Transjugular Intrahepatic Portosystemic Shunt for Refractory Ascites: A Meta-analysis of Individual Patient Data
2007; Elsevier BV; Volume: 133; Issue: 3 Linguagem: Inglês
10.1053/j.gastro.2007.06.020
ISSN1528-0012
AutoresFrancesco Salerno, Calogero Cammà, Marco Enea, Martin Rössle, Florence Wong,
Tópico(s)Organ Transplantation Techniques and Outcomes
ResumoBackground & Aims: Several randomized controlled trials have compared a transjugular intrahepatic portosystemic shunt (TIPS) with large-volume paracentesis in cirrhotic patients with refractory ascites. Although all agree that TIPS reduces the recurrence rate of ascites, survival is controversial. The aim of this study was to compare the effects of TIPS and large-volume paracentesis in cirrhotic patients with refractory ascites by means of meta-analysis of individual patient data from 4 randomized controlled trials. Methods: The study population consisted of 305 patients: 149 allocated to TIPS and 156 to paracentesis. Cumulative probabilities of transplant-free survival and of hepatic encephalopathy (HE) were estimated by the Kaplan–Meier method and differences assessed by log-rank test. The total number of HE episodes per patient was also compared between TIPS and paracentesis. Results: Tense ascites recurred in 42% of patients allocated to TIPS and 89% allocated to paracentesis (P < .0001). Sixty-five patients in the TIPS group and 78 in the paracentesis group died. The actuarial probability of transplant-free survival was significantly better in the TIPS group (P = .035). Cox regression analysis performed in a subgroup of 235 patients (114 allocated to TIPS and 121 to paracentesis) showed that age, serum bilirubin level, plasma sodium level, and treatment allocation were independently associated with transplant-free survival. The average number of HE episodes was significantly higher in the TIPS group (1.13 ± 1.93 vs 0.63 ± 1.18; P = .006), although the cumulative probability of developing the first episode of HE was similar between the groups (P = .19). Conclusions: The present meta-analysis of individual patient data provides further evidence to the previous meta-analyses of literature data showing that TIPS significantly improves transplant-free survival of cirrhotic patients with refractory ascites. Background & Aims: Several randomized controlled trials have compared a transjugular intrahepatic portosystemic shunt (TIPS) with large-volume paracentesis in cirrhotic patients with refractory ascites. Although all agree that TIPS reduces the recurrence rate of ascites, survival is controversial. The aim of this study was to compare the effects of TIPS and large-volume paracentesis in cirrhotic patients with refractory ascites by means of meta-analysis of individual patient data from 4 randomized controlled trials. Methods: The study population consisted of 305 patients: 149 allocated to TIPS and 156 to paracentesis. Cumulative probabilities of transplant-free survival and of hepatic encephalopathy (HE) were estimated by the Kaplan–Meier method and differences assessed by log-rank test. The total number of HE episodes per patient was also compared between TIPS and paracentesis. Results: Tense ascites recurred in 42% of patients allocated to TIPS and 89% allocated to paracentesis (P < .0001). Sixty-five patients in the TIPS group and 78 in the paracentesis group died. The actuarial probability of transplant-free survival was significantly better in the TIPS group (P = .035). Cox regression analysis performed in a subgroup of 235 patients (114 allocated to TIPS and 121 to paracentesis) showed that age, serum bilirubin level, plasma sodium level, and treatment allocation were independently associated with transplant-free survival. The average number of HE episodes was significantly higher in the TIPS group (1.13 ± 1.93 vs 0.63 ± 1.18; P = .006), although the cumulative probability of developing the first episode of HE was similar between the groups (P = .19). Conclusions: The present meta-analysis of individual patient data provides further evidence to the previous meta-analyses of literature data showing that TIPS significantly improves transplant-free survival of cirrhotic patients with refractory ascites. See CME quiz on page 1004.Refractory ascites is one of the most dreaded complications of liver cirrhosis. It is associated with an increased risk of further serious complications, such as spontaneous bacterial peritonitis (SBP) and hepatorenal syndrome (HRS), and with a very short survival.1Arroyo V. Gines P. Gerbes A.L. et al.Definition and diagnostic criteria of refractory ascites and hepatorenal syndrome in cirrhosis International Ascites Club.Hepatology. 