Lipopolysaccharide-Binding Protein Plasma Levels and Liver TNF-Alpha Gene Expression in Obese Patients: Evidence for the Potential Role of Endotoxin in the Pathogenesis of Non-Alcoholic Steatohepatitis

Background Some lines of evidence suggest that endotoxin may induce non-alcoholic steatohepatitis (NASH) in a background of fatty liver. However, a clear association between increased endotoxemia and development of steatohepatitis in obese patients has not been confirmed. We aim to assess the endotoxemic state of patients with non-alcoholic fatty liver disease (NAFLD) and its relationship with the liver expression of TNF-α and the presence of NASH. Methods Prospective study comprising 40 patients with morbid obesity who were diagnosed with NAFLD. Blood samples and liver biopsies were collected. Endotoxemia was assessed by the evaluation of circulating level of LPS-binding protein (LBP). Plasma levels of LBP and TNF-α were assessed by ELISA. The expression of TNF-α in liver tissue was evaluated by real-time PCR. Histological examination was performed to evaluate the presence of steatosis or NASH. Results Levels of LBP were increased in obese patients with NAFLD. In addition, plasma level of LBP was increased in patients with steatohepatitis (14.2 ± 3.9 μg/mL) when compared with patients with simple steatosis (11.5 ± 3.2 μg/mL), P = 0.041.The TNF-α mRNA expression in liver tissue was significantly higher in patients with NASH.This increment correlated with the rise in plasma levels of LBP (r = 0.412, P = 0.036). Conclusion NAFLD patients have elevated plasma levels of LBP and they are further increased in patients with NASH. This increase is related to a rise in TNF-α gene expression in the hepatic tissue which supports a role for endotoxemia in the development of steatohepatitis in obese patients.     

Lipoprotein Lipase Expression in Livers of Morbidly Obese Patients Could be Responsible for Liver Steatosis

Background  Most patients with morbid obesity develop non-alcoholic fatty liver disease (NAFLD). The origins of lipid deposition in the liver and the effects of bariatric surgery in the obese with NAFLD are controversial. Methods  We analyzed lipids and lipoprotein lipase (LPL) in both plasma and liver biopsies performed before and 12–18 months after Roux-en-Y gastric bypass surgery in 26 patients. Results  In the livers of morbidly obese patients, the levels of LPL messenger RNA (mRNA) were higher (4.5-fold) before surgery than afterwards than control livers. In these patients, LPL activity was also significantly higher (91 ± 7 mU/g) than in controls (51 ± 3 mU/g, p = 0.0026) and correlated with the severity of the liver damage. All hepatic lipids were significantly increased in obese patients; however, after bariatric surgery, these lipids, with the exception of NEFA, tended to recover to normal levels. Conclusions  The liver of obese patients presented higher LPL activity than controls, and unlike the controls, this enzyme could be synthesized in the liver because it also present LPL mRNA. The presence of the LPL activity could enable the liver to capture circulating triacylglycerides, thus favoring the typical steatosis observed in these patients.     

The Utility of the “NAFLD Fibrosis Score” in Morbidly Obese Subjects with NAFLD

Background To date, the noninvasive diagnostic tests for hepatic fibrosis in subjects with nonalcoholic fatty liver disease (NAFLD) have proven to be suboptimal. We evaluated the validity of a recently proposed “NAFLD fibrosis score” to identify liver fibrosis in morbidly obese individuals with elevated and normal alanine aminotransferase (ALT) levels. Methods Medical records of 401 patients that underwent a gastric bypass operation and intraoperative liver biopsy were analyzed. Three hundred thirty one patients with biopsy-proven NAFLD were included in the study (group A). These patients were divided into two ALT groups based on their levels according to the new proposed normal range: group B elevated level (ALT > 19 U/L in females and >30 U/L in males, n = 221) and group C normal ALT (n = 110). Diagnostic accuracy of the system was assessed for the presence/absence of any fibrosis, significant fibrosis (stage 2–4), and advanced fibrosis (stages 3 and 4) in all of the groups. Results The prevalence of advanced fibrosis in our cohort was about 14%. The low NAFLD fibrosis score demonstrated high accuracy for ruling out advanced fibrosis, with negative predictive value (NPV) of 98 and 99% in groups A and B, respectively. The NPV for significant fibrosis in groups A, B, and C was 87, 88, and 88%, respectively. The respective positive predictive value for the high NAFLD fibrosis score for the presence of any fibrosis was 88, 95, and 77% in groups A, B, and C. Conclusions The NAFLD fibrosis score may be a useful noninvasive approach for excluding significant and advanced fibrosis and in morbidly obese patients.     

