Reply:
Authors: Winston Dunn, Patrick S. Kamath, Russell H. Wiesner, W. Ray Kim, Vijay Shah
Journal: Hepatology (2005)

We thank Forrest and colleagues for their interest in our study. They comment on the limitations of our study1 and three independently conducted studies that corroborate with our results.2-4 They also highlight the use of their prognostic model in alcoholic hepatitis (AH). These criticisms of the Model for End-Stage Liver Disease (MELD) scoring suggest a misunderstanding of MELD. MELD is effective in ranking severity of illness in patients with liver disease both with and without gastrointestinal bleeding.5 This is a positive feature of MELD in AH, not a detractor as suggested by Forrest and coworkers. The relationship between cut-point and treatment also requires clarification. The cut-point reflects the point of highest sensitivity and specificity on the ROC curve and does not dictate the point at which a therapy must be instituted. For AH, a benign therapy may be initiated at a lower MELD score, while a higher MELD score might be used for a more risky intervention. Our website calculator at http://www.mayoclinic.org/gi-rst/mayomodel7.html provides convenient calculation of MELD and translation to 90-day mortality in AH, thereby allowing clinicians to make their own treatment decision. The variations in cut-point between studies relating to MELD and AH largely reflect the different MELD formulations that were used. We used the United Network for Organ Sharing (UNOS) MELD, whereas Sheth et al.3 used the original MELD because the UNOS modification had not yet been conceived at that time. A constant of 6.4 points accounts for the majority of the difference of optimal MELD cut-point between these two studies. With regard to Forrest et al.'s scoring system, only independent validation that comes with the "test of time" will support or refute their model. MELD has begun to pass this test, having been validated for a variety of liver conditions. In the meantime, it is important to point out some limitations of Forrest et al.'s model. First, the model is not continuous and therefore suffers from the same limitations as all models that employ categorical discrimination. Second, the model seems to be compared with historical optimal cut-point of MELD rather than optimal cut-points from their own data set. This would be necessary for a head-to-head comparison within their data set. Even more worrisome is that Forrest et al. apparently have made an error in their MELD calculations. Table 1 in their "in press" manuscript that was provided for us depicts a MELD calculation with an International Normalized Ratio constant of 1.2—this should be 11.2! Hopefully, this error will be rectified in their published manuscript. Third, the model is not weighted, thus allocating equal footing to each criterion. Actually, most of the criteria that constitute Forrest et al.'s model are variables that constitute MELD; thus, it would be interesting to see how much age and white blood cell count add to Forrest et al.'s model beyond bilirubin, international normalized ratio, and renal function. Last, individuals with gastrointestinal bleeding—a sizeable percentage of patients with AH—were excluded in Forrest et al.'s analysis. In the presence of gastrointestinal bleeding, we wonder whether Forrest et al.'s model will be valid, because BUN is confounded by gastrointestinal bleeding. We agree with Forrest and colleagues that development and validation of new models of prognostication in AH is important. Hopefully, advances will facilitate and translate into better treatment of this difficult condition. Winston Dunn*, Patrick S. Kamath*, Russell H. Wiesner*, W. Ray Kim*, Vijay Shah*, * Advanced Liver Disease Study Group, Mayo Clinic, Rochester, MN.