Systematic screening for primary sclerosing cholangitis with magnetic resonance cholangiography in inflammatory bowel disease

doi:10.1016/j.dld.2018.06.024

Digestive and Liver Disease

Volume 50, Issue 10, October 2018, Pages 1012-1018

https://doi.org/10.1016/j.dld.2018.06.024 Get rights and content

Abstract

Background

Primary sclerosing cholangitis (PSC) is a major concern in inflammatory bowel disease (IBD).

Aims

Evaluating the use of magnetic resonance cholangiography (MRC) as a screening tool for PSC in IBD patients.

Methods

A single-center cohort study investigating systematic MRC to assess PSC in IBD patients with (cohort 1) and without (cohort 2) liver function tests (LFTs) abnormality, combined with a retrospective analysis of MRCs in a control group of non-IBD patients with abnormal LFTs (cohort 3).

Results

In total, 420 patients (cohort 1: n = 203, cohort 2: n = 30, cohort 3: n = 187) underwent imaging. MRC was classified ‘abnormal’ in 49/203 (24.1%) patients in cohort 1, in 1/30 (3.3%) patients in cohort 2, and in 66/187 (35.3%) patients in cohort 3 (p < 0.004 for all comparisons). PSC was diagnosed in 20/203 (9.9%) patients in cohort 1, in 1/30 (3.3%) patients in cohort 2, and in 13/187 (7.0%) patients in cohort 3 (p = 0.44). Gamma-glutamyl transpeptidase was the only independent factor predicting the diagnosis of PSC in IBD (OR 1.8, 95% CI 1.3–2.5, p = 0.001).

Conclusions

MRC revealed PSC in one tenth of IBD patients with abnormal LFTs and should be systematically performed in IBD patients with abnormal LFTs, especially if gamma-glutamyl transpeptidase level is elevated.

Introduction

Primary sclerosing cholangitis (PSC) and inflammatory bowel disease (IBD) are highly linked [1]. Approximately 50–80% of PSC patients have concomitant IBD [2]. PSC is a chronic progressive disease characterized by inflammation and fibrosis of mainly medium and large bile ducts [3]. Biliary strictures may eventually lead to recurrent cholangitis, biliary cirrhosis and end-stage liver disease [4]. There is an increased risk for the development of cholangiocarcinoma in PSC [5], while surveillance strategies are limited [6]. Patients with IBD and PSC also have a higher risk of colorectal carcinoma compared to IBD patients without PSC or normal controls [7], [8], [9]. PSC is the most common liver disease specific to IBD [2]. Prevalence in ulcerative colitis (UC) and Crohn’s disease (CD) has been documented from 0.8% to 5.4% and from 1.2% to 3.4%, respectively [10]. However values of alkaline phosphatase (ALP) are normal in 10% of IBD patients with PSC, liver function tests (LFTs) typically show a cholestatic profile [2], [11]. Perinuclear anti-neutrophil cytoplasmic antibodies are positive in 26–94% of PSC patients but are not disease specific [6]. If cholestasis is present and secondary causes of sclerosing cholangitis (such as infection, immunodeficiency, ischemia, pancreatic disease, and immunoglobulin (Ig)G4-related conditions) are excluded, the diagnosis of PSC in IBD patients is made based on typical findings on magnetic resonance cholangiography (MRC) [2]. A liver biopsy is only warranted in patients showing biochemical and serological features of autoimmune hepatitis or if small-duct PSC, a disease variant of PSC with normal MRC, is suspected [2], [3], [4], [12].

In a recent Norwegian study, the prevalence of PSC detected with MRC in patients with IBD was 8.1%, around 3-fold higher than that detected based on symptoms [13]. However, all examined patients had long-term (20 years) disease and only 42.6% of the original cohort underwent MRC. Furthermore, a control group of non-IBD patients was missing [13]. Therefore, whether MRC has to be performed systematically in every IBD patient, regardless of the LFTs, remains unknown.

We report our single-centre experience with the systematic use of MRC to assess PSC in IBD patients with and without abnormal LFTs. The primary aims of the study were to evaluate the prevalence of PSC and to identify factors associated with the development of PSC in a large IBD cohort. Secondary aim was to compare MRC findings in IBD patients with MRC findings in non-IBD patients that underwent MRC in the assessment of abnormal LFTs.

