Cholangiopathies - Towards a molecular understanding.

Liver diseases constitute an important medical problem, and a number of these diseases, termed cholangiopathies, affect the biliary system of the liver. In this review, we describe the current understanding of the causes of cholangiopathies, which can be genetic, viral or environmental, and the few treatment options that are currently available beyond liver transplantation. We then discuss recent rapid progress in a number of areas relevant for decoding the disease mechanisms for cholangiopathies. This includes novel data from analysis of transgenic mouse models and organoid systems, and we outline how this information can be used for disease modeling and potential development of novel therapy concepts. We also describe recent advances in genomic and transcriptomic analyses and the importance of such studies for improving diagnosis and determining whether certain cholangiopathies should be viewed as distinct or overlapping disease entities.

Natural history and risk factors for rupture of thoracic aortic arch aneurysms.

OBJECTIVE: The management of degenerative aneurysms of the aortic arch requires careful selection of patients, taking into consideration risk of rupture and operative risks, which is more relevant with the emergence of hybrid debranching and branched and fenestrated endovascular options. The natural history of true arch aneurysms has not been previously studied. We aimed to determine the expansion rate of thoracic aortic arch aneurysm and to identify predictors for rupture. METHODS: Consecutive patients with known true thoracic aortic arch aneurysms monitored with serial computed tomography from 2000 to 2014 were retrospectively reviewed. Thoracoabdominal aneurysms and aneurysms due to aortic dissection and connective tissue diseases were excluded. Variables studied included patient demographics, aneurysm morphology, and ascending aorta diameter. A size expansion curve for each patient was plotted with serial computed tomography scan data, and the slope obtained by linear interpolation was taken as the expansion rate. Multiple logistic regression analysis was performed to identify independent predictors of rupture. Average yearly risks of rupture for overall and expansion rate substrata were calculated from life-table analysis. RESULTS: A total of 45 arch aneurysms were followed up for a mean of 36.6 months (3-104). Aneurysm growth was largely linear, with an average rate of 2.5 mm/y (0-16). During surveillance, 10 aneurysms ruptured (22%) and 8 patients died. There was one additional arch aneurysm-related death during follow-up, whereas 14 patients (31%) died of other causes. Aneurysms expanding at >5.5 mm/y have a 67% likelihood of rupture compared with 8.3% of those expanding at <5.5 mm/y. Aneurysm size >6.5 cm (P = .0001) and hyperlipidemia (P = .0321) were positively correlated with fast expansion. On univariate analysis, only aneurysm size and expansion rate were significant predictors of rupture. On multivariate analysis, aneurysm expansion rate was the sole independent risk factor of aneurysm rupture (odds ratio, 1.43; 95% confidence interval, 1.06-1.92; P = .018). CONCLUSIONS: Aneurysm expansion rate >5.5 mm/y is a significant rupture predictor in addition to size compared with aneurysm morphology and other demographic factors. Aneurysm size >6.5 mm and hyperlipidemia are determining factors of expansion rate. These may have implications in selection of patients for surgery. Better control of hyperlipidemia may alleviate the risk of rupture.