The Effects of Bariatric Surgeries on Non-Alcoholic Fatty Liver Disease

NCT01619215 | Unknown DMC

• 1 other identifier: KSULDRCBSMH001
• Study Type: observational
• Target: 35
• Locations: 1 country
• Sites: 2

Brief Summary

Non-alcoholic fatty liver disease (NAFLD) is the most common form of chronic liver disease. In the absence of chronic alcohol abuse or other liver diseases, NAFLD incorporates a wide spectrum of liver pathologies and is defined by fatty infiltration of the liver (simple hepatosteatosis). It can progress to non-alcoholic steatohepatitis (NASH) and later fibrosis, cirrhosis, and eventually some patients may develop hepatocellular carcinoma with or without cirrhosis. The exact cause of NAFLD is yet to be cleared and it is, therefore, an active area for research. The diagnosis of NAFLD is achieved through histological examination of liver biopsies (invasive), non-invasive markers using serum biomarkers and imaging techniques are still under development. Pathological diagnosis can be then subcategorized based on several scoring systems. More widely used are the Brunt Score or NAS (NAFLD activity score) and the Kleiner's modified NAS. Obesity is highly associated with NAFLD, as the epidemic of obesity has made NAFLD more prevalent. In addition insulin resistance has been linked to NAFLD and this is explained by the increased influx of free fatty acids (FFAs) into the liver. FFA undergoes either β-oxidation or esterification with glycerol to form triglycerides (TGs), resulting in an additional source of fat in the liver. Due to the strong association of NAFLD with obesity, weight reduction procedures are used for the management of NAFLD. In fact, this has been shown to be effective by several studies. However, other studies have reported liver deterioration after bariatric intervention. This conflict is what makes the effects of bariatric procedures a challenging field for further studies. Consequently in this study we are aimed to examine histologic, metabolic and liver function changes induced by the different therapeutic bariatric procedures.

Conditions

Obesity, Morbid; Non-Alcoholic Fatty Liver Disease

Outcome Measures

Primary Outcomes (1)

• Assessment of NAFLD histological changes after bariatric surgery (adjustable gastric banding, sleeve gastrectomy, gastric bypass, and duodenal switch).

  Histological evaluation is done by applying the NAFLD activity score (NAS). The stage of fibrosis will be determined by the five-point (stage 0 to 4) scale.

  Intra-operatively, 3 months and 1 year postoperatively.

Secondary Outcomes (8)

• Assessment of liver function after bariatric surgery.

  Preoperatively, 3 months, 6 months, 1 year and annually for 5 year postoperatively.

• Assessment of NAFLD associated morbidities by detecting the systemic inflammatory changes after bariatric surgery.

  preoperatively, 3 months, 6 months, 1 year and annually for 5 year postoperatively.

• Assessment of NAFLD associated morbidities by detecting the local inflammatory changes after bariatric surgery.

  Baseline (tissues obtained intraoperatively).

• Assessment of NAFLD associated morbidities by detecting the metabolic changes after bariatric surgery.

  Preoperative, 3 months, 6 months, 1 year and annually for 5 years postoperatively.

• Assessment of NAFLD associated morbidities by detecting the endothelial changes after bariatric surgery.

  Preoperative, 6 months, 1, 2 and 5 years postoperatively.

Study Arms (1)

Bariatric Surgery

As the number of patients dropping out during follow-up, we had difficulty achieving our secondary outcomes, and so the team decided to continue the recruitment until all our outcomes are reached. Main part of the primary outcomes is finalised and published The effects of bariatric surgeries on nonalcoholic fatty liver disease. Aldoheyan T, Hassanain M, Al-Mulhim A, Al-Sabhan A, Al-Amro S, Bamehriz F, Al-Khalidi H. Surg Endosc. 2016 Jul 12

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

NAFLD patients

You may qualify if:

• Age between 18 to 60 years.
• Eligible for obesity surgery according to the following criteria:
• BMI \> 30 kg/m2.
• Ability to demonstrate eating habit control by reducing 10% of the original weight prior to surgery
• Pass the nutritional and the psychological assessment
• Pass the preoperative testing to determine the operative risk
• Ultrasound diagnosis of NAFLD prior to surgery.
• Written informed consent.

