HCC Screening Evidence ‘Weak’ for Chronic Liver Disease Patients

A literature review challenges the practice of screening for hepatocellular cancer in patients with chronic liver disease

medwireNews: There is little evidence to support screening for hepatocellular carcinoma (HCC) in patients with chronic liver disease, suggest the authors of a systematic review published in the Annals of Internal Medicine.

Devan Kansagara, from Portland Veterans Affairs Medical Center in Oregon, USA, and team say there are “substantial shortcomings” in the research underpinning the recommendations for screening by organisations such as the American Association for the Study of Liver Diseases, and the European Association for the Study of the Liver–European Organisation for Research and Treatment of Cancer.

“Screening can identify more patients with earlier-stage disease who are candidates for potentially curative treatments, but there is limited evidence from which to draw firm conclusions about the balance of health outcome benefits and harms of using routine screening to identify HCC”, the team says.

Overall, 22 English-language studies assessing benefits and harms of screening versus non-screening were identified. The results of a large randomised, controlled trial in China pointed to a reduced risk of HCC mortality in patients who underwent regular ultrasound screening, with a rate ratio of 0.63. But the current study researchers note major methodological flaws, including a lack of baseline patient information and weak methods used to ascertain death from HCC.

A second screening trial of patients with hepatitis B did not show a benefit for alpha-fetoprotein screening with regard to HCC mortality, and again the study had flaws, including poor uptake of testing and potential for bias.

Two trials assessed ultrasound screening intervals. The first showed that patients with hepatitis B or C who were screened every 4 months were more likely to be diagnosed with very early stage HCC than those screened at 12-month intervals, but that frequent screening had no impact on survival. The second study found similar rates of HCC diagnosis and all-cause mortality in patients screened at 3- and 6-month intervals.

The researchers also reviewed 18 observational studies comparing the survival of patients whose HCC was detected by ultrasound or alpha-fetoprotein screening and those whose cancer was identified by other means.

Screen-detected HCC was generally diagnosed at an earlier stage than HCC diagnosed incidentally or by symptoms, and screened patients were more likely to receive potentially curative treatment and to have a longer survival time, Devan Kansagara and co-authors report.

However, they note that most reports were single-centre, retrospective studies with a risk of selection bias and no comprehensive assessment of mortality outcomes, as well as a significant potential for length- and lead-time bias. And survival benefits were lost in three of the five studies that attempted to adjust for lead-time bias.

Finally, none of the studies reviewed reported direct harms of screening for HCC or the psychological impact of screening on patients.

“In conclusion, there is very-low-strength evidence from which to draw conclusions about the effects of HCC screening on mortality in high-risk patients with chronic liver disease”, the researchers write.

In an accompanying editorial, David Atkins, from the Department of Veterans Affairs in Washington D.C., USA, and co-authors say that in the absence of stronger evidence, screening programmes should not be initiated or expanded. But they emphasise that the “range of uncertainty includes a clinically important benefit of screening.”

“Screening has a much greater potential to produce benefits exceeding harms in the highest-risk patients, such as those with hepatitis C and cirrhosis, than in the general population”, the commentators add.

“It is appropriate to allow clinicians caring for these patients to continue to offer screening, but offers should be targeted to those who are good candidates for treatment and should include a shared decision-making approach that explicitly acknowledges the limitations of the evidence.”


Kansagara D, Papak J, Pasha A, et al. Screening for hepatocellular carcinoma in chronic liver disease. A systematic review. Ann Intern Med 2014; Published online 17 June. doi:10.7326/M14-0558

Atkins D, Ross D, Kelley M. Acting in the face of uncertainty. Ann Intern Med 2014; Published online 17 June. doi:10.7326/M14-1344

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