Over the last 20 years, there have been significant advances in the
management of portal hypertension, with the introduction of drug therapy and
the transjugular intrahepatic portosystemic stent-shunt (TIPSS). This
development continues at a strong pace as our understanding of the
pathogenesis of portal hypertension deepens. There are 2 aims of this thesis:
1. To study the haemodynamic effects of two novel vasoactive agents on the
portal and systemic circulations.
a. Carvedilol, a vasodilating non-cardioselective beta-blocker with op
antagonism. The acute and chronic haemodynamic effects of this
agent will be studied, with particular attention paid to patient
b. Losartan, an angiotensin II receptor antagonist. The chronic effects of
this agent will be studied in patients with well compensated cirrhosis.
These laboratory based studies will assist in determining the suitability
of these agents for use in controlled clinical trials on patients at risk of
2. TIPSS has been used extensively in the management of portal
hypertension, particularly variceal bleeding. Two studies will be presented in
this thesis aimed at answering the following questions.
a. Is TIPSS effective for the management of gastric variceal bleeding?
Gastric variceal bleeding is less common than oesophageal variceal
bleeding, hence there are relatively few studies investigating the effect
of TIPSS on bleeding gastric varices. This study will also compare
gastric variceal bleeding with oesophageal variceal bleeding, and aim
to correlate clinical outcomes with haemodynamic data.
b. Is it necessary to continue portographic TIPSS surveillance
indefinitely if variceal band ligation is combined with TIPSS for the
prevention of oesophageal variceal rebleeding? This is the hypothesis
for a randomised controlled trial comparing TIPSS alone with TIPSS
plus variceal band ligation. This study will address 2 drawbacks of
TIPSS, namely the need for long-term portographic to ensure TIPSS
patency and hepatic encephalopathy.