Primary sclerosing cholangitis from childhood to adult age : risk factors, monitoring and outcome

Research output: ThesisDoctoral ThesisCollection of Articles


BACKGROUND AND AIM This thesis includes two studies conducted in a paediatric and two studies conducted in an adult primary sclerosing cholangitis (PSC) population. The common denominator was endoscopic retrograde cholangiography (ERC) with brush cytology that was performed in all patients. The aims were to: i) identify the possible environmental risk factors (Study I) and report the long-term outcome (Study II) of paediatric-onset PSC, ii) compare ERC and magnetic resonance imaging with cholangiopancreatography (MRI-MRCP) in the evaluation of disease activity and severity of patients with PSC (Study III) and evaluate the role of ERC with brush cytology as screening for cholangiocarcinoma (CC) in patients with PSC (Study IV). MATERIAL AND METHODS PSC was diagnosed, followed-up (or both) in Helsinki University Hospital (HUH). Study I: 71 patients with a new diagnosis of paediatric-onset (age <16 years) PSC, autoimmune hepatitis (AIH) or PSC-AIH (togheter autoimmune liver diseases or AILD) between 1985-2011. Two control groups were used: 1) 91 IBD patients matched for gender and age, collected from the IBD Population Registry at HUH and 2) 716 healthy subjects matched for gender, age and also place of birth at the time of AILD diagnosis, collected from the Population Registry Centre. A questionnaire of 22 items was administered. Study II: 41 patients with a new diagnosis of paediatric-onset PSC between 1993-2011. Study III: 48 patients with PSC who underwent ERC and MRI-MRCP within + 3 months for the diagnosis or the follow-up of the disease. Study IV: 261 patients with a new diagnosis of PSC (age > 18 years) between 1 January 2006 and 31 October 2011. All cholangiographic images were scored according to the modified Amsterdam PSC score. RESULTS Study I: In multivariate analysis, children ‘living with a cat in a block of flats’ had a higher risk (OR 3.6; 95% CI: 1.2-10.8) of having AILD than healthy controls, but not IBD controls. Study II: At the end of follow-up (9 years, range 2-20 years) all children were alive and no malignancy occurred. 29/33 (88%) were not transplanted; 26/29 (78%) were not cirrhotic and 3/29 (10%) were cirrhotic. 4/33 (12%) were transplanted after a median of 7.5 years; no PSC recurrence in the graft occurred. Study III: MRCP and ERC scores for IHBD were associated with alkaline phosphatase (p = 0.016 and p = 0.018, respectively) and CA19-9 level (p <0.001 and p = 0.030, respectively); MRCP score for EHBD was also associated with CA19-9 level (p = 0.021). Finally, peribiliary enhancement detected on MRI correlated with cytology findings for both IHBD (Spearman’s rho = 0.322, SE: 0.095, p = 0.022) and EHBD (Spearman’s rho = 0.319, SE: 0.113, p = 0.025, respectively). Study IV: Most of the patients were asymptomatic (211/261; 80.8%) and had only mild changes on cholangiography (149/261; 57.1%) at time of first ERC. Follow-up was completed in 249/261 (95%). CC developed in 7 patients and biliary dysplasia in 8 patients; brush cytology was suspicious or malignant in 8 patients at time of PSC diagnosis. Advanced EHBD cholangiographic changes (HR: 1.7; 95% CI: 1.2-2.3) and alanine aminotransferase (HR: 14.2; 95% CI: 1.9-106.4) were associated with increased risk of biliary neoplasia. CONCLUSIONS An unidentified environmental risk factor (i.e., microbial) especially associated with cats may increase the risk of PSC in children. The clinical course and outcome of paediatric-onset PSC seems to be good until adulthood with a high survival rate, with no occurrence of malignancy and LT required in only a minority of patients. MRI-MRCP use in PSC follow-up seems to be low. In this respect, ERC with brush cytology is a good screening tool for detection of biliary dysplasia or neoplasia (or both) in patients with PSC. Advanced extrahepatic disease and alanine aminotransferase elevation may predict the occurrence of CC.TITLE IN FINNISH: Primaarinen sklerosoiva kolangiiitti lapsuudesta aikuisuuteen: riskitekijät, seuranta ja selviytyminen
Original languageEnglish
Place of PublicationHelsinki
Print ISBNs978-951-51-3499-8
Publication statusPublished - 2017
MoE publication typeG5 Doctoral dissertation (article)

Fields of Science

  • 3121 General medicine, internal medicine and other clinical medicine

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