MELDNa improves discrimination of the risk of death or transplant within 6 months as compared to MELD in patients undergoing non-emergent TIPS for refractory ascites or recurrent variceal bleeding. The clinical implication of this finding is most evident in patients with low MELD scores who are reclassified to a higher risk based on their MELDNa score. We determined that a MELDNa score of 15 best optimizes discrimination between events and non-events, with less than 10% experiencing death or transplant with MELDNa ≤ 15 as compared to 44% with MELDNa > 15.
Several studies have shown that serum sodium, in addition to MELD, captures additional risk of death in cirrhotic patients 14–20
. In patients undergoing elective TIPS, investigators have similarly demonstrated that serum sodium is an independent predictor of outcomes 13, 24
. Our study provides further support of these observations and suggests that for every 1 mEq/dl decrease in serum sodium there is a 6% increase in the risk of death or transplant within 6 months after TIPS. The important statistical interaction of MELD and serum sodium that has been documented here and in other studies resulted in the development of the MELDNa model 16, 18–20
. Our results support the expansion of the application of the MELDNa model to cirrhotic patients undergoing elective TIPS.
MELDNa is particularly effective at predicting risk in patients with low MELD scores, and results in the reclassification of some patients to a higher risk of death or transplant 19, 20
. Patients undergoing elective TIPS typically have low MELD scores. The median MELD score in our cohort was 15, which is similar to other studies 8, 11–13
. We demonstrated that low MELD score patients continue to have an increased risk of death or transplant after TIPS, and that the MELDNa model more effectively captures this risk, resulting in the reclassification of up to 25% of patients.
To evaluate the effectiveness of MELDNa and MELD based-models, we employed the Harrell’s C index 23
. This index compares the expected to observed outcomes generated by Cox proportional models and is analogous to the receiver operative curve statistic, or C statistic, that is derived from logistic regression models. A higher C index indicates improved model performance. The C indices for MELD in patients with scores of ≤ 18 and ≤ 15 were 0.58 (0.51, 0.67) and 0.62 (0.49, 0.74), suggesting that this model performs inadequately in patients with low scores. In comparison, the C indices for MELDNa in patients with scores of ≤ 18 and ≤ 15 were 0.65 (0.55, 0.71) and 0.72 (0.60, 0.85). Clinically, the application of MELDNa in those with low MELD scores improves discrimination of risk of death or transplant by over 12%. As expected, because our population of patients undergoing non-emergent TIPS does not represent the entire spectrum of MELD scores (less than 10% of patients have a MELD > 22), the C indices in our analysis are lower than those reported in previous studies that evaluated MELD and MELDNa in patients awaiting liver transplant where the full range of scores is represented 20, 25
Our findings are subject to some limitations. The size of the cohort and the relatively small number of outcomes within 6 months tempers our ability to validate the MELDNa score of 15 we generated as the optimal cut-off for discrimination of events versus non-events. Application of this score in a larger cohort would strengthen this conclusion by providing a continuous estimation of risk rather than a dichotomous cut-point and could allow for testing in shorter post-TIPS time intervals. Our cohort consisted mainly of patients undergoing non-emergent TIPS for the indication of refractory ascites, in contrast to other studies that included emergent variceal bleeding or where the majority of patients underwent elective TIPS for prevention of variceal re-bleeding 6–8, 10
. We excluded patients with emergent variceal bleeding due to their higher risk of death in the early post-TIPS period as compared with patients undergoing TIPS for non-emergent indications 7, 9, 26
. Advances in endoscopic and pharmacologic management of variceal bleeding likely contribute to the decreased number of patients undergoing TIPS for prevention of variceal rebleeding in our cohort 5, 27
. To confirm that MELDNa performs well independent of indication for TIPS, we conducted a sensitivity analysis restricting the results to ascitic patients alone and found very similar hazards ratios, p values, and C indices [data not shown]. This would be expected since ascites as compared to bleeding was no longer a significant predictor of outcomes in multivariate models accounting for MELD or MELDNa. These findings suggest that the MELDNa model is applicable for both non-emergent indications.
Given ongoing controversy regarding the optimal management strategy for refractory ascites 24, 28–32
and the continued improvements in endoscopic and pharmacologic management of variceal bleeding 2, 33
, our results establishing that MELDNa is a superior risk prediction tool compared to MELD can be helpful to clinicians who must determine the risk-benefit ratio of elective TIPS for individual patients. Furthermore, this analysis suggests that a MELD score of ≤18 is falsely reassuring, particularly in patients with concurrent hyponatremia. A cut-off MELDNa score of 15 may become the new benchmark for categorizing risk of elective TIPS in the future, though a validation study is necessary before widespread application is adopted.