Early Use of Transjugular Intrahepatic Portosystemic Shunt (TIPSS) in Patients With Cirrhosis and Variceal Bleeding

Background and Rationale for the Study

Gastro-oesophageal varices are present in 50% of patients with cirrhosis [2] and are the most serious complication of portal hypertension as their rupture results in potentially life threatening variceal haemorrhage with overall mortality rates historically reported as 30-50% [3]. Although mortality can be up to 40% at 6 weeks, it can be up to 70% at one year [2]. With the generally improved management of critically ill cirrhotic patients, together with vasoactive therapy and new endoscopic techniques for managing variceal haemorrhage, overall mortality has reduced, with one centre in Europe showing a reduction from 42% in 1980 to 14% in 2000 [4]. 60-80% of patients who bleed from varices will re-bleed if not treated [5-8], and the risk of re-bleeding is greatest in the first 10 days [1,9], during which 50% of those who are going to re-bleed, do so. The risk of re-bleeding gradually falls over the first month when an additional 10% re-bleed [7, 8]; the risk after the first six weeks then plateaus out.

Despite the advent of endoscopic therapies and early pharmacological therapies, re-bleeding rates are still higher early on, with factors predictive of early re-bleeding /treatment failure at 5 days including: active bleeding at index endoscopy; severity of liver disease (Child-Pugh class); severity of bleed; and severity of portal hypertension [1, 10]. Hepatic Venous Pressure Gradient (HVPG) is one of the best predictors of identifying those who will re-bleed. After an index variceal bleed, a reduction of HVPG to less than 12mmHg or by at least 20%, reduces the risk of re-bleeding from 46-65% to 0.13% [11]. HVPG measurement is usually limited to specialist centres.

The early use of TIPSS has been explored in two studies [1,12]. The first [12] categorised patients presenting with a variceal bleed to be either high or low risk of re-bleeding determined by their HVPG. Those with an HVPG greater or equal to 20mmHg went on to receive an early TIPSS and had an improved outcome compared with those treated medically. However, the results must be interpreted with caution, as the medical management was not current standard of care.

A further study investigating the use of early TIPSS for variceal haemorrhage was carried out by Garcia-Pagan and colleagues [1]. This landmark study selected patients for early TIPSS (within 3 days) determined by Child-Pugh score. Participants, who had Child's B or C cirrhosis and on-going bleeding, progressed to early use of TIPSS (with an e-PFTE-covered stent). The results of this trial demonstrated a significant reduction in the failure to control bleeding and re-bleeding with no increase in the risk of hepatic encephalopathy. The study also demonstrated a significant survival benefit with early TIPSS at all time points. There were, however, several features of this study that raised concern.