Protocol for the Assessment of Variability in Histology and Gene Expression in Bariatric Surgery Patients.
Condition: Obesity
MeSH terms: Obesity
Study type: Observational

Summary: 
      It is known that a vast majority of patients seeking a bariatric surgery weight reduction
      procedure have non-alcoholic fatty liver disease (NAFLD), while a smaller subset of patients
      within this group have a more serious liver problem known as nonalcoholic steatohepatitis
      (NASH). NASH is a serious liver disease that can lead to cirrhosis, liver failure and
      ultimately liver transplantation. The purpose of this study is to explore the effects of
      bariatric surgery on the progression of NASH. The investigators also hope to gain insight
      into which genes may be responsible for the development of NAFLD and NASH. The knowledge
      gained from this study will advance the field of fatty liver disease and help design rational
      treatments to prevent disease progression.
    

Detailed description: 
      Nonalcoholic fatty liver disease (NAFLD) is the most common cause of abnormal liver tests in
      the United States. NAFLD is often found in association with obesity and diabetes and it is
      expected to become increasingly prevalent as the incidence of diabetes and obesity continues
      to increase. NAFLD represents a range of diseases from simple fatty deposition in the liver
      to more aggressive inflammation and fibrosis, termed nonalcoholic steatohepatitis (NASH). The
      distinction of NASH as an entity within NAFLD is an important one, as the natural history of
      this disease is different. Ultimately, NASH may progress to cirrhosis in up to 25% of
      patients, compared to simple steatosis which is a benign condition.

      NAFLD has been estimated at 10-24% in various populations and is significantly higher in
      obese populations (57.5-74%). NASH is a subset of NAFLD characterized by fatty change with
      lobular inflammation, hepatocellular injury, progressive fibrosis and cirrhosis. The
      bariatric surgery population is an ideal cohort to study a large subset of NASH; those with
      morbid obesity.

      The purpose of this study is to examine variability of hepatic histology as well as
      expression of key metabolic genes in NAFLD/NASH patients undergoing bariatric surgery.
      Patients will undergo pre-operative laboratory testing, followed by intra-operative liver and
      fat biopsies. A 12-month follow up will consist of repeat liver biopsy and laboratory
      testing. We predict that histologic variability of inflammation and fibrosis in NASH is
      accompanied by differential gene expression. Furthermore, if this variability is pronounced,
      this will temper the reliance on percutaneous liver biopsy in NASH as the "gold standard" and
      further emphasize the need for global markers of disease progression.
    

Observational model: Case-Control
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        This will be a prospective trial of obese patients with presumed NAFLD undergoing bariatric
        surgery. Patients will be enrolled at Northwestern Memorial Hospital through the bariatric
        surgery clinic.
      
Keywords: NAFLD; NASH; Obesity; Bariatric Surgery; Weight Reduction