Systematic Review and Meta-analysis of the Impact of Metabolic Surgery on Hepatic Stiffness.

BACKGROUND: Bariatric surgery is one of the effective therapeutic options for people with obesity and obesity-related co-morbidities. In addition to weight-related co-morbid diseases, including diabetes, hypertension, and hypercholesterolemia, non-alcoholic fatty liver disease (NAFLD) is common in patients with morbid obesity. Bariatric surgery is one of the therapeutic options in the management of NAFLD. Hence, this review focused on the potential role of bariatric surgery on hepatic elasticity measured through shear wave elastography. METHODS: A systematic literature search was performed, and the studies regarding heterogeneity were evaluated using the random-effects model. RESULTS: The meta-analysis on 6 trials (3-12 months follow-up) including 350 participants showed a significant reduction of liver elasticity after surgery (WMD: -1.149, 95% CI: -1.767, -0.532, p < 0.001; I2:81.55%). CONCLUSION: Bariatric surgery is associated with decreased liver elasticity. This improvement could be related to weight loss or other mechanisms of bariatric surgery.

Gastric bypass surgery in morbid obesity: Influence on thyroid function tests and insulin resistance status.

Background: There are inconsistent results about the effect of gastric bypass surgery on thyroid function tests in morbidly obese subjects. The aim of this study was to investigate the changes in thyroid function tests and insulin resistance status in euthyroid morbidly obese subjects before and three months after gastric bypass surgery (GBS). Methods: Twenty-nine subjects with morbid obesity (BMI≥40) were enrolled in this before-after study. Patients with known thyroid disorders or a history of thyroid ablative therapy, users of drugs that affect thyroid function, or fasting blood sugar and insulin were excluded. TSH, Free T4, total T3, fasting blood sugar and insulin level, and BMI were measured before and 3 months after GBS. Statistical analysis was performed with appropriate tests and p<0.05 was considered significant. Results: Body mass index (BMI), insulin sensitivity index (HOMA-IR), and total T3 significantly decreased after bypass surgery (all with p<0.001) but no significant changes were seen in TSH (P=0.203) and FreeT4 (P=0.33). There was a significant negative correlation between changes in HOMA-IR and changes in FreeT4 (P=0.038, r= -0.38). There was no statistically significant correlation between the percentage of excess BMI loss (%EBMIL) and changes in T3 (P=0.66), Free T4 (P=0.92), TSH (P= 0.27), and HOMA-IR (P=0.17). Conclusion: Although significant changes can occur in BMI, insulin sensitivity index, fasting blood sugar, and T3 in short-time follow-up after bariatric surgery, significant TSH and FreeT4 changes may need longer follow-ups.

Evaluation of the diagnostic value of Sentinel Lymph Node in patients with gastric adenocarcinoma.

Objectives: Sentinel lymph node biopsy (SLNB) has been proven as a safe and efficient procedure in some cancers like breast cancer and melanoma with a reduction of complications and side effects of unnecessary lymphadenectomy in many patients. However, the diagnostic value of SLNB in gastric cancer is a point of debate. This study evaluated the diagnostic value of SLNB using radiotracer and isosulphan blue dye injection in patients with Gastric Adenocarcinomas (GA). Methods: This descriptive study was performed at Imam-Reza HOSPITAL on 39 patients diagnosed with GA with no lymphatic metastasis using two methods: the combination of radionuclide with isosulphan together (R&I) method compared with the isosulphan alone method. Lymphatic dissection was performed in all patients. The pathological results were compared between the sentinel lymph nodes (SLN) and other lymph nodes and their accordance rate was calculated. Results: In the T1 group, the sentinel lymph node biopsy detection rate was 100% for the combination of the R&I method and 60% for the isosulphan method and the false negative rate was zero. These values respectively were 88.8% and 88.8% in the T2 group with a false negative rate of 75%. In the T3 group, the values were 100% for the combination of the R&I method and 93.7% for the isosulphan method with a false negative rate of 40%. In the combination of the R&I method, the sensitivity, specificity, and positive and negative predictive values were 57.9, 100, 100, and 69.2 percent respectively. Conclusion: Based on the false negative rate (47.4%), SLNB by injection of isosulphan blue dye alone is not a diagnostic enough value for predicting lymph node metastasis in GA. Although, SLNB by combination of the R&I had better accuracy compared to the isosulphan alone, more studies with larger samples are needed to prove this result.