Gastric Emptying of Solids and Semi-solids in Morbidly Obese and Non-obese Subjects: An Assessment Using the <Superscript>13</Superscript>C-Octanoic Acid and <Superscript>13</Superscript>C-Acetic Acid Breath Tests

Background It has been suggested that obesity is associated with an altered rate of gastric emptying. The objective of the present study was to determine whether the rates of solid and semi-solid gastric emptying differ between morbidly obese patients and lean subjects. Methods The Gastric-emptying time (GET) of solid and semi-solid meals were compared between lean healthy subjects and morbidly obese patients enrolled in two previously published studies. GET of solid and semi-solid meals was measured using the ¹³C-octanoic acid breath test and ¹³C-acetic acid breath test, respectively, in 24 lean and 14 morbidly obese individuals of both sexes. Student t-test was used to compare the mean data between the lean and morbidly obese groups. The influence of sex, gender, BMI and morbid obesity on the GET of solid meals was verified by linear regression analysis. Results Mean t(1/2) values of solid GET (± standard deviation) were 203.6 ±  76.0 min and 143.5 ± 19.1 min for lean and obese subjects, respectively (P = 0.0010). Mean t(lag) values of solid GET were 127.3 ± 42.7 min and 98.4 ± 13.0 min for lean and obese subjects, respectively (P = 0.0044). No significant difference in semi-solid GET was observed between the lean and morbidly obese groups. Conclusion The present study demonstrated a significantly enhanced gastric emptying of the solid meal test in morbidly obese patients when compared to lean subjects. This finding is compatible with the hypothesis that rapid gastric emptying in morbidly obese subjects increases caloric intake due to a more rapid loss of satiety.     

Adipokine Serum Levels Are Related to Liver Histology in Severely Obese Patients Undergoing Bariatric Surgery

Background  Leptin, adiponectin, and resistin are adipokines linked to the development of insulin resistance, which plays a central role in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). We aimed to define adipokine serum levels in severely obese patients undergoing bariatric surgery and to correlate these with anthropometric and metabolic variables, liver function tests, and histopathological parameters of NAFLD and nonalcoholic steatohepatitis (NASH). Methods  Surgical liver biopsies were obtained from 50 bariatric patients with no history of liver disease or significant alcohol consumption. Serum leptin, adiponectin, and resistin levels were measured, and histology was assessed using Brunt’s and Kleiner’s scoring systems. Results  Waist/hip ratio was significantly higher in men (p = 0.0001), and leptin (p = 0.036) and adiponectin (p = 0.0001) serum levels were higher in women. Forty-one of 50 patients (82%) had histological NAFLD, including 10 (20%) with NASH. Nine patients (18%) had normal liver histology (obese control subgroup). In NAFLD patients, serum adiponectin was negatively correlated with activity grade and fibrosis stage, resistin was negatively correlated with steatosis grade (p = 0.033), while leptin was not related to histology. Leptin/adiponectin ratio showed positive association with stage (p = 0.044). In the subgroup of NASH patients, adiponectin was negatively correlated only with stage (p = 0.01), while there was no correlation between leptin, resistin, or leptin/adiponectin and histology. Conclusions  Serum adiponectin and resistin levels are related to liver histology in bariatric patients and may be indicative of the histological severity of NAFLD and the extent of hepatic steatosis, respectively. Serum leptin levels are not informative of underlying liver histology in severely obese patients. Marianna Argentou and Dina G. Tiniakos contributed equally to this work. The authors disclose no conflict of interest.     

