Laparoscopic sleeve gastrectomy reverses non-alcoholic fatty liver disease modulating oxidative stress and inflammation

Metabolism ◽  
2019 ◽  
Vol 99 ◽  
pp. 81-89 ◽  
Author(s):  
Noemí Cabré ◽  
Fedra Luciano-Mateo ◽  
Salvador Fernández-Arroyo ◽  
Gerard Baiges-Gayà ◽  
Anna Hernández-Aguilera ◽  
...  
2020 ◽  
Vol 13 (3) ◽  
pp. 190-200
Author(s):  
Aleksandra Mitsinskaya ◽  
Victor Kaschenko ◽  
Mikhail Fishman ◽  
Alexey C. Sokolov ◽  
V. S. Samoilov ◽  
...  

Introduction. Non-alcoholic fatty liver disease (NAFLD) is one of the most common pathologies in obesity, at the same time the impact of bariatric operations on the course of NAFLD remains unresolved and debatable, the issue determining the relevance of this work.The aim of the study was to assess the effect of laparoscopic sleeve gastrectomy (LSG) on the course of NAFLD and determine the criteria that affect the dynamics of NAFLD after a performed bariatric intervention.Materials and methods. The study included clinical outcomes of 64 patients who underwent LSG between 2014 and 2017. Intraoperative liver biopsy, laboratory and instrumental investigations, the calculation of FibroTest in dynamics were performed to all patients. The frequency of postoperative complications was assessed. Follow up examinations including 58 (90.6%) patients were carried out during 2 years.Results. Initially, 29 (45,3%) patients manifested signs of fibrosis according to METAVIR, and 19 (29,7%) patients manifested signs of non-alcoholic steatohepatitis (NASH). Elevated transaminases were registered in 14 (21,9%) patients, elevated levels of gamma-glutamyl transpeptidase (GGTP) were registered in 47 (73,4%) patients, increased total bilirubin were registered in 12 (18,8%) patients, increased alkaline phosphatase (ALP) were registered in 21 (32,8%) patients. There was an increased level of trygliceride (TG) and decreased level of high density lipoproteins (HDL) in 54 (84,4%) patients. Ultrasound investigation of the liver revealed an increased liver size in 46 (71,9%) patients, diffuse heterogeneity of the liver in 61 (95,3%), hyperechogenicity in 60 (93,8%) patients. Manifestations of liver cirrhosis were registered in 1 (1,6%) patient.There was a significant decrease in the excess body weight in the postoperative period, and hereat, the % EBMIL (Excess Body Mass Index Loss, percentage of overweight loss) in 1 year after laparoscopic sleeve gastrectomy achieved satisfactory values and amounted to 68,30 [58,67-78,77] %. ALT, AST findings were normal in 79,7% of operated patients, cholestasis parameters - in 76,5% of operated patients, FibroTest findings - in 42,2% of cases. In 6 months after surgery there was a deterioration of the clinical and biochemical properties of non-alcoholic fatty liver disease, which was transient and regressed in one year after surgery. The mortality rate during the entire follow-up period was 0%. The effect of the surgery on the signs of non-alcoholic fatty liver disease persisted for 2 years after surgery.Laparoscopic sleeve gastrectomy demonstrated high effectiveness in patients under 45 years old compared to the patients over 45 years old, and in patients with initial stages of fibrosis F0-F2 by METAVIR compared to patients with stages F3-F4 by METAVIR. In addition, patients with BMI higher than 40 kg/m2 achieved higher FibroTest findings after 6 months compared to subjects with BMI lower than 40 kg/m2, and in fewer cases FibroTest findings normalized in 1 year after surgery, respectively.Conclusions. Therefore, it was noted the efficacy of laparoscopic sleeve gastrectomy in patients with obesity and non-alcoholic fatty liver disease; at the same time, it was revealed a transient worsening of the course of the disease in 6 months after surgery.


