Expression and Relations of Unique miRNAs Investigated in Metabolic Bariatric Surgery: A Systematic Review.

Several studies have indicated that miRNAs play crucial roles in adipogenesis, insulin resistance, and inflammatory pathways associated with obesity and change after metabolic bariatric surgery (MBS). This systematic review explores and maps the existing literature on how miRNAs are expressed and investigates the unique miRNAs with the effects after MBS. The Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, and EMBASE were searched from 2019 until February 2024. This SR found 825 miRNAs from 25 studies, identifying 507 unique ones not used twice in the same study. A total of 21 studies (84%) measured RNA before and after surgery. The miRNA used per study ranged from 1 to 146 miRNA types, with a median study sample size of just 27 patients per study, raising concerns about some conclusions' robustness. From the 507 unique miRNAs, only 16 were consistently analyzed in 4 to 7 studies, which gave 77 different outcomes in relation to miRNA after MBS. MiRNA 122 and 122-5p were analyzed the most. Others were 106b-5p, 140-5p, 183-5p, 199b-5p, 20b-5p, 424-5p, 486-5p, 7-5p, 92a, 93-5p, 194-5p, 21-5p, 221, 320a, and 223-3p. A gap was observed in many studies, whereby the results were not the same, or there was no explanation for the effects after MBS was given within the same miRNA. Fifteen miRNAs were reported to have the same upward and downward trend, although not within the same study, and only 26.1% employed some form of statistical modeling to account for bias or confounding factors. Directions and effects in miRNA are visible, but still, inconsistent outcomes linked to the same miRNA after MBS, underscoring the need for clarity in miRNA-outcome relationships. Collaborative efforts, consensus-driven miRNA dictionaries, and larger, more rigorous studies are necessary to improve methodology designs and improve outcomes.

Effect of Cytokeratin-18, C-peptide, MHR, and MACK-3 Biomarkers in Metabolic Dysfunction-Associated Fatty Liver Disease After Laparoscopic Sleeve Gastrectomy.

Background: Laparoscopic sleeve gastrectomy (LSG) has emerged as a valuable treatment for various metabolic disorders, including metabolic dysfunction-associated fatty liver disease (MAFLD) in patients with obesity. Consequently, there is a pressing need to develop noninvasive biomarkers for diagnosing and monitoring disease progression. Objectives: This study aimed to evaluate specific biomarkers, including Cytokeratin-18 (CK-18), C-peptide, monocyte to HDL cholesterol ratio (MHR), and MACK-3, in patients with obesity with MAFLD undergoing LSG. Design: A prospective cohort study on patients with obesity before and 6 months after the LSG procedure. Methods: 70 patients with obesity with confirmed MAFLD, determined by Transient Elastography (TE), were pre- and 6 months postoperatively tested. Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), lipid profile, ghrelin, leptin, peptide YY, GLP-1, and liver fibrosis scores, including AST/ALT ratio (AAR), Fibrosis-4 index (FIB-4), and BARD Score were tested. Results: BMI significantly decreased in all participants, with a % excess weight loss of 62.0% ± 15.4%. TE measurements revealed a significant postoperative reduction from 100% to 87.1% (P = .006). All selected biomarkers showed significant postoperative improvement-a significant association of CK-18 with MAFLD markers, including AAR, FIB-4, and BARD score, were found. MACK-3 had positive associations with FIB-4. C-peptide and MHR showed no association with MAFLD markers. Furthermore, there was a positive correlation between CK-18 and MACK-3 tests and between C-peptide and CK-18 and MACK-3. Additionally, a receiver operating characteristic (ROC) curve was constructed, with CK-18 performing the best, with an estimated area under the curve of 0.863. Conclusion: Serum CK-18 outperformed other selected biomarkers in predicting and monitoring MAFLD in patients with obesity, suggesting its prospective utility in clinical practice. Further studies are needed to validate the accuracy of the MACK-3 test.

Effect on biomarkers in patients with fatty liver after weight loss surgery A sleeve gastrectomy is an operation when patient have obesity and need to lose weight. This operation help people with obesity who also have fatty liver disease that's not related to alcohol use. Researchers are looking for simple blood tests to track the disease. In this study, they checked how well 4 of these tests worked before and after the surgery in 70 people. They found that the patients lost a lot of weight and their liver health improved. One test, in particular, called CK-18, was really good at showing these changes. Another test, MACK-3, also showed promise, but more research is needed to be sure. The other 2 tests didn't seem to be linked to signs of fatty liver disease. This suggests that CK-18 could be a useful tool for doctors to see how patients are doing after this surgery.

Effect of Weight Regain on Body Composition and Metabolic Biomarkers After Sleeve Gastrectomy: a Cross-Sectional Study from a Hospital Database.

