EVIDENCE-BASED ANSWER
Screening patients with chronic hepatitis B infection (HBsAg+) for hepatocellular carcinoma by alpha-fetoprotein (AFP) or by AFP plus ultrasound (AFP/US) detects hepatocellular carcinoma tumors at earlier stages and increases resection rates (strength of recommendation [SOR]: B, based on a systematic review of fair-quality randomized controlled trials). It is unclear whether screening with AFP or AFP/US improves disease-specific or all-cause mortality (SOR: B).
CLINICAL COMMENTARY
Offer screening to all with chronic hepatitis B infection, but stratify risk for HCC first
Michael Mendoza, MD, MPH
ACCESS Community Health Network and Department of Family Medicine, University of Chicago
Because no mortality benefit to screening for hepatocellular carcinoma has been shown, we should give added consideration to how we counsel our patients before offering screening, particularly since positive screening results can lead to further invasive studies. An important consideration for me is whether a patient has, or is at risk, for cirrhosis, because the incidence of hepatocellular carcinoma is higher if cirrhosis is present. Screening for coinfection with hepatitis C or a history of alcohol abuse becomes especially critical in this situation. Biochemical evidence of chronic active liver inflammation, whatever the cause, should also be an important factor in deciding whether to screen. While I still offer screening to all patients with chronic hepatitis B infection, it helps to have stratified a patient’s underlying risk for hepatocellular carcinoma first and counseling him or her accordingly.
Evidence summary
Many serum markers and screening methods have been proposed to detect hepatocellular carcinoma at a treatable stage, but only 2—AFP and US—are in clinical use.1
A Cochrane systematic review on screening for hepatocellular carcinoma in the HBsAg+ population was published in 2003 and updated May 2004.2 Our literature search did not find any subsequent relevant trials. The Cochrane review included 2 randomized control trials. The larger trial was performed in Shanghai, China and included 18,816 HBsAg+ patients aged 35 to 55 years.3 Subjects were recruited from their place of employment and randomized to either AFP/US every 6 months (n=9373) or to no screening (n=9443).
Fifty-one hepatocellular carcinomas were diagnosed in the control group and 86 in screened group. Screened subjects had a significantly higher percentage of tumors that were less than 5 cm at the time of diagnosis and a higher number of patients who underwent resection. While the 5-year survival for those with hepatocellular carcinoma in the screened group was higher, the disease-specific mortality rate was not statistically different between the 2 groups.
Additional data became available in 2002. The original study authors claimed the new data showed a statistically significant disease-specific mortality rate ratio of 0.63, favoring the screened group.4 However, the Cochrane group performed their own analysis on the same data and determined that no statistically significant difference in the disease-specific mortality rates existed between the 2 groups.2 Therefore, it is not clear whether these new data definitively demonstrate that screening provides any benefit.