Conflict of interest: Nothing to report.
Benefit of TIPS for patients with refractory or recidivant ascites: Serum bilirubin may make the difference†
Article first published online: 23 DEC 2004
Copyright © 2004 American Association for the Study of Liver Diseases
Volume 41, Issue 1, page 217, January 2005
How to Cite
Gerbes, A. L. and Gülberg, V. (2005), Benefit of TIPS for patients with refractory or recidivant ascites: Serum bilirubin may make the difference. Hepatology, 41: 217. doi: 10.1002/hep.20509
- Issue published online: 23 DEC 2004
- Article first published online: 23 DEC 2004
To the Editor:
The recent Italian trial of transjugular intrahepatic portosystemic stent shunt (TIPS) versus paracentesis for patients with refractory or recidivant ascites1 provides valuable information and stimulates considerations regarding the real value of TIPS for these patients. The study also adds to the three other large randomized trials recently published.2–4 These four studies, with a total of 305 patients, provide unanimous evidence that TIPS allows for much better control of ascites compared with repeated paracentesis: a complete response following TIPS has been observed in 51% to 79% compared with 3% to 24% in the paracentesis groups. Furthermore, quality of life is improved in patients with ascites after TIPS, particularly in patients with a complete response,5 supporting earlier investigations of quality of life after TIPS for various indications.6, 7
However, the effect of TIPS on patient survival has been controversial. The present study1 confirms our previous observations2 and tips the balance toward improved survival. A North American trial3 found a nonsignificant trend in favor of TIPS, while a Spanish study4 clearly argued against a survival benefit for TIPS. How can these discrepant results be reconciled? The etiology of cirrhosis (alcoholic in 42% and 79% of the trials showing survival benefit1, 2 vs. 51% and 62%, respectively, in the trials without survival benefit3, 4) does not seem a likely explanation. Nor is the proportion of patients with Child-Turcotte-Pugh class C (76% and 38% vs. 37% and no detailed information in the Sanyal trial). Rather, we hypothesize that inclusion of patients with a serum bilirubin level above 3 mg/dL may make the difference. In our study,2 as well as in the Spanish trial,4 serum bilirubin was found to be an independent predictor of survival in multivariate and univariate analyses, respectively. The present study did not analyze bilirubin because it is a part of the MELD (model for end-stage liver disease) score, which was identified as a survival predictor by the authors.1 Interestingly, baseline serum bilirubin was also described as a powerful independent predictor of mortality after TIPS for variceal bleeding.8 Table 1 shows that in the Spanish trial, patients could be included with a serum bilirubin level of up to 10 mg/dL, whereas cutoff values were much lower for the other studies. Although the actual baseline values do not seem to differ much when given as mean and standard error, a closer look reveals that a substantial proportion of the Spanish trial must have been patients with a baseline bilirubin level greater than 3 mg/dL. Unfortunately, the exact percentage is only available in our trial (21%). Serum bilirubin concentrations 3 and 6 months after TIPS were increased in all studies. Interestingly however, the variation is much lower in the trials with survival benefit1, 2 compared with the studies showing no benefit.3, 4 Judging from the mean values and standard error provided, some patients in the Spanish and United States trials had serum bilirubin levels above 12 mg/dL 6 months following TIPS. Not surprisingly, liver failure was reported as the most common cause of death in these studies.
|Cutoff for study inclusion||6||5||10||5|
|Baseline||1.6 ± 0.1||1.7 ± 0.2||2.0 ± 0.2||1.9 ± 0.2|
|Follow-up||2.1 ± 0.2||2.9 ± 0.9||4.6 ± 2||2.2 ± 2.1|
Another aspect deserves attention. All studies were analyzed as intent-to-treat and allowed for crossover of treatments. Interestingly, the proportion of patients randomized to paracentesis but ultimately receiving TIPS was higher in the Italian and German trials (11 of 33 and 10 of 31, respectively) than in the other two studies (3 of 35 and 2 of 57). Thus, one may speculate that the actual benefit of TIPS may be even higher than demonstrated. Altogether, the publication by Salerno et al.1 is in accordance with our contention that TIPS may be particularly useful for patients with massive ascites and serum bilirubin levels below 3 mg/dL.
- 1Randomized conrolled study of TIPS versus paracentesis plus albumin in cirrhosis with severe ascites. HEPATOLOGY 2004; 40: 629–635., , , , , , et al.
- 2A comparison of paracentesis and transjugular intrahepatic portosystemic shunting in patients with ascites. N Engl J Med 2000; 342: 1701–1707., , , , , , et al.
- 3The North American study for the treatment of refractory ascites. Gastroenterology 2003; 124: 634–641., , , , , , et al.
- 4Transjugular intrahepatic portosystemic shunting versus paracentesis plus albumin for refractory ascites in cirrhosis. Gastroenterology 2002; 123: 1839–1847., , , , , , et al.
- 5Improved quality of life in patients with refractory or recidivant ascites after insertion of transjugular intrahepatic portosystemic shunts. Digestion 2002; 66: 127–130., , , , , .
- 6Effect of transjugular intrahepatic portosystemic shunt on quality of life. AJR Am J Roentgenol 1996; 167: 963–969., , , , , , et al.
- 7Long-term results and quality of life in patients treated with transjugular intrahepatic portosystemic shunts. AJR Am J Roentgenol 2002; 179: 1597–1603., , , , , .
- 8Serum bilirubin and early mortality after transjugular intrahepatic portosystemic shunts: results of a multivariate analysis. J Vasc Interv Radiol 2002; 13: 155–161., , .
Alexander L. Gerbes*, Veit Gülberg*, * Department of Medicine II University of Munich-Großhadern Germany.