1996; 23: 164-176Crossref PubMed Google Scholar, 2Epstein M. Treatment of refractory ascites.N Engl J Med. 1989; 321: 1675-1677Crossref PubMed Scopus (21) Google Scholar Moreover, the quality of life of patients with refractory ascites is markedly compromised, and these patients are frequently admitted to the hospital for recurrence of tense ascites, renal failure, infection, or other related morbidities.1Arroyo V. Gines P. Gerbes A.L. et al.Definition and diagnostic criteria of refractory ascites and hepatorenal syndrome in cirrhosis International Ascites Club.Hepatology. 1996; 23: 164-176Crossref PubMed Google Scholar, 3Guardiola J. Xiol X. Escriba J.M. et al.Prognosis assessment of cirrhotic patients with refractory ascites treated with a peritoneovenous shunt.Am J Gastroenterol. 1995; 90: 2097-2102PubMed Google Scholar, 4Ginès P. Guevara M. Arroyo V. et al.Hepatorenal syndrome.Lancet. 2003; 362: 1819-1827Abstract Full Text Full Text PDF PubMed Scopus (492) Google Scholar Accordingly, an effective treatment should be able to reduce the recurrence of tense ascites and the rate of complications, as well as to improve survival.So far, the standard therapy for patients with refractory ascites is large-volume paracentesis that rapidly relieves abdominal tension.5Moore K.W. Wong F. Gines P. et al.The management of ascites in cirrhosis: report on the consensus conference of the International Ascites Club.Hepatology. 2004; 38: 258-266Crossref Scopus (682) Google Scholar In most cases, however, it cannot prevent the reaccumulation of ascites because it does not correct the mechanisms causing formation of ascites and does not impact on survival. Conversely, a transjugular intrahepatic portosystemic shunt (TIPS) relieves portal hypertension, which is one of the main pathogenetic mechanisms of ascites formation; therefore, it should be able to reduce the recurrence of ascites and the incidence of complications related to portal hypertension, as well as to improve the survival in such patients. Indeed, many uncontrolled studies reported elimination or reduction of ascites after TIPS implantation in most cases.6Ochs A. Rossle M. Haag K. et al.The transjugular intrahepatic portosystemic stent-shunt procedure for refractory ascites.N Engl J Med. 1995; 332: 1192-1197Crossref PubMed Scopus (433) Google Scholar, 7Quiroga J. Sangro B. Nuñez M. et al.Transjugular intrahepatic portosystemic shunt in the treatment of refractory ascites: effect on clinical, renal, humoral, and hemodynamic parameters.Hepatology. 1995; 21: 986-994PubMed Google Scholar, 8Forrest E.H. Stanley A.J. Redhead D.N. et al.Clinical response after transjugular intrahepatic portosystemic stent shunt insertion for refractory ascites in cirrhosis.Aliment Pharmacol Ther. 1996; 10: 801-806Crossref PubMed Scopus (37) Google Scholar, 9Najarian G.K. Bjarnason H. Dietz Jr, C.A. et al.Refractory ascites: midterm results of treatment with a transjugular intrahepatic portosystemic shunt.Radiology. 1997; 205: 173-180Crossref PubMed Scopus (78) Google Scholar However, randomized controlled trials (RCTs) comparing uncovered TIPS with large-volume paracentesis showed that a major efficacy of TIPS is counterbalanced by an increased rate of hepatic encephalopathy (HE), whereas the results on survival were broadly discrepant.10Lebrec D. Giuily N. Hadengue A. et al.Transjugular intrahepatic portosystemic shunt: comparison with paracentesis in patients with cirrhosis and refractory ascites: a randomized trial.J Hepatol. 1996; 25: 135-144Abstract Full Text PDF PubMed Scopus (382) Google Scholar, 11Rössle M. Ochs A. Gulberg V. et al.A comparison of paracentesis and transjugular intrahepatic portosystemic shunting in patients with ascites.N Engl J Med. 2000; 342: 1701-1707Crossref PubMed Scopus (486) Google Scholar, 12Ginès P. Uriz J. Calahorra B. et al.Transjugular intrahepatic portosystemic shunting versus paracentesis plus albumin for refractory ascites in cirrhosis.Gastroenterology. 