Cost-Effectiveness of Hepatic Venous Pressure Measurements
Background: Measurement of the hepatic venous pressure gradient may identify a sub-optimal response to drug prophylaxis in patients with a history of variceal bleeding. However, the cost-effectiveness of routine hepatic venous pressure gradient measurements to guide secondary prophylaxis has not been examined.
Methods: A Markov model was constructed using specialized software (DATA 3.5, Williamstown, MA, USA). Three strategies involved secondary prophylaxis without haemodynamic monitoring using beta-blockers alone, beta-blockers plus isosorbide mononitrate or endoscopic variceal ligation alone. Four strategies involved secondary prophylaxis with beta-blockers plus isosorbide mononitrate or beta-blockers alone, accompanied by one or two hepatic venous pressure gradient measurements to identify haemodynamic non-responders, who underwent endoscopic variceal ligation as an alternative. The total expected costs, variceal bleeding episodes and total deaths were calculated for each strategy over 3 years.
Results: The two most effective strategies were combination therapy alone and combination therapy with two hepatic venous pressure gradient measurements. The incremental cost-effectiveness ratio of the latter strategy was $136 700 per year of life saved compared with combination therapy alone. The ratio improved as the time horizon was extended or the rates of variceal re-bleeding were increased.
Conclusions: The cost-effectiveness of haemodynamic monitoring to guide secondary prophylaxis of recurrent variceal bleeding is highly dependent on local hepatic venous pressure gradient measurement costs, life expectancy and re-bleeding rates.

Variceal re-bleeding is a significant cause of morbidity and mortality in patients with portal hypertension. Over the past three decades, multiple treatment regimens have been investigated in order to decrease the incidence of variceal re-bleeding in patients with portal hypertension, including portal-systemic shunts, endoscopic therapy and pharmacological agents. The use of non-selective beta-blockers, alone or in combination with isosorbide mononitrate, has been shown to decrease variceal bleed rates in multiple studies of patients with oesophageal varices. They have therefore become the most common therapy in the secondary prophylaxis of variceal bleeding.

The benefit of beta-blocker therapy has been attributed to a decrease in portal pressure, as demonstrated by a decrease in the hepatic venous pressure gradient (HVPG). Variceal bleed rates are directly related to HVPG measurements, as demonstrated by the absence of variceal bleeding in patients with an absolute HVPG of less than 12 mmHg, and rates of 5-8% over 2-3 years when secondary prophylaxis results in a 20% reduction in HVPG from baseline. However, several studies have demonstrated that 49-64% of patients do not respond to pharmacotherapy with a drop in HVPG to less than 12 mmHg or by 20%. These studies have also shown that, in patients who fail to 'respond' to therapy, variceal bleed rates are high, ranging from 39% to 62% over 2-3 years.

It would be beneficial to identify patients who do not respond to pharmacological therapy in order for alternative therapies to be implemented. Due to a lack of a non-invasive test to evaluate reliably the response of portal pressure to pharmacotherapy, measurement of HVPG has been suggested as a way to identify patients who fail to attain an adequate haemodynamic response with medical therapy. HVPG measurement has not been studied as a tool for the modification of prophylaxis in patients with bleeding oesophageal varices. We used data from previous studies to construct a Markov model of prophylaxis for recurrent variceal haemorrhage, comparing therapy guided by HVPG measurement with all other primary therapies. In our model, HVPG measurement was used to identify patients who do not respond to pharmacotherapy in order to offer alternative therapy, including endoscopic variceal ligation.