Cholangiocarcinoma (CCA) presents significant diagnostic challenges, resulting in late patient diagnosis and poor survival rates. Primary sclerosing cholangitis (PSC) patients pose a particularly difficult clinical dilemma because they harbor chronic biliary strictures that are difficult to distinguish from CCA. MicroRNAs (miRs) have recently emerged as a valuable class of diagnostic markers; however, thus far, neither extracellular vesicles (EVs) nor miRs within EVs have been investigated in human bile. We aimed to comprehensively characterize human biliary EVs, including their miR content. We have established the presence of extracellular vesicles in human bile. In addition, we have demonstrated that human biliary EVs contain abundant miR species, which are stable and therefore amenable to the development of disease marker panels. Furthermore, we have characterized the protein content, size, numbers, and size distribution of human biliary EVs. Utilizing multivariate organization of combinatorial alterations (MOCA), we defined a novel biliary vesicle miR-based panel for CCA diagnosis that demonstrated a sensitivity of 67% and specificity of 96%. Importantly, our control group contained 13 PSC patients, 16 with biliary obstruction of varying etiologies (including benign biliary stricture, papillary stenosis, choledocholithiasis, extrinsic compression from pancreatic cysts, and cholangitis), and 3 with bile leak syndromes. Clinically, these types of patients present with a biliary obstructive clinical picture that could be confused with CCA. Conclusion: These findings establish the importance of using extracellular vesicles, rather than whole bile, for developing miR-based disease markers in bile. Finally, we report on the development of a novel bile-based CCA diagnostic panel that is stable, reproducible, and has potential clinical utility. (Hepatology 2014;60:896–907)

This is a retrospective review of consecutive adult patients (age ≥18) with a positive real-time reverse-transcription polymerase chain reaction test for severe acute respiratory syndrome coronavirus 2 recorded between March 4 and April 9, 2020, at 1 of our 2 hospitals in Manhattan (an academic tertiary referral center and a smaller community hospital). The history, laboratory data, and outcome measures were extracted from patients’ medical records, using an structured abstraction tool. All vital signs and laboratory data were collected at presentation. "GI manifestation" was defined as presence of nausea, vomiting, diarrhea, or abdominal pain. Patients were considered to have indication of liver injury at presentation if they had elevated alanine aminotransferase, aspartate aminotransferase, total bilirubin, or alkaline phosphatase. The primary clinical outcome for admitted patients was defined as a composite of intensive care unit (ICU) admission or death (details of methods are available in the supplementary material).