Section snippets

Study design

We analysed MRC findings in three different cohorts of patients from our tertiary referral gastroenterology/hepatology centre (Nancy University Hospital, France). In cohort 1, MRCs were prospectively collected in IBD patients with abnormal LFTs. In cohort 2, MRCs were collected in IBD patients with normal LFTs. In cohort 3, which served as a control group, MRCs performed in non-IBD patients with abnormal LFTs were retrospectively assessed.

Cohort 1: IBD patients with LFTs abnormality

Cohort 1 grouped MRC findings in IBD patients with LFT

Baseline patient characteristics

In total, MRC findings were collected in 420 patients. There were 203 IBD patients with LFTs abnormality (cohort 1), 30 IBD patients without LFTs abnormality (cohort 2) and 187 non-IBD patients with LFTs abnormality (cohort 3). Baseline demographic and clinical characteristics of the IBD patients (cohorts 1 and 2) are summarized in Table 1. There was no difference between cohorts 1 and 2 in terms of age, disease duration, disease type, disease extension, disease behavior, and previous surgical

Discussion

Timely detection of PSC in IBD patients is essential. In a recent meta-analysis of 16 observational studies, including 13379 IBD patients of whom 1022 also had PSC, the risk of colorectal cancer was 3.4 times higher in the group of IBD patients with PSC, compared with patients with IBD alone [16]. IBD patients with PSC need annual screening colonoscopy [17]. There is also an increased risk for the development of cholangiocarcinoma in PSC [5]. In a large retrospective review of 399 PSC-IBD

Conflicts of interest

Arthur Belle, Valérie Laurent, Hélène Rousseau, Cédric Baumann, Xavier Orry and Jean-Pierre Bronowicki have nothing to disclose. Lieven Pouillon received travel fees from Ferring, Takeda. Arthur Lopez was a board member for Amgen, received lecture fees from Vifor Pharma, and received research grants from Roche. Laurent Peyrin-Biroulet received consulting fees from Merck, Abbvie, Janssen, Genentech, Mitsubishi, Ferring, Norgine, Tillots, Vifor, Pharmacosmos, BMS, UCB-pharma, Hospira, Celltrion,

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Primary sclerosing cholangitis (PSC) was declared one of the biggest unmet needs in hepatology during International Liver Congress 2016 in Berlin. Since then, not much has changed unfortunately, largely due to the still elusive pathophysiology of the disease. One of the most striking features of PSC is its association with inflammatory bowel disease (IBD), with the majority of patients with PSC being diagnosed with extensive colitis. This review describes the epidemiology of IBD in PSC, its specific phenotype, complications and potential pathophysiological mechanisms connecting the two diseases. Whether PSC is merely an extra-intestinal manifestation of IBD or if PSC and IBD are two distinct diseases that happen to share a common susceptibility that leads to a dual phenotype is debated. Implications for the management of the two diseases together are also discussed. Overall, this review summarises the available data in PSC-IBD and discusses whether PSC and IBD are one or two disease(s).
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Alimentary TractSystematic screening for primary sclerosing cholangitis with magnetic resonance cholangiography in inflammatory bowel disease

Abstract

Background

Aims

Methods

Results

Conclusions

Introduction

Section snippets

Study design

Cohort 1: IBD patients with LFTs abnormality

Baseline patient characteristics

Discussion

Conflicts of interest

J Hepatol

Lancet

Lancet

Gastrointest Endosc

Gastroenterology

Am J Gastroenterol

Extraintestinal manifestations of inflammatory bowel disease

Inflamm Bowel Dis

The first European evidence-based consensus on extra-intestinal manifestations in inflammatory bowel disease

J Crohns Colitis

Incidence and risk factors for cholangiocarcinoma in primary sclerosing cholangitis

Am J Gastroenterol

Review article: colorectal neoplasia in patients with primary sclerosing cholangitis and inflammatory bowel disease

Aliment Pharmacol Ther

Primary sclerosing cholangitis as an independent risk factor for colorectal cancer in the context of inflammatory bowel disease: a review of the literature

World J Gastroenterol

Systematic review: the epidemiology of the hepatobiliary manifestations in patients with inflammatory bowel disease

Aliment Pharmacol Ther

Alimentary Tract
Systematic screening for primary sclerosing cholangitis with magnetic resonance cholangiography in inflammatory bowel disease