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Risk score for development of HCC: ready for use in practice?
The Lancet Oncology, Volume 12, Issue 6, Pages 517 - 518, June 2011
doi:10.1016/S1470-2045(11)70085-7
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Published Online: 15 April 2011
Original Text
Surveillance is widely accepted in clinical practice in patients who are at increased risk of developing hepatocellular carcinoma (HCC), including those with chronic hepatitis B virus (HBV) infection. Surveillance in patients with HBV infection has been recommended on the basis of findings from one randomised controlled trial from China showing a survival benefit,1 and other non-randomised or observational studies showing that surveillance detects earlier disease and improves survival. The most recent update of practice guidelines from the American Association for the Study of Liver Diseases (AASLD) recommends surveillance for HCC in Asian male hepatitis B carriers older than 40 years, Asian female hepatitis B carriers older than 50 years, hepatitis B carriers with a family history of HCC, African and North American black patients with hepatitis B, and hepatitis B carriers with cirrhosis.2
One of the main elements of surveillance is to establish what level of risk for HCC should lead to initiation of surveillance. In this issue of The Lancet Oncology, Hwai-I Yang and colleagues3 report the development and validation of a predictive score for the risk of development of HCC in patients with chronic hepatitis B. Although other groups, such as Yuen and colleagues,4 have reported risk scores for the development of this disease, this is the first group to provide validation of their risk score. The study analysed data from 3584 patients from a community-based Taiwanese cohort who were not receiving antiviral therapy and did not have cirrhosis, and validated their risk score in hospital-based cohorts from Hong Kong and South Korea.3 Variables associated with an increased risk of HCC included patient factors (male sex, increasing age), disease factors (raised concentrations of serum alanine aminotransferase), and virological factors (HBeAg positivity and increased levels of serum HBV DNA). The risk score accurately estimated the risk of development of HCC at 3, 5, and 10 years. The investigators have contributed to the evolving work into risk scores for HCC by providing validation in a large, independent multicentre cohort. They conclude that this score could allow evidenced-based decisions for clinical management of hepatitis B carriers at variable risk of HCC.
The key question for clinicians is whether or not this risk score can lead to tailored decisions in the management of patients with chronic hepatitis B, such as no surveillance in patients with a low score or a change to more frequent surveillance or use of more sensitive imaging techniques in those with a high score. Prospective studies of surveillance every 3—4 months versus 6 months, or use of CT or MRI rather than ultrasound in high-risk patients with chronic hepatitis B would be needed before a clinician could with confidence change from the standard recommendation of ultrasonography every 6 months, usually with α-fetoprotein.2 The population that was the basis of the Yang and colleagues’ risk score did not include patients with cirrhosis, which is known to be the major risk factor for HCC and is present in up to three-quarters of HBV-related HCC.5 Moreover, cirrhosis was the most important independent risk score for development of HCC in Yuen and colleagues’ risk score.4
Many Asian—American patients who are undergoing antiviral therapy have undetectable HBV DNA, normal alanine aminotransferase concentrations, and are HBeAg negative; they would have a low risk score but yet fit the criteria for surveillance recommended in the AASLD guidelines on the basis of their age or other factors (eg, presence of cirrhosis or a family history of HCC). How to resolve the different advice provided by a risk score versus a society guideline is a dilemma for the clinician. Risk scores might be most helpful in identification of patients with a very low risk of HCC who do not need surveillance, rather than leading to a change in surveillance practices in patients with a high score. Additionally, the incidence of HCC differs according to the geographical distribution of risk factors, and surveillance strategies derived from a Taiwanese or Asian populations might not apply globally. Finally, scoring systems should include known risk factors such as the presence of cirrhosis, use of alcohol, and family history of HCC, and should be validated in white and African patients who are often infected in adulthood and whose risks for HCC differ substantially from those in Asian patients with chronic HBV infection dating from birth or early childhood. Thus, risk scores for the development of HCC are in the preliminary stages of development and not yet ready for widespread use in practice.
I have no conflicts of interest.
1 Zhang BH, Yan BH, Tang ZY. Randomized controlled trial of screening for hepatocellular carcinoma. J Cancer Res Clin Oncol 2004; 130: 417-422. PubMed
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3 Yang H-I, Yuen M-F, Chan HL-Y, et alfor the REACH-B Working Group. Risk estimation for hepatocellular carcinoma in chronic hepatitis B (REACH-B): development and validation of a predictive score. Lancet Oncol 201110.1016/S1470-2045(11)70077-8. published online April 15. PubMed
4 Yuen MF, Tanaka Y, Fong DY, et al. Independent risk factors and predictive score for the development of hepatocellular carcinoma in chronic hepatitis B. J Hepatol 2009; 50: 80-88. CrossRef PubMed
5 Yuen MF, Yuan HJ, Wong DK, et al. Prognostic determinants for chronic hepatitis B in Asians: therapeutic implications. Gut 2005; 54: 1610-1614. CrossRef PubMed
http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(11)70085-7/fulltext
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