Histological Changes in the Liver of Morbidly Obese Patients: Correlation with Metabolic Parameters

Background: Obesity is a major risk factor for fatty liver disease. The purpose of this study was: 1) to determine the degree of steatosis, inflammation and fibrosis in liver biopsies of morbidly obese patients in relation to their body fat distribution and metabolic status, and 2) to examine the course of liver enzyme changes with surgically-induced weight loss. Methods: The study population included 179 morbidly obese bariatric surgical patients (82% female, 18% male, mean age 39±0.7 (SEM) years, BMI 52±0.6 kg/m², excess body weight 80±1.8 kg). All patients tested negative for hepatitis and HIV. Liver biopsies were taken intra-operatively. Hepatic enzyme activities were measured along with lipid parameters, fasting glucose, insulin and leptin. Results: Liver biopsies showed that 47% of morbidly obese females and 85% of males had >30% of hepatocytes filled with fat droplets. Clinically significant hepatic steatosis was associated (P<0.01) with: a) metabolic aberrations, i.e.hyperlipidemia, hyperglycemia, b) male gender, c) abdominal adiposity, and d) elevated hepatic aminotransferase activities. Hepatic inflammation was found in 47% of females and 55% of males, and 'moderate' fibrosis occurred in 12% of males and 6% of females. Postoperatively, the activity of hepatic aminotransferases declined after an initial increase in response to weight loss, with normalization of values occurring at an excess weight loss of 50% (P<0.0001). Conclusion: The majority of morbidly obese patients have >30% steatosis of the liver. The incidence of steatosis is higher for males than females, possibly due to their visceral obesity and associated metabolic aberrations.     

Relationship between Obstructive Sleep Apnea and Liver Abnormalities in Morbidly Obese Patients: A Prospective Study

Background Morbid obesity is a risk factor of nonalcoholic steatohepatitis (NASH). Obstructive sleep apnea (OSA) could also be an independent risk factor for elevated liver enzymes and NASH. The relationships between liver injuries and OSA in morbidly obese patients requiring bariatric surgery were studied prospectively. Methods Every consecutive morbidly obese patient (BMI ≥40 kg/m² or ≥35 kg/m² with severe comorbidities) requiring bariatric surgery was included between January 2003 and October 2004. Polygraphic recording, serum aminotransferases (ALT, AST), γ-glutamyltransferase (GGT) and liver biopsy were systematically performed. OSA was present when the apnea–hypopnea index (AHI) was >10/h. Results 62 patients (54 F; age 38.5 ± 11.0 (SD) yrs; BMI 47.8 ± 8.4 kg/m²) were included. Liver enzymes (AST, ALT or GGT) were increased in 46.6%. NASH was present in 34.4% and OSA in 84.7%. Patients with OSA were significantly older (P = 0.015) and had a higher BMI (P = 0.003). In multivariate analysis, risk factors for elevated liver enzymes were the presence of OSA and male sex.The presence of NASH was similar in patients with or without OSA (32.7% vs 44.4% of patients, P = 0.76). Conclusion In this cohort of morbidly obese patients requiring bariatric surgery, one-third of patients had NASH, a prevalence similar to previous studies. OSA was found to be a risk factor for elevated liver enzymes but not for NASH.     

Lipid Peroxidation in Bariatric Candidates with Nonalcoholic Fatty Liver Disease (NAFLD) – Preliminary Findings