You may not qualify if:

• Unwilling to take part in the study, or asked to be removed from the study at any time.
• History of alcohol intake \> 20 g/day for 5 or more years
• Evidence autoimmune hepatitis, chronic hepatitis B or C virus, HIV, genetic hemochromatosis, alpha-1 antitrypsin deficiency, Wilson disease, or cirrhosis.
• Pregnancy.
• Currently taking known hepatotoxic medications.
• Failure to attend follow-up for a minimum of 1 year.
• Non-Saudi patients

Sponsors & Collaborators

• King Saud University: lead

Study Sites (2)

King Khalid University Hospital

Riyadh, 7805, Saudi Arabia

RECRUITING

King Khalid University Hospital

Riyadh, 7805, Saudi Arabia

RECRUITING

Related Publications (19)

• Beymer C, Kowdley KV, Larson A, Edmonson P, Dellinger EP, Flum DR. Prevalence and predictors of asymptomatic liver disease in patients undergoing gastric bypass surgery. Arch Surg. 2003 Nov;138(11):1240-4. doi: 10.1001/archsurg.138.11.1240.

  PMID: 14609874 BACKGROUND

• Gholam PM, Kotler DP, Flancbaum LJ. Liver pathology in morbidly obese patients undergoing Roux-en-Y gastric bypass surgery. Obes Surg. 2002 Feb;12(1):49-51. doi: 10.1381/096089202321144577.

  PMID: 11868297 BACKGROUND

• Oliveira CP, Faintuch J, Rascovski A, Furuya CK Jr, Bastos Mdo S, Matsuda M, Della Nina BI, Yahnosi K, Abdala DS, Vezozzo DC, Alves VA, Zilberstein B, Garrido AB Jr, Halpern A, Carrilho FJ, Gama-Rodrigues JJ. Lipid peroxidation in bariatric candidates with nonalcoholic fatty liver disease (NAFLD) -- preliminary findings. Obes Surg. 2005 Apr;15(4):502-5. doi: 10.1381/0960892053723493.

  PMID: 15946429 BACKGROUND

• Frantzides CT, Carlson MA, Moore RE, Zografakis JG, Madan AK, Puumala S, Keshavarzian A. Effect of body mass index on nonalcoholic fatty liver disease in patients undergoing minimally invasive bariatric surgery. J Gastrointest Surg. 2004 Nov;8(7):849-55. doi: 10.1016/j.gassur.2004.07.001.

  PMID: 15531238 BACKGROUND

• Dixon JB, Bhathal PS, O'Brien PE. Nonalcoholic fatty liver disease: predictors of nonalcoholic steatohepatitis and liver fibrosis in the severely obese. Gastroenterology. 2001 Jul;121(1):91-100. doi: 10.1053/gast.2001.25540.

  PMID: 11438497 BACKGROUND

• Ruhl CE, Everhart JE. Determinants of the association of overweight with elevated serum alanine aminotransferase activity in the United States. Gastroenterology. 2003 Jan;124(1):71-9. doi: 10.1053/gast.2003.50004.

  PMID: 12512031 BACKGROUND

• Spaulding L, Trainer T, Janiec D. Prevalence of non-alcoholic steatohepatitis in morbidly obese subjects undergoing gastric bypass. Obes Surg. 2003 Jun;13(3):347-9. doi: 10.1381/096089203765887633.

  PMID: 12841891 BACKGROUND

• Moretto M, Kupski C, Mottin CC, Repetto G, Garcia Toneto M, Rizzolli J, Berleze D, de Souza Brito CL, Casagrande D, Colossi F. Hepatic steatosis in patients undergoing bariatric surgery and its relationship to body mass index and co-morbidities. Obes Surg. 2003 Aug;13(4):622-4. doi: 10.1381/096089203322190853.

  PMID: 12940291 BACKGROUND

• Silverman EM, Sapala JA, Appelman HD. Regression of hepatic steatosis in morbidly obese persons after gastric bypass. Am J Clin Pathol. 1995 Jul;104(1):23-31. doi: 10.1093/ajcp/104.1.23.

  PMID: 7611176 BACKGROUND

• Dixon JB, Bhathal PS, Hughes NR, O'Brien PE. Nonalcoholic fatty liver disease: Improvement in liver histological analysis with weight loss. Hepatology. 2004 Jun;39(6):1647-54. doi: 10.1002/hep.20251.

  PMID: 15185306 BACKGROUND

• Blackburn GL, Mun EC. Effects of weight loss surgeries on liver disease. Semin Liver Dis. 2004 Nov;24(4):371-9. doi: 10.1055/s-2004-860866.

