Gastroenterology 2020 Projects

Project Title: Understanding the impact of medical marijuana use on quality of life in patients suffering from inflammatory bowel disease: chart review and subsequent patient survey

Faculty Mentor: Marcus Muehlbauer
Email: marcus.muehlbauer@medicine.ufl.edu 

Student: Phoebe Jin 
Email: pjin@ufl.edu 

Research Project Description:

1.6 million Americans suffer from inflammatory bowel disease (IBD), most commonly, Crohn’s disease and ulcerative colitis. Globally, the burden of IBD is increasing with time for both incidence and prevalence (1). IBD is an umbrella term for diseases that are characterized by chronic inflammation of the GI tract. The inflammation causes deterioration of the mucosa and destruction of the wall leading to burdensome symptoms that diminish quality of life including chronic abdominal pain, diarrhea and extraintestinal manifestations like arthritis, hepatobiliary diseases and episcleritis (2,3). Historically, goals of therapy have evolved from relief of IBD-related symptoms to mucosal healing. This shift was due to poor correlation between endoscopic findings and symptoms-based scores (4) as well as longitudinal studies that support the correlation between mucosal healing and long-term prognosis (5–7).
Currently, the mainstay of therapy is immunosuppression but many patients continue to suffer from chronic abdominal pain despite achieving mucosal healing. In the past, pain management consisted of chronic narcotic use; however, this leads to unwanted long-term complications including narcotic dependence. Over the last couple of years, many states have allowed the use of medical marijuana for inflammatory bowel disease patients. Many of the 1600 IBD patients cared for by the University of Florida Division of Gastroenterology started using medical marijuana. With this study, we want to investigate the impact of medical marijuana on the quality of life in our patient population. Molodecky NA, Soon IS, Rabi DM, et al. Increasing incidence and prevalence of the inflammatory bowel diseases with time, based on systematic review. Gastroenterology. 2012;142(1):46-54.e42. doi:10.1053/j.gastro.2011.10.001

Satsangi J, Silverberg MS, Vermeire S, Colombel JF. The Montreal classification of inflammatory bowel disease: Controversies, consensus, and implications. Gut. 2006;55(6):749-753. doi:10.1136/gut.2005.082909

Levine JS, Burakoff R. Extraintestinal manifestations of inflammatory bowel disease. Gastroenterology & hepatology. 2011;7(4):235-241. http://www.ncbi.nlm.nih.gov/pubmed/21857821. Accessed April 21, 2020.

Jones J, Loftus E v., Panaccione R, et al. Relationships Between Disease Activity and Serum and Fecal Biomarkers in Patients With Crohn’s Disease. Clinical Gastroenterology and Hepatology. 2008;6(11):1218-1224. doi:10.1016/j.cgh.2008.06.010

Shah SC, Colombel J-F, Sands BE, Narula N. Systematic review with meta-analysis: mucosal healing is associated with improved long-term outcomes in Crohn’s disease. Alimentary Pharmacology & Therapeutics. 2016;43(3):317-333. doi:10.1111/apt.13475

Peyrin-Biroulet L, Ferrante M, Magro F, et al. Results from the 2nd Scientific Workshop of the ECCO (I): Impact of mucosal healing on the course of inflammatory bowel disease. Journal of Crohn’s and Colitis. 2011;5(5):477-483. doi:10.1016/j.crohns.2011.06.009

Shah SC, Colombel JF, Sands BE, Narula N. Mucosal Healing Is Associated With Improved Long-term Outcomes of Patients With Ulcerative Colitis: A Systematic Review and Meta-analysis. Clinical Gastroenterology and Hepatology. 2016;14(9):1245-1255.e8. doi:10.1016/j.cgh.2016.01.015

Project Title: Liver disease progression in alpha-1 antitrypsin deficiency: role of metabolic syndrome and liver fibrosis at diagnosis

Faculty Mentor: Marcus Muehlbauer
Email: marcus.muehlbauer@medicine.ufl.edu 

Student: Gayle Wiesemann  
Email: gayle89@ufl.edu 

Research Project Description:

Classical alpha-1 antitrypsin deficiency (AATD) is characterized by individuals with a homozygous mutation for the Z allele (PI*ZZ), causing a Glu342Lys substitution to a gene in the SERPINA1 gene family. The defective alpha—1 antitrypsin protein polymerizes in the rough ER of liver hepatocytes, leading to an abnormal accumulation of the protein in the liver(1). These accumulations are the periodic acid-Schiff positive inclusions that characteristic of AATD liver disease(2).

