HRQoL in Patients With Primary Sclerosing Cholangitis

In This Article

Abstract and Introduction

Abstract

Background & Aims: Data regarding health-related quality of life (HRQoL) in primary sclerosing cholangitis (PSC) are sparse and have only been studied cross-sectionally in a disease which runs a fluctuating and unpredictable course. We aim to describe HRQoL longitudinally by using repeated measurements in a population-based cohort.

Methods: Every 3 months from May 2017 up to August 2020, patients received digital questionnaires at home. These included the EQ-5D, 5-D Itch, patient-based SCCAI and patient-based HBI. The SF-36, measuring HRQoL over eight dimensions as well as a physical component summary (PCS) and mental component summary (MCS) score, was sent annually. Data were compared with Dutch reference data and a matched IBD disease control from the population-based POBASIC cohort. Mixed-effects modelling was performed to identify factors associated with HRQoL.

Results: Three hundred twenty-eight patients completed 2576 questionnaires. A significant reduction of small clinical relevance in several mean HRQoL scores was found compared with the Dutch reference population: 46.4 versus 48.0, p = .018 for PCS and 47.5 versus 50.5, p = .004 for MCS scores. HRQoL outcomes were significantly negatively associated with coexisting active IBD (PCS −12.2, p < .001 and MCS −12.0, p < .001), which was not the case in case of quiescent IBD. Decreasing HRQoL scores were also negatively associated with increasing age (PCS −0.1 per 10 years, p = .002), female sex (PCS -2.8, p < .001), diagnosis of AIH overlap (PCS -3.7, p = .059), end-stage liver disease (PCS -3.7, p = .015) and presence of itch (PCS -9.2, p < .001 and MCS −3.1, p = .078). The odds of reporting a clinically relevant reduction in EQ-5D scores showed seasonal variation, being lowest in summer (OR = 0.48 relative to spring, p = .037). In patients with liver transplant, HRQoL outcomes were comparable to the Dutch general population.

Conclusions: PSC patients report impaired HRQoL of small clinical relevance compared with the general population. After liver transplantation, HRQoL scores are at comparable levels to the general population. HRQoL scores are associated with potentially modifiable factors such as itch and IBD activity.

Introduction

Primary sclerosing cholangitis (PSC) is a cholestatic liver disease in which inflammation and fibrosis lead to multifocal bile duct strictures comprising the whole biliary tree. Two-thirds of patients with PSC are male and mean age at diagnosis is 40 years. Inflammatory bowel disease (IBD), predominantly ulcerative colitis (UC), occurs in 70% of patients.^[1] Symptoms that are most frequently reported are pruritus, fatigue and right upper quadrant (RUQ) abdominal pain. With disease progression, complications such as dominant strictures or signs of decompensated cirrhosis may occur.^[1] Currently, the only evidence-based treatment option to extend survival is liver transplantation (LT). Median transplant-free survival is reported to be 21 years.^[2] The natural history of PSC is fluctuating and highly variable; female sex, small duct PSC and Crohn's disease (CD) relative to UC are associated with a more favourable prognosis.^[1]

The disease burden that is associated with PSC is thought to have a significant effect on health-related quality of life (HRQoL), although only limited evidence is available.^[3] Proper estimation of HRQoL of PSC patients is needed for various purposes such as disease burden estimation, treatment evaluation in daily clinical practice and clinical trials, and for health-economic evaluation of new interventions. Both the US Food and Drug Administration and the European Medicines Agency have stressed the importance of HRQoL as an outcome measure in chronic diseases such as PSC.^[4] Moreover, in a survey of patient organization 'PSC patients Europe', improving HRQoL was mentioned in the top 10 recommendations for further research and was ranked as the third most important treatment target for PSC.^[5] Patient-reported outcome measures (PROMs) are critical in the assessment of HRQoL. Generic and disease-specific measures have sparsely been used to measure HRQoL in PSC in the absence of validated PSC-specific measures. There is limited evidence on the usefulness of the few developed PSC-specific measures, the PSC PRO, the SCCS and NIDDK-QA.^[6,7] Moreover, representative estimation of HRQoL in this population is hampered by variability, both between patients and within patients over time. Study site may induce noteworthy differences as tertiary centres generally treat patients with more advanced disease. Additionally, because of the fluctuating disease course of PSC, repeated measurements are essential to make a reliable population estimate. In this study, we use longitudinal data to describe the HRQoL of a population-based PSC cohort relative to the general population. By comparing patients with PSC alone, PSC with coexistent IBD and patients with IBD alone, we further aim to identify the impact of coexisting IBD on HRQoL. The longitudinal prospective study design enabled us to study the effect of time-varying determinants. Finally, we describe the HRQoL of PSC patients after LT.