  PMID: 15605305 BACKGROUND

• Grimm IS, Schindler W, Haluszka O. Steatohepatitis and fatal hepatic failure after biliopancreatic diversion. Am J Gastroenterol. 1992 Jun;87(6):775-9.

  PMID: 1590319 BACKGROUND

• Vandanmagsar B, Youm YH, Ravussin A, Galgani JE, Stadler K, Mynatt RL, Ravussin E, Stephens JM, Dixit VD. The NLRP3 inflammasome instigates obesity-induced inflammation and insulin resistance. Nat Med. 2011 Feb;17(2):179-88. doi: 10.1038/nm.2279. Epub 2011 Jan 9.

  PMID: 21217695 BACKGROUND

• DeFronzo RA, Tobin JD, Andres R. Glucose clamp technique: a method for quantifying insulin secretion and resistance. Am J Physiol. 1979 Sep;237(3):E214-23. doi: 10.1152/ajpendo.1979.237.3.E214.

  PMID: 382871 BACKGROUND

• Hompesch M, Rave K. An analysis of how to measure glucose during glucose clamps: are glucose meters ready for research? J Diabetes Sci Technol. 2008 Sep;2(5):896-8. doi: 10.1177/193229680800200522.

  PMID: 19885275 BACKGROUND

• Mathurin P, Gonzalez F, Kerdraon O, Leteurtre E, Arnalsteen L, Hollebecque A, Louvet A, Dharancy S, Cocq P, Jany T, Boitard J, Deltenre P, Romon M, Pattou F. The evolution of severe steatosis after bariatric surgery is related to insulin resistance. Gastroenterology. 2006 May;130(6):1617-24. doi: 10.1053/j.gastro.2006.02.024.

  PMID: 16697725 BACKGROUND

• Mathurin P, Hollebecque A, Arnalsteen L, Buob D, Leteurtre E, Caiazzo R, Pigeyre M, Verkindt H, Dharancy S, Louvet A, Romon M, Pattou F. Prospective study of the long-term effects of bariatric surgery on liver injury in patients without advanced disease. Gastroenterology. 2009 Aug;137(2):532-40. doi: 10.1053/j.gastro.2009.04.052. Epub 2009 May 4.

  PMID: 19409898 BACKGROUND

• Moschen AR, Molnar C, Geiger S, Graziadei I, Ebenbichler CF, Weiss H, Kaser S, Kaser A, Tilg H. Anti-inflammatory effects of excessive weight loss: potent suppression of adipose interleukin 6 and tumour necrosis factor alpha expression. Gut. 2010 Sep;59(9):1259-64. doi: 10.1136/gut.2010.214577. Epub 2010 Jul 21.

  PMID: 20660075 BACKGROUND

• Phillips ML, Boase S, Wahlroos S, Dugar M, Kow L, Stahl J, Slavotinek JP, Valentine R, Toouli J, Thompson CH. Associates of change in liver fat content in the morbidly obese after laparoscopic gastric banding surgery. Diabetes Obes Metab. 2008 Aug;10(8):661-7. doi: 10.1111/j.1463-1326.2007.00793.x. Epub 2007 Oct 17.

  PMID: 17941875 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Blood (serum, plasma, and RNA isolate) Liver core biopsy Subcutaneous fat Visceral fat Abdominal wall muscle

MeSH Terms

Conditions

Obesity, Morbid; Non-alcoholic Fatty Liver Disease

Condition Hierarchy (Ancestors)

Obesity; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Fatty Liver; Liver Diseases; Digestive System Diseases

Study Officials

• Dr.Mazen Hassanain, MBBS FRCSC PhD

  King Khalid University Hospital,King Saud University,Riyadh,KSA.

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Manal Hassan, BPharm

CONTACT

+966566905250; ManHassan.c@KSU.EDU.SA

Atheer Al-Sabhan, MBBS

CONTACT

+966505299995; Atheer.Sabhan@gmail.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor & consultant HPB and Transplant surgeon

Study Record Dates

• First Submitted: May 27, 2012
• First Posted: June 14, 2012
• Study Start: June 1, 2012
• Primary Completion: July 1, 2018
• Study Completion: July 1, 2018
• Last Updated: March 30, 2018

Record last verified: 2018-03

Locations

SA (2)