Screening for Hepatocellular Cancer
in Chronic Liver Disease:
A Systematic Review
Devan Kansagara, M.D., M.C.R.
Janice H. Jou, M.D., M.H.S.
Joel Papak, M.D.
Amirala S. Pasha, D.O., M.S.
Maya O'Neil, Ph.D.
Michele Freeman, M.P.H.
Rose Relevo, MLIS, M.S.
Ana Quinones, Ph.D.
Makalapua Motu'apuaka, B.S.
Evidence-based Synthesis Program (ESP) Center, Portland VA Medical Center,
Washington (DC): Department of Veterans Affairs; January 2014
Download PDF: Complete Report, Executive Summary, Report, Appendices
In the Veterans Health Administration (VHA), there has been a marked increase in the prevalence
of cirrhosis from chronic hepatitis C infection with a corresponding increase in the number of
hepatocellular cancer (HCC) diagnoses. From 1996 to 2006, the prevalence of cirrhosis among
Veterans with chronic hepatitis C infection rose from 9 to 18.5%, and the prevalence of HCC
rose from 0.07 to 1.3%. In the general population, the incidence of HCC rose between 1992 and
2005 from 3.1/100,000 to 5.1/100,000, with localized tumors accounting for most of the increase.
While, on average, the 5-year survival of HCC is low (13 to 16.5%), the survival of early-stage
disease has risen.
The rationale for screening is that imaging tests such as ultrasound can identify patients with
early stage HCC and there are several potentially curative treatment options for patients with
early stage HCC including liver transplantation, radiofrequency ablation, and liver resection.
Several professional society guidelines currently recommend HCC screening using imaging
studies and tumor markers mainly in patients with chronic hepatitis B or liver cirrhosis.
However, recommendations for HCC screening remain controversial in part because of concerns
over the quality and paucity of existing evidence, and because there have been concerns raised
about overdiagnosis and patient harms in other cancer screening programs.
We conducted a systematic review of the published literature to better understand the incremental
benefits and harms of routine HCC screening in patients with chronic liver disease compared to
clinical or incidental diagnosis. We looked for direct evidence of the health outcome effects of
screening. We also looked for indirect evidence of the effects of screening by evaluating studies
examining the health outcome benefits and harms of treating early-stage HCC which, because
the intent and result of routine screening is detection of early-stage disease, is a proxy for screendetected
- Screening for Hepatocellular Carcinoma in Chronic Liver Disease: A Systematic Review. Kansagara, D; Papak, J; Pasha, A S; O'Neil, M; Freeman, M; Relevo, R; Quinones, A; Motu'apuaka, M; and Jou, J. Ann Intern Med. Published online 17 June 2014 doi:10.7326/M14-0558
Acting in the Face of Uncertainty. Atkins, D; Ross, D; and Kelley, M. Ann Intern Med. Published online 17 June 2014 doi:10.7326/M14-1344
Cyberseminar on Screening for Hepatocellular Cancer in Chronic Liver Disease: A Systematic Review
- A Systematic Review: Screening for Hepatocellular Cancer in Chronic Liver Disease (Management eBrief)