Predicting the prognosis of chronic liver disease: An evolution from child to MELD

Although Child and Turcotte were not the first to stratify patients undergoing shunt surgery to relieve portal hypertension according to their risk, their classification system, published in a monograph in 1964, has become the predominant method to assess prognosis in cirrhotic patients.1 They selected empirically five parameters (serum albumin, serum bilirubin, ascites, encephalopathy, and nutritional status) to which they attributed one of three risk levels, and converted the composite into one of three classes. However, as Conn pointed out, the Child-Turcotte classification can be cumbersome to use in practice.2 Three of the elements (ascites, nutrition, and encephalopathy) are very subjective. It is difficult to know how to combine the grades for the individual elements into the final class. Furthermore, the final result places the patient in one of just three classes, rather than reflect a spectrum of urgency. However, in conclusion, Conn made the prescient comment that “perhaps, it can predict . the development of any of the complications of cirrhotics. ” In 1972, Pugh modified the Child-Turcotte classification in line with the criticisms of Conn.3 Once again, the object was an instrument to predict outcome after portosystemic surgery. Pugh introduced points for each element making it easier to compute. He substituted prothrombin time in place of nutritional status, thereby obviating the most subjective element. The Pugh modification has become widely used, and has been cited more than 1,700 times. The frequency of citation is in keeping with Conn’s prediction, because the Child’s class in its original form or in the Pugh modification has been applied widely to descriptive studies of liver disease and clinical trials of therapy among cirrhotic patients.4,5 However, the Child-Turcotte-Pugh classification is an instrument of its time. In the years that have followed, several attempts have been made to develop a better prognostic model for cirrhosis by drawing on prospective data sets using logistic regression analysis and receiver operating characteristic analysis. For example, Schlichting et al. developed a prognostic index with prospectively gathered data on patients with cirrhosis.6 Subsequently these investigators compared their index to the Child-Turcotte classification, and found that although the Child criteria were predictive of survival, the prospectively derived prognostic index was superior.7 On the other hand, separate prospective studies of short-term prognosis in cirrhotic patients, using appropriate statistical methods, have confirmed the child-Turcotte-Pugh criteria as a useful clinical tool.8 At the same time, the wider requirement for predicting prognosis in cirrhosis rather than the outcome of specific surgery, led some experts to advocate measuring liver function rather than constructing a composite prognostic score.9 Three of the candidate global liver function tests have been the aminopyrine breath test, the indocyanine green half life, and the monoethylglycinezylidide (MEGX) lidocaine metabolism test. In this context, Villeneuve et al. found using a Cox proportional hazards model among 187 cirrhotic patients studied prospectively, that four of the elements of the Child-TurcottePugh criteria but not the aminopyrine breath test were independent variables significantly related to survival.10 Oellerich et al. prospectively studied the prognostic value of the ChildTurcotte-Pugh score, indocyanine green tests, and MEGX among cirrhotic patients awaiting transplantation.11 They found that all three had prognostic capability, but a combination of Child-Turcotte-Pugh and MEGX seemed to provide the greatest accuracy. Nevertheless, up to now none of these new composite prognostic instruments, or tests of total liver function have managed to usurp the place of the Child-Turcotte-Pugh system, either in clinical research or day-to-day clinical practice. The resilience of the Child-Turcotte-Pugh criteria is due to a number of factors. In the area of clinical research, the difficulties of randomness and subjectivity are diminished because the same observers tend to conduct the tests, thereby reducing interobserver bias. In clinical practice, the difficulties of calculating the exact score and determining its significance are lessened by the tendency of working physicians to make rough estimates of each of the subjective components and then to use that general estimate as an indicator of severity of liver disease. Conn called this “the gestalt method. ”2 The focus on Child-Turcotte-Pugh scores in clinical practice has shifted in the United States with the changing demographics of orthotopic liver transplantation. Where once the general “gestalt” sufficed, in recent years we have returned to trying to count and sum the score with accuracy. This change in use of Child-Turcotte-Pugh has come about as the number of patients placed on the liver transplant waiting list has outstripped the available supply of livers. The philosophy underlying allocation of scarce donor livers is, and has been, that candidates with more urgent disease should take priority over those with less urgent indications. This is sometimes referred to as the “sickest first” policy. The “sickest first” policy mandates that we have a system that grades the urgency of patients on the waiting list. Paradoxically, for many years UNOS has utilized an allocation scheme that has conferred a value on Abbreviations: MEGX, monoethylglycinezylidide; IOM, Institute of Medicine; MELD, Mayo End-Stage Liver Disease. From the Division of Gastroenterology, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA. Received December 19, 2000; accepted December 20, 2000. Address reprint requests to: Michael R. Lucey, M.D., F.R. C.P.I. , Division of Gastroenterology, 3 Ravdin Building, Hospital of the University of Pennsylvania, 34th and Spruce Street, Philadelphia, PA 19104. E-mail: lucey@mail.med.upenn.edu; fax: 215-349-5915. Copyright © 2001 by the American Association for the Study of Liver Diseases. 0270-9139/01/3302-0023$35.00/0 doi:10.1053/jhep.2001. 22481