Kidist Yimam

Diagnosis and classification of primary sclerosing cholangitis

Primary sclerosing cholangitis (PSC) is a chronic cholestatic disease of the liver and that is characterized by progressive inflammation, fibrosis, and stricturing of the intrahepatic and extrahepatic bile ducts. It is progressive in most patients and leads to cirrhosis. It is a rare disease, mostly affecting people of northern European descent, males greater than females. The diagnosis is best established by contrast cholangiography, which reveals a characteristic picture of diffuse, multifocal strictures and focal dilation of the bile ducts, leading to a beaded appearance. Inflammatory bowel disease (IBD) is present in ~75% of the patients with PSC, mostly ulcerative colitis (~85% of the cases). In addition to biliary cirrhosis, complications of PSC include dominant strictures of the bile ducts, cholangitis, cholangiocarcinoma, colon dysplasia and cancer in patients with IBD, gallbladder polyps and cancer, and hepatic osteodystrophy. The etiology of PSC is not clear, but studies are ongoing. The median survival without liver transplantation is 12 to 15 years after diagnosis. Currently there are no effective treatments except liver transplantation. Immunosuppressive medications have not been shown to be effective but antibiotics and anti-fibrotic agents seem promising.

Obeticholic acid for the treatment of primary biliary cirrhosis

Introduction: Primary biliary cirrhosis (PBC) is a rare autoimmune liver disease, in which the epithelial cells of small bile ducts are targeted for immune attack leading to cholestasis and cirrhosis. Although it is considered an autoimmune disease, immune modulators have not been effective to date in the treatment of PBC. Ursodeoxycholic acid (UDCA) has been the mainstay of treatment of over two decades, but a significant minority of PBC patients do not have a complete response to UDCA and are at risk of continued disease progression. Area covered: Obeticholic acid (OCA) is a novel derivative of chenodeoxycholic acid, a primary human bile acid and natural ligand of the nuclear hormone receptor farnesoid X receptor (FXR). Activation of FXR inhibits bile acid (BA) synthesis and protects against the toxic accumulation of BAs. We reviewed published preclinical, efficacy, and safety data of OCA for the treatment of PBC. Expert opinion: OCA in combination with UDCA leads to significant improvement in liver biochemistries shown to predict outcomes in PBC patients with an incomplete response to UDCA. Dose-dependent pruritus is the most common adverse effect. Long-term efficacy of OCA and its efficacy in patients with advanced PBC need to be delineated, as well as its role as monotherapy compared with UDCA.

Primary Sclerosing Cholangitis Is Not Rare Among Blacks in a Multicenter North American Consortium

Primary sclerosing cholangitis (PSC) is a progressive autoimmune liver disease characterized by bile duct inflammation and fibrosis. Our understanding of PSC is shaped largely from populations in Europe and the US that almost exclusively included white patients of Northern European descent.1–5 In an ongoing NIH-sponsored PSC cohort study of 1,000 patients, only 5% of subjects are non-Caucasian.6 As a result, little is known about PSC in minority populations in the US, particularly patients of black race, and it is unknown if PSC is a rare disease in patients of black race, or reflects selection bias of sampled cohorts.

HLA haplotypes in primary sclerosing cholangitis patients of admixed and non‐European ancestry

Primary sclerosing cholangitis (PSC) is strongly associated with several human leukocyte antigen (HLA) haplotypes. Due to extensive linkage disequilibrium and multiple polymorphic candidate genes in the HLA complex, identifying the alleles responsible for these associations has proven difficult. We aimed to evaluate whether studying populations of admixed or non‐European descent could help in defining the causative HLA alleles. When assessing haplotypes carrying HLA‐DRB1*13:01 (hypothesized to specifically increase the susceptibility to chronic cholangitis), we observed that every haplotype in the Scandinavian PSC population carried HLA‐DQB1*06:03. In contrast, only 65% of HLA‐DRB1*13:01 haplotypes in an admixed/non‐European PSC population carried this allele, suggesting that further assessments of the PSC‐associated haplotype HLA‐DRB1*13:01‐DQA1*01:03‐DQB1*06:03 in admixed or multi‐ethnic populations could aid in identifying the causative allele.

Su1046 Early-Onset Colorectal Cancer Is Independently Associated With Shorter Overall Survival

BACKGROUND: Colorectal cancer (CRC) is the third most common cancer, as well as the third most common cause of cancer deaths in the United States. Bisphosphonates are antiresorptive agents widely used in treating and preventing osteoporosis. Several large studies have recently reported a reduced risk of CRC with bisphosphonate use, however no meta-analysis on the subject exists. AIM: We aimed to conduct a meta-analysis of existing observational studies and thus provide a quantitative estimate of the association between bisphosphonate use and the risk of CRC. METHODS: We followed the Meta-Analysis of Observational Studies in Epidemiology (MOOSE) guidelines in performing our systematic review. A search was conducted through Medline, PubMed, Embase, and Current