Etiology and Clinical Outcome of Budd-Chiari Syndrome and Portal Vein Thrombosis

The liver receives approximately one-third of the resting cardiac output. Blood flow to the liver is supplied by both an arterial (hepatic artery) and a venous (portal vein) system and three hepatic veins provide drainage of blood from the liver to the inferior vena cava. The hepatic vascular system is quite dynamic and has the ability to function as a reservoir for blood within the general circulation. Different conditions can interfere with hepatic blood flow and cause disease. The most important clinical syndrome affected by obstruction within the liver vasculature is portal hypertension. Portal hypertension is defined by an increase in the pressure of the portal venous system which results from a disruption of normal blood flow at either a prehepatic, intrahepatic or posthepatic level. The most common cause of portal hypertension in the Western world is liver cirrhosis, leading to an elevated portal pressure due to an increased resistance to intrahepatic blood flow as a result of architectural distortion of the liver. In the absence of liver cirrhosis, numerous less common disorders are known to cause, socalled, non-cirrhotic portal hypertension. Two rare diseases, characterized by thrombosis of the large hepatic vessels are Budd-Chiari syndrome (BCS) and portal vein thrombosis (PVT). Both these disorders share certain features, such as etiologic factors causing thrombosis and the development of portal hypertension, but are considered as separate disease entities based on the location of venous obstruction and their variable clinical presentation. BCS is defined as an obstruction of the hepatic venous outflow tract, ranging from the level of the small hepatic veins up to the junction of the inferior vena cava with the right atrium. Most cases of BCS in the Western world are caused by thrombosis of the hepatic veins, sometimes in combination with thrombosis of the inferior vena cava. The exact incidence of BCS is unknown but is estimated around 1 per million. Thrombotic occlusion of the portal vein is somewhat more common, especially as a complication in patients with liver cirrhosis. Noncirrhotic PVT has a diverse etiology but a significantly better outcome than in patients with underlying liver cirrhosis or hepatobiliary malignancies

Tofacitinib for ulcerative colitis:results of the prospective Dutch Initiative on Crohn and Colitis (ICC) registry

Background: Tofacitinib is a Janus kinase inhibitor approved for the treatment of ulcerative colitis (UC). Aim: To evaluate effectiveness, safety and use of tofacitinib in daily practice. Methods: UC patients initiating tofacitinib were prospectively enrolled in 15 hospitals in the Netherlands. Corticosteroid-free clinical remission (short clinical colitis activity index [SCCAI] ≤2), biochemical remission (faecal calprotectin level ≤250 µg/g), combined corticosteroid-free clinical and biochemical remission, predictors of remission, safety outcomes, treatment dose and effect on lipids were determined at weeks 12 and 24. Endoscopic outcomes were evaluated in centres with routine endoscopic evaluation. Results: In total, 123 UC patients (95% anti-TNF, 62% vedolizumab and 3% ustekinumab experienced) were followed for a median duration of 24 weeks (interquartile range 12-26). The proportion of patients in corticosteroid-free clinical, biochemical, and combined corticosteroid-free clinical and biochemical remission rate at week 24 was 29% (n: 22/77), 25% (n: 14/57), and 19% (n: 11/57) respectively. Endoscopic remission (Mayo = 0) was achieved in 21% of patients at week 12 (n: 7/33). Prior vedolizumab exposure was associated with reduced clinical remission (odds ratio 0.33, 95% confidence interval [CI] 0.11-0.94). At week 24, 33% (n: 14/42) of patients still on tofacitinib treatment used 10 mg twice daily. In total, 33 tofacitinib-related adverse events (89 per 100 patient years) occurred, 7 (6% of total cohort) resulted in discontinuation. Cholesterol, HDL and LDL levels increased during induction treatment by 18% (95% CI 9-26), 18% (95% CI 8-28) and 21% (95% CI 14-39) respectively. Conclusion: Tofacitinib is an effective treatment for UC after anti-TNF and vedolizumab failure. However, a relatively high rate of adverse events was observed resulting in discontinuation in 6% of patients