Colectomy Patients with Ulcerative Colitis May Lead to Increased Risk of Gallstone Disease

Roy Davenport, Mercer University College of Pharmacy

Patients diagnosed with ulcerative colitis (UC) may undergo a colectomy if medical treatment fails.  A colectomy entails a resection of a short segment of the ileum.  This can cause malabsorption of bile acids and lead to a supersaturation of biliary cholesterol.  The increase in biliary cholesterol has been stated to increase the risk of symptomatic gallstones.  After a colectomy and with restorative proctectomy with ileal pouch-anal anastomosis (IPAA), bowel continuity restoration has been observed.  Eventually, the pouch may undergo colonic metaplasia and impair the reabsorption of primary bile acids leading to symptomatic gallstones. [1]

Increased Risk of Gallstone Disease Following Colectomy for Ulcerative Colitis 
Design Cohort; N= 48,920
Objective To determine if the risk of gallstone disease increases following colectomy and ileal pouch-anal anastomosis (IPAA)
Study Groups Colectomy (n= 4,548); without colectomy (n= 44,372)
Methods Subjects were matched by gender, calendar year, and year of birth.  Cox regression examined the effect of colectomy on the hazard rates of gallstone disease and cholecystectomy, adjusting for confounding conditions and diseases.  The effect of an IPAA was determined for patients who had a colectomy by including the procedure as a time-dependent variable.  Statistical analysis was based on two sub-studies.

Sub-study one compared the incidence of gallstones between UC patients with colectomy and without IPAA and UC patients with an intact colon.  Cumulative risk of gallstones was determined by the cumulative incidence function.

Sub-study two compared the incidence of gallstones between UC patients with colectomy and IPAA versus UC patients with colectomy and without an IPAA. Patients were all considered in the “colectomy” state in which some transitioned to the IPAA state.  Patients were assigned a defined time dependent variable from 0 (meaning those in the colectomy state) to 1(meaning those who had transitioned to the IPPA state) to be used in the Cox proportional hazards model for adjustment of confounding variables.
The time at which a subject received a colectomy was considered the index date. Risk assessment of gallstones did not occur until one year after the index date to account for perioperative effects.

Duration 11.9 years
Primary Outcome Measure

Hazard ratios for the incidence of gallstones and cholecystectomy in patients with colectomy

Baseline Characteristics
Without Colectomy With colectomy
Mean age at index date, yrs (SD) 42.9 (18) 42.7 (18)
Females, n (%) 21,641 (48.7) 2,233 (49.1)
IPAA, n (%) N/A 1,898 (41.7)
Results
Unadjusted hazard ratio for gallstones (95% CI) Adjusted hazard ratio for gallstones (95% CI) Unadjusted hazard ratio for cholecystectomy (95% CI) Adjusted hazard ratio for cholecystectomy (95% CI)
Colectomy 1.63 (1.41–1.89) 1.63 (1.39–1.91) 1.41 (1.12–1.76) 1.55 (1.22–1.98)
Alcoholism 1.08 (0.81–1.45) 0.98 (0.70–1.37) 0.34 (0.16–0.72) 0.41 (0.19–0.89)
Cancer 2.28 (1.99–2.61) 1.63 (1.39–1.92) 1.32 (1.04–1.67) 1.46 (1.10–1.95)
Hepatobiliary and pancreatic cancer 83.98 (62.22–113.35) 77.59 (27.66–217.63) 106.88 (77.74–146.94) 142.23 (34.24–590.89)
Hypothyroidism 1.29 (0.87–1.90) 0.85 (0.55–1.31) 0.61 (0.28–1.37) 0.55 (0.24–1.26)
Cirrhosis 2.52 (1.64–3.87) 2.20 (1.30–3.73) N/A N/A
Renal failure 2.16 (1.53–3.07) 1.19 (0.77–1.83) 1.45 (0.80–2.63) 0.76 (0.35–1.69)
Metabolic syndrome 2.16 (1.95–2.40) 1.69 (1.39–1.91) 1.61(1.37-1.89) 1.82 (1.49-2.23)
Adverse Events Common Adverse Events: N/A
Serious Adverse Events: N/A
Percentage that Discontinued due to Adverse Events: N/A
Study Author Conclusions The risk of developing gallstones increased following colectomy for UC, and concurrent or subsequent restorative proctectomy with IPAA did not add to this risk.

This study was the first of its kind to associate colectomy to gallstone formation in a population-based setting using control groups from the same cohort as the exposed patients.  A loss of bile in those following a colectomy was assessed, but there was no account for gallbladder functioning prior to colectomy.  Mechanisms in the study concerning the cause and development of gallstones were not addressed.  The assessment of weight loss and fiber intake prior to the study was not mentioned and could have affected the outcome of those undergoing a colectomy.  Furthermore, there was no mentioning of whether or not patients were on any type of medication that would ultimately lead to a cholecystectomy regardless of being diagnosed with UC.  Medications such high-dose steroids and total parenteral nutrition can affect the functioning of the pancreas and gallbladder which may have been present in some individuals, resulting in the need for a cholecystectomy.

References

[1] Shepherd NA, Jass JR, Duval I et al. Restorative proctocolectomy with ileal reservoir: pathological and histochemical study of mucosal biopsy specimens. J Clin Pathol 1987;40:601–607.

[2] Anders Mark-Christensen MD, Søren Brandsborg MD, PhD, et al. Increased Risk of Gallstone Disease Following Colectomy for Ulcerative Colitis. Am J Gastroenterol 2017; 112:473–478; doi:10.1038/ajg.2016.564.

 

 

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