Background: Pathogenesis of nonalcoholic fatty liver disease (NAFLD) remains incompletely known, and oxidative stress is one of the mechanisms incriminated. The aim of this study was to evaluate the role of liver oxidative stress in NAFLD affecting morbidly obese patients. Methods: 39 consecutive patients with BMI >40 kg/m² submitted to Roux-en-Y gastric bypass were enrolled, and wedge liver biopsy was obtained during operation. Oxidative stress was measured by concentration of hydroperoxides (CEOOH) in liver tissue. Results: Female gender was dominant (89.7%) and median age was 43.6 ± 11.1 years. Histology showed fatty liver in 92.3%, including 43.6% with nonalcoholic steatohepatitis (NASH), 48.7% with isolated steatosis and just 7.7% with normal liver. Liver cirrhosis was present in 11.7% of those with nonalcoholic steatohepatitis. Concentration of CEOOH was increased in the liver of patients with NASH when compared to isolated steatosis and normal liver (0.26± 0.17, 0.20± 0.01 and 0.14± 0.00 nmol/mg protein, respectively) (P <0.01). Liver biochemical variables were normal in 92.3% of all cases, and no difference between NASH and isolated steatosis could be demonstrated. Conclusions: 1) Nonalcoholic steatosis, steatohepatitis and cirrhosis were identified in substantial numbers of morbidly obese patients; 2) Concentration of hydroperoxides was increased in steatohepatitis, consistent with a pathogenetic role for oxidative stress in this condition.     

Histological Behavior of Hepatic Steatosis in Morbidly Obese Patients after Weight Loss Induced by Bariatric Surgery

Background: Hepatic steatosis has a high prevalence among morbidly obese patients. Its relation to steatohepatitis and cirrhosis has been extensively studied among these patients. The aim of this study was to evaluate the behavior of hepatic steatosis with weight loss 1 year after bariatric surgery. Methods: This study is a historical cohort that compared liver biopsies obtained from morbidly obese patients during the bariatric operation, with percutaneous biopsies taken from the same patient 1 year after surgery. The results were compared with weight loss, patients' profile (gender, age, body mass index (BMI) and waist/hip ratio), and with the presence of co-morbidities such as diabetes, hypertension, and dyslipidemia. Results: 90 patients who had liver biopsies taken at the operation and postoperative period for bariatric surgery were included. The prevalence of hepatic steatosis was 87.6%. The average percent of excess weight loss was 81.4%. On the second biopsy, 16 patients (17.8%) of the total had the same degree of steatosis, 25 (27.8%) improved their steatosis pattern and 49 (54.4%) had normal hepatic tissue. There was no statistical difference regarding age, BMI, waist/hip ratio, and co-morbidities (P>0.05), but there was a difference in gender (P=0.044). Conclusion: Significant improvement in the hepatic histology of steatosis was observed after weight loss induced by bariatric surgery in most patients. There was no patient with a worsening in the histology.     

Laparoscopic bariatric surgery: what else are we uncovering? Liver pathology and preoperative indicators of advanced liver disease in morbidly obese patients

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the US, and obesity is the most common cause of NAFLD. Obesity and NAFLD are associated with hyperlipidemia, type 2 diabetes, and hypertension, all components of the metabolic syndrome. The purpose of this study was to examine the incidence of NAFLD among morbidly obese patients undergoing bariatric surgery and to determine if advanced liver disease can be predicted by demographics, comorbidities, and/or preoperative biochemical profiles. 135 nonconsecutive patients (109 female, average age 46) with mean body mass index (BMI) 50 (SD 7.6) who underwent liver biopsies during bariatric surgery were studied. Patient data including age, BMI, comorbidities, and preoperative liver function tests were analyzed against liver biopsy pathology. 86% of patients had abnormal liver biopsy results. 60% of patients had steatosis, and 27% had advanced liver disease (7% steatohepatitis, 16% fibrosis, and 4% cirrhosis). Patients were grouped according to liver biopsy pathology. Group A included patients with normal results and steatosis only. Group B included those patients with advanced liver disease:steatohepatitis, fibrosis, and cirrhosis. Of 37 patients in group B, 27% had abnormal preoperative liver function tests (LFTs) compared to 10% of patients in group A (p = 0.022). Patients in group B were more likely to have preoperative hyperlipidemia (p = 0.020) and were also found to have a significantly higher BMI (p = 0.042). Diabetes mellitus, male gender, and age were not predictive of advanced liver disease on liver biopsy, with p = 0.056, p = 0.074, p = 0.26, respectively. Liver disease is common in the morbidly obese. More than one quarter of morbidly obese patients undergoing bariatric surgery have advanced liver disease. Patients with increased preoperative LFTs, hyperlipidemia, and increased BMI are more likely to have non-alcoholic steatohepatitis, fibrosis, or cirrhosis on liver biopsy during weight loss surgery. Diabetes, male gender, and age did not predict advanced liver disease.     