2002; 123: 1839-1847Abstract Full Text Full Text PDF PubMed Scopus (444) Google Scholar, 13Sanyal A.J. Genning C. Reddy K.R. et al.The North American Study for the treatment of refractory ascites.Gastroenterology. 2003; 124: 634-641Abstract Full Text Full Text PDF PubMed Scopus (349) Google Scholar, 14Salerno F. Merli M. Riggio O. et al.Randomized controlled study of TIPS versus paracentesis plus albumin in cirrhosis with severe ascites.Hepatology. 2004; 40: 629-635Crossref PubMed Scopus (294) Google Scholar Three meta-analyses, performed on literature data of those RCTs, concluded that TIPS significantly increases the risk of HE without a significant improvement in survival.15Albillos A. Banares R. Gonzalez M. et al.A meta-analysis of transjugular intrahepatic portosystemic shunt versus paracentesis for refractory ascites.J Hepatol. 2005; 43: 990-996Abstract Full Text Full Text PDF PubMed Scopus (136) Google Scholar, 16D’Amico G. Luca A. Morabito A. et al.Uncovered transjugular intrahepatic portosystemic shunt for refractory ascites: a meta-analysis.Gastroenterology. 2005; 129: 1282-1293Abstract Full Text Full Text PDF PubMed Scopus (171) Google Scholar, 17Saab S. Nieto J.M. Ly D. et al.TIPS versus paracentesis for cirrhotic patients with refractory ascites.Cochrane Database Syst Rev. 2004; 3 (CD004889)PubMed Google Scholar The unavailability of individual data, however, precluded the possibility to analyze survival as a time-dependent variable and to separate the confounding effect that liver transplantation (LT) had on survival of patients with advanced cirrhosis. This last aspect could have been relevant because the proportion of patients who underwent LT in the 5 RCTs ranged from 5% to 20%.To overcome the limitations associated with the use of literature data, increase the relevance of the statistical analysis, and improve estimates of effect size, we performed a new meta-analysis using individual patient data (MIPD). The aims of the current MIPD were (1) to assess the differences between TIPS and large-volume paracentesis with respect to transplant-free survival, occurrence of HE, and recurrence of tense ascites; (2) to identify predictors of mortality after treatment; and (3) to evaluate risk factors for post-TIPS HE.Materials and MethodsPatientsThe current MIPD was designed to pool the data of a number of individuals from tertiary referral specialty units participating in RCTs comparing the efficacy of TIPS and large-volume paracentesis in cirrhotic patients with refractory ascites, regardless of the cause of liver disease. We identified trials, defined primary and secondary outcomes, checked data, and planned statistical analyses according to previously described procedures.18Early Breast Cancer Trialists’ Collaborative GroupSystemic treatment of early breast cancer by hormonal, cytotoxic, or immune therapy. 133 randomized trials involving 31000 recurrences and 24000 deaths among 75000 women.Lancet. 1992; 339: 1-15Abstract PubMed Google ScholarStudies were selected if they were published as full articles, if they included cirrhotic patients with refractory or recidivant ascites defined according to the International Ascites Club criteria,1Arroyo V. Gines P. Gerbes A.L. et al.Definition and diagnostic criteria of refractory ascites and hepatorenal syndrome in cirrhosis International Ascites Club.Hepatology. 1996; 23: 164-176Crossref PubMed Google Scholar and if the transplant-free survival was the primary end point of the study. Five RCTs10Lebrec D. Giuily N. Hadengue A. et al.Transjugular intrahepatic portosystemic shunt: comparison with paracentesis in patients with cirrhosis and refractory ascites: a randomized trial.J Hepatol. 1996; 25: 135-144Abstract Full Text PDF PubMed Scopus (382) Google Scholar, 11Rössle M. Ochs A. Gulberg V. et al.A comparison of paracentesis and transjugular intrahepatic portosystemic shunting in patients with ascites.N Engl J Med. 2000; 342: 1701-1707Crossref PubMed Scopus (486) Google Scholar, 12Ginès P. Uriz J. Calahorra B. et al.Transjugular intrahepatic portosystemic shunting versus paracentesis plus albumin for refractory ascites in cirrhosis.Gastroenterology. 