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

NCT ID: NCT01619215

Last Updated: 2018-03-30

Basic Information

• Recruitment Status: UNKNOWN
• Total Enrollment: 35 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2012-06-30
• Study Completion Date: 2018-07-31

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.

Detailed Description

35 consecutive patients referred for bariatric surgery will be recruited either at the obesity clinic, or from inpatient (scheduled for bariatric surgery). A detailed history and a complete physical examination will be done at the first visit along with anthropometric measures; routine blood tests, liver function, hormonal assessment, and certain metabolic and inflammatory markers will be evaluated. They will also have an abdominal ultrasound for initial NAFLD assessment, fibroscan to detect liver fibrosis, and an MRI to measure hepatic fat content and body fat composition including intra-abdominal and extra-abdominal fat. These patients will be asked to lose a certain amount of kilos (depending on their BMI and the surgeon preference) out of their original weight, in order to become candidates for bariatric surgery at King Saud University Hospital (KKUH).

At the second visit, (if they lose the recommended amount weight) we will assess their weight loss; obtain blood for the same hormonal and inflammatory markers assessment. Nonetheless, if they did not lose weight and the treating surgeon gave them a third appointment, we will consider their third visit as a second visit; preforming all the investigations mentioned above. In this case we will interpret their results with respect to the total duration of "before surgery" weight loss.

During the operation, tissue biopsy will be taken with a core needle biopsy for the liver and a sharp non-thermal instrument for subcutaneous fat, visceral fat, and abdominal muscle immediately after skin incision. A CAP certified tissue manager would process all tissues. Liver biopsy will be sliced it to two parts; the first half is for histological evaluation, but the other half will be stored for tissue studies. The histologic slides will be stained with hematoxylin and eosin (H&E), and Masson Trichrome stains for microscopic evaluation. This evaluation will be provided by a single histopathologist who will be blinded to the patients' clinical condition, and the order of the biopsy.

Follow Up:

After the surgery follow up appointments will be scheduled 3 months, 6 months, 1 year, and annually till 5 years. The followings will be done in each visit:

1. Thorough physical exam as per the CRF.

2. Take a blood sample to evaluate liver function, metabolic, and inflammatory changes using the same parameters as those in the baseline.

3. Request for: fibroscan and abdominal ultrasound. Second, third and fourth liver biopsies will be taken percutaneously 3 months, 1 year, and 5 years following the initial biopsy respectively. These biopsies will be obtained using core tissue biopsy with ultrasound guidance for the same histological assessment and tissue studies. Another MRI will be schedule 1 year after the surgery.

Specimens collected under this trial will be part of the King Saud University Liver Disease Research Centre Biobanking and will follow all policy and procedures within the biobanking protocol as approved by the IRB committee.

Conditions

Obesity, Morbid; Non-Alcoholic Fatty Liver Disease

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

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

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

King Saud University

OTHER

Sponsor Role: lead

Responsible Party

Mazen Hassanain

Assistant Professor & consultant HPB and Transplant surgeon

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Dr.Mazen Hassanain, MBBS FRCSC PhD

Role: PRINCIPAL_INVESTIGATOR

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

Locations

King Khalid University Hospital

Riyadh, , Saudi Arabia

Site Status: RECRUITING

King Khalid University Hospital

Riyadh, , Saudi Arabia

Site Status: RECRUITING

Countries

Saudi Arabia

Central Contacts

Manal Hassan, BPharm

Role: CONTACT

ManHassan.c@KSU.EDU.SA

+966566905250

Atheer Al-Sabhan, MBBS

Role: CONTACT

Atheer.Sabhan@gmail.com

+966505299995

Facility Contacts

Tamader AlDoheyan, (MBBSc)

Role: primary

AlDoheyan.Tamader@gmail.com

+966500083720

Maram AlKhamash

Role: backup

Malkhamash.c@KSU.EDU.SA

+966548327049

Tamader Al-Doheyan, (MBBSc)

Role: primary

AlDoheyan.Tamader@gmail.com

+966500083720

Maram AlKhamash

Role: backup

Malkhamash.c@KSU.EDU.SA

+966548327049

References

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.

Reference Type: BACKGROUND

PMID: 14609874 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 11868297 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 15946429 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 15531238 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 11438497 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 12512031 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 12841891 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 12940291 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 7611176 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 15185306 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 15605305 (View on PubMed)

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

Reference Type: BACKGROUND

PMID: 1590319 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 21217695 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 382871 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 19885275 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 16697725 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 19409898 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 20660075 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 17941875 (View on PubMed)

Other Identifiers

KSULDRCBSMH001

Identifier Type: -

Identifier Source: org_study_id