Assessment of Prognosis of Cirrhosis

François Durand, M.D.; Dominique Valla, M.D.


Semin Liver Dis. 2008;28(1):110-122. 

In This Article

Meld Score Derivatives

With the implementation of the MELD score, refractory ascites was removed from the list of variables used for assessing the prognosis. However, even though its interpretation can be subjective, ascites was shown to be associated with the poorest prognosis.[40] It was felt that patients with refractory ascites, normal creatinine, and preserved hepatic function could be under-scored with MELD. In particular, it was shown that persistent ascites and low serum sodium identified a subset of patients with relatively low MELD score (below 21) and a high risk of early death.[41]

Serum sodium is a simple, readily available, and objective marker of disease severity. During cirrhosis, hyponatremia results from solute-free water retention. Systemic arterial vasodilation leads to the release of antidiuretic hormone which, in turn, induces dilution hyponatremia. The activation of these mechanisms correlates with the degree of portal hypertension.[42] In this view, hyponatremia can be considered an indirect marker of portal hypertension during cirrhosis.

Several studies have shown that hyponatremia is a strong predictor of early mortality, independent of MELD score.[41,43,44,45] Changes in survival are especially pronounced for sodium concentrations ranging from 120 to 135 mEq/L. Within this range, a decrease in serum sodium of 1 mEq/L corresponds to a 12% decrease in 3-month probability of survival.[45] A modified score including serum sodium, termed MELD-Na, has been proposed as an alternative to MELD score ( Table 3 ).[44] The accuracy of MELD-Na was shown to be slightly superior to that of MELD in candidates for transplantation.[43,44,45] The effect of hyponatremia is higher in patients with low MELD score compared with those with high MELD score.

A limitation to the incorporation of serum sodium into MELD is that during cirrhosis, marked changes in serum sodium concentration can result from several factors, including the administration of diuretics and intravenous hypotonic fluids. For example, the administration of diuretics leads to a 4 mEq/L decrease in serum sodium, on average.[46] In some patients the decrease may reach 10 mEq/L. In contrast, the use of V2-receptor antagonists for treating refractory ascites is encouraging. These agents induce a significant increase in serum sodium. Again, serum sodium is not as objective as it was thought to be. Further validation is needed and practical guidelines regarding the incorporation of sodium should be proposed to avoid misclassification.

INR is the variable which has the highest weight in MELD score ( Table 3 ). Unfortunately, INR is hardly interpretable in patients receiving anticoagulation therapy. It is not exceptional that patients with cirrhosis receive anticoagulation due to portal vein thrombosis, an underlying prothrombotic state, or any other concomitant condition.[47] Most patients with Budd-Chiari syndrome also receive anticoagulation with anti-vitamin K. In this population, INR is artificially increased. Using MELD score in this context would result in overestimating disease severity.

With the aim of overcoming this difficulty, a modified MELD score termed MELD-XI (for MELD excluding INR) has been proposed.[48] This modified score relies only on bilirubin and creatinine. Thus, neither INR nor any other marker of coagulation is taken into account ( Table 3 ). The coefficients ascribed to creatinine and bilirubin have been changed to obtain the optimal linear correlation between MELD and MELD-XI. In other words, the adjusted coefficients mean that patients with a given MELD-XI score have a mortality risk comparable to that of patients with interpretable INR and a similar MELD score.

The validation of MELD-XI score shows that its accuracy for assessing 3-month mortality risk is comparable to that of MELD (with a c statistic of ∼0.83).[48] Omission of INR and the use of adjusted coefficients did not much change the predictive accuracy of the score, which is somewhat surprising since INR was a strong, independent prognostic marker in the original series from which MELD score is derived. Moreover, it must be noted that both creation and validation of MELD-XI score have been made in populations of patients who did not receive anticoagulation. Patients receiving anticoagulation are expected to have comorbidities and/or a different natural history. These patients may have specific risk profiles with a higher risk compared with patients without thrombotic complications. Therefore, further validation in this particular population is needed.

Intuitively, it can be anticipated that taking into account changes in MELD score over time may add prognostic information.[49] Patients with a rapid increase in MELD over time might be expected to have a worse outcome than those with stable or even decreasing MELD score. Delta MELD is defined as the difference between current MELD and the lowest MELD measured within 30 days prior to current MELD ( Table 3 ). Delta MELD was shown to be predictive of early mortality in patients with cirrhosis on univariate analysis. However, delta MELD was no longer predictive of mortality when entered into a multivariate model with current MELD score.[50] These results suggest that current MELD score is the only predictor of mortality regardless of how that score was reached.


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