Benefits and harms of screening for hepatocellular carcinoma in high-risk populations: systematic review and meta-analysis

Objective

The incidence and mortality of hepatocellular carcinoma (HCC) have been increasing around the world. Current guidelines recommend HCC screening in high-risk population. However, the strength of evidence of benefits and harms of HCC screening to support the recommendation was unclear. The objective is to systematically synthesize current evidence on the benefits and harms of HCC screening.

Methods

We searched PubMed and nine other databases until August 20, 2021. We included cohort studies and RCTs that compared the benefits and harms of screening and non-screening in high-risk population of HCC. Case series studies that reported harms of HCC screening were also included. Pooled risk ratio (RR), according to HCC screening status, was calculated for each benefit outcome (e.g., HCC mortality, survival rate, proportion of early HCC), using head-to-head meta-analysis. The harmful outcomes (e.g., proportion of physiological harms provided by non-comparative studies were pooled by prevalence of meta-analysis. Analysis on publication bias and quality of life, subgroup analysis, and sensitivity analysis were also conducted.

Results

We included 70 studies, including four random clinical trials (RCTs), 63 cohort studies,three case series studies. The meta-analysis of RCTs showed HCC screening was significantly associated with reduced HCC mortality (RR [risk ratio], 0.73 [95% CI, 0.56–0.96]; I² = 75.1%), prolonged overall survival rates (1-year, RR, 1.72 [95% CI, 1.13–2.61]; I² = 72.5%; 3-year, RR, 2.86 [95% CI, 1.78–4.58]; I² = 10.1%; and 5-year, RR, 2.76 [95% CI, 1.37–5.54]; I² = 28.3%), increased proportion of early HCC detection (RR, 2.68 [95% CI, 1.77–4.06]; I² = 50.4%). Similarly, meta-analysis of cohort studies indicated HCC screening was more effective than non-screening. However, pooled proportion of physiological harms was 16.30% (95% CI: 8.92%–23.67%) and most harms were of a mild to moderate severity.

Conclusion

The existing evidence suggests HCC screening is more effective than non-screening in high-risk population. However, harms of screening should not be ignored.