Surveillance for Hepatocellular Carcinoma: Long Way to Achieve Effectiveness

Abstract

Surveillance for hepatocellular carcinoma (HCC) in high risk groups including those with cirrhosis as well as with chronic HBV infection is recommended by several practice guidelines including those by the Asian Pacific Association for the Study of Liver (APASL) [1], the American Association for the Study of Liver Disease (AASLD) and the European Association for Study of The Liver (EASL). The evidence supporting the surveillance recommendations in these guidelines is based on evidence of intermediate strength, although arguably the evidence is strongest for HCC surveillance in individuals infected with HBV in Southeast Asia. For example, two randomized controlled trials were conducted in China among individuals with chronic HBV infection with and without cirrhosis. In one placebo-controlled randomized study of nearly 19,000 HBV-infected patients, it was shown that HCC surveillance with both abdominal ultrasound and serum AFP repeated at 6-month intervals resulted in a 37 % reduction in HCCrelated mortality [2]. However, the other randomized controlled trial of 5,581 HBV-infected patients reported that serum AFP repeated at 6-month intervals did not result in a significant reduction in overall mortality [3]. The latter study was smaller and had detected HCC less frequently than the first study and therefore could have suffered from a lack of adequate statistical power. In addition to these two randomized trials, a population-based surveillance program using serum AFP every 6-months among HBVinfected patients in Alaska reported that, during a 16-year follow-up period, patients with HCC who received surveillance had significantly longer 5-year survival compared with historical controls (42 vs. 0 %, respectively) [4]. Last in the evidence hierarchy, several nonrandomized trials and observational cohort and case–control studies have reported that patients who undergo HCC surveillance are diagnosed at an earlier stage of HCC, are more likely to receive potentially curative therapy, and have a significant reduction in cancer-specific mortality compared with patients detected with symptomatic HCC [5, 6]. The ‘‘efficacy’’ of HCC surveillance reflects the degree to which surveillance produces the expected result under controlled conditions chosen to maximize the likelihood of observing an effect if it exists. By contrast, ‘‘effectiveness’’ addresses the extent to which HCC surveillance is beneficial when deployed in medical practice settings [7]. Effectiveness takes into account external factors such as individual patient characteristics, health system features, and societal influences. For HCC surveillance to be effective, several steps need to be enacted. These include (1) identification of high risk patients who are appropriate for surveillance (HBV and HCV with advanced fibrosis/ cirrhosis), (2) availability and accessibility of HCC surveillance to patients at risk in appropriate health care settings, (3) recommendation of the intervention by health care providers, (4) acceptance of HCC surveillance by patients, (5) adherence to surveillance, recall and follow-up at the recommended intervals, the benefits of therapy, (6) availability of appropriate diagnostic test follow-up for abnormal surveillance, and (7) availability of efficacious curative or palliative treatment once HCC is diagnosed. Given the multiplicity of components involved with determining HCC surveillance effectiveness, one could assess the interactions between these factors to arrive with an estimate of how one particular intervention would H. B. El-Serag (&) Dan L Duncan Professor of Medicine, Michael E DeBakey VA Medical Center, Houston Center for Quality of Care and Utilization Studies, Baylor College of Medicine, Houston, TX, USA e-mail: hasheme@bcm.edu