Gastrointestinal bleeding

Early use of TIPS in patients with cirrhosis and variceal bleeding (García-Pagán et al., New Engl J Med 2010 [1])

Variceal bleeding is one of the most fatal complications of portal hypertension and its mortality rate is much higher than that of other types of gastrointestinal bleeding. Combined endoscopic therapy with vasoactive agents and prophylactic antibiotics is the conventional treatment but recurrent bleeding still occurs in 10 % – 15 % of patients, leading to multiple endoscopies, multiple transfusions, and death. The use of transjugular intrahepatic portosystemic shunts (TIPS) is known to be highly effective in controlling the bleeding by reducing portal pressure but it does lead almost inevitably to hepatic encephalopathy. Therefore, the conventional recommendation is to continue with pharmacotherapy combined with endoscopic treatment of bleeding varices and use TIPS only as rescue therapy. There is always a dilemma that TIPS prevents bleeding but results in comatose patients due to hepatic failure, and hence does not improve survival.

So, what is the best timing for TIPS? A recent randomized controlled trial attempted to address this question. Patients with Child’s B or C cirrhosis presenting with variceal bleeding were first treated with endoscopic band ligation (EBL) or endoscopic injection sclerotherapy (EIS) and vasoactive agents such as terlipressin, somatostatin or octreotide. Patients were then randomized within 24 hours to either continue with pharmacotherapy plus EBL or undergo early TIPS? In the pharmacotherapy-EBL group, patients received a nonselective beta-blocker (either propranolol or nadolol) and EBL scheduled every 10 – 14 days until all varices were obliterated. In the early TIPS group, patients received TIPS within 72 hours after the initial therapy. In a median follow-up period of 16 months, re-bleeding or failure to control bleeding occurred much more frequently in the pharmacotherapy-EBL therapy group (14 out of 31 patients) than in the early TIPS group (1 out of 32 patients) (P < 0.001). More importantly, mortality was also significantly higher in the pharmacotherapy-EBL therapy group (12 out of 31 patients) than in the early TIPS group (4 out of 31 patients) (P < 0.01). Seven patients in the pharmacotherapy-EBL group received TIPS as rescue therapy but four died. Interestingly in this study, more patients were reported to have hepatic encephalopathy in the pharmacotherapy-EBL group (40 %) than that in the early TIPS group (28 %), although the difference did not reach statistical significance (absolute difference of 12 %, 95 % confidence interval [CI] –18 to 40; P = 0.13). With all of the parameters favoring early TIPS, the authors concluded that in patients with cirrhosis who present with acute variceal bleeding and at high risk of treatment failure, the early use of TIPS is recommended to reduce treatment failure and mortality.

The result of this study is contradictory to the conventional belief that TIPS reduces bleeding but increases hepatic encephalopathy and hence confers no improvement in survival [2] [3]. The authors point out that, unlike previous studies, which used bare stents [3], they used the e-PTFE (expanded polytetrafluoroethylene)-covered stents and, hence, expected to have less TIPS dysfunction and recurrence of complications related to portal hypertension. In previous studies, the study design actually precluded the possibility of demonstrating the benefit of TIPS in these high-risk patients. In the García-Pagán study, the decision to perform TIPS was based on the measurement of hepatic venous pressure gradient, a test that is not widely available especially under emergency conditions. However, if this can be done, it serves an important function to identify the high-risk patients that might benefit most from TIPS.

References

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