2002; 123: 1839-1847Abstract Full Text Full Text PDF PubMed Scopus (444) Google Scholar, 13Sanyal A.J. Genning C. Reddy K.R. et al.The North American Study for the treatment of refractory ascites.Gastroenterology. 2003; 124: 634-641Abstract Full Text Full Text PDF PubMed Scopus (349) Google Scholar, 14Salerno F. Merli M. Riggio O. et al.Randomized controlled study of TIPS versus paracentesis plus albumin in cirrhosis with severe ascites.Hepatology. 2004; 40: 629-635Crossref PubMed Scopus (294) Google Scholar were identified as potential participating centers. Four RCTs11Rössle M. Ochs A. Gulberg V. et al.A comparison of paracentesis and transjugular intrahepatic portosystemic shunting in patients with ascites.N Engl J Med. 2000; 342: 1701-1707Crossref PubMed Scopus (486) Google Scholar, 12Ginès P. Uriz J. Calahorra B. et al.Transjugular intrahepatic portosystemic shunting versus paracentesis plus albumin for refractory ascites in cirrhosis.Gastroenterology. 2002; 123: 1839-1847Abstract Full Text Full Text PDF PubMed Scopus (444) Google Scholar, 13Sanyal A.J. Genning C. Reddy K.R. et al.The North American Study for the treatment of refractory ascites.Gastroenterology. 2003; 124: 634-641Abstract Full Text Full Text PDF PubMed Scopus (349) Google Scholar, 14Salerno F. Merli M. Riggio O. et al.Randomized controlled study of TIPS versus paracentesis plus albumin in cirrhosis with severe ascites.Hepatology. 2004; 40: 629-635Crossref PubMed Scopus (294) Google Scholar met our inclusion criteria. One RCT by Lebrec et al10Lebrec D. Giuily N. Hadengue A. et al.Transjugular intrahepatic portosystemic shunt: comparison with paracentesis in patients with cirrhosis and refractory ascites: a randomized trial.J Hepatol. 1996; 25: 135-144Abstract Full Text PDF PubMed Scopus (382) Google Scholar was excluded because refractory ascites was not defined according to the International Ascites Club criteria1Arroyo V. Gines P. Gerbes A.L. et al.Definition and diagnostic criteria of refractory ascites and hepatorenal syndrome in cirrhosis International Ascites Club.Hepatology. 1996; 23: 164-176Crossref PubMed Google Scholar and mortality was not the primary end point of the study. Nevertheless, all the principal investigators of the 5 RCTs were invited to provide individual data for further sensitivity analysis. The authors of 3 of these RCTs11Rössle M. Ochs A. Gulberg V. et al.A comparison of paracentesis and transjugular intrahepatic portosystemic shunting in patients with ascites.N Engl J Med. 2000; 342: 1701-1707Crossref PubMed Scopus (486) Google Scholar, 13Sanyal A.J. Genning C. Reddy K.R. et al.The North American Study for the treatment of refractory ascites.Gastroenterology. 2003; 124: 634-641Abstract Full Text Full Text PDF PubMed Scopus (349) Google Scholar, 14Salerno F. Merli M. Riggio O. et al.Randomized controlled study of TIPS versus paracentesis plus albumin in cirrhosis with severe ascites.Hepatology. 2004; 40: 629-635Crossref PubMed Scopus (294) Google Scholar agreed to provide the individual data of their patients by written consent, whereas the authors of two RCTs10Lebrec D. Giuily N. Hadengue A. et al.Transjugular intrahepatic portosystemic shunt: comparison with paracentesis in patients with cirrhosis and refractory ascites: a randomized trial.J Hepatol. 1996; 25: 135-144Abstract Full Text PDF PubMed Scopus (382) Google Scholar, 12Ginès P. Uriz J. Calahorra B. et al.Transjugular intrahepatic portosystemic shunting versus paracentesis plus albumin for refractory ascites in cirrhosis.Gastroenterology. 2002; 123: 1839-1847Abstract Full Text Full Text PDF PubMed Scopus (444) Google Scholar did not consent to participate. Therefore, the individual survivals of the patients included in these 2 RCTs10Lebrec D. Giuily N. Hadengue A. et al.Transjugular intrahepatic portosystemic shunt: comparison with paracentesis in patients with cirrhosis and refractory ascites: a randomized trial.J Hepatol. 1996; 25: 135-144Abstract Full Text PDF PubMed Scopus (382) Google Scholar, 12Ginès P. Uriz J. Calahorra B. et al.Transjugular intrahepatic portosystemic shunting versus paracentesis plus albumin for refractory ascites in cirrhosis.Gastroenterology. 2002; 123: 1839-1847Abstract Full Text Full Text PDF PubMed Scopus (444) Google Scholar were retrieved from the total number and the actuarial curve of survival according to the method described by Fine et al.19Fine H.A. Dear K.B. Loeffler J.S. et al.Meta-analysis of radiation therapy with and without adjuvant chemotherapy for malignant gliomas in adults.Cancer. 