An in vitro investigation of the effects of urolithins A and B on low-density lipoprotein uptake and its regulatory genes.

Introduction: This study aimed to evaluate the possible role of urolithin A (UA) and urolithin B (UB) on the mRNA expression levels of LDL receptor (LDLR) and PSCK9 genes, and also of the uptake of LDL particles in HepG2 cells. Material and methods: The potential role of UA and UB on the induction of LDL uptake and the expression of its regulatory genes was explored using HepG2 cells and curcumin (20 µM), berberine (50 µM), UA (80 µM), and UB (80 µM) as the treatments in the experimental tests. Results: The LDL uptake and cell-surface LDLR were higher in cells treated with UA in comparison with cells treated with UB, and even in relation to the cells treated with curcumin and berberine as positive controls. In addition, cells treated with UB showed approximately 2 times greater LDLR expression levels compared with curcumin (FC = 2.144, p = 0.013) and berberine (FC = 2.761, p = 0.006). However, UA treatment resulted in significantly lower expression levels of LDLR compared with curcumin (FC = 0.274, p < 0.001) and berberine (FC = 0.352, p = 0.009). UB demonstrated approximately 8 times higher LDLR expression levels when compared with UA (FC = 7.835, p = 0.001). Compared with UB, as well as curcumin and berberine as positive controls, UA was more efficient in reducing PCSK9 expression levels. Although UB did not show any significant differences compared with curcumin and berberine, it showed higher levels of PCSK9 expression when compared with the UA group (FC = 3.694, p < 0.001). Conclusions: The present results suggest that UA was more effective than UB in promoting LDL uptake as well as cell surface LDLR in HepG2 cells. This effect seems to be mostly mediated through the suppression of PCSK9 expression but not the induction of LDLR expression.

A rare presentation of gastro-pleural fistula after Roux-en-Y gastric bypass, simultaneous fistula of gastric pouch, and remnant to the pleural space.

Key Clinical Message: Although gastro-pleural fistulas after bariatric surgeries are rare, they are life-threatening complications that should be suspected in patients who present with gastrointestinal or respiratory symptoms after bariatric surgery. Abstract: Previous studies showed an incidence rate of 0.2%-0.37% for gastro-pleural fistulas after bariatric surgery. We report a 56-year-old female with a rare presentation of gastro-pleural fistula after Roux-en-Y gastric bypass, simultaneous fistula of the gastric pouch, and remnant to the pleural space.

The Potential Effect of Royal Jelly on Biomarkers Related to COVID-19 Infection and Severe Progression.

Royal jelly is a yellowish to white gel-like substance that is known as a "superfood" and consumed by queen bees. There are certain compounds in royal jelly considered to have health-promoting properties, including 10-hydroxy-2-decenoic acid and major royal jelly proteins. Royal jelly has beneficial effects on some disorders such as cardiovascular disease, dyslipidemia, multiple sclerosis, and diabetes. Antiviral, anti-inflammatory, antibacterial, antitumor, and immunomodulatory properties have been ascribed to this substance. This chapter describes the effects of royal jelly on COVID-19 disease.

Isolated greater omentum solid mass, a rare manifestation of hydatid disease; A Case Report and Review of Literature.

Background: Echinococcus granulosus causes hydatid disease, which is found in various countries of the world, including Iran. The liver and lungs are prevalent involved structures in hydatid disease. One of the least common sites in hydatid disease seems to be the omentum. Seven cases of mesenteric, diaphragmatic, omental, pelvic, and retroperitoneal hydatid cysts have been reported in Iran within last 20 years. The appearance of hydatid disease as a primary mass in the greater omentum without hepatic involvement is very rare and no similar case was introduced in Iran in our searches. Case Presentation: Our patient was a 33-year-old woman who underwent a diagnostic laparoscopy due to abdominal pain and an abdominal mass. During laparoscopy, there was a solid mass with a size of about 10 × 5 cm in the greater omentum that was resected. The histopathological examination of the mass showed the hydatid disease. Conclusion: The hydatid cyst can appear anywhere on the body, and no part of the body is guarded. Since these uncommon locations often cause nonspecific symptoms, the hydatid cyst should be included in the differential diagnosing of omental cysts, particularly in endemic countries like Iran.

