Using data from large international databases, a collaborative research team led by Philip J. Johnson, MD, of the University of Liverpool in Liverpool, United Kingdom, has developed a new staging system that may provide a better approach to assessment of liver function in patients with hepatocellular carcinoma (HCC).1
Drawing on data from 1,313 patients with HCC in Japan, the researchers determined that demographics, characteristics of the patient’s cancer, serum albumin levels, and serum bilirubin were strong prognostic factors.
Eliminating the effect of the HCC itself revealed that serum albumin and bilirubin levels alone were significant predictors of survival (using the equation [log10 bilirubin x 0.66] + [albumin x –0.085], where bilirubin is in µmol/L and albumin is in g/L).
Under this grading system, called ALBI, patients could be classified into one of three prognostic groups, termed ALBI grade 1 to 3, designating the lowest- to highest-risk patients, respectively.
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When the researchers compared the patients’ ALBI grade with their Child-Pugh score, the most-widely employed system for estimating liver function, they found a close correspondence in their ability to predict survival, with ALBI grades 1, 2, and 3 closely matching Child-Pugh grades A, B, and C.
The researchers then applied the ALBI model to cohorts of patients with HCC from Hong Kong, Europe, and the United States, and again found a close correspondence with Child-Pugh grades in terms of predictive power.
The Child-Pugh System: Ready for Replacement?
HCC is most commonly staged using the Barcelona Clinic Liver Cancer (BCLC) system, which links tumor stage, performance status, symptoms, and liver function. Patients with BCLC stage C—advanced stage disease—generally have invasive or metastatic disease but well-preserved liver function, as determined by the Child-Pugh grade. These are the patients who benefit from treatment with sorafenib, whereas patients with early-stage or terminal disease do not.
Thus the Child-Pugh grade is a key guide to treatment decisions in HCC, but the Child-Pugh system has notable limitations. It was developed in the 1960s to evaluate liver function in patients with cirrhosis, but a substantial proportion of patients with HCC do not have underlying cirrhosis.
Moreover, the Child-Pugh grade is based on albumin, bilirubin, INR, ascites, and encephalopathy and thus relies on interrelated variables, in that low serum albumin contributes to ascites.
In addition, the grading of ascites and encephalopathy are subjective and no clear guidelines are available to guide the clinician in scoring them.
Finally, the Child-Pugh system does a poor job of discriminating among patients with HCC, most of whom fall into the A grade.