Cláudio Corá Mottin

The Role of Ultrasound in the Diagnosis of Hepatic Steatosis in Morbidly Obese Patients

Background: Hepatic steatosis is prevalent in obese patients. Although it requires histology for diagnosis, ultrasound may indicate its presence. We evaluated the importance of ultrasound in the diagnosis of steatosis in morbidly obese patients, and considered its clinical relevance for patients with BMI of 35-40 kg/m2 without co-morbidities. Methods: 187 morbidly obese patients submitted to bariatric surgery were prospectively studied. All patients had ultrasound before the operation, and hepatic biopsies during the operation, which were compared. Results: The prevalence of steatosis histologically was 91.4%. The sensitivity and specificity of ultrasound in diagnosing steatosis was 49.1% and 75%, respectively,with a positive predictive value of 95.4%. Conclusion: The biopsies found a very high prevalence of steatosis in the studied population. The ultrasound results yielded a high positive predictive value (95.4%), suggesting its use as a diagnostic tool for this co-morbidity in morbidly obese patients.The low sensitivity of the method could be related to the lack of objective criteria for the ultrasound diagnosis of steatosis, and probably, technical problems in performing ultrasound in such patients. We believe that in patients with a BMI of 35-40 kg/m2 without other comorbidities, the ultrasound finding of steatosis could be of value as an indication for bariatric surgery.

Effect of Bariatric Surgery on Liver Fibrosis

BackgroundAlthough bariatric surgery has been shown to improve hepatic steatosis in morbidly obese patients, the effect of weight loss on hepatic fibrosis has not been determined. Since the prognosis of patients with nonalcoholic fatty liver disease is closely related to the development of hepatic fibrosis, it is important to determine the hepatic histology of these patients after weight loss. We therefore evaluated the prevalence of hepatic fibrosis in morbidly obese patients undergoing bariatric surgery and assessed the correlation of histologic changes with weight loss.MethodsWe retrospectively evaluated 78 morbidly obese patients who underwent gastric bypass. Liver biopsies were taken during surgery and after weight loss, and the correlations between histologic findings and hepatic fibrosis were determined.ResultsOf the 78 patients, 35 (44.8%) had fibrosis at first biopsy, and 24 (30.8%) had hepatic fibrosis after weight loss, including 19 of the 35 patients (54.3%) with fibrosis at first biopsy and 5 of the 43 (11.6%) without hepatic fibrosis at first biopsy (P = 0.027).ConclusionsWeight loss in morbidly obese patients was associated with a reduction in the prevalence of hepatic fibrosis.

SIRT1 Transcription Is Decreased in Visceral Adipose Tissue of Morbidly Obese Patients with Severe Hepatic Steatosis

BackgroundVisceral adipose tissue is known to release greater amounts of adipokines and free fatty acids into the portal vein, being one of the most predictive factors of nonalcoholic fatty liver disease (NAFLD). Our study has the purpose to evaluate sirtuin 1 (SIRT1), adiponectin, Forkhead/winged helix (FOXO1), peroxisome proliferator-activated receptor (PPAR)γ1–3, and PPARβ/δ mRNA expression in morbidly obese patients in three different lipid depots: visceral (VAT), subcutaneous (SAT), and retroperitoneal (RAT). Recent studies suggest that SIRT1, a NAD+-dependent deacetylase, protects rats from NAFLD.MethodsWe divided the patients in two groups: those with slight or moderate steatosis (hepatic steatosis, HS) and other comprising individuals with severe steatosis associated or not with necroinflammation and fibrosis (severe hepatic steatosis, SHS). The adipose tissue depots were obtained during bariatric surgery. Total RNAs were extracted using TRIzol. The amount of genes of interest was determined by quantitative real-time polymerase chain reaction.ResultsWhen comparing the two groups of patients, a decrease in SIRT1 was observed in VAT of morbidly obese patients in SHS group (p = 0.006). The mRNA expression of the other genes showed no differences in VAT. No difference was found either in SAT or in RAT for all genes in the study. In addition, the homeostasis model assessment for insulin resistance (HOMA-IR) value was higher in SHS group compared to HS (p = 0.006). Also, our results show that the mRNA expression of SIRT1 and the value of HOMA-IR were positively correlated in VAT of SHS patients (r = 0.654; p = 0.048).ConclusionsDownregulation of SIRT1 mRNA expression in VAT of SHS could be possible impairing mitochondria biogenesis and fatty acid oxidation, promoting severe steatosis in obese patients. Our results provide a possible proof of SIRT1 protective potential in VAT against NAFLD in humans.

