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Corresponding author. Address: Medical Center University of Freiburg, Department of Medicine II, Hugstetter Str. 55, D- 79106 Freiburg, Germany; Tel.: +49 761/270-34010.
Department of Medicine II, Medical Center University of Freiburg, Faculty of Medicine, University of Freiburg, Hugstetter Str. 55, 79106 Freiburg, GermanyBerta-Ottenstein-Programme, Faculty of Medicine, University of Freiburg, Germany
Department of Medicine II, Medical Center University of Freiburg, Faculty of Medicine, University of Freiburg, Hugstetter Str. 55, 79106 Freiburg, Germany
Department of Medicine II, Medical Center University of Freiburg, Faculty of Medicine, University of Freiburg, Hugstetter Str. 55, 79106 Freiburg, Germany
Department of Medicine II, Medical Center University of Freiburg, Faculty of Medicine, University of Freiburg, Hugstetter Str. 55, 79106 Freiburg, Germany
Transjugular intrahepatic portosystemic shunt (TIPS) implantation is an effective and safe treatment for complications of portal hypertension. Survival prediction is important in these patients as they constitute a high-risk population. Therefore, the aim of our study was to develop an alternative prognostic model for accurate survival prediction after planned TIPS implantation.
With great interest we read the excellent article by Bettinger and colleagues. In their well-designed study the authors proposed the newly developed Freiburg index of post-TIPS survival (FIPS) as a valuable tool for risk stratification before transjugular intrahepatic portosystemic shunt (TIPS) implantation.1 The establishment of robust criteria for the selection of patients eligible for TIPS is crucial. Bettinger et al. collected a large, multicenter TIPS cohort and convincingly demonstrated the high prognostic capacity of the FIPS score for post-TIPS survival in various subgroups of patients including those with refractory ascites.
and their analyses that confirmed the prognostic impact of the Freiburg index of post-TIPS survival (FIPS) score and even expanded it to patients with decompensated cirrhosis without transjugular intrahepatic portosystemic shunt (TIPS) implantation.
With great interest, we recognize their efforts in addressing some important remaining questions from our study, especially with respect to the clinical application of the FIPS score for allocation to TIPS implantation. The authors point out several important issues which, however, require further attention.
First, they show that the FIPS score is also applicable to decompensated patients without TIPS implantation.
To address this hypothesis, we analyzed 612 patients with cirrhosis (baseline characteristics: Table S1) by stratifying according to decompensation stages defined by d'Amico et al.
These stages are defined according to the kind and number of decompensating events (Table S2) and therefore reflect the severity of decompensation. Indeed, as shown in Fig. S1, the FIPS score significantly increased with progressing decompensation. Notably, only in the higher decompensation stages (stage 4 and 5) were patients allocated to the FIPS high-risk group, highlighting that this new risk score is especially useful for patients with decompensated cirrhosis and may also reflect the severity of decompensation.
Second, we highly appreciate that the authors added a control group without TIPS implantation. However, although patient numbers were small after sufficient propensity score matching, the authors showed that in the FIPS low-risk group, patients with TIPS implantation had significantly better overall survival compared to patients treated with paracenteses.
Indeed, as suggested by the authors, this observation may further underline the rationale that TIPS implantation should not be delayed in patients with ascites. To further address this interesting aspect, we analyzed 296 patients who received TIPS implantation for refractory ascites at the University Medical Center Freiburg (baseline characteristics: Table S3) and in whom the time between first ascitic decompensation and TIPS implantation was recorded. Patients were stratified according to the duration of decompensation (≤3 vs. >3 months). Patients with preexisting decompensation >3 months presented with higher FIPS score compared to patients with a shorter history of decompensation (-0.24±1.04 vs. 0.04±1.13; p = 0.016; Fig. 1A). The proportion of FIPS high-risk patients was significantly higher in patients with long-term decompensation (20.6% vs. 10.8%; p = 0.036, Fig. 1B) which underlines the need for early TIPS implantation in patients with ascites.
Fig. 1FIPS score in ascites patients with different duration of decompensation.
(A) Patients with decompensation >3 months showed a significantly higher FIPS score compared to patients with a shorter duration of decompensation. Differences were calculated using a Mann-Whitney U test. (B) Patients with decompensation >3 months were significantly more often allocated to the FIPS high-risk group (FIPS >0.92). Differences in the proportion of FIPS high-risk patients between the groups were calculated using a Χ2 test. Error bars indicate 95% CI; ∗p <0.05. FIPS, Freiburg index of post-TIPS survival; TIPS, transjugular intrahepatic portosystemic shunt.
Third, Stockhoff et al. found no difference in overall survival in FIPS high-risk patients being treated with TIPS or paracentesis. Importantly, the comparability of these patient groups is limited due to different contraindications for TIPS in the paracentesis group. Further, the course of disease in FIPS high-risk patients with regard to development of acute-on-chronic liver failure, persistence of ascites and development of post-TIPS hepatic encephalopathy has to be analyzed. These results are necessary to identify a subgroup of high-risk patients who still benefit from TIPS implantation.
Collectively, in TIPS patients, beside patient-specific parameters such as sarcopenia or hepatic encephalopathy, the new FIPS score is an objective component in decision-making and may be an important step towards personalized medicine.
Financial support
DB is supported by the Berta-Ottenstein-Programme, Faculty of Medicine, University of Freiburg.
Authors’ contributions
Design of the study: DB, MS. Acquisition of data: DB, TB, MS. Analysis of the data: DB. Statistical analyses and consulting: DB, RK. Interpretation of the data: DB, RK, TB, RT, MS. Drafting the manuscript: DB, MS. Revision for important intellectual content: RK, RT, TB.
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