Association of C-reactive protein with histological, elastographic, and sonographic indices of non-alcoholic fatty liver disease in individuals with severe obesity.

BACKGROUND: Inflammation is critical in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). hs-CRP, an inflammatory marker, is considered one of the prognostic predictors of hepatic damage progression in NAFLD in some studies. METHODS: We assessed the concordance of hs-CRP concentrations and liver steatosis, steatohepatitis, and fibrosis based on elastography, sonography and liver biopsy findings in patients with severe obesity undergoing bariatric surgery. RESULTS: Among 90 patients, 56.7% showed steatohepatitis and 8.9% severe fibrosis. Hs-CRP were significantly associated with liver histology in an adjusted regression model (OR 1.155, 95% CI 1.029-1.297, p = 0.014; OR 1.155, 1.029-1.297, p = 0.014; OR 1.130, 1.017-1.257, p = 0.024 for steatosis, steatohepatitis, and fibrosis, respectively). The ROC curve, a cutoff of hs-CRP = 7 mg/L, showed a reasonable specificity (76%) for detecting biopsy-proven fibrosis and steatosis. CONCLUSION: hs-CRP was associated with any degree of histologically diagnosed liver damage, and it had a reasonable specificity for predicting biopsy-proven steatosis and fibrosis in obese individuals. Further studies are needed to identify non-invasive biomarkers that could predict NALFD progression due to the relevant health risks linked to liver fibrosis.

Impact of gastric bypass surgery on the liver fibrosis of patients with extreme obesity and nonalcoholic fatty liver disease in 30-month follow-up.

Roux-en-Y gastric bypass surgery (RYGB) has shown efficacy in weight loss, but its role in liver fibrosis remains unknown and contentious. The present study aimed to investigate the effect of RYGB on liver fibrosis measured by non-invasive methods and assess the impact of weight loss on hepatic fibrosis in the midterm follow-up after RYGB. This longitudinal study was conducted on patients with extreme obesity, and NAFLD referred for RYGB during 2016-2018 for 3 years after their surgery. A liver biopsy was performed intraoperatively. The patient demographics, anthropometrical parameters, biochemical variables, and Liver stiffness (LS) using two-dimensional shear-wave elastography were recorded and analyzed before and in short-term and midterm follow-ups. Fifty-four patients were included with a mean age of 40.3 years; 83.3% were women. At a median follow-up of 30 months (range: 24-36 months), the excessive body mass index loss of the patients was 78.1% and, a significant reduction was seen in LS measurement. Two patients (4%) had worsening showed in the fibrosis stage, 28 (54%) no change, and 24 (42%) showed improvement, 30 months after the surgery. Moreover, the liver fibrosis stage regressed to F0 in 91% of the patients. Hepatic fibrosis resolved in the midterm follow-up in some patients whose fibrosis had progressed and deteriorated in the short-term follow-up. In addition, Liver enzymes were decreased. RYGB seems to be an effective procedure for sustained weight loss and improved liver fibrosis in EO and NAFLD patients in midterm follow-up.

Diagnostic Value of Non-invasive Liver Function Tests in Liver Fibrosis and Changes in These Parameters Post-metabolic Surgery.

PURPOSE: This study aimed to ascertain the diagnostic accuracy of non-invasive liver function tests in liver fibrosis and assess their changes after metabolic surgery. MATERIALS AND METHODS: 1005 individuals with severe obesity who were referred for metabolic surgery were analysed. All participants had blood samples taken for liver enzymes and lipid profile. In addition, hepatic indexes, including AAR, APRI, NFS and Fibrosis-4 (FIB4), were checked. Furthermore, all participants underwent two-dimensional shear wave elastography (2D-SWE). All investigations were repeated 6-8 months after metabolic surgery. The receiver operating characteristic (ROC) curve and the area under the ROC curve was utilised to determine the optimal cut-off values for baseline study parameters. Logistic regression was applied to predict the relationship between study parameters-as predictors-and change in 2D-SWE. RESULTS: AST/ALT (AAR) was the most sensitive (79%) pre-operative non-invasive serological marker for detecting liver fibrosis, whereas NAFLD Fibrosis Score (NFS) was the most specific (84%). AST/upper limit of the normal AST range × 100/platelets (× 109/L) (APRI) showed a positive correlation with 2D-SWE post-metabolic surgery (p-value = 0.021). Regression analysis from both adjusted and unadjusted models showed that baseline AAR was a predictor of postoperative liver status in terms of hepatic fibrosis. CONCLUSION: AAR has a high sensitivity, whereas NFS exhibits a high specificity in diagnosing liver fibrosis. The authors recommend using both investigations in conjunction with 2D-SWE to increase the likelihood of detecting liver fibrosis.

