Eleven studies with 2,178 participants (1,223 receiving IFN treatment, 955 receiving no treatment) were included in the review. There was 1 randomised controlled trial with 90 participants, 6 non-randomised retrospective studies, and 4 non-randomised prospective studies.
There was a 100% agreement between the reviewers for the selection of relevant articles.
HCC developed significantly more frequently in untreated than in IFN- treated participants; the OR was 3.0 (95% CI: 2.3, 3.9, p<0.001). There was no evidence of heterogeneity between the studies (p=0.57).
The number-needed-to-treat to prevent HCC in one patient was 9 (95% CI: 7, 11).
The assessment of publication bias showed that 171 null or negative studies would be needed to render the result of the analysis non significant.
Sensitivity analyses.
In the 5 studies reporting HCC incidence in patients with and without sustained response to IFN, HCC was detected at a much higher rate in patients without a sustained response (OR 3.7, 95% CI: 1.7, 7.8, p=0.001). There was no evidence of heterogeneity between the studies (p=1.00).
HCC developed significantly more frequently in the untreated participants than in the in non-sustained responders (OR 2.7, 95% CI: 1.9, 3.9, p<0.001). There was no evidence of heterogeneity between the studies (p=0.62).
The benefit of IFN on HCC was not influenced by study type, duration of follow-up, or the origin of the study (Japan versus other countries).