INTRODUCTION: Weight regain (WR) is described in approximately 30% of patient's post-bariatric surgery. It is related to the progression or recurrence of associated medical problems and decline in health-related quality of life. This study aimed to test the return of body composition and metabolic biomarkers to pre-operative levels when WR occurs. METHODS: In this cross-sectional study conducted in 2021, patients were randomly selected from the hospital's electronic databases between 2001 and 2020. Patient demographic data, comorbidities, body compositions, and metabolic biomarkers were collected. Three groups were defined: groups A (WR), B (weight loss), and C (control group; patients with obesity who had not yet undergone bariatric surgery). RESULTS: A total of 88 patients were enrolled in this study and matched with the control group. The body mass index in group A was 43.8 ± 6.9 kg/m2; group B was 28.6 ± 4.2; group C was 43.9 ± 7.1. Body muscle mass, body fat mass, and visceral fat significantly differed between groups A and B (p < 0.001) but not between groups A and C (p = 0.8). There was a significant difference in leptin, ghrelin, postprandial glucagon-like peptide-1, insulin, and fibroblast growth factor-21 (but not retinol-binding protein-4) between groups A and B. Most metabolic biomarkers in group A returned to the pre-operative values as in group C. CONCLUSION: WR had a direct negative effect on body composition and metabolic biomarkers, whereby the values returned to pre-operative levels. Early detection of WR and possible additional therapy are necessary to prevent associated medical problems.

Can Leptin/Ghrelin Ratio and Retinol-Binding Protein 4 Predict Improved Insulin Resistance in Patients with Obesity Undergoing Sleeve Gastrectomy?

INTRODUCTION: Obesity is associated with metabolic syndrome (MBS), a cluster of components including central obesity, insulin resistance (IR), dyslipidemia, and hypertension. IR is the major risk factor in the development and progression of type 2 diabetes mellitus in obesity and MBS. Predicting preoperatively whether a patient with obesity would have improved or non-improved IR after bariatric surgery would improve treatment decisions. METHODS: A prospective cohort study was conducted between August 2019 and September 2021. We identified pre- and postoperative metabolic biomarkers in patients who underwent laparoscopic sleeve gastrectomy. Patients were divided into two groups: group A (IR < 2.5), with improved IR, and group B (IR ≥ 2.5), with non-improved IR. A prediction model and receiver operating characteristics (ROC) were used to determine the effect of metabolic biomarkers on IR. RESULTS: Seventy patients with obesity and MBS were enrolled. At 12-month postoperative a significant improvement in lipid profile, fasting blood glucose, and hormonal biomarkers and a significant reduction in the BMI in all patients (p = 0.008) were visible. HOMA-IR significantly decreased in 57.14% of the patients postoperatively. Significant effects on the change in HOMA-IR ≥ 2.5 were the variables; preoperative BMI, leptin, ghrelin, leptin/ghrelin ratio (LGr), insulin, and triglyceride with an OR of 1.6,1.82, 1.33, 1.69, 1.77, and 1.82, respectively (p = 0.009 towards p = 0.041). Leptin had the best predictive cutoff value on ROC (86% sensitivity and 92% specificity), whereas ghrelin had the lowest (70% sensitivity and 73% specificity). CONCLUSION: Preoperative BMI, leptin, ghrelin, LGr, and increased triglycerides have a predictive value on higher postoperative, non-improved patients with HOMA-IR (≥ 2.5). Therefore, assessing metabolic biomarkers can help decide on treatment/extra therapy and outcome before surgery.

Impact of Zinc to Copper Ratio and Lipocalin 2 in Obese Patients Undergoing Sleeve Gastrectomy.

Worldwide, obesity constitutes a significant health issue. There is the perception that obesity is influenced by subclinical inflammation caused by trace elements (TE). Lipocalin 2 (Lcn2) is an adipokine that is abundantly expressed in adipose tissue, largely in response to metabolic stress; TE deficiency is expressed in metabolic dysfunction as increased oxidative stress, the development of dyslipidaemia and insulin resistance. The primary aim of this study is to explore the relationship between Lcn2 inflammatory biomarkers and the TE status of subjects with morbid obesity who are undergoing laparoscopic sleeve gastrectomy (LSG); the secondary aim is to evaluate the Zn-to-Cu ratio in those with a detected TE deficiency. When this prospective cohort study was conducted, 107 subjects with morbid obesity (i.e., 69 women, 38 men) ranging in age from 20 to 55 years were recruited. Anthropometric measurements and laboratory investigations were performed preoperatively and nine months postoperatively; and blood samples were collected to determine the subjects' iron, Zn, Cu, Lcn2, and other inflammatory biomarkers. The results revealed 16.82% of the subjects exhibited preoperative Zn deficiency, which increased to 22.43% postoperatively; none of studied subjects exhibited Cu deficiency in the two consecutive measurements; and the 10.28% preoperative prevalence of iron deficiency increased to 15.89% postoperatively. While a negative correlation was observed between the delta body weight change and Lcn2, leptin, and HOMA-IR, a positive correlation was observed between the delta body weight change and the Zn-to-Cu ratio. These findings suggest the existence of preoperative obesity is associated with inflammatory status that may be triggered by TE deficiency and impaired insulin sensitivity; moreover, LSG may accentuate TE deficiency. As such, a patient's Lcn2 and Zn-to-Cu ratio may be utilized as potential biomarkers of their TE status and metabolic improvement after LSG.