2018 ◽  
Vol 1 (2) ◽  
pp. 24-28
Author(s):  
Tanita Suttichaimongkol

Non-alcoholic fatty liver disease (NAFLD) is a leading cause of death from liver cirrhosis, endstage liver disease, and hepatocellular carcinoma. It is also associated with increased cardiovasculardisease and cancer related mortality. While lifestyle modifications are the mainstay of treatment,only a proportion of patients are able to make due to difficult to achieve and maintain, and so moretreatment options are required such as pharmacotherapy. This review presents the drugs used inmanaging NAFLD and their pharmacologic targets. Therapies are currently directed towards improvingthe metabolic status of the liver, insulin resistance, cell oxidative stress, apoptosis, inflammation orfibrosis. Several agents are now in large clinical trials and within the next few years, the availability oftherapeutic options for NAFLD will be approved.     Keywords: nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, fibrosis, cirrhosis  


Biomedicines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 687
Author(s):  
Daniela Gabbia ◽  
Luana Cannella ◽  
Sara De De Martin

A peculiar role for oxidative stress in non-alcoholic fatty liver disease (NAFLD) and its transition to the inflammatory complication non-alcoholic steatohepatitis (NASH), as well as in its threatening evolution to hepatocellular carcinoma (HCC), is supported by numerous experimental and clinical studies. NADPH oxidases (NOXs) are enzymes producing reactive oxygen species (ROS), whose abundance in liver cells is closely related to inflammation and immune responses. Here, we reviewed recent findings regarding this topic, focusing on the role of NOXs in the different stages of fatty liver disease and describing the current knowledge about their mechanisms of action. We conclude that, although there is a consensus that NOX-produced ROS are toxic in non-neoplastic conditions due to their role in the inflammatory vicious cycle sustaining the transition of NAFLD to NASH, their effect is controversial in the neoplastic transition towards HCC. In this regard, there are indications of a differential effect of NOX isoforms, since NOX1 and NOX2 play a detrimental role, whereas increased NOX4 expression appears to be correlated with better HCC prognosis in some studies. Further studies are needed to fully unravel the mechanisms of action of NOXs and their relationships with the signaling pathways modulating steatosis and liver cancer development.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Mihiri Goonetilleke ◽  
Nathan Kuk ◽  
Jeanne Correia ◽  
Alex Hodge ◽  
Gregory Moore ◽  
...  

Abstract Background Non-alcoholic fatty liver disease is the most common liver disease globally and in its inflammatory form, non-alcoholic steatohepatitis (NASH), can progress to cirrhosis and hepatocellular carcinoma (HCC). Currently, patient education and lifestyle changes are the major tools to prevent the continued progression of NASH. Emerging therapies in NASH target known pathological processes involved in the progression of the disease including inflammation, fibrosis, oxidative stress and hepatocyte apoptosis. Human amniotic epithelial cells (hAECs) were previously shown to be beneficial in experimental models of chronic liver injury, reducing hepatic inflammation and fibrosis. Previous studies have shown that liver progenitor cells (LPCs) response plays a significant role in the development of fibrosis and HCC in mouse models of fatty liver disease. In this study, we examined the effect hAECs have on the LPC response and hepatic oxidative stress in an experimental model of NASH. Methods Experimental NASH was induced in C57BL/6 J male mice using a high-fat, high fructose diet for 42 weeks. Mice received either a single intraperitoneal injection of 2 × 106 hAECs at week 34 or an additional hAEC dose at week 38. Changes to the LPC response and oxidative stress regulators were measured. Results hAEC administration significantly reduced the expansion of LPCs and their mitogens, IL-6, IFNγ and TWEAK. hAEC administration also reduced neutrophil infiltration and myeloperoxidase production with a concurrent increase in heme oxygenase-1 production. These observations were accompanied by a significant increase in total levels of anti-fibrotic IFNβ in mice treated with a single dose of hAECs, which appeared to be independent of c-GAS-STING activation. Conclusions Expansion of liver progenitor cells, hepatic inflammation and oxidative stress associated with experimental NASH were attenuated by hAEC administration. Given that repeated doses did not significantly increase efficacy, future studies assessing the impact of dose escalation and/or timing of dose may provide insights into clinical translation.


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