several medical societies suggest routine hepatocellular carcinoma (HCC) screening in patients with chronic hepatitis b or cirrhosis. a systematic review in annals of intl medicine, commissioned by the VA administration (see doi:10.7326/M14-0558), reviewed the data, finding “very low strength evidence” on the effects of screening on mortality. they found 22 adequate english-literature studies, with results:
–1 large RCT done in China from 1993-95 included 9757 screened patients vs 9443 controls (screening with a-feto protein, AFP, and ultrasound every 6 months), found decreased HCC mortality of 83.2 vs 131.5/100K person-yrs, or rate ratio of 0.63 [95% CI 0.41-0.98]. but significant methodological flaws, including whether there was true randomization (concern that patients in each group did not have same HCC risk, questions about ascertainment of deaths in each group/selective reporting or analysis).
–another Chinese study from 1989-92 compared screening with AFP followed by ultrasound if AFP high (3712 pts) vs control (1869 pts). fewer screened patients had stage III HCC (19.8% vs 41.0%). HCC mortality similar in both groups (1138 vs 1114/100K person-yrs). BUT poor reporting of randomization/allocation, and only 28.8% of screening group completed all the prescribed tests.
–2 trials in Taiwan found no survival diff between shorter (3-4 month) vs longer (6-12 month) screening (37.5% vs 6.7%), but HCC survival rates at 1-, 2-, and 4-yrs were not statistically different
–1 found no survival benefit to using AFP screening in those with hepatitis B
–18 observational studies from around the world found earlier-stage HCC with screening and generally higher survival from the time of HCC diagnosis, but unclear if reflected lead-time or length-time biases. for example, if they postulated a 90-120 day or longer tumor doubling-time , the survival advantage disappeared.
–harms of screening not assessed well in any of these studies, and other studies have found issues (eg a meta-analysis of 8 studies has found 2.7% with needle-track seeding from liver biopsy for suspected HCC. also reactions to contrast-enhnced CT or MRI. or other issues with biopsy, surgery, chemotherapies. or false positive results. or tumors that revert spontaneously. or….)
so… the data supporting aggressive screening (and medicalization, and cost) are not very good. a cochrane review for patients with hepatitis B in 2012 found insufficient evidence. another important issue in the US is that the RCTs (with their flaws) only dealt with patients with hepatitis B, and generalizing to other hepatitis (eg hep C, the more common one here) may not be appropriate, esp given the very different pathophysiologies of the different types of hepatitis. my sense is that, with the lack of conclusive evidence one way or another, we are stuck adhering to the guidelines about screening (which have largely dropped the AFP component, though there was a recent study suggesting some utility if the AFP were really high), with ultrasounds every 6 months or so. as always, would be better to have better data on which to make recommendations.
geoff