Hepatic Steatosis In Patients Undergoing Bariatric Surgery and its Relationship to Body Mass Index and Co-Morbidities

Background: Although non-alcoholic hepatitis usually is asymptomatic and benign, this condition may progress to cirrhosis and hepatic failure. Some findings are similar to alcoholic hepatitis, but there is no history of excessive alcohol consumption. Among the factors associated with non-alcoholic hepatitis, obesity, diabetes and dyslipidemia are the most important. Methods: 77 consecutive patients undergoing bariatric surgery had their liver biopsy compared to the presence of co-morbidities and BMI. Results: 67 patients (87.1%) had an abnormal liver biopsy, mostly due to steatosis (83.1%), but also steatohepatitis (2.6%) and cirrhosis (1.3%). The degree of liver damage was related to higher BMI scores. Co-morbidities were present in 46.9% of the patients with hepatic steatosis. Conclusions: The authors suggest that a liver biopsy should be performed in all patients at bariatric surgery, in order to evaluate possible liver damage and to assist postoperative care.

Bariatric surgery in the treatment of obstructive sleep apnea in morbidly obese patients.

Background: Weight loss has been shown effective in the treatment of the obstructive sleep apnea-hypopnea syndrome. Regrettably, many obese patients are unable to achieve sustained and useful weight loss by dietary means. Recently, bariatric surgery has emerged as an alternative to treat obesity and many of its comorbidities, although its role for sleep apnea treatment is still not defined. Objectives: To evaluate the impact of bariatric surgery on obstructive sleep apnea in morbidly obese patients. Methods: In this cohort study, polysomnography, Epworth Sleepiness Scale questionnaire and clinical assessment were performed in 12 of 13 morbidly obese patients with moderate to severe obstructive sleep apnea treated with bariatric surgery through Roux-en-Y gastric bypass procedure after a minimum of 18 months post surgery. Results: The mean (±SD) loss of excess body weight was 70.5 ± 24%. The mean level obtained in the Epworth Scale was 4.8. There was a significant reduction in the apnea-hypopnea index, from a median of 46.5 (range: 33–140) to 16 (range: 0.9–87) events per hour (p < 0.05), an improvement in mean oxygen saturation from 85.7 ± 5.1 to 94.5 ± 3.6% (p < 0.05) and in minimum oxygen saturation from 64.7 ± 13.4 to 78.7 ± 13.7% (p < 0.05). The magnitude of the weight loss and the improvements in mean and minimum oxygen saturation were positively correlated, (r = 0.76; p ≤ 0.05, and r = 0.59; p ≤ 0.05, respectively). Conclusions: Weight loss achieved by bariatric surgery is associated with significant long-term improvements in obstructive respiratory event, oxygenation and resolution of daytime somnolence.

Resveratrol Upregulated SIRT1, FOXO1, and Adiponectin and Downregulated PPARγ1–3 mRNA Expression in Human Visceral Adipocytes

BackgroundThe SIRT1 enzyme is involved in adipose tissue (AT) lipolysis. FOXO1 is a protein that plays a significant role in regulating metabolism. Adiponectin is an adipokine, secreted by the AT, which has been considered to have an antiobesity function. PPARγ is one of the key actors in adipocytes differentiation. This study was undertaken to investigate whether resveratrol can regulate SIRT1, FOXO1, adiponectin, PPARγ1–3, and PPARβ/δ in human AT.MethodsThe effects of resveratrol were analyzed in freshly isolated adipocytes prepared from visceral fat tissue samples obtained during bariatric surgery. Genes messenger ribonucleic acid (mRNA) levels were determined by qRT-PCR.ResultsOurs results show that resveratrol modulates the studied genes, increasing SIRT1 (p = 0.021), FOXO1 (p = 0.001), and adiponectin (p = 0.025) mRNA expression and decreasing PPARγ1–3 (p = 0.003) mRNA in human visceral adipocytes.ConclusionsResveratrol, in vitro and at low concentration, modulates genes that are related to lipid metabolism, possibly preventing metabolic disease in human visceral adipose tissue (VAT).

Obesity depresses the anti‐inflammatory HSP70 pathway, contributing to NAFLD progression

To evaluate whether reduced activity of the anti‐inflammatory HSP70 pathway correlates with nonalcoholic fatty liver disease (NAFLD) progression and with markers of oxidative stress because obesity activates inflammatory JNKs, whereas HSP70 exerts the opposite effect.

