Assessment of Prognosis of Cirrhosis

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

Disclosures

Semin Liver Dis. 2008;28(1):110-122. 

In This Article

Perspectives: Beyond MELD Score

Several aspects or conditions associated with chronic liver disease may be of prognostic value in addition to the MELD score. Portal hypertension, nutritional status, and glucose tolerance have long been considered in this regard and deserve further attention.

In models elaborated for predicting death, variables related with portal hypertension (size of esophageal varices and history of gastrointestinal bleeding) generally bring additional information to Child-Pugh score or its components.[2,78] Moreover, HVPG was shown to have an independent predictive value in the majority of the available multivariate analyses, including Child-Pugh score or its components.[2,79] However, various HVPG thresholds have been used across studies for their positive as well as negative predictive value. Furthermore, it is still not clear when the most predictive HVPG value should be collected, at presentation or after a few months of follow-up.[80] It was recently suggested that HVPG would be more informative in patients with compensated than with decompensated cirrhosis.[2] Indeed, HVPG, MELD, and albumin were recently identified as independent predictors of decompensation in patients with compensated cirrhosis: an HVPG < 10 mm Hg was associated with a 90% probability of not developing clinical decompensation in a median follow-up of 4 years.[81]

Considerable interest recently arose from data on the prognostic value for mortality of a reduction in HVPG obtained with pharmacological agents (mainly nadolol or propranolol, with or without mononitrates). A multivariate analysis identified age, HVPG reduction by ≥20% or to ≤12 mm Hg, and serum albumin, not Child-Pugh score, as independent predictors for 8-year mortality.[82] In a recent systematic review, such an HVPG reduction was associated with an odds ratio of 0.39 (95%; CI 0.19 to 0.81) for mortality,[83] although it is still unclear what the added value of HVPG reduction to Child-Pugh or MELD scores would be. Further limitation in interpreting the data is the uncertainty regarding the optimal timing of the second measurement following the introduction of beta blockers. Further developments are expected as HVPG reduction in a single acute pharmacological study might prove of prognostic value for survival.

Various indices for nutritional status have been tested for their predictive value independently from Child-Pugh class.[23,84,85,86] Indeed, as mentioned above, the transition from Child-Turcotte classification to Child-Pugh score consisted in part in the substitution of nutritional status by prothrombin time. The results are not completely clear. As a rule, indices of poor nutrition are strongly associated with worsening Child-Pugh class. The prognostic information added to Child-Pugh class may be more marked in Child-Pugh class A and B patients.[23,84] What remains to be clarified is the optimal index for nutrition in terms of reproducibility, clinical availability, and prognostic performance.

The relationship between diabetes and cirrhosis is difficult to interpret as diabetes can be a causal factor for, as well as a consequence of, cirrhosis. There are a limited number of studies addressing the prognostic impact of diabetes. Multivariate analyses have usually shown an independent negative effect of glucose intolerance or frank diabetes, after Child-Pugh score or its components were taken into account.[87,88,89,90,91] Interestingly, cause of death in diabetic patients was more frequently related to liver failure than to complications of diabetes.[87,91] Tight glycemic control was related to a better outcome in HCV-related cirrhosis, although not in HBV-related cirrhosis.[90]

As shown above, general prognostic scores based upon readily available and objective variables help predict the outcome of patients with cirrhosis at different stages. More specific prognostic scores can be even more accurate for particular causes of cirrhosis. Prognostic scores make it possible to assess the prognosis of cirrhotic patients undergoing a given therapeutic intervention. Scores also help identify patients who are the most likely to benefit from transplantation in a context of organ shortage. However, the usefulness of prognostic scores remains limited for identifying the optimal first-line option among different strategies. These scores are also limited for defining when to use different therapeutic options when the options are not exclusive one to the other and can be used in a stepwise approach. Finally, existing scores have obvious limitations for identifying which sequence of therapeutic options provides the optimal benefit in terms of survival and cost-effectiveness. Comparing different stepwise strategies with controlled studies would be especially difficult due to the large number of patients which might be involved in any comparative studies. Statistical models represent an attractive way to address these complex issues.

In recent years, several studies based upon Markov models or multistate models have been published in this area.[92,93] Most studies focused on the optimal timing for transplantation or cost-effectiveness issues.[94] Several unresolved issues concerning the management of patients with cirrhosis and the overall prognosis could be investigated with multistate models. However, the strengths and limitations of statistical models require further assessment.

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