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Portal hypertension: from pathophysiology to clinical practice

Authors


Frederik Nevens, MD, PhD, Department of Hepatology, University Hospital Gasthuisberg, K.U. Leuven, B-3000 Leuven, Belgium.
Tel: +32-16-344299
Fax: +32-16-344387
e-mail: frederik.nevens@uz.kuleuven.ac.be

Abstract

Abstract: Portal hypertension (PHT) is responsible for the more severe and often lethal complications of cirrhosis such as bleeding oesophageal varices, ascites, renal dysfunction and hepatic encephalopathy. Because of the combined impact of these complications, PHT remains the most important cause of morbidity and mortality in patients with cirrhosis. Over the years, it has become clear that a decrease in portal pressure is not only protective against the risk of variceal (re)bleeding but is also associated with a lower long-term risk of developing complications and an improved long-term survival. A milestone in therapy was the introduction of non-selective β-blockers for the prevention of bleeding and rebleeding of gastro-esophageal varices. However, in practice, less than half the patients under β-blockade are protected from these risks, supporting the overall demand for innovation and expansion of our therapeutic armamentarium. Recent advances in the knowledge of the pathophysiology of cirrhotic PHT have directed future therapy towards the increased intrahepatic vascular resistance, which, in part, is determined by an increased hepatic vascular tone. This increased vasculogenic component provides the rationale for the potential use of therapies aimed at increasing intrahepatic vasorelaxing capacity via gene therapy, liver-selective nitric oxide donors and statines on the one hand, and at antagonizing excessive intrahepatic vasoconstrictor force through the use of endothelin antagonists, angiotensin blockers, α1 adrenergic antagonists or combined α1- and non-selective β-blockers or somatostatin analogues on the other. The focus of this review is to give an update on the pathophysiology of PHT in order to elucidate these potential novel strategies subsequently.

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