Hepatobiliary phase hypointense nodule without arterial phase hyperenhancement: are they at risk of HCC recurrence after ablation or surgery? A systematic review and meta-analysis

Objective To perform a systematic review and meta-analysis to determine intrahepatic distant recurrence (IDR) risk of hepatobiliary phase (HBP) hypointense nodules without arterial phase hyperenhancement (APHE) on pretreatment gadoxetic acid–enhanced MRI in patients with hepatocellular carcinoma (HCC) treated with either hepatectomy or radiofrequency ablation (RFA). Methods PubMed and EMBASE databases were searched up to April 6, 2019. We included studies that evaluated HBP hypointense nodules without APHE as risk factors for IDR in HCC patients treated with either hepatectomy or RFA. Hazard ratios (HR) were meta-analytically pooled using random effects model. Subgroup analyses stratified to clinicopathologic variables were performed to explore heterogeneity. Methodological quality of included studies was assessed using Quality in Prognostic Studies (QUIPS) tool. Results Eight studies with 842 patients were analyzed. The overall pooled HR for IDR was 2.44 (95% CI, 1.99–2.98) and were 2.14 (95% CI, 1.66–2.76) and 3.07 (95% CI, 2.19–4.31) for patients that underwent hepatectomy and RFA, respectively. No significant heterogeneity was present ( I 2 = 0%). The presence of these nodules was consistently shown to be significant factors for IDR in other subgroups (HR = 1.74–3.07). Study quality was generally moderate. Conclusions HBP hypointense nodules without APHE are risk factors for IDR in HCC patients treated with either RFA or hepatectomy. Stratification of patient management with regard to performing additional tests or treatment for these nodules and modification of proper follow-up strategies may be required in patients with HCC who have these nodules on pretreatment gadoxetic acid–enhanced MRI. Key Points • HBP hypointense nodules without APHE constitute an entity that is unique in gadoxetic acid–enhanced MRI. • HBP hypointense nodules without APHE are risk factors for IDR in HCC patients treated with either RFA or hepatectomy. • Stratification of management and modification of proper follow-up strategies may be required in HCC patients who have these nodules on pretreatment gadoxetic acid–enhanced MRI.