Meta-analysis: surveillance with ultrasound for early-stage hepatocellular carcinoma in patients with cirrhosis

Abstract

Background: A majority of studies investigating the accuracy of ultrasound for detecting hepatocellular carcinoma (HCC) do not reflect how this test is used for surveillance vs. diagnosis.

Aim: To determine the performance characteristics of surveillance with ultrasound for the detection of HCC, particularly early HCC as defined by the Milan criteria.

Methods: A systematic literature review using the MEDLINE and SCOPUS databases yielded six studies that evaluated the accuracy of ultrasound for HCC at any stage and 13 studies that were specific to early HCC.

Results: Surveillance ultrasound detected the majority of tumours before they presented clinically, with a pooled sensitivity of 94%. However, ultrasound was less effective for detecting early HCC with a sensitivity of 63%. Alpha-fetoprotein provided no additional benefit to ultrasound. Meta-regression analysis demonstrated a significantly higher sensitivity for early HCC with ultrasound every 6 months than with annual surveillance. Current studies have limitations such as verification bias and are of suboptimal quality.

Conclusions: Surveillance with ultrasound demonstrates limited sensitivity for early HCC, although this may be improved by testing at 6-month intervals. Currently available evidence evaluating surveillance ultrasound has significant limitations and future studies are necessary to determine optimal surveillance methods for early HCC.

Figure 1

Map of the literature search and selection process. HCC, hepatocellular carcinoma; AFP, alpha-fetoprotein.

Figure 2

Performance characteristics of ultrasound for the detection of hepatocellular carcinoma (HCC) at any stage: (a) forest plot for the sensitivity of ultrasound to detect HCC at any stage; (b) forest plot for the specificity of ultrasound to detect HCC at any stage; (c) forest plot for the odds ratio of ultrasound to detect HCC at any stage; (d) summary receiver operator curve plot for the detection of HCC at any stage by ultrasound. Q, chi-squared test of heterogeneity; I², inconsistency index; AUC, area under the curve.

Figure 3

Sensitivity of ultrasound with and without afp for the detection of early-stage hepatocellular carcinoma (HCC): (a) forest plot for the sensitivity of ultrasound to detect early HCC; (b) forest plot for the sensitivity of ultrasound with AFP to detect early HCC. Q, chi-squared test of heterogeneity; I², inconsistency index.

Figure 4

Meta-regression using surveillance intervals for the sensitivity of ultrasound to detect early hepatocellular carcinoma (HCC). Studies with surveillance at least every 6 months had a significantly higher sensitivity for early-stage HCC than studies performing surveillance on an annual basis (P = 0.001).