Impact of direct-acting antivirals on leukocytic DNA telomere length in hepatitis C virus-related hepatic cirrhosis.

BACKGROUND: Direct-acting antiviral (DAAs) represent advancement in the management of hepatitis C virus (HCV)-related hepatic cirrhosis. A high proportion of patients achieve a sustained virologic response; eradication of HCV is coupled with a decreased risk of hepatocellular carcinoma. Recent evidence suggests that shortening of the DNA telomere may be linked to cellular senescence as well as predisposition to malignant transformation. OBJECTIVE: This study aimed to assess pretreatment leukocytic DNA telomere length in HCV-related cirrhosis and post viral eradication using DAAs. PATIENTS AND METHODS: This study included 24 patients with HCV-related cirrhosis, Child-Pugh A. Whole-blood samples were obtained from patients before treatment and 12 weeks after the end of treatment, as well as from 24 healthy controls. Terminal restriction fragment, corresponding to telomere length, was measured using a nonradioactive Southern blot technique, detected by chemiluminescence. RESULTS: DNA telomere length was significantly shorter before treatment compared with 12 weeks after end of treatment in HCV-related cirrhotic patients. Also, it was significantly shorter in patients before treatment compared with healthy individuals. CONCLUSION: Telomere elongation in blood leukocytes can be considered a marker of recovery of inflammation after DAAs-induced HCV eradication. Still, the possibility of activation by cancer initiation cannot be excluded.

Role of serotonin hormone in weight regain after sleeve gastrectomy.

Laparoscopic sleeve gastrectomy (LSG) is gaining popularity as bariatric surgery, a small percentage of subjects regain weight after surgery. This study was designed to evaluate body weight changes over a period of two years after LSG and investigate the role of serotonin in regulating energy balance. This is a prospective cohort study. A total of 92 patients with morbid obesity (64 women and 28 men) underwent LSG. All the participants were subjected to physical examination and detailed medical history. Anthropometric measurements were accomplished pre-operative and post-operatively at a frequency of four times per year for two years follow-up. Laboratory investigations were performed pre-operatively, and one and two years post-operatively. Blood samples were collected in the fasting state; for glucose, lipid profile and hormonal assays. Hormones measured were plasma insulin, leptin, serotonin and ghrelin. Results revealed that 35.7% weight loss occurred after one year. However, there was variability in the individual weight loss curve during the period between the first and second post-operative years. Thus, patients were divided into two groups: group I included 78 patients (84%) who maintained the lost weight, and group II included 14 patients (16.0%) who regained weight within 24 months post-operatively. Correlation with BMI revealed positive correlation with leptin and serotonin, whilst negative correlation with ghrelin in group II patients. Mechanisms of weight loss after LSG are not only attributable to gastric restriction but also to the neurohormonal changes. In addition, serotonin may possibly contribute to the interplay of regulatory systems of energy homeostasis.

Detection of MicroRNA in Hepatic Cirrhosis and Hepatocellular Carcinoma in Hepatitis C Genotype-4 in Egyptian Patients.

BACKGROUND: In Egypt, the prevalence of chronic hepatitis C (CHC) infection is 13.8% of whole population and about 80% of the patients with hepatocellular carcinoma have underling hepatitis C. AIM: This study was designed to assess the diagnostic value of plasma miR-122 and miR-21 in patients with CHC, genotype-4, to detect fibrosis progression versus noninvasive indices and their diagnostic value in detection of early stages of hepatocellular carcinoma (HCC). METHODOLOGY: A prospective study that included 180 patients, divided into 3 groups: healthy controls (group I), CHC patients (group II), and hepatitis C patients with HCC (group III); all cases were subjected to thorough clinical, radiological, and laboratory investigations. Selected biomarkers were evaluated and correlated with degree of liver damage. Results revealed that miR-122 followed by miR-21 had the highest efficiency in prediction of liver cell damage. Also, miR-21 was strongly correlated with vascular endothelial growth factor (VEGF) and alpha fetoprotein (α-FP) in HCC patients. CONCLUSIONS: Plasma miR-122 and miR-21 had strong correlation with degree fibrosis in HCV genotype-4 patients; consequently they can be considered as potential biomarker for early detection of hepatic fibrosis. Moreover, miR-21 can be used as a potential biomarker, for early detection of HCC combined with VEGF and α-FP.