Diabetic Markers, Five Years after Bariatric Surgery.

Background: Bariatric surgery delivers substantial weight loss for obese patients with comorbidities like diabetes mellitus. We aimed to investigate the impacts of bariatric surgery on diabetic markers after 5 years of follow-up. Methods: This is a retrospective study on patients with diabetes and a history of bariatric surgery between 2016-2017. The diabetic markers before and 5 years following surgery, including a lipid profile, glucose level, and the required antidiabetic medications, were evaluated. Results: 34 consecutive patients were included, 30 (88.2%) women, with a mean age of 52.71±8.53 years. The majority (65%) of surgeries were Roux-en-Y gastric bypass (RYGB), and the remaining were one anastomosis gastric bypass (OAGB) and sleeve gastrectomy (SG). The serum levels of diabetic markers reduced during follow-up (P=0.001), except for high-density lipoprotein levels and serum total cholesterol, which increased (P=0.011, P=0.838). Low-density lipoprotein levels reduced, but it was insignificant (P=0.194). Surgery types had affected the changes of diabetic markers (P>0.05). Demand for oral medication was reduced significantly, but insulin injection reduction was not significant (P=0.006 and P=0.099, respectively). Conclusion: Our study showed favorable bariatric surgery results on patients with diabetes in long-term follow-up. However, dyslipidemia is still a concern.

Identifying the Predictors of Short Term Weight Loss Failure after Roux-En-Y Gastric Bypass.

Introduction: Gastric bypass surgery is a gold standard therapy for severe obesity. This study aimed to evaluate anthropometric predictors for short-term excess weight loss (EWL) after Roux-en-Y gastric bypass surgery (RYGB) in a sample of severely obese patients. Materials and Methods: This cohort study was conducted on severely obese candidates for RYGB bariatric surgery in Mashhad, Iran. Indirect calorimetry, anthropometric measurements, and body composition data were collected before, one, and six months after RYGB. Results: Fifty-four participants (43, 79.6% women and 11, 20.4% men) with a mean age of 39.63 ± 9.66 years participated in this study. The mean total weight and BMI loss within six months were 32.89 ± 20.22 kg and 12.37 ± 7.34 kg/m2, respectively. The mean reduction in adipose tissue and fat-free mass was 24.49 kg and 7.46 kg, respectively. The mean resting metabolism rate (RMR) reduction at one and six months after RYGB was 260.49 kcal and 396.07 kcal, respectively. There was a significant difference in mean RMR between the baseline and one and six months after RYGB (p < 0.001). There was no significant gender difference in mean weight and BMI loss percentage at six months post-RYGB (p > 0.05). Baseline skeletal muscle mass (SMM), excess BMI loss (EBMIL) at first month after surgery, and baseline neck circumference (NC) could predict EWL six months after surgery. Conclusion: Reduced RMR shortly after RYGB may be due to FFM reduction. Some anthropometric and their acute changes after RYGB may predict the short-term EWL in RYGB patients.

Mesh migration following abdominal hernia repair: A case report, and literature review.

