Association Of Primary Sclerosing Cholangitis Research Articles

S3234 The Association of Microscopic Colitis and Primary Sclerosing Cholangitis

Introduction: Microscopic colitis (MC) and primary sclerosing cholangitis (PSC) are immunological disorders. The association of ulcerative colitis (UC) with PSC is well-known. Patients with PSC without UC could have MC. We studied clinical features and outcomes in patients with MC and PSC. Methods: Patients with MC and PSC were retrospectively identified from January 1st, 1980 to December 31st, 2020. Details including demographics, mode of diagnoses, treatment and response to MC therapy, presence of UC or Crohn’s disease, complications and risk of neoplasia were gathered. Results: Twelve patients (8 male; median age 54.4 years [range 22.6-75.3]; 7 with lymphocytic colitis, 5 with collagenous colitis) were found. Nine (75%) were diagnosed with MC after PSC (median 2.5 weeks [range 0-1221.5]). Six of 12 (50%) were symptomatic for MC with diarrhea, and 6 (50%) were incidentally found to have MC during screening for IBD or dysplasia. One patient had an adenomatous polyp, no patient had flat dysplasia or cancer, and none underwent colon resection. Six (50%) who were asymptomatic for MC required no treatment, treatment data was missing for 1 symptomatic patient, the remaining 5 symptomatic patients were treated with budesonide (3), prednisone (1), and bismuth subsalicylate (1). All experienced complete resolution of diarrhea. One had pre-existing UC that transformed to MC after 8 years and another transformed from chronic colitis to MC after 1 year. Diagnosis of PSC was made by ERCP in 6 patients (50%), liver biopsy in 4 (33.3%) and MRCP in 3 (25%). Cholangitis developed in 5 patients (41.6%), strictures requiring stenting in 7 (58.3%), cirrhosis in 4 (33.3%) and cholangiocarcinoma in 2 patients (16.6%). No patient required a liver transplant, 1 (8.3%) died one year after PSC diagnosis due to cholangiocarcinoma. CONCLUSION: Concomitant diagnosis of MC and PSC was uncommon. Most patients were male, which is typical for PSC but atypical for MC. Microscopic colitis was often found incidentally by colonoscopy done to rule out IBD. Half the patients did not have symptoms of MC and required no treatment. Patients that were treated for MC had a complete resolution of symptoms. Primary sclerosing cholangitis tended to have complications. The association of PSC with UC is well-known. When managing patients with PSC and unexplained diarrhea or patients with MC and abnormal liver chemistries, MC-PSC should be considered.

PTU-070 Fine mapping of the IL-2/IL-21 and IL2RA loci in primary sclerosing cholangitis

IntroductionRecent genetic studies in Primary sclerosing cholangitis (PSC), a chronic bile duct disease, have shown suggestive association at IL-2/21 (4q27) and IL2RA (10p15). IL-2 and IL2RA are key regulators of...

Genetic polymorphisms of matrix metalloproteinase 3 in primary sclerosing cholangitis

The damaging cholestasis inherent to primary sclerosing cholangitis (PSC) results from bile duct stricturing because of progressive fibrosis. The matrix metalloproteinase 3 (MMP3) degrades a wide range of matrix components and is expressed by activated liver stellate cells, and so is a candidate for involvement with the fibrotic processes underlying PSC. Moreover, the MMP3 gene harbours polymorphisms associated with variation in its activity directly impacting clinical phenotypes. We aimed to examine the influence of MMP3 polymorphisms on PSC risk and progression. Nine single nucleotide polymorphisms (SNPs) tagging the common genetic variation of MMP3 were genotyped in 266 PSC patients and 407 controls. SNPs and inferred haplotypes were assessed for PSC association by logistic regression and score tests. The effect of SNPs on survival to liver transplant or death was analysed using Cox regression, and Kaplan-Meier curves were constructed. No association of PSC with individual SNPs or haplotypes of MMP3 was detected. However, progression to death or liver transplant was significantly associated with homozygosity for minor alleles of rs522616, rs650108 and rs683878, particularly among PSC patients with concurrent ulcerative colitis (UC) (strongest in redundant SNPs rs650108/rs683878, hazard ratio=3.23, 95% confidence interval 1.45-7.25, P=0.004). Genetic variation in MMP3 influences PSC progression, possibly in the context of coexisting UC. While the functional variants and specific mechanisms remain unknown, this finding implicates the turnover of the extracellular matrix as an important and variable component of PSC pathogenesis. Efforts to understand this process could form the basis for developing effective treatments, which are currently lacking for PSC.