Role of ADC in differentiating hepatocellular adenoma vs. hepatocellular carcinoma and metastatic liver lesions: systematic review and meta-analysis.

PURPOSE: Differentiating hepatocellular adenoma (HCA) from malignant focal liver lesions (FLLs), including hepatocellular carcinoma (HCC), and metastases, is challenging yet clinically important. Given biopsy-associated bleeding risks in suspected HCA and differing treatment strategies, accurate noninvasive imaging biomarkers are needed.

METHODS

A systematic literature search of PubMed, Embase, Web of Science, and Cochrane Library up to August 10, 2025, identified studies reporting quantitative apparent diffusion coefficient (ADC) values for histologically or imaging-confirmed HCA and malignant FLLs. Data extraction and risk-of-bias assessment were performed independently by two reviewers using QUADAS-2. Random-effects meta-analysis calculated pooled mean ADC values, mean differences, standardized mean differences (SMDs), and percentage differences.

RESULTS

Sixteen studies comprising 1279 lesions (212 HCA, 697 HCC, 370 metastases) were included. Mean ADC values were 1.34 × 10⁻³ mm²/s for HCA, 1.23 × 10⁻³ mm²/s for HCC, and 1.25 × 10⁻³ mm²/s for metastases. HCA demonstrated modest yet significantly higher ADC than HCC (mean difference = 0.12 × 10⁻³ mm²/s, p = 0.042; SMD = 0.35). No significant difference was observed between HCA and metastases (mean difference = 0.17 × 10⁻³ mm²/s, p = 0.153; SMD = 0.54), likely reflecting heterogeneity in metastatic biology. Publication bias assessment was negative for all comparisons.

CONCLUSION

ADC values were slightly higher in HCA than HCC but largely overlapped with metastases; given the small effect sizes and substantial unexplained heterogeneity, despite the claims by several included studies, ADC currently has only a limited, complementary role in lesion characterization and cannot reliably replace biopsy.