Hepatocellular carcinoma screening may not affect mortality in chronic liver disease

Screening for hepatocellular carcinoma (HCC) may not affect mortality in patients with chronic liver disease, according to a review of existing evidence.

Researchers performed a systematic review of English-language studies published through April 2014 to examine the benefits and harms of HCC screening in patients with chronic liver disease. Trials and observational studies that compared screening with no screening were included, along with studies of harms and trials that compared different screening intervals. Screening was defined as “any surveillance or screening program in which specific tests (ultrasonography, computed tomography, magnetic resonance imaging, or α-fetoprotein measurement) were performed explicitly to detect HCC in asymptomatic patients.” The review's primary outcomes were mortality and adverse events. Results were published online June 17 by Annals of Internal Medicine.

Twenty-two studies were included in the review. The authors found that the overall strength of the evidence regarding the effects of screening was very weak. Decreased HCC mortality was seen with periodic ultrasonographic screening in 1 trial; however, it was limited by methodological flaws. Periodic alpha-fetoprotein screening was found to have no survival benefit in another trial of patients with hepatitis B. Eighteen observational studies demonstrated that HCC was diagnosed at an earlier stage in screened versus unscreened patients, but effects on mortality were confounded by lead- and length-time bias. In 2 trials, no survival differences were seen between shorter and longer screening intervals (3 to 4 months vs. 6 to 12 months). Available data on harms of screening were limited.

The authors noted that they included only studies written in English, that few trials were available, and that most had methodologic issues. However, they concluded that evidence regarding the effects of HCC screening on mortality in patients with chronic liver disease is very weak. “Screening tests can identify early-stage HCC, but whether systematic screening leads to a survival advantage over clinical diagnosis is uncertain,” the authors wrote. They stressed that their findings “neither support nor refute” current guidance on HCC screening and said that while strength of evidence is important, clinical experience, patients' preferences, and cost also play a role.

“If screening is pursued, it will be important to implement programs in ways that minimize potential harms, especially given the limited empirical evidence of benefit,” the authors wrote. “For example, targeting screening to higher-risk individuals with less severe underlying liver disease and developing a better understanding of how to target invasive treatment to those with more aggressive screen-detected tumors might help to increase the detectable benefits of screening while limiting the population exposed to potential harms.”

The authors of an accompanying editorial discussed the need for better evidence and said that until it is available, “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.” Screening should also be paired with efforts to collect better data, they wrote, such as baseline characteristics and long-term outcomes in both screened and unscreened patients.