The best care for digestive diseases requires accurate risk assessment and leading-edge treatment. Physician-researchers in Cleveland Clinic’s Digestive Disease & Surgery Institute are making advances in both areas.
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Here’s a roundup of our recent work on liver comorbidity in inflammatory bowel disease (IBD), risk stratification in Barrett’s esophagus, and stem cells’ potential in IBD treatment.
IBD increases risk of liver disease
Clinicians have long suspected it, but now two national studies have confirmed it: IBD patients are more likely than the general population to have nonalcoholic fatty liver disease, nonalcoholic steatohepatitis and nonalcoholic cirrhosis.
Miguel Regueiro, MD, Chair of Cleveland Clinic’s Department of Gastroenterology, Hepatology and Nutrition, and colleagues analyzed a national database of more than 62 million patients. They identified nearly 160,000 patients with Crohn’s disease and more than 125,000 patients with ulcerative colitis diagnosed between 1999 and 2018.
Nonalcoholic fatty liver disease was comorbid in 2.4% of those with Crohn’s and 1.95% of those with ulcerative colitis — a much higher prevalence than researchers expected. Prevalence of nonalcoholic steatohepatitis and nonalcoholic cirrhosis also was relatively high — 0.3% and 0.9%, respectively, in patients with Crohn’s and 0.23% and 1.01%, respectively, in patients with ulcerative colitis.
Researchers suggest that a pro-inflammatory cytokine process, IBD-related metabolic changes, an alteration to the microbiome and/or genetic factors could be causes. They recommend regular liver disease screenings in IBD patients.
Test accurately predicts progression in Barrett’s esophagus
Cleveland Clinic researchers have validated that the TissueCypher® pathology test effectively identifies patients with Barrett’s esophagus who have a heightened risk of esophageal cancer — even if they show no dysplasia.
Traditionally, care of patients with Barrett’s esophagus was determined solely by presence of dysplasia, an indicator of precancerous changes. However, most patients with Barrett’s esophagus — including some who will develop esophageal cancer — do not have dysplasia.
TissueCypher uses imaging analysis to measure nine protein-based biomarkers in biopsy samples. Scores indicate likelihood of progression to high-grade dysplasia and esophageal adenocarcinoma within five years.
To assess the test’s accuracy, Prashanthi Thota, MD, Medical Director of Cleveland Clinic’s Esophageal Center, and colleagues compared patients’ TissueCypher results with clinical outcomes. In the blinded review of nearly 270 patients, the test accurately stratified patients with no, indefinite or low-grade dysplasia as low, intermediate or high risk. The test’s prevalence-adjusted positive predictive value at five years was 22.6%, indicating a progression rate of 4.6% per year in patients who the assay identified as high-risk.
These findings assure physicians that TissueCypher is a reliable tool to help determine which patients need endoscopic ablation and which require only surveillance.
Stem cell therapy shows promise for Crohn’s disease
Stem cell therapy is more effective than medication and surgery for perianal fistulizing Crohn’s disease, according to multiple clinical trials.
“We don’t know exactly why stem cells work, but they seem to migrate to sites of inflammation or injury,” says Amy Lightner, MD, a leading translational researcher and clinical trials director in stem cell therapy for Crohn’s disease, who joined Cleveland Clinic in 2019. “They then seem to release cytokines that recruit other cells to treat inflammation and immunity. This kind of action seems to increase T regulatory cells and interleukin 10, which is important in Crohn’s disease. It probably alters the macrophage ratio, which also helps healing in Crohn’s disease.”
Dr. Lightner is currently involved in phase I trials of stem cell therapy for perianal fistulizing Crohn’s disease, recto-vaginal fistulizing Crohn’s disease and fistulizing disease of the ileal pouch. Another trial is studying arterial delivery of stem cells for luminal Crohn’s disease.
Her research focuses on identifying donor characteristics that affect mesenchymal stem cell function, and exploring extracellular vesicles (mesenchymal stem cell secretions) as an alternative to whole stem cells.
“They’re a lot less expensive than whole stem cells, easier to transport to different facilities for multicenter trials, and have a longer shelf life,” she says. “And we can grow our mesenchymal stem cells in certain conditions that make these vesicles more immunosuppressive.”