Background: Postoperative hematoma and seroma, foreign body reaction, infection, mesh rejection, and fistula formation are the complications associated with the use of surgical mesh. Mesh migration is a rare but serious and challenging complication after hernia repair. When this happens, infection, abscess, fistula, and bowel obstruction are the most common sequelae. Case presentation: Our patient was a 62-year-old woman with a history of appendectomy 30 years ago and then underwent 3 incisional hernia repair surgeries which the last one was 5 years ago using laparoscopic IPOM. The patient was nominated for surgery with a diagnosis of recurrent incisional hernia. The patient underwent laparotomy and after enterolysis, a small bowel loop was seen that adhered to McBurney's region, which was released. There was a mass inside the small bowel. Resection and anastomosis of the involved intestine were performed. After enterotomy, it was determined that this mass was the mesh used in the previous surgery. Conclusion: Mesh migration is a rare consequence of incisional hernia repair with a prosthetic mesh. It can happen years after a hernia repair and it is additionally crucial to consider as a differential diagnosis in all patients who show unusual symptoms or abdominal pain.

Impact of Bariatric Surgery on Carotid Intima-Media Thickness in Patients with Morbid Obesity: a Prospective Study and Review of the Literature.

BACKGROUND AND AIM: One of the main causes of mortality among obese patients is cardiovascular disease (CVD). Carotid intima-media thickness (CIMT) is an independent predictor for atherosclerosis and risk of CVD, and has been demonstrated to be related with obesity. This study aimed to evaluate the effect of substantial weight loss after bariatric surgery on CIMT. METHODS: This prospective study was performed on patients with morbid obesity and standard indications for bariatric surgery in a tertiary referral center in Iran. The mean CIMT values were assessed using B-mode ultrasonography before and 6 months after bariatric surgery. RESULTS: A total of 32 patients (25 females, 7 males) with a mean age of 38.18 ± 1.18 years were enrolled. Body mass index (BMI) was significantly reduced from 43.66 ± 6.44 to 29.01 ± 2.56 kg/m2 during 6 months following surgery (p: 0.001). The mean CIMT values at 6 months after surgery were significantly lower than the baseline (0.53 ± 0.06 vs. 0.50 ± 0.08; p: 0.001). Along with a significant hypertension and metabolic syndrome remission, we observed considerable reduction in FBS (p: 0.019), cholesterol (p: 0.061), triglycerides (p: 0.001), and insulin levels (p: 0.001). Besides, liver stiffness was significantly decreased after surgery (6.15 ± 0.82 vs. 5.26 ± 0.83; p: 0.001). There was no statistically significant correlation between changes in quantitative variables and changes in CIMT. CONCLUSION: Bariatric surgery results in significant reduction in CIMT, metabolic syndrome factors, and liver stiffness in patients with morbid obesity.

The Predictive Role of Parathyroid Hormone for Nonalcoholic Fatty Liver Disease following Bariatric Surgery.

Background: Morbid obesity is frequently complicated by chronic liver diseases, including nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH), and fibrosis. Parathyroid hormone (PTH) is found to be elevated in morbid obesity due to the defective hepatic metabolism of vitamin D. Bariatric surgery is performed to help patients with BMI>40 kg/m2 to effectively lose weight, particularly in patients with obesity who are afflicted with complications such as NAFLD/NASH. Objective: This study aimed to evaluate the PTH level as a predictor of hepatic function in individuals with morbid obesity who have undergone bariatric surgery. Methods: Ninety subjects with morbid obesity referred for Roux en-Y gastric bypass surgery were recruited. After IRB approval, demographic profiles, anthropometric factors, liver biopsy, and laboratory tests were obtained. The two-dimensional shear wave elastography (2D-SWE) technique was applied to assess hepatic stiffness. Results: A significant reduction occurred six months after bariatric surgery in the anthropometric indices (p < 0.001), hepatic elasticity (p=0.002), alanine aminotransferase (p < 0.001), serum alkaline phosphatase (p < 0.001), gamma-glutamyl transpeptidase (GGT) (p < 0.001), and nonalcoholic fatty liver disease fibrosis score (NFS) (p < 0.001). Serum PTH concentration was not predictive of postsurgical liver fibrosis and steatosis at six months but could predict weight loss success rate. No significant alteration in serum PTH levels was observed between presurgical vs. postsurgical time points. Conclusion: A significant reduction was observed in the anthropometric parameters, liver enzymes, and hepatic elasticity after bariatric surgery. No significant effect was found on PTH levels.

Association between Thyroid Hormones and Non-alcoholic Fatty Liver Disease and Non-alcoholic Steatohepatitis in Obese Individuals Undergoing Bariatric Surgery.

