1. In patients with severe liver disease and variceal bleeding, early transjugular intrahepatic portosystemic shunt (TIPS) significantly reduced the rate of treatment failure, length of hospitalization, and mortality
2. Early TIPS was not associated with a difference in the rate of adverse events compared to control
Original Date of Publication: June 24, 2010
Study Rundown: Variceal bleeding is a major cause of death for patients with liver cirrhosis and portal hypertension. Guidelines at the time of the study recommended treatment consisting of vasoactive drugs (e.g., octreotide), prophylactic antibiotics, and endoscopic techniques such as variceal ligation for dealing with variceal bleeding. When standard treatment fails, transjugular intrahepatic portosystemic shunt (TIPS) has been shown to be effective, though associated with substantial mortality due in large part to hepatic encephalopathy. Previous studies have suggested that the earlier use of TIPS can decrease mortality for patients with severe liver disease who are at a high risk of treatment failure. This trial was the first trial to compare the use of early TIPS with the current standard of care for acute variceal bleeding at the time. Results showed that early use of TIPS was associated with a significant decrease in the rate of rebleeding and failure to control bleeding. Early TIPS also significantly reduced mortality (1 year survival of 86% vs 61%, p<0.001) and led to shorter stays in the intensive care unit (ICU). Notably, early TIPS use was not associated with a signfiicantly higher rate of adverse events, such as hepatic encephalopathy.
A major limitation of the study was its small size (only 63 patients were randomized), meaning the study was insufficiently powered for subgroup analyses. Thus, for example, the study could not determine whether early TIPS had greater benefit for the study’s more severe cases of liver disease (those classified as Child-Pugh class C) in comparison to the study’s less severe cases (those classified as Child-Pugh class B).
In summary, results of this study support the early use of TIPS for the treatment of patients with severe liver disease and variceal bleeding. Importantly, results suggest that use of early TIPS is not associated with an increased risk of hepatic encephalopathy that was reported by previous studies.
In-Depth [randomized, controlled study]: Originally published in 2010 in NEJM, this randomized, controlled trial enrolled 63 patients from nine centers in Europe. Eligible patients had liver disease classified as Child-Pugh class B (i.e. moderately severe) or class C (i.e. most severe), had liver cirrhosis with acute bleeding of esophageal varices, and were already receiving treatment in the form of vasoactive drugs (e.g., octreotide), antibiotics, and endoscopic band ligation (EBL). Patients who were older than 75 years, were pregnant, had hepatocellular carcinoma, had previous TIPS, had portal-vein thrombosis, or had heart failure were excluded. Within 24 hours of admission, 31 patients were randomized to the “early-TIPS” group, where they received treatment with a polytetrafluoroethylene-covered stent within 72 hours after randomization. The remaining 32 patients were randomized to the “pharmocotherapy-EBL” group, where they continued to receive vasoactive drug therapy followed by treatment with nonspecific beta-blockers (e.g. propranolol and nadolol) and EBL – TIPS was provided as a rescue therapy. The primary endpoint was the composite outcome of failure to control bleeding and the failure to prevent rebleeding in the next 1 year. Secondary endpoints included mortality at 6 weeks and 1 year, the development of sequelae associated with portal hypertension, and the number of days spent in the ICU.
Results demonstrated that 97% of the early-TIPS group avoided occurrence of the primary endpoint, compared to 50% in the pharmacotherapy-EBL group (p<0.001). At 1 year, the survival rate was 86% in the early-TIPS group compared to 61% in the pharmacotherapy-EBL group (p<0.001). Patients in the pharmacotherapy-EBL group spent a higher proportion of their follow-up time in the ICU (p=0.01). There was no difference in the rate of adverse rates for both treatment groups, including for hepatic encephalopathy (p=0.13), and development of ascites (p= 0.11).
By Evan Chen and Andrew Cheung, M.D.
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