Chronic inflammation associated with inflammatory bowel disease (IBD) results in increased oxidative stress that damages the colonic microenvironment. Low levels of serum bilirubin, an endogenous antioxidant, have been associated with increased risk for Crohn’s disease (CD). Therefore, the aim of this study was to examine whether total serum bilirubin levels are associated with ulcerative colitis (UC). We identified a retrospective case-control population (n = 6,649) from a single tertiary care center, Penn State Hershey Medical Center (PSU) and a validation cohort (n = 1,996) from Virginia Commonwealth University Medical Center (VCU). Cases were age- and sex-matched to controls (PSU: CD n = 254, UC n = 187; VCU: CD n = 233, UC n = 124). Total serum bilirubin levels were obtained from de-identified medical records and segregated into quartiles. Logistic regression analysis was performed on each quartile of total serum bilirubin compared to the last quartile (highest bilirubin levels) to determine the association of total serum bilirubin with UC. Similar to CD patients, UC patients demonstrated reduced levels of total serum bilirubin compared to controls at PSU and VCU. The lowest quartile of total serum bilirubin was independently associated with UC for the PSU (OR: 1.98 [95% CI: 1.09–3.63]) and VCU cohorts (OR: 6.07 [95% CI: 3.01–12.75]). Lower levels of the antioxidant bilirubin may reduce the capability of UC patients to remove reactive oxygen species leading to an increase in intestinal injury. Therapeutics that reduce oxidative stress may be beneficial for these patients.

Introduction: Patients with c hronic liver disease accounts for 30-45% of the adult population in North America; among them, more die from cardiovascular disease (CVD) than from liver cirrhosis. Reduction of CVD-mortality in this high risk population requires understanding of CVD-risk across the whole spectrum of liver disease progression ranging from mild forms (i.e. nonalcoholic fatty liver disease) to advanced forms (i.e. nonalcoholic- and alcoholic-liver cirrhosis) as well as understanding of the increase of CVD-risks by time. Hypothesis: We assessed two hypotheses that (1) CVD-risk and mortality are dependent on type of liver disease; and that (2) CVD-risk and mortality increase in five years in all three types of chronic liver disease. One exploratory hypothesis was (3) the increment of CVD-risk in five years is higher in advanced forms than in a mild form of chronic liver disease. Methods: A secondary data analysis was conducted using 2,765 records of patients with nonalcoholic fatty liver disease, nonalcoholic- and alcoholic-liver cirrhosis identified by the International Classification of Disease -9 codes. Framingham risk scores were calculated for each patient based on their sex, age, systolic blood pressure, total cholesterol and high density lipoprotein level or body mass index, smoking status, and the presence of diabetes with five year interval from 2009 to 2014. Results: Framingham CVD risk scores were significantly different among patients of nonalcoholic fatty liver disease (21.4%), nonalcoholic- (21.3%) and alcoholic-liver cirrhosis (28.1%) ( F =5.610, p= .004). The all-cause mortality rate was significantly different among nonalcoholic fatty liver disease (5.8%), nonalcoholic- (20.5%) and alcoholic-liver cirrhosis (23.4%) ( [[Unsupported Character - Symbol Font ]] 2 =101.54, p =.000). In five years, CVD risk increased from 22.9 to 28.4% ( F =55.7, p =.000) with the greater extent in alcoholic- and nonalcoholic liver cirrhosis (increased by 7.2 and 6.0%, respectively) than in nonalcoholic fatty liver disease (increased by 3.4%) ( F =5.21, p =.023). Conclusions: We conclude that cardiovascular risks and mortality increase are dependent on type of liver disease. We also conclude that CVD risk increases in 5 years with the greater extent in advanced forms than in a mild form of chronic liver disease. To prevent CVD mortality, tailored risk reduction in earlier phases of chronic liver disease is crucial and may offer better outcomes.