lipids were the decreased compounds in thyroid lesions. Lactate and alanine were increased in malignant versus benign thyroid lesions, while, myo-inositol, scyllo-inositol, citrate, choline, and phosphocholine were found to be decreased. The meta-analysis yielded significant results for three metabolites of lactate, alanine, and citrate in malignant versus benign specimens.
DISCUSSION
In this study, we provided a concise summary of 12 included metabolomic studies, making it easier for future researchers to compare their results with the prior findings.
CONCLUSION
It appears that the field of TC metabolomics will experience notable advancement, leading to the discovery of trustworthy diagnostic and prognostic biomarkers.
Topics: Humans; Thyroid Neoplasms; Metabolomics; Metabolome; Biomarkers, Tumor; Thyroid Gland; Magnetic Resonance Spectroscopy
PubMed: 38646957
DOI: 10.1002/cam4.7184 -
Frontiers in Microbiology 2024Hemorrhagic fever with renal syndrome (HFRS) is an acute infectious disease comprising five stages: fever, hypotension, oliguria, diuresis (polyuria), and convalescence....
INTRODUCTION
Hemorrhagic fever with renal syndrome (HFRS) is an acute infectious disease comprising five stages: fever, hypotension, oliguria, diuresis (polyuria), and convalescence. Increased vascular permeability, coagulopathy, and renal injury are typical clinical features of HFRS, which has a case fatality rate of 1-15%. Despite this, a comprehensive meta-analyses of the clinical characteristics of patients who died from HFRS is lacking.
METHODS
Eleven Chinese- and English-language research databases were searched, including the China National Knowledge Infrastructure Database, Wanfang Database, SinoMed, VIP Database, PubMed, Embase, Scopus, Cochrane Library, Web of Science, Proquest, and Ovid, up to October 5, 2023. The search focused on clinical features of patients who died from HFRS. The extracted data were analyzed using STATA 14.0.
RESULTS
A total of 37 articles on 140,295 patients with laboratory-confirmed HFRS were included. Categorizing patients into those who died and those who survived, it was found that patients who died were older and more likely to smoke, have hypertension, and have diabetes. Significant differences were also observed in the clinical manifestations of multiple organ dysfunction syndrome, shock, occurrence of overlapping disease courses, cerebral edema, cerebral hemorrhage, toxic encephalopathy, convulsions, arrhythmias, heart failure, dyspnea, acute respiratory distress syndrome, pulmonary infection, liver damage, gastrointestinal bleeding, acute kidney injury, and urine protein levels. Compared to patients who survived, those who died were more likely to demonstrate elevated leukocyte count; decreased platelet count; increased lactate dehydrogenase, alanine aminotransferase, and aspartate aminotransferase levels; prolonged activated partial thromboplastin time and prothrombin time; and low albumin and chloride levels and were more likely to use continuous renal therapy. Interestingly, patients who died received less dialysis and had shorter average length of hospital stay than those who survived.
CONCLUSION
Older patients and those with histories of smoking, hypertension, diabetes, central nervous system damage, heart damage, liver damage, kidney damage, or multiorgan dysfunction were at a high risk of death. The results can be used to assess patients' clinical presentations and assist with prognostication.https://www.crd.york.ac.uk/prospero/, (CRD42023454553).
PubMed: 38638893
DOI: 10.3389/fmicb.2024.1329683 -
World Journal of Virology Mar 2024Cholangiocarcinoma is the second most common primary liver malignancy. Its incidence and mortality rates have been increasing in recent years. Hepatitis C virus (HCV)...
BACKGROUND
Cholangiocarcinoma is the second most common primary liver malignancy. Its incidence and mortality rates have been increasing in recent years. Hepatitis C virus (HCV) infection is a risk factor for development of cirrhosis and cholangiocarcinoma. Currently, surgical resection remains the only curative treatment option for cholangiocarcinoma. We aim to study the impact of HCV infection on outcomes of liver resection (LR) in intrahepatic cholangiocarcinoma (ICC).
AIM
To study the outcomes of curative resection of ICC in patients with HCV ( HCV+) compared to patients without HCV ( HCV-).
METHODS
We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) and observational studies to assess the outcomes of LR in ICC in HCV+ patients compared to HCV- patients in tertiary care hospitals. PubMed, EMBASE, The Cochrane Library and Scopus were systematically searched from inception till August 2023. Included studies were RCTs and non-RCTs on patients ≥ 18 years old with a diagnosis of ICC who underwent LR, and compared outcomes between patients with HCV+ HCV-. The primary outcomes were overall survival (OS) and recurrence-free survival. Secondary outcomes include perioperative mortality, operation duration, blood loss, intrahepatic and extrahepatic recurrence.
RESULTS
Seven articles, published between 2004 and 2021, fulfilled the selection criteria. All of the studies were retrospective studies. Age, incidence of male patients, albumin, bilirubin, platelets, tumor size, incidence of multiple tumors, vascular invasion, bile duct invasion, lymph node metastases, and stage 4 disease were comparable between HCV+ and HCV- group. Alanine transaminase [MD 22.20, 95%confidence interval (CI): 13.75, 30.65, < 0.00001] and aspartate transaminase levels (MD 27.27, 95%CI: 20.20, 34.34, < 0.00001) were significantly higher in HCV+ group compared to HCV- group. Incidence of cirrhosis was significantly higher in HCV+ group [odds ratio (OR) 5.78, 95%CI: 1.38, 24.14, = 0.02] compared to HCV- group. Incidence of poorly differentiated disease was significantly higher in HCV+ group (OR 2.55, 95%CI: 1.34, 4.82, = 0.004) compared to HCV- group. Incidence of simultaneous hepatocellular carcinoma lesions was significantly higher in HCV+ group (OR 8.31, 95%CI: 2.36, 29.26, = 0.001) compared to HCV- group. OS was significantly worse in the HCV+ group (hazard ratio 2.05, 95%CI: 1.46, 2.88, < 0.0001) compared to HCV- group.
CONCLUSION
This meta-analysis demonstrated significantly worse OS in HCV+ patients with ICC who underwent curative resection compared to HCV- patients.
PubMed: 38616852
DOI: 10.5501/wjv.v13.i1.88946