salicylates and Hypertension--Portal

Transjugular intrahepatic portosystemic shunt (TIPS) is nowadays the benchmark treatment of severe portal hypertension complications. However, besides usual contraindication to the procedure (namely recurrent hepatic encephalopathy, severe liver dysfunction, right heart failure and/or pulmonary hypertension), TIPS appears regularly unfeasible due to abnormal and/or distorted anatomy. In this situation, the only non-surgical approaches to treat severe portal hypertension consist in the creation of an intrahepatic portocaval shunt from percutaneous (direct intrahepatic portocaval shunt - DIPS) or transjugular route (transjugular transcaval intrahepatic portosystemic shunt - TTIPS). These procedures have been rapidly adopted in patients with Budd-Chiari syndrome but are only poorly reported in patients with cirrhosis and without BCS. Considering the broadening landscape of TIPS indication in patients with cirrhosis within the last ten years, we aimed to describe the techniques, safety and efficacy of DIPS and TTIPS procedures as an alternative to TIPS in case of unfavourable anatomy.

Topics: Budd-Chiari Syndrome; Humans; Hypertension, Portal; Liver Cirrhosis; Portasystemic Shunt, Transjugular Intrahepatic; Salicylates; Treatment Outcome

Portal hypertension resulting from increased intrahepatic resistance is a common complication of chronic liver diseases and a leading cause of death in patients with liver cirrhosis, a scarring process of the liver that includes components of both increased fibrogenesis and wound contraction. A reduced production of nitric oxide (NO) resulting from an impaired enzymatic function of endothelial NO synthase and an increased contraction of hepatic stellate cells (HSCs) have been demonstrated to contribute to high intrahepatic resistance in the cirrhotic liver. 2-(Acetyloxy) benzoic acid 3-(nitrooxymethyl) phenyl ester (NCX-1000) is a chemical entity obtained by adding an NO-releasing moiety to ursodeoxycholic acid (UDCA), a compound that is selectively metabolized by hepatocytes. In this study we have examined the effect of NCX-1000 and UDCA on liver fibrosis and portal hypertension induced by i.p. injection of carbon tetrachloride in rats. Our results demonstrated that although both treatments reduced liver collagen deposition, NCX-1000, but not UDCA, prevented ascite formation and reduced intrahepatic resistance in carbon tetrachloride-treated rats as measured by assessing portal perfusion pressure. In contrast to UDCA, NCX-1000 inhibited HSC contraction and exerted a relaxing effect similar to the NO donor S-nitroso-N-acetylpenicillamine. HSCs were able to metabolize NCX-1000 and release nitrite/nitrate in cell supernatants. In aggregate these data indicate that NCX-1000, releasing NO into the liver microcirculation, may provide a novel therapy for the treatment of patients with portal hypertension.

Topics: Animals; Carbon Tetrachloride; Collagen; Hypertension, Portal; Liver; Liver Cirrhosis; Male; Nitrates; Nitric Oxide; Nitric Oxide Donors; Rats; Rats, Wistar; Salicylates; Ursodeoxycholic Acid

Topics: Child; Child, Preschool; Hematemesis; Humans; Hypertension, Portal; Infant; Liver Diseases; Liver Function Tests; Portacaval Shunt, Surgical; Radiography; Salicylates; Splenectomy; Splenomegaly; Thrombophlebitis

Topics: Adolescent; Biopsy; Child; Child, Preschool; Diet Therapy; Esophageal and Gastric Varices; Female; Gastrointestinal Hemorrhage; Gold Isotopes; Humans; Hypertension, Portal; Infant; Liver; Liver Circulation; Male; Mercury Isotopes; Portography; Pregnancy; Pregnancy Complications, Hematologic; Radionuclide Imaging; Salicylates