18 research outputs found
The role of macrophage-inducible C-type lectin in different stages of chronic liver disease
The macrophage-inducible C-type lectin (mincle) is part of the innate immune system and acts as a pattern recognition receptor for pathogen-associated molecular patterns (PAMPS) and damage-associated molecular patterns (DAMPs). Ligand binding induces mincle activation which consequently interacts with the signaling adapter Fc receptor, SYK, and NF-kappa-B. There is also evidence that mincle expressed on macrophages promotes intestinal barrier integrity. However, little is known about the role of mincle in hepatic fibrosis, especially in more advanced disease stages. Mincle expression was measured in human liver samples from cirrhotic patients and donors collected at liver transplantation and in patients undergoing bariatric surgery. Human results were confirmed in rodent models of cirrhosis and acute-on-chronic liver failure (ACLF). In these models, the role of mincle was investigated in liver samples as well as in peripheral blood monocytes (PBMC), tissues from the kidney, spleen, small intestine, and heart. Additionally, mincle activation was stimulated in experimental non-alcoholic steatohepatitis (NASH) by treatment with mincle agonist trehalose-6,6-dibehenate (TDB). In human NASH, mincle is upregulated with increased collagen production. In ApoE deficient mice fed high-fat western diet (NASH model), mincle activation significantly increases hepatic collagen production. In human cirrhosis, mincle expression is also significantly upregulated. Furthermore, mincle expression is associated with the stage of chronic liver disease. This could be confirmed in rat models of cirrhosis and ACLF. ACLF was induced by LPS injection in cirrhotic rats. While mincle expression and downstream signaling via FC receptor gamma, SYK, and NF-kappa-B are upregulated in the liver, they are downregulated in PBMCs of these rats. Although mincle expressed on macrophages might be beneficial for intestinal barrier integrity, it seems to contribute to inflammation and fibrosis once the intestinal barrier becomes leaky in advanced stages of chronic liver disease
Best practice approach for redo-surgeries after sleeve gastrectomy, an expert's modified Delphi consensus
Background: Sleeve gastrectomy (SG) is the most common metabolic and bariatric surgical (MBS) procedure worldwide. Despite the desired effect of SG on weight loss and remission of obesity-associated medical problems, there are some concerns regarding the need to do revisional/conversional surgeries after SG. This study aims to make an algorithmic clinical approach based on an expert-modified Delphi consensus regarding redo-surgeries after SG, to give bariatric and metabolic surgeons a guideline that might help for the best clinical decision.
Methods: Forty-six recognized bariatric and metabolic surgeons from 25 different countries participated in this Delphi consensus study in two rounds to develop a consensus on redo-surgeries after SG. An agreement/disagreement ≥ 70.0% on statements was considered to indicate a consensus.
Results: Consensus was reached for 62 of 72 statements and experts did not achieve consensus on 10 statements after two rounds of online voting. Most of the experts believed that multi-disciplinary team evaluation should be done in all redo-procedures after SG and there should be at least 12 months of medical and supportive management before performing redo-surgeries after SG for insufficient weight loss, weight regain, and gastroesophageal reflux disease (GERD). Also, experts agreed that in case of symptomatic GERD in the presence of adequate weight loss, medical treatment for at least 1 to 2 years is an acceptable option and agreed that Roux-en Y gastric bypass is an appropriate option in this situation. There was disagreement consensus on efficacy of omentopexy in rotation and efficacy of fundoplication in the presence of a dilated fundus and GERD.
Conclusion: Redo-surgeries after SG is still an important issue among bariatric and metabolic surgeons. The proper time and procedure selection for redo-surgery need careful considerations. Although multi-disciplinary team evaluation plays a key role to evaluate best options in these situations, an algorithmic clinical approach based on the expert's consensus as a guideline can help for the best clinical decision-making.info:eu-repo/semantics/publishedVersio
One Anastomosis Gastric Bypass-Mini-Gastric Bypass (OAGB-MGB) Versus Roux-en-Y Gastric Bypass (RYGB)—a Mid-Term Cohort Study with 612 Patients
Mouse Models of Nonalcoholic Steatohepatitis: Head-to-Head Comparison of Dietary Models and Impact on Inflammation and Animal Welfare
A variety of dietary nonalcoholic steatohepatitis (NASH) mouse models are available, and choosing the appropriate mouse model is one of the most important steps in the design of NASH studies. In addition to the histopathological and metabolic findings of NASH, a sufficient mouse model should guarantee a robust clinical status and good animal welfare. Three different NASH diets, a high-fat diet (HFD60), a western diet (WD), and a cafeteria diet (CAFD), were fed for 12 or 16 weeks. Metabolic assessment was conducted at baseline and before scheduled sacrifice, and liver inflammation was analyzed via fluorescence-associated cell sorting and histopathological examination. Clinical health conditions were scored weekly to assess the impact on animal welfare. The HFD60 and WD were identified as suitable NASH mouse models without a significant strain on animal welfare. Furthermore, the progression of inflammation and liver fibrosis was associated with a decreased proportion of CD3+ NK1.1+ cells. The WD represents a model of advanced-stage NASH, and the HFD60 is a strong model of nonalcoholic fatty liver disease (NAFLD) and metabolic syndrome. However, the CAFD should not be considered a NASH model
Insulin resistance is the main characteristic of metabolically unhealthy obesity (MUO) associated with NASH in patients undergoing bariatric surgery
(1) Background: Metabolically healthy obesity (MHO) is a concept that applies to obese patients without any elements of metabolic syndrome (metS). In turn, metabolically unhealthy obesity (MUO) defines the presence of elements of metS in obese patients. The components of MUO can be divided into subgroups regarding the elements of inflammation, lipid and glucose metabolism and cardiovascular disease. MUO patients appear to be at greater risk of developing non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) compared to MHO patients. The aim of this study was to evaluate the influence of different MUO components on NAFLD and NASH in patients with morbid obesity undergoing bariatric surgery. (2) Methods: 141 patients undergoing bariatric surgery from September 2015 and October 2021 at RWTH Aachen university hospital (Germany) were included. Patients were evaluated pre-operatively for characteristics of metS and MUO (HbA1c, HOMA, CRP, BMI, fasting glucose, LDL, TG, HDL and the presence of arterial hypertension). Intraoperatively, a liver biopsy was taken from the left liver lobe and evaluated for the presence of NAFLD or NASH. In ordinal regression analyses, different factors were evaluated for their influence on NAFLD and NASH. (3) Results: Mean BMI of the patients was 52.3 kg/m (36–74.8, SD 8.4). Together, the parameters HbA1c, HOMA, CRP, BMI, fasting glucose, LDL, TG, HDL and the presence of arterial hypertension accounted for a significant amount of variance in the outcome, with a likelihood ratio of χ (9) = 41.547, p < 0.001, for predicting the presence of NASH. Only HOMA was an independent predictor of NASH (B = 0.102, SE = 0.0373, p = 0.007). Evaluation of steatosis showed a similar trend (likelihood ratio χ (9) = 40.272, p < 0.001). Independent predictors of steatosis were HbA1c (B = 0.833, SE = 0.343, p = 0.015) and HOMA (B = 0.136, SE = 0.039, p < 0.001). (4) Conclusions: The above-mentioned model, including components of MUO, was significant for diagnosing NASH in patients with morbid obesity undergoing bariatric surgery. Out of the different subitems, HOMA independently predicted the presence of NASH and steatosis, while HbA1c independently predicted steatosis and fibrosis. Taken together, the parameter of glucose metabolism appears to be more accurate for the prediction of NASH than the parameters of lipid metabolism, inflammation or the presence of cardiovascular disease