1993; 71: 2585-2597Crossref PubMed Scopus (838) Google Scholar Briefly, the number of steps in the Kaplan–Meier survival curve, allowing for larger steps representing 2 or more nearly concurrent deaths, implies that any remainder of patients not accounted for must have been censored. Careful measurement of the survival probabilities at each step, and hence of the size of the successive steps, indicates where censoring times must have occurred. This is possible because the size of any step depends on the number of patients at risk at that time; when a death occurs among a group of k remaining patients, the survival curve drops by a factor of (k − 1)k. The loss of a patient from the group of those remaining at risk therefore means that the following step, when a patient next died, is larger than it would otherwise have been.The general characteristics of the 4 RCTs11Rössle M. Ochs A. Gulberg V. et al.A comparison of paracentesis and transjugular intrahepatic portosystemic shunting in patients with ascites.N Engl J Med. 2000; 342: 1701-1707Crossref PubMed Scopus (486) Google Scholar, 12Ginès P. Uriz J. Calahorra B. et al.Transjugular intrahepatic portosystemic shunting versus paracentesis plus albumin for refractory ascites in cirrhosis.Gastroenterology. 2002; 123: 1839-1847Abstract Full Text Full Text PDF PubMed Scopus (444) Google Scholar, 13Sanyal A.J. Genning C. Reddy K.R. et al.The North American Study for the treatment of refractory ascites.Gastroenterology. 2003; 124: 634-641Abstract Full Text Full Text PDF PubMed Scopus (349) Google Scholar, 14Salerno F. Merli M. Riggio O. et al.Randomized controlled study of TIPS versus paracentesis plus albumin in cirrhosis with severe ascites.Hepatology. 2004; 40: 629-635Crossref PubMed Scopus (294) Google Scholar included in the meta-analysis are reported in Table 1. All studies referred to the International Ascites Club criteria to define refractory and recidivant ascites1Arroyo V. Gines P. Gerbes A.L. et al.Definition and diagnostic criteria of refractory ascites and hepatorenal syndrome in cirrhosis International Ascites Club.Hepatology. 1996; 23: 164-176Crossref PubMed Google Scholar and used uncovered stents for TIPS and large-volume paracentesis with intravenous albumin infusion as comparable treatments. Comparisons between treatment groups were always based on the intention-to-treat principle.Table 1Design Characteristics of the 4 Multicenter RCTs on TIPS Versus Large-Volume Paracentesis in Patients With Refractory or Recidivant AscitesAuthor, year (reference)PublicationPopulationExclusion criteriaEnd pointsRössle et al, 199911Rössle M. Ochs A. Gulberg V. et al.A comparison of paracentesis and transjugular intrahepatic portosystemic shunting in patients with ascites.N Engl J Med. 2000; 342: 1701-1707Crossref PubMed Scopus (486) Google ScholarPeer-reviewed60 cirrhotic patients with refractory (55%) or recidivant (45%) ascitesHE ≥grade II, portal vein thrombosis, bilirubin level >5 mg/dL, creatinine level >3 mg/dL, advanced HCC, hepatic hydrothorax, failure of paracentesisMortalityRecurrence of ascitesOther complications of cirrhosisGinès et al, 200212Ginès P. Uriz J. Calahorra B. et al.Transjugular intrahepatic portosystemic shunting versus paracentesis plus albumin for refractory ascites in cirrhosis.Gastroenterology. 2002; 123: 1839-1847Abstract Full Text Full Text PDF PubMed Scopus (444) Google ScholarPeer-reviewed70 cirrhotic patients with refractory ascitesYounger than 18 years or older than 75 years, HE ≥grade II, portal vein thrombosis, bilirubin level >10 mg/dL, HCC, prothrombin time <40%, platelet level 3 mg/dL, cardiac failure, parenchymal renal diseaseMortalityRecurrence of ascitesOther complications of cirrhosisCostsSanyal et al, 200313Sanyal A.J. Genning C. Reddy K.R. et al.The North American Study for the treatment of refractory ascites.Gastroenterology. 