Boussignac CPAP in the Postoperative Period in Morbidly Obese Patients

Background In the postoperative period hypoventilation and hypoxia with hypercarbia may occur in morbidly obese patients due to the residual influence of general anesthesia drugs, postoperative atelectasis and postoperative pain. Non-Invasive Ventilation (NIV) is a method of improvement of respiratory efficiency in patients not requiring mechanical ventilation. The aim of the study was to compare NIV (Boussignac) CPAP and traditional oxygen delivery via nasal catheter in the postoperative acute care unit (PACU) in morbidly obese patients after open Roux-en-Y gastric bypass (RYGBP). Methods 19 morbidly obese patients scheduled for elective open RYGBP, were randomly divided into 2 groups: CPAP (10 patients) or control (nasal catheter – 9 patients). Patients consisted of: 8 male and 11 female, mean weight 127.76 ± 18.5 kg, height 173.41 ± 9.41 cm, BMI 42.43 ± 3.3 kg/m2, age 35.84 ± 9.05 years. In the PACU, capillary blood gas measurements were taken at 3 Time Points: T1 – 30 min, T2 – 4 hours and T3 – 8 hours after admission. Sample T0 was taken before surgery. For management of postoperative pain, patients received morphine 2 mg/h intravenously and tramadol 100 mg. Results Mean blood gas measurements of all postoperative time points were: pO₂ 81.0 ± 16.0 (range 78.1–85.7) mmHg vs 65.9 ± 4.9 (range 63.8–68.1) mmHg (P < 0.05); pCO₂ 40.6 ± 2.4 (range 39.4–41.8) mmHg vs 41.5 ± 4.0 (range 39.6–43.4) mmHg (P > 0.05), in the CPAP and control groups respectively. In every case, pulse-oxymetry oxygenation was >94%. Conclusion Boussignac CPAP improved blood oxygenation compared to passive oxygenation with a nasal catheter but had no influence on CO₂ elimination in non-CO₂ retaining morbidly obese patients.     

Resolution of Nonalcoholic Steatohepatits after Gastric Bypass Surgery

Background Nonalcoholic fatty liver disease (NAFLD) has been increasingly recognized as a common chronic liver condition. Previous studies have been variable regarding the histological outcomes after rapid weight loss. The aim of this study was to characterize the histopathologic changes in NASH following laparoscopic Roux-en-Y Gastric Bypass surgery (LRYGBP). Methods We retrospectively analyzed paired needle liver biopsies taken during and following LRYGBP in 39 patients according to the recent NIH-based NAFLD criteria. Results The cohort included 33 females and 6 males (range 24–57 years). 23 patients (58.9%) had steatohepatitis, 12 with fatty liver (30.7%), and 4 were normal (10.2%). Follow-up needle liver biopsies were performed at a mean interval of 18 months (range 6–41 months). No significant differences in length or number of portal tracts between the paired biopsies were noted. The mean decrease in weight and BMI was 50.2 kg and 18.2 kg/m², respectively. The initial prevalence of hepatic pathology: steatosis (89.7%), hepatocellular ballooning (58.9%), and centrilobular/perisinusoidal fibrosis (50%) improved significantly after LRYGBP: steatosis (2.9%), ballooning (0%), and centrilobular fibrosis (25%). Mitigation in the lobular inflammation score (2.23 ± 0.63 vs 1.95 ± 0.56, P = 0.01) and stage of fibrosis (1.14 ± 1.05 to 0.72 ± 0.97, P = 0.002) were also noted. However, no improvements were detected in portal tract inflammation and fibrosis. Conclusions Over a mean period of 18 months, histological improvements and resolution of NASH occurs after LRYGBP. Long-term studies are warranted to assess for potential changes in the portal regions or relapse of NASH that could result with weight regain or malnutrition.     

