We read with great interest in the article by Yoon Jung Hwang, et