Simple Calculation Assesses Liver Function in Hepatocellular Carcinoma

By Will Boggs MD

NEW YORK (Reuters Health) - A simple model based on albumin and bilirubin levels can help assess liver function in patients with hepatocellular carcinoma (HCC), researchers have found.

"It has long been recognized that, within Child-Pugh (C-P) 'A' there is a wide variation in liver function, or 'liver reserve,'" Dr. Philip J. Johnson from University of Liverpool in the UK told Reuters Health by email. "The Albumin-Bilirubin (ALBI) approach might allow physicians to identify those C-P 'A's with a good prognosis."

The C-P grade is based on a score derived from five parameters, including conventional liver function tests, extent of ascites, and degree of hepatic encephalopathy, and was originally developed to assess prognosis in patients with cirrhosis and portal hypertension undergoing surgery for variceal bleeding.

Dr. Johnson's team used data from large international databases to identify objective measures of liver dysfunction that independently influence survival in patients with HCC and then combined them in a model that they compared with the conventional C-P grade.

Their ALBI score eliminates the need for the subjective variables required in the C-P grade (i.e., ascites and encephalopathy). The cut points of their linear predictor place patients with a calculated score of -2.60 or less into ALBI grade 1, those with a score higher than -1.39 into ALBI grade 3, and those in between into ALBI grade 2.

The equation for the linear predictor is (log10 bilirubin x 0.66) + (albumin x -0.085), where bilirubin is in mcmol/L and albumin is in g/L, the researchers report in the Journal of Clinical Oncology, online December 15.

The resulting model provides good discrimination between three prognostic groups. Moreover, the ALBI grade clearly differentiates patients in C-P grade A into two distinct prognostic groups.

"In Europe and the United States, for example, when C-P grade A patients were reclassified into ALBI grade 1 or 2, there was a 10-month difference in survival between the two ALBI grades," the researchers explain. "Our analysis has focused on the impact of liver function on survival, and not on liver disease-related events or death, because in practice, it is difficult to specifically attribute the cause of death to the HCC or the underlying liver disease."

Dr. Johnson cited three examples where ALBI might change the management of patients: "a) Among patients undergoing potentially curative treatment it might help decide whether resection or transplantation is most appropriate. Those with poor liver function (i.e., C-P 'A' but ALBI 2) may be more appropriately transplanted. b) We might be able to monitor liver function in response to therapeutic interventions, e.g., anti-viral therapy or portal vein embolization. d) Identification of sub-groups of HCC patients that benefit from specific interventions, most obviously within the treatment of advanced disease with targeted therapies."

As for the future of ALBI versus C-P, Dr. Johnson said, "My guess is that, if investigators in the HCC field are generally supportive, the two systems will run side by side until people get a feel for the relative value of each. This will not be difficult since the components of ALBI are also contained within C-P -- so no extra work."

"We should be moving to evidence-based measures of liver function; C-P was very useful in the last century but its limitations are now well known," he concluded. "An approach to assessment of liver function in general hepatology, using a similar statistical modeling approach to that used in the ALBI paper, might yield a new score for the next century. My guess is that it would probably come up with albumin and bilirubin as the key features again, but maybe in different models for different liver diseases."

Dr. Jennifer J. Knox, who wrote an editorial on the findings, told Reuters Health by email that, "For advanced HCC patients (the non-curative majority) the ALBI system is a clear improvement over C-P given its validation in modern patient populations with good representation of the world's HCC population. It is simple (2 commonly measured labs) and objective and so just a better general, reproducible alternative to take forward now as a measure of liver function in HCC patients."

"Advanced HCC is where we have so few effective therapies and where a large focus of research needs to be," said Dr. Knox from the University of Toronto in Canada. "ALBI should replace C-P in therapeutic clinical trials planned to evaluate new treatments we desperately need."

"The other key message is that there still needs to be a lot of work done to find better therapies for these patients, but perhaps ALBI will facilitate an easier path to discovery," she said. "C-P still plays a role in contributing to the assessment of liver function reserve prior to surgery, much closer to the use for which it was originally developed."

Dr. Alejandro Forner Gonzalez from University of Barcelona's Barcelona Liver Cancer Clinic in Spain, who was not involved in the study, said, "My personal opinion is that Child-Pugh score is not accurate enough in HCC patient but is not worse than the ALBI proposal."

"Moreover, one of the most important prognostic parameters in cirrhotic patients with HCC is the presence of decompensation, mainly ascites, and this variable is captured by Child-Pugh but not by ALBI," he told Reuters Health by email.

SOURCE: https://bit.ly/1w5EcPN and https://bit.ly/1C8dn5V

J Clin Oncol 2014.

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