Table 1. Baseline demographics.
Baseline demographics^a	Responded (n = 328)		Never responded (n = 31)		p-value	Total (n = 359)
Baseline demographics^a	n	%	n	%	p-value	n	%
Male	202	62	20	65	.748	222	6
Age (mean [SD])	52	(13.2)	50	(14.3)	.364	52	(13.3)
BMI (mean [SD])	25	4				25	4
Years after diagnosis (median [IQR])	11	(7–18)	13	(8–20)	.494	11	(7–18)
Large duct	296	91	26	84	.215	322	90
Small duct	30	9	5	16	.215	35	10
AIH overlap	26	8	6	20	.033	32	9
Post LT	52	16	9	29	.062	61	17
Patients with IBD	217	66	23	74	.399	240	67
Of which UC	149	69	17	74	.604	166	70
Of which CD	55	26	5	22	.704	60	25
Of which intermediate	13	5	1	4	.749	14	5
Tertiary centre treatment	214	65	22	71	.521	236	67
Of which transplant centre	70	33	15	68	.002	85	36
End-stage liver disease	13	4	1	3	.839	14	4
Hepatobiliary malignancy^b	11	3	1	3	1.000	12	3
Colorectal cancer^b	5	2	1	3	.421	6	2

^aAt time of the first received questionnaire.
^bDiagnosis prior to or during follow-up.

Table 2. Linear mixed-effects model SF-36.
	PCS			MCS^a
	Estimate	95% CI	p-value	Estimate	95% CI	p-value
Intercept	50.6	48.2–53.0		48.9	46.9–50.7
Female	−2.8	−5.0 to −0.7	>.001
Age per 10 years (reference 40y)	−0.1	−0.2 to −0.0	.002
End-stage liver disease	−4.3	−7.8 to −0.9	.015	3.5	- 0.0–6.7	.057
AIH overlap	−3.7	−7.4 to 0.1	.059
IBD
None		(reference)			(reference)
Ulcerative Colitis	2.3	−0.1 to 4.8	.066	2.5	−0.0 to 4.8	.052
Crohn's Disease	3.3	0.2–6.4	.036	−0.3	−3.8 to 2.8	.851
IBD activity^b	−12.2	−16.7 to −7.6	<.001	−12.0	−18.9 to 5.9	<.001
Itch^b	−9.2	−12.2 to −6.2	<.001	−3.1	−6.9 to 0.3	.078

Note: The intercept indicates the reference value of the PCS and MCS score for all patients without or before LT conditional on the reference value of the other variables included. The estimate of the listed factors indicates the particular effect of each factor.
^aThe MCS outcome was transformed using a squared root transformation for negatively skewed data (sqrt(max(x + 1) − x)) to safeguard normal residues in regression analyses. Coefficients are reported back to the original scale for ease of interpretation, but note that joint effects of multiple predictor variables are only interpretable on the original scale (see supplementary material).
^bItch and IBD activity are transformed to a 0–1 scale. 1 equals most severe complaints.

Table 3. Generalized linear mixed-effects model EQ-5D.
	Small clinically relevant difference			Large clinically relevant difference
	Estimate^a	95% CI	p-value	Estimate^a	95% CI	p-value
Intercept (%)	19	11–39		1	0–2
Season
Spring		(reference)			(reference)
Summer	0.48	0.31–0.74	<.001	0.62	0.36–1.07	.087
Fall	0.80	0.51–1.24	.319	1.28	0.73–2.23	.393
Winter	0.63	0.40–0.99	.047	1.24	0.69–2.23	.466
Itch	1.16	1.09–1.23	<.001	1.11	1.04–1.19	.003
IBD activity	1.43	1.27–1.61	<.001	1.50	1.33–1.69	<.001
AIH overlap	5.97	1.11–32.13	.037	3.61	0.59–22.19	.165
ESLD	8.59	1.70–43.35	.001
Number of completed questionnaires	0.92	0.88–0.97	<.001
COVID-19				0.96	0.47–1.97	.910
COVID-19: AIH overlap				0.00	NA^b	.999

^aIntercept is reported as percentage with a (small or large) clinically relevant difference at covariate reference values, and estimates of covariates are reported as odds ratios relative to reference values.
^bConfidence interval could not be computed because of zero cell count: none of the 20 patients with AIH overlap who filled in a questionnaire during COVID-19 reported a large clinically relevant difference.