Albuminuria and insulin resistance in children with biopsy proven non-alcoholic fatty liver disease

Insulin resistance may favor increased urinary albumin excretion (UAE), leading progressively to chronic kidney disease (CKD). A recent study on non-alcoholic fatty liver disease (NAFLD), a condition of insulin resistance, associated this disease with the incidence of CKD in patients with type 2 diabetes. The aim of our study was to determine whether there is an association between insulin resistance and kidney function, based on estimates of UAE and creatinine clearance in children with biopsy-proven NAFLD. Kidney function was assessed in 80 patients with NAFLD and 59 individuals of normal weight matched for age and sex. Insulin resistance was measured by means of the homeostatic model assessment-insulin resistance (HOMA-IR) and limited to NAFLD patients by using the whole-body insulin sensitivity index. The HOMA-IR was found to differ significantly between the two groups (2.69 ± 1.7 vs. 1.05 ± 0.45; p = 0.002), while UAE (9.02 ± 5.8 vs. 8.0 ± 4.3 mg/24 h; p = 0.9) and creatinine clearance (78 ± 24 vs. 80 ± 29 mg/min; p = 0.8) did not. We found a significant but weak inverse correlation between insulin sensitivity and creatinine clearance in NAFLD patients (r _s = –0.25;p = 0.02). No difference was observed in kidney function between NAFLD children presenting with or without metabolic syndrome, low or normal HDL-cholesterol, and different degrees of histological liver damage (grade of steatosis ≥2, necro-inflammation, and fibrosis). Patients with hypertension had increased levels of UAE (p = 0.04). A longer exposure to insulin resistance may be required to cause the increase in urinary albumin excretion and to enable the detection of the effect of the accelerated atherogenic process most likely occurring in children with fatty liver disease. Longitudinal studies are needed to rule out any causative relationship between insulin resistance and urinary albumin excretion.     

Gastroesophageal Reflux in Patients with Morbid Obesity: A Role of Obstructive Sleep Apnea Syndrome?

Background  Obesity is a risk factor for gastroesophageal reflux disease (GERD) and for obstructive sleep apnea (OSA). Our aim was to evaluate in morbidly obese patients the prevalence of OSA and GERD and their possible relationship. Methods  Morbidly obese patients [body mass index (BMI) >40 or >35 kg/m² in association with comorbidities] selected for bariatric surgery were prospectively included. Every patient underwent a 24-h pH monitoring, esophageal manometry, and nocturnal polysomnographic recording. Results  Sixty-eight patients [59 women and 9 men, age 39.1 ± 11.1 years; BMI 46.5 ± 6.4 kg/m² (mean ± SD)] were included. Fifty-six percent of patients had an abnormal Demester score, 44% had abnormal time spent at pH <4, and 80.9% had OSA [apnea hypopnea index (AHI) >10] and 39.7% had both conditions. The lower esophageal sphincter (LES) pressure was lower in patients with GERD (11.6 ± 3.4 vs 13.4 ± 3.6 mm Hg, respectively; P = 0.039). There was a relationship between AHI and BMI (r = 0.337; P = 0.005). Patients with OSA were older (40.5 ± 10.9 vs 33.5 ± 10.4 years; P = 0.039). GERD tended to be more frequent in patients with OSA (49.1% vs 23.1%, respectively; P = 0.089). There was no significant relationship between pH-metric data and AHI in either the 24-h total recording time or the nocturnal recording time. In multivariate analysis, GERD was significantly associated with a low LES pressure (P = 0.031) and with OSA (P = 0.045) but not with gender, age, and BMI. Conclusion  In this population of morbidly obese patients, OSA and GERD were frequent, associated in about 40% of patients. GERD was significantly associated with LES hypotonia and OSA independently of BMI.     

