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INCREASED RISK OF CIRRHOSIS IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE: A DANISH REGISTRY-BASED COHORT STUDY (1998-2018)

Parakkal Deepak 1, Scott McHenry 1, Mohammad Zamani 1, Anastasia Karachalia Sandri 2, Tine Jess 3

Affiliations

1 Washington University in St. Louis, St. Louis, United States

2 Aalborg University, Copenhagen, Denmark

3 Aalborg University Copenhagen, Hellerup, Denmark

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Abstract

Introduction

Prior studies suggest an increased risk of non-alcoholic fatty liver disease (NAFLD) in patients (pts) with inflammatory bowel disease (IBD). There is no data available on the risk of cirrhosis in IBD. Our aim was to investigate the risk of cirrhosis (compensated or decompensated) in IBD pts compared to a matched non-IBD population in a population-based cohort.

Aims & Methods

A registry-based cohort study was conducted in the Danish health registries (including the pathology register) using data, between (and including) 1998 and 2018. Incident IBD was identified using ICD-8/10 codes for Crohn’s disease (CD) or ulcerative colitis (UC), with two IBD registrations up to two years apart, living in Denmark for at least one year prior to their first IBD registration and without a diagnosis of cirrhosis prior to their IBD registrations. Those with IBD were matched 1:10 to non-IBD persons on the basis of sex, age, calendar year, and the municipality of residence. Persons were followed from index date (IBD diagnosis date/matching date) until a diagnosis of cirrhosis (study outcome), death, emigration, or end of follow-up, whichever came first. The diagnosis of cirrhosis, including both compensated and decompensated cirrhosis, and the underlying etiology, were recorded by ICD-8/10 and SNOMED codes. Kaplan-Meier approach was used to calculate the cumulative incidence of cirrhosis and Cox proportional regression analysis to calculate hazard ratios (HRs) with corresponding 95% confidence intervals (CIs) for cirrhosis among pts with IBD, compared to the non-IBD population.

Results

In a study population of 495,220 persons, a total of 2,741 cirrhosis cases were identified (median [IQR] time in years between index date and diagnosis of cirrhosis: 6.3 [3.0-10.7]), with a higher proportion of cases among pts with IBD (N = 45,020) compared to non-IBD persons (0.9% vs. 0.5%, respectively). After adjusting for sex, age, and index year, pts with IBD had a higher risk of cirrhosis, compared to non-IBD persons (adjusted HR (95% CI): 1.84 [1.65 – 2.04]). Cirrhosis was diagnosed on the basis of liver biopsy and/or imaging (ultrasound, CT or MRI) in 77.3% of IBD pts vs. 69.3% of non-IBD persons. The leading etiology of cirrhosis was NAFLD (51.6%) followed by alcohol (39.0%). The risk of cirrhosis among IBD pts (compared to non-IBD persons) was more pronounced among younger persons (adjusted HR (95% CI): 3.08 [2.45-3.87] among ≤ 40 years of age; 1.63 [1.45-1.84] among > 40 years of age, p-value <0.001) and CD pts (adjusted HR (95% CI): 2.20 [1.80-2.67] among CD; 1.72 [1.52-1.95]; among UC, p-value 0.0402). The risk was also consistent across the year of cohort entry (IBD diagnosis year/index year): 1998-2001 (794 events, 1.37 [1.07-1.66]), 2002-2005 (776 events, 1.98 [1.63-2.40]), 2006-2009 (612 events, 1.94 [1.56-2.41]), 2010-2013 (378 events, 2.01 [1.53-2.64]), 2014-2018 (181 events, 2.89 [2.03-4.10]).

The hazard ratio for cirrhosis in IBD compared to matched controls in Denmark 1998-2018
		No. of events	Adjusted HR (95% CI)	p-value
Overall		2,741	1.84 (1.65-2.04)
IBD type	UC/UC controls	2,033	1.72 (1.52-1.95)	0.04
IBD type	CD/CD controls	708	2.20 (1.80-2.67)	0.04
Sex	Female	1,208	1.93 (1.65-2.25)	0.42
Sex	Male	1,533	1.77 (1.53-2.04)	0.42
Age group (in years) at IBD diagnosis/index date	≤ 40	414	3.08 (2.45-3.87)	<.0001
Age group (in years) at IBD diagnosis/index date	> 40	2,327	1.63 (1.45-1.84)	<.0001

Conclusion

IBD pts had a higher incident risk of cirrhosis compared to matched non-IBD persons, especially with age at IBD diagnosis ≤ 40 years and those with CD. These data point towards a need for focused screening for cirrhosis among IBD pts, especially in certain risk groups.

Conference

UEG Week Copenhagen 2023

Topics

IBD

Submission format

Abstract

Session

PP 05 IBD (Posters)

Citation

United European Gastroenterology Journal 2023; 11 (Supplement 8)

Published

2023

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Outcome	N		N events		Incidence rate per 1000 person-years (95% CI)		Hazard Ratio* (95%CI)	Adjusted Hazard Ratio** (95%CI)	NNT*** per 1 year of statin treatment
IBD-related surgery	Statin users	Non-statin users	Statin users	Non-statin users	Statin users	Non-statin users
UC	1733	1733	24 (1.4%)	34 (2.0%)	3.4 (2.1-4.8)	6.3 (4.2-8.5)	0.56 (0.33-0.95)	0.55 (0.31-0.97)	345
CD	962	962	36 (3.7%)	48 (5.0%)	9.2 (6.2-12.2)	15.4 (11.0-19.7)	0.59 (0.39-0.90)	0.54 (0.33-0.88)	161
IBD-hospitalization
UC	1733	1733	113 (6.5%)	121 (7.0%)	17.0 (13.9-20.2)	23.9 (19.6-28.1)	0.77 (0.59-0.99)	0.68 (0.51-0.91)	145
CD	962	962	76 (7.9%)	84 (8.7%)	20.3 (15.8-24.9)	28.2 (22.2-34.2)	0.78 (0.57-1.06)	0.78 (0.56-1.09)	-
Disease flare
UC	1733	1733	819 (47.3%)	825 (47.6%)	207.4 (193.2-221.6)	275.0 (256.2-293.8)	0.85 (0.77-0.94)	0.86 (0.77-0.97)	15
CD	962	962	496 (51.6%)	478 (49.7%)	245.5 (223.9-267.1)	292.3 (266.1-318.5)	0.96 (0.85-1.08)	1.02 (0.88-1.19)	-