Addressing the Interplay of Liver Disease and Hepatocellular Carcinoma on Patient Survival: The ALBI Scoring Model
Authors: Jennifer J. Knox
Journal: Journal of Clinical Oncology (2014)

Hepatocellular carcinoma (HCC) is a complex disorder with a poor overall prognosis. In most cases, it presents on a background of chronic liver disease, and the interplay of the underlying liver disease and the cancer itself drives treatment decisions. The clinician must consider factors such as the stage and extent of tumor, the underlying liver function, and the patient’s performance status. There is a clear need for staging systems to best guide therapeutic approaches, but the lack of a universally accepted prognostic system has been problematic. Treatment guidelines vary in different countries or regions of the globe and may be influenced by the staging system accepted. In addition, despite advances in surveillance programs of at-risk populations leading to curative treatments for early disease, the reality is that we are faced with growing numbers of patients presenting with advanced or recurrent incurable HCC. Progress in the field of advanced HCC has been slow and modest. We have been successful in accruing patients globally and completing both earlyand late-phase therapeutic trials, yet most phase III trials in advanced HCC have been negative. We are at a point when we need to re-evaluate some of our assumptions. Staging and its impact on trial eligibility is one place to start. The evaluation of liver function within HCC patient populations as part of staging is the focus of the article by Johnson et al that accompanies this editorial. There are many HCC staging systems—including Okuda, Cancer of the Liver Italian Program, TNM, Chinese University Prognostic Index, Japanese Integrated Staging Score, Barcelona Clinic Liver Cancer (BCLC) system—and these have been compared and reviewed often. Perhaps the most widely recognized and useful system is the BCLC system. It was developed on the basis of the results of randomized control trials and cohort studies and appropriately links tumor stage, performance status or cancer-related symptoms, and liver function to a current evidence-based treatment algorithm. To summarize briefly, patients classified as very early (stage O) or early (stage A) disease are both amenable to curative approaches. Intermediate (stage B) disease is amenable to locoregional therapy aimed at control. Patients with BCLC advanced-stage (stage C) disease generally have macrovascular invasion by tumor and/or metastatic disease but have preserved liver function as defined by the Child-Pugh (CP) cirrhosis score. It is this population that has been shown to benefit from sorafenib systemic therapy. Patients with terminal (stage D) HCC have severe cancer symptoms or clearly decompensated liver cirrhosis, and appropriate treatment is supportive/symptomatic care alone. The BCLC system guides treatment plans for patients and enables identification of those best directed to clinical trials. However, it is noteworthy to highlight that the grading of liver function that is a key component of the BCLC staging system is the CP assessment. Some historical perspective is required to appreciate our current conventions. The CP score was developed in the 1960s as a clinical tool to access the prognosis of surgery for variceal bleeding in patients with cirrhosis with portal hypertension. The score comprises five variables: albumin, bilirubin, INR, ascites, and encephalopathy. Since its development, the CP score has become widely adopted as an assessment tool for presurgical hepatic reserve. But more recently in the research and development of new treatments, primarily drugs in the setting of advanced HCC, the CP score has become the default hepatic reserve assessment criteria. It makes sense that we would want to eliminate the prognostic contribution of decreasing liver function when attempting to prove whether a treatment impacts survival from HCC. But is the CP score relevant in patient stratification for advanced HCC? Trials with novel therapies, radiation, radioembolization, transarterial chemoembolization, or various classes of systemic therapies and their potential combinations are very different from the surgical genesis of the CP score. For additional context, the Sorafenib HCC Assessment Randomized Protocol (SHARP) study was the first ever demonstration of a drug (sorafenib) prolonging survival in advanced HCC (BCLC stage C) and was studied in a population with CP score A (CP-A) liver function status at enrollment. The CP-A criteria, without specific validation, has since been incorporated into most advanced HCC drug trials. Many have concerns as to whether CP-A stratifies disease appropriately for novel therapies. The limitations of CP score in the setting of HCC are discussed by Johnson et al and include issues such as interrelated variables counting twice (low serum albumin also leads to ascites) and subjective variables (definition of ascites and whether it is mild, moderate, or easily controlled and/or is mild encephalopathy present or absent). The contributions of liver dysfunction and tumor cannot always be separated clinically, and the CP score may not discriminate sufficiently regarding influence on drug-related toxicity or benefits. This overall lack of validation of CP score in JOURNAL OF CLINICAL ONCOLOGY E D I T O R I A L VOLUME 33 NUMBER 6 FEBRUARY 2