Accumulation of these misfolded proteins can lead to further polymerization and retention in the ER of hepatocytes due to an overwhelmed or insufficient intracellular clearance mechanism. This predisposes the affected individuals to an increased risk of liver injury and scarring(3). Although clinical liver disease can be diagnosed at any age, cirrhosis is often used as an indicator for liver transplant(4).

Due to limited data on natural disease progression of individuals with AATD, we have conducted a prospective longitudinal biopsy study of individuals with AATD and no known liver disease. From this study, we have shown that 30% of asymptomatic patients have clinically significant liver fibrosis at baseline, and the risk was greatest in those with metabolic syndrome. In addition, a small but significant percentage of patients had high levels of AAT accumulation on liver biopsy(5). Based on these findings, we have the following hypothesis:

  1. Fibrosis at baseline biopsy is important in predicting risk for future liver disease.
  2. Metabolic syndrome increases risk of fibrosis progression.
  3. AAT accumulation within hepatocytes even in the absence of fibrosis is a risk for progression of liver disease.

Overall, the goal of the AAT Liver Disease Progression Project is to provide additional support for our hypothesis that fibrosis predicts risk for future liver disease. However, to do this prospectively would take many years. Therefore, we seek to identify a cohort of AAT patients retrospectively and determine if any clinical liver events have occurred. We will search the electronic medical records for the diagnosis codes of Alpha-1 antitrypsin deficiency (ICD10 – E88.01, ICD9 273.4) from 2008-2019. AATD is considered a rare disease, so we anticipate identifying <500 patients that have been cared for here. These patient will need to be evaluated by an extended period of time because of the slow natural history of liver disease progression.Data elements collected would include demographic data, date of diagnosis, metabolic syndrome features (DM, lipids, BMI, HTN) at baseline, liver biopsy results, baseline liver function, and liver imaging. Liver related outcomes collected would be development of cirrhosis, esophageal varices, ascites, hepatic encephalopathy, hepatocellular carcinoma, and liver transplant or death.

Categorial variables will be studied using chi square testing. Continuous variables will be expressed as mean +/- SD. Event rates for liver related outcomes will be calculated using Kaplan-Meier methods. Cox proportional hazard will be used to identify factors associated with progressive disease and liver related outcomes.

  1. Blank CA, Brantly M. Clinical features and molecular characteristics of alpha 1-antitrypsin deficiency. Ann Allergy 1994;72:105-120; quiz 120-102.
  2. Edgar RGPM, Bayliss S, Crossley D, Sapey E, Turner AM. Treatment of lung disease in alpha-1 antitrypsin deficiency: a systematic review. Int J Chron Obstruct Pulmon Dis 2018;12:1295-1308.
  3. Greene CM, Marciniak SJ, Teckman J, Ferrarotti I, Brantly ML, Lomas DA, et al. Alpha1-antitrypsin deficiency. Nat Rev Dis Primers 2016;2:16051.
  4. Townsend SA, Edgar RG, Ellis PR, Kantas D, Newsome PN, Turner AM. Systematic review: the natural history of alpha-1 antitrypsin deficiency, and associated liver disease. Aliment Pharmacol Ther 2018;47:877–885.
  5. Clark VC, Marek G, Liu C, Kurtz T, Nolte J, Brantly M. Clinical and histologic features of adults with alpha-1 antitrypsin deficiency in a non-cirrhotic cohort. J Hepatol 2018;69:1357-1364.

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