Background: Non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), and hepatic fibrosis have emerged as one of the leading causes of chronic liver disease. The prevalence of the NAFLD spectrum has increased, which can be attributed to the rise in obesity. As NAFLD can ultimately lead to liver cirrhosis, it is imperative to identify modifiable risk factors associated with its onset and progression to provide timely intervention to prevent potentially disastrous consequences. Considering the pivotal role of the endocrine axis in several metabolic pathways such as obesity and insulin resistance, thyroid hormones are crucial in the pathophysiology of NAFLD. The study is focused on the identification of an association between thyroid function and radiographic and histological parameters of NAFLD in patients with severe obesity. Methods: Ninety patients were recruited for this study and underwent initial assessments, including demographic profiles, anthropometric measurements, hepatic biopsy, and basic laboratory tests. Liver stiffness was evaluated using two-dimensional shear wave elastography (2D-SWE) at least 2 weeks before liver biopsy. Results: Among the 90 participants, 80% were women. The mean age was 38.5±11.1 years, and the mean body mass index (BMI) was 45.46±6.26 kg/m2. The mean levels of serum T3 and free T4 in patients with positive histology were not statistically significant compared with patients with negative histology. Furthermore, there was no statistical significance in the mean T3 and free T4 levels between patients diagnosed with hepatic steatosis or fibrosis (on ultrasonography and elastography) and those with negative hepatic imaging. Serum levels of thyroid-stimulating hormone (TSH) were negatively correlated with ultrasonography (P=0.007). Binary logistic regression analysis revealed that none of the thyroid hormones was a predictive factor for liver histology in both adjusted and crude models. Conclusion: The results from our analysis did not suggest an association between thyroid hormones and NAFLD, which is in line with several previously published studies. However, the authors note that there are published data that do propose a link between the two entities. Therefore, well-designed large-scale clinical studies are required to clarify this discrepancy.

The predictive role of parathyroid hormone for non-alcoholic fatty liver disease based on invasive and non-invasive findings in candidates of bariatric surgery.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH) and hepatic fibrosis are the most detrimental hepatic abnormalities associated with increased body weight with devastating clinical outcomes. Therefore, there is a substantial necessity for efficient management strategies, including significant weight reduction. Bariatric surgery has been used as a therapeutic approach in a selected obese patient with NAFLD/NASH and other cardiometabolic comorbidities. PURPOSE: The study is focused on the predictive role of PTH with the indices of hepatic steatosis/NAFLD and NASH based on liver biopsy, elastography, and sonography in morbidly obese patients. METHODS: Ninety patients with BMI between 35 and 40 kg/m2 with more than two comorbidities who referred to Imam Reza outpatient clinic from December 2016 to September 2017 were recruited and underwent initial assessments, including demographic profiles, psychological assessment, anthropometric measurements, hepatic biopsy, and basic laboratory tests. Liver stiffness was evaluated using two-dimensional shear wave elastography (2D-SWE) at least two weeks before liver biopsy. The histological analysis of the liver was performed using biopsy samples which obtained from left hepatic lobe during bariatric surgery under direct surgeon observation using a 16-gauge Tru-cut needle. The study was approved by the ethical committee (IR.MUMS.fm.REC.1396.312). RESULTS: The level of PTH was significantly high in patients with positive histology for hepatic fibrosis, steatosis, and NASH/NAFLD compared to patients with negative histology (p = 0.005, p = 0.009, and p = 0.013, respectively). Also, patients with liver fibrosis confirmed by elastography had significantly higher serum PTH concentration than patients without fibrosis (p = 0.011). PTH was also positively correlated with hepatic fibrosis, NASH, and steatosis (p = 0.007, p = 0.012, p = 0.023, respectively). CONCLUSION: High levels of PTH was significantly associated with histological indices of (hepatic fibrosis, steatosis, NAFLD and NASH) and elasticity indices. Therefore, it is imperative to assess for high levels of PTH in the morbidly obese population pre-and post-bariatric surgery. However, for a more robust and comprehensive assessment, a randomized controlled trial is needed. The study was conducted in accordance with the practice guidance in the diagnosis and management of NAFLD from the American association for the study of liver disease (AASLD) 2018. LEVEL III: Evidence obtained from well-designed cohort or case-control analytic studies.