Prioritization of Therapeutic Targets and Trial Design in Cirrhotic Portal Hypertension.

Abraldes, J G; Trebicka, J; Chalasani, N; D'Amico, G; Rockey, D; Shah, V; Bosch, Jaime; Garcia-Tsao, G (2019). Prioritization of Therapeutic Targets and Trial Design in Cirrhotic Portal Hypertension. Hepatology, 69(3), pp. 1287-1299. Wiley Interscience 10.1002/hep.30314

[img]
Preview
Text
Abraldes_et_al-2018-Hepatology.pdf - Accepted Version
Available under License Publisher holds Copyright.

Download (1MB) | Preview

Portal hypertension is the main driver of cirrhosis decompensation, the main determinant of death in patients with cirrhosis. Portal hypertension results initially from increased intrahepatic vascular resistance. Later, increased inflow from splanchnic vasodilation and increased cardiac output lead to a further increase in portal pressure. Reducing portal pressure in cirrhosis results in better outcomes. Removing the cause of cirrhosis might improve portal pressure. However, this is a slow process and patients may continue to be at risk of decompensation. Additionally, for some chronic liver diseases, such as non-alcoholic fatty liver disease, etiological treatments are not yet available. Therefore, there is a need to develop better therapies specifically aimed at reducing portal pressure. For over 35 years, the mainstay of such therapy has been the use of nonselective beta-blockers that act by reducing portal venous inflow. Recently, many drugs (mainly targeting intrahepatic mechanisms) have shown promise in pre-clinical and early clinical studies and may act alone or synergistically with nonselective beta-blockers in reducing portal pressure in cirrhosis. The objective of this position paper is to propose a novel framework for the design of clinical trials (phase 1, 2 and 3) in patients with cirrhosis and portal hypertension and to prioritize novel targets and pharmacological therapies in this setting. We have focused the discussion on patients with compensated cirrhosis. The paper summarizes discussions held at The American Association for the Study of Liver Diseases (AASLD) Industry Colloquium in January 2018, with the participation of clinical and translational investigators, regulatory professionals and industry partners.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine > Hepatology
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Hepatologie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Hepatologie

UniBE Contributor:

Bosch, Jaime

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0270-9139

Publisher:

Wiley Interscience

Language:

English

Submitter:

Thi Thao Anh Pham

Date Deposited:

17 Dec 2018 09:49

Last Modified:

23 Oct 2019 21:09

Publisher DOI:

10.1002/hep.30314

PubMed ID:

30318607

Uncontrolled Keywords:

Cirrhosis drug targets pharmacokinetics phase 2 trials phase 3 trials portal hypertension pre-clinical studies trial design

BORIS DOI:

10.7892/boris.122122

URI:

https://boris.unibe.ch/id/eprint/122122

Actions (login required)

Edit item Edit item
Provide Feedback