2003; 124: 634-641Abstract Full Text Full Text PDF PubMed Scopus (349) Google ScholarPeer-reviewed109 cirrhotic patients with refractory ascitesHE ≥grade II, portal vein thrombosis, bilirubin level >5 mg/dL, creatinine level >1.5 mg/dL, HCC, bacterial infection, alcoholic hepatitis, cardiopulmonary failure, pulmonary hypertension, parenchymal renal disease, recent gastrointestinal bleedRecurrence of ascitesMortalityOther complications of cirrhosisQuality of lifeSalerno et al, 200414Salerno F. Merli M. Riggio O. et al.Randomized controlled study of TIPS versus paracentesis plus albumin in cirrhosis with severe ascites.Hepatology. 2004; 40: 629-635Crossref PubMed Scopus (294) Google ScholarPeer-reviewed66 cirrhotic patients with refractory (68%) or recidivant (32%) ascitesAge older than 72 years, HE ≥grade II, total portal vein thrombosis, bilirubin level >6 mg/dL, Child–Pugh score >11, advanced HCC, bacterial infection, creatinine level >3 mg/dL, cardiopulmonary failure, recent gastrointestinal bleedMortalityRecurrence of ascitesOther complications of cirrhosisNeed for rehospitalizationHCC, hepatocellular carcinoma. Open table in a new tab An electronic form containing the data fields to be completed for individual patients was sent to all principal investigators of the trials. The patient-level data were pooled and then analyzed by two authors (C. C. and M. E.) who had not participated in any of the included RCTs. Databases were checked for completeness and internal consistency and were amended through correspondence with the investigators. In particular, because different centers used different cutoff values of serum albumin and prothrombin time values in calculating Child–Pugh scores, the score of any patient was recalculated using the thresholds of 3.5 and 2.8 g/dL for albumin level and 70% and 50% for prothrombin time activity. Finally, this report was circulated to all members of the collaborative group and revised in accordance with their comments.The current study was performed in accordance with the principles of Good Clinical Practice, the principles of the Declaration of Helsinki and its appendices, and local and national laws. To maintain patients’ privacy, patient names were replaced in the database by codes and dates of birth.OutcomesFollow-up time was defined as the number of months from randomization to death, LT, or the last contact with the patient. Data for patients who did not have the event of interest were censored at the date of the last follow-up visit. Data for patients who underwent transplantation were censored at the date of LT. The primary end point of this analysis was death from any cause before LT. A secondary outcome was liver-related death. This outcome included the deaths caused by end-stage liver failure, HRS, SBP or sepsis, portal hypertension–related bleeding, or hepatocellular carcinoma. Finally, subgroup analyses of survival were performed considering the end point combining death and LT as an event, or excluding from the analysis the patients who underwent transplantation or those who crossed over treatments.The assessment of HE was performed according to clinical criteria.20Conn H.O. Libertal M.M. The hepatic coma syndromes and lactulose.in: Williams and Wilkins, Baltimore, MD1979: 46-84Google Scholar Any episode of HE was graded from 1 to 4 according to severity; episodes of grade 1 or 2 were classified as mild, and episodes of grade 3 or 4 were classified as severe. The cumulative probability for developing the first episode of HE was assessed in the subgroup of 235 patients for whom the individual data were available. The cumulative probability for developing severe HE was also determined. Finally, we calculated the average number of episodes of HE per patient during follow-up.Recurrence of tense ascites was defined as a reaccumulation of ascites up to a volume requiring drainage because of patients’ marked discomfort. We also calculated the average number of paracenteses per patient performed during follow-up in both arms of treatment.Statistical AnalysisContinuous variables are expressed as mean ± SD. The χ2 test was used as appropriate, with all P values being 2-tailed. The Kaplan–Meier method was used to estimate the cumulative probability of transplant-free survival, liver-related death, and development of HE. Differences in the observed probability were assessed by the log-rank test. The following variables at baseline were considered for univariate analysis: participating centers, age, sex, allocation to treatment, bilirubin level, albumin level, international normalized ratio (INR), creatinine level, Model For End-Stage Liver Disease (MELD) score, sodium level, potassium level, baseline encephalopathy, mean arterial pressure (MAP), heart rate, type of ascites (refractory vs recidivant), and pre-TIPS and post-TIPS portosystemic pressure gradient (PSPG). Variables with a P value <.10 at univariate analysis were included in the final multivariate model. To avoid the effect of colinearity, the individual components of the MELD score (bilirubin, INR, and creatinine) were not included in multivariate models including MELD score. In all multivariate models, the variable center was introduced to take into account the heterogeneity among the different centers.The Cox proportional hazards model was used to identify the risk factors for transplant-free survival, liver-related death, and occurrence of HE in a multiple regression analysis. Risk factors for recurrent ascites were identified by logistic regression.All analyses were conducted with the Statistical Analysis System, version 6.08, subroutine PROC LOGISTIC and PHREG (SAS Institute, Inc, Cary, NC).21SAS Technical Report SAS/STAT software. Changes and enhancements, release 6.07. SAS Institute, Inc, Cary, NC1992Google Scholar All P values were 2-tailed, and all confidence intervals (CIs) were 95%. We verified that the most important issue of the Cox model (ie, the assumption of proportional hazard) was not violated. To estimate expected transplant-free survival time for a hypothetical patient with a combination of prognostic factors, the estimated survival function was computed.Role of the Funding SourceThis study was not supported by any company or grants. The cost was borne by the authors’ institutions.ResultsBaseline Characteristics of PatientsThe final database of the present study consisted of 305 patients: 149 allocated to TIPS treatment and 156 allocated to paracentesis treatment. No significant differences were found according to the baseline data of the pooled population stratified according to random assignment (Table 2). This confirms that the 2 groups of patients were well matched. In particular, the distributions of patients into Child B and C classes were similar, as well as the distribution of refractory and recidivant ascites, while the follow-up duration was slightly longer in patients allocated to TIPS treatment (65.3 ± 65.0 vs 51.8 ± 61.7 weeks; P = .06). TIPS insertion was successful in 141 of 149 patients (94.6%), and the average PSPG decreased from 21.4 ± 7.7 to 11.4 ± 5.6 mm Hg.Table 2Baseline Demographic, Clinical, and Laboratory Characteristics of Cirrhotic Patients Pooled According to Random Assignment to TIPS or Large-Volume ParacentesisVariablePatients allocated to TIPS (n = 149)Patients allocated to paracentesis (n = 156)P valueAge (y)57.5 ± 9.756.6 ± 9.7.38Sex (M/F)108/41106/50.40Etiology (viral/alcohol/other)42/86/2151/87/18.82s-bilirubin (mg/dL)1.9 ± 1.12.0 ± 1.3.80s-albumin (g/dL)3.0 ± 0.52.99 ± 0.6.38INR1.29 ± 0.231.27 ± 0.23.61s-creatinine (mg/dL)1.24 ± 0.411.23 ± 0.56.48s-sodium (mEq/L)131.5 ± 5.9132 ± 5.6.70s-potassium (mEq/L)4.4 ± 0.64.5 ± 0.6.19Ascites (refractory/recidivant)120/29131/25.43Baseline encephalopathy (absent/mild) (n)80/6991/65.41Child–Pugh score9.56 ± 1.79.47 ± 1.7.89Child C (n)7077.85MELD score12.5 ± 4.612.2 ± 4.6.58MAP (mm Hg)87 ± 1289 ± 13.36Heart rate (beats/min)80 ± 1180 ± 10.40Basal plasma renin activity (ng · mL−1· h−1)12.9 ± 13.912 ± 10.2.20Mean follow-up (wk)65.3 ± 6551.8 ± 61.7.06No. of patients who underwent transplantation (%)19 (12.7)24 (15.4).51Pre-TIPS PSPG (mm Hg)aData were available in 89 patients.21.80 ± 7.77——Post-TIPS PSPG (mm Hg)aData were available in 89 patients.11.50 ± 5.54——NOTE. Data are reported as means ± SD or absolute numbers. Plasma renin activity was obtained only in patients from 2 RCTs (references 12Ginès P. Uriz J. Calahorra B. et al.Transjugular intrahepatic portosystemic shunting versus paracentesis plus albumin for refractory ascites in cirrhosis.Gastroenterology. 2002; 123: 1839-1847Abstract Full Text Full Text PDF PubMed Scopus (444) Google Scholar and 14Salerno F. Merli M. Riggio O. et al.Randomized controlled study of TIPS versus paracentesis plus albumin in cirrhosis with severe ascites.Hepatology. 2004; 40: 629-635Crossref P
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