Higher Content of Trans Fatty Acids in Abdominal Visceral Fat of Morbidly Obese Individuals undergoing Bariatric Surgery compared to Non-Obese Subjects

Background: The purpose of this study was to determine the total content of trans fatty acids (TFA) in subcutaneous, retroperitoneal and visceral fat of morbidly obese and non-obese patients submitted to bariatric surgery or plastic and abdominal surgery. Methods: The adipose tissues were obtained by surgery; lipids were extracted, saponified and esterified. TFA were measured by FTIR-ATR spectroscopy. Results: The TFA average in obese patients was 6.3% for retroperitoneal and 8.7% for visceral fat. For non-obese patients, the figures were 6.9% (subcutaneous) and 9.3% (visceral). There was no difference between the groups. However, the TFA depot in visceral fat was higher than other fatty tissues for morbidly obese (P<0.001) and non-obese (P<0.05) patients. Conclusions: Our values for TFA content in all adipose tissues analyzed are higher than reported in other countries (3-6%). We showed more TFA in visceral adipose tissue than in other abdominal fat (subcutaneous and retroperitoneal) stores. The visceral adipose tissue level is worrisome because the higher rate of lipolysis in this tissue appears to be an important indicator of metabolic alterations and the levels of TFA found in adipose tissue presumably reflect the higher dietary intake of TFA by Brazilians.

Weight‐loss interventions and gut microbiota changes in overweight and obese patients: a systematic review

Imbalances in the gut microbiota, the bacteria that inhabit the intestines, are central to the pathogenesis of obesity. This systematic review assesses the association between the gut microbiota and weight loss in overweight/obese adults and its potential manipulation as a target for treating obesity. This review identified 43 studies using the keywords ‘overweight’ or ‘obesity’ and ‘microbiota’ and related terms; among these studies, 17 used dietary interventions, 11 used bariatric surgery and 15 used microbiota manipulation. The studies differed in their methodologies as well as their intervention lengths. Restrictive diets decreased the microbiota abundance, correlated with nutrient deficiency rather than weight loss and generally reduced the butyrate producers Firmicutes, Lactobacillus sp. and Bifidobacterium sp. The impact of surgical intervention depended on the given technique and showed a similar effect on butyrate producers, in addition to increasing the presence of the Proteobacteria phylum, which is related to changes in the intestinal absorptive surface, pH and digestion time. Probiotics differed in strain and duration with diverse effects on the microbiota, and they tended to reduce body fat. Prebiotics had a bifidogenic effect and increased butyrate producers, likely due to cross‐feeding interactions, contributing to the gut barrier and improving metabolic outcomes. All of the interventions under consideration had impacts on the gut microbiota, although they did not always correlate with weight loss. These results show that restrictive diets and bariatric surgery reduce microbial abundance and promote changes in microbial composition that could have long‐term detrimental effects on the colon. In contrast, prebiotics might restore a healthy microbiome and reduce body fat.

A Comparison of Wedge and Needle Hepatic Biopsy in Open Bariatric Surgery

Background: Morbidly obese patients, despite normal laboratory tests and no clinical evidence of liver disease, present a high prevalence of hepatic histological changes. Liver biopsy is able to provide the diagnosis, staging and assessment of follow-up of hepatic disease, thus helping to define clinical management. There is no agreement on which biopsy technique provides better material for analysis. Considering that subcapsular fibrosis is a common finding, sampling from deeper sites is necessary to achieve an adequate histological assessment. Methods: A study was done in 264 consecutive morbidly obese patients who underwent open Roux-en-Y gastric bypass between July 2001 and Sept 2004, in whom an intraoperative liver biopsy was taken. The first 107 were wedge biopsies, and the last 157 were needle biopsies. The histological degree of steatosis, presence of fibrosis and adequacy of material from the 2 biopsy techniques were compared. Results: Degree of steatosis in both sampling techniques showed no statistical difference (P=0.132). The presence of fibrosis in wedge biopsies (46.1% fibrosis, n 41) was significantly higher than in needle biopsies (13.7% fibrosis, n 20), P<0.001. As expected, sample size of needle biopsies was smaller than that obtained by the wedge technique (P<0.001), but there was no difference in the quality of material obtained (P=0.95). Conclusion: Needle biopsies were as effective as wedge biopsies in assessing the degree of steatosis in morbidly obese patients. More important, the presence of subcapsular fibrosis in needle biopsies was less than in wedge biopsies, suggesting an adequate tissue sample by the less invasive technique.