Diagnostic Value of Ultrasonographic Examination for Nonalcoholic Steatohepatitis in Morbidly Obese Patients Undergoing Laparoscopic Bariatric Surgery

Background There are few data relating to the role of fatty score (FS) and modified fatty score (MFS) in ultrasonographic (US) examination on the diagnosis of nonalcoholic steatohepatitis (NASH) in patients undergoing bariatric surgery. Methods We investigated consecutive patients undergoing laparoscopic bariatric surgery with biopsy-proven nonalcoholic fatty liver disease. Patients with other liver diseases and significant alcohol consumption were excluded. Clinico-demographic and anthropometric data were collected before surgery. Each biopsy specimen was assessed by the same pathologist. Liver US examinations were performed by an independent and experienced sonographer before surgery. FS and MFS, determined by the US scoring system based on degrees of parenchymal echogenicity, far gain attenuation, gallbladder wall blurring, portal vein wall blurring and hepatic vein blurring, were used to assess the severity of fatty liver. US findings were correlated with histologic results. Results Totally 101 patients were enrolled. The mean BMI of the patients was 44.6 ± 5.4 kg/m². 29 patients (29%) were categorized with simple steatosis and 72 (71%) with NASH. FS and MFS were significantly correlated with the histological steatosis, fibrosis and the presence of NASH (P < 0.001). A receiver operating characteristic curve identified the MFS of 2 as the best cut-off point for the prediction of NASH, yielding measures of sensitivity, specificity, positive predictive value, and accuracy for 72%, 86%, 93% and 76%, respectively. The positive likelihood ratio of 5.24 for MFS approximately doubled the post-test probability of NASH from 30% to 70%. Conclusion FS and MFS on US examination exhibit acceptable sensitivity and high specificity for the detection of the presence of NASH in morbidly obese patients and may aid in the selection of patients for closer follow-up or liver biopsy.     

Duodenal Switch Has No Detrimental Effects on Hepatic Function and Improves Hepatic Steatohepatitis after 6 Months

Background: Nonalcoholic steatohepatitis (NASH) is a common histological finding on liver biopsy in morbidly obese patients. The condition, although benign, can progress to cirrhosis and liver failure. We investigated the effect of the duodenal switch (DS) operation on hepatic function and architecture, specifically hepatic steatosis and NASH. Methods: Between November 1999 and June 2004, 697 DS operations were performed for the treatment of morbid obesity. A Tru-Cut needle liver biopsy was routinely performed during the DS operation. Liver function tests were drawn preoperatively for AST and ALT, and again postoperatively at 6, 12 and 18 months and yearly thereafter. Repeat Tru-Cut liver biopsy was performed on all patients (n = 78) who underwent a second intra-abdominal operation for any indication ≥6 months postoperatively. The pathologist evaluated the 2 sets of liver biopsies in a blinded fashion. The hepatic adipose tissue content and the degree of hepatitis were compared in these patients. Results: A transient worsening of the AST (13% of the baseline value, P<.02) and ALT ( 130-160% of the baseline value, P<.0001) levels was found at 6 months after the DS operation. Normal levels were achieved by 12 months postoperatively. A progressive improvement of about 3 grades in severity of NASH and a 60% improvement in hepatic steatosis, were seen by 3 years after the DS operation. Conclusion: DS improves both hepatic steatosis and its resulting inflammation. No detrimental effects on hepatic function were noted after 6 months.     

Changes in Liver Histology Accompanying Massive Weight Loss after Gastroplasty for Morbid Obesity

Background: Nonalcoholic steatohepatitis (NASH) is common in morbid obesity. Our goal was to evaluate the alterations in liver histology and biochemistry before and after weight loss in 51 morbidly obese patients following Mason's vertical banded gastroplasty. Methods: Two biopsies were performed (on entry and after an average of 18 months), while 16 of these subjects had a third biopsy 17 months after the second. Results: On entry, steatosis and steatohepatitis (mostly grade 3) were present in 98.0% and fibrosis (mostly stage 2) in 94.1% of the subjects. After an excess weight loss of 66%, steatosis and steatohepatitis improved significantly (P<0.001). Although a significant overall decrease in fibrosis occurred (P=0.002), 21 patients (41.1%) did not change and only 6 patients (11.7%) increased in fibrosis. None developed cirrhosis. The decrease in steatohepatitis was significantly correlated (P=0.011) with the reduction of BMI. Fasting serum glucose, lipids, lipoproteins, transaminases, gamma-glutamyl transpeptidase, alkaline phosphatase and fibrinogen were also significantly improved at the time of the second biopsy. The third biopsy performed in 16 of the subjects showed further significant improvement in liver histology. Conclusion: NASH improved significantly with massive weight loss in non-diabetic, non-alcoholic, morbidly obese subjects, while fibrosis improved in nearly half of the patients.     

Relationship between the Upper Airway and Obstructive Sleep Apnea-Hypopnea Syndrome in Morbidly Obese Women

Background The authors studied changes in the upper airway in morbidly obese women and the relationship to sleep apnea-hypopnea syndrome (OSAS). Methods Patients underwent a cardiorespiratory polygraphic study, respiratory function test (spirometry, plethysmography, maximum inspiratory pressures and arterial blood gas analysis), and computed tomographic studies of the upper airway. Results 40 morbidly obese women being evaluated for bariatric surgery (mean age 39.6 ± 9.6 years old, BMI 48.7 ± 5.6 kg/m²) were studied. 37 women had OSAS, and 14 had severe OSAS. Results on respiratory function tests were normal. BMI and weight had a positive correlation with apnea-hypopnea index (AHI), apnea index (AI), desaturation index (DI), lowest oxygen saturation and CT90. Uvula diameter had a negative correlation with FEV₁, FVC, VC IN and a positive correlation with TLC. Retropharynx soft tissue at the retropalatal level had a negative correlation with FEV₁, FVC and VC IN. The oropharynx area at maximal inspiration (total lung capacity) obtained a negative correlation with the AHI (r = −0.423, P = 0.044), AI (r = −0.484, P = 0.042) and DI (r = −0.484, P = 0.019). Conclusions Prevalence of OSAS in morbidly obese women is very high. Our results show the significant correlation between BMI and AHI in morbidly obese women. Uvula diameter and retropharynx soft tissue are the upper airway parameters with higher relationship with pulmonary function. A reduction in the cross-sectional area of the airway at the level of the oropharynx could be related to the severity of OSAS in morbidly obese women.     

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.     

Gastro-Esophageal Reflux and Esophageal Motility Disorders in Morbidly Obese Patients before and after Bariatric Surgery

Background Obesity is a predisposing factor to gastro- esophageal reflux disease (GERD), but esophageal function remains poorly studied in morbidly obese patients and could be modified by bariatric surgery. Methods Every morbidly obese patient (BMI ≥40 kg/m² or ≥35 in association with co-morbidity) was prospectively included with an evaluation of GERD symptoms, endoscopy, 24-hour pH monitoring and esophageal manometry before and after adjustable gastric banding (AGB) or Roux-en-Y gastric bypass (RYGBP). Results Before surgery, 100 patients were included (84 F, age 38.4 ± 10.9 years, BMI 45.1 ± 6.02 kg/m2), of whom 73% reported GERD symptoms. Endoscopy evidenced hiatus hernia in 39.4% and esophagitis in 6.4%. The DeMeester score was pathological in 53.3%; 69% of patients had lower esophageal sphincter (LES) pressure <15 mmHg and 7 had esophageal dyskinesia. BMI was significantly related to the DeMeester score (P = 0.018) but not to LES tone or esophageal dyskinesia. Postoperative data were available in 27 patients (AGB n = 12/60, RYGBP n = 15/36). The DeMeester score (normal <14.72) was significantly decreased after RYGBP (24.8 ± 13.7 before vs 5.8 ± 4.9 after; P < 0.001) but tended to increase after AGB (11.5 ± 5.1 before vs 51.7 ± 70.7 after; P = 0.09), with severe dyskinesia in 2 cases. Conclusion: GERD and LES incompetence are highly prevalent in morbidly obese patients. Preliminary postoperative data show different effects of RYGBP and AGB on esophageal function, with worsening of pH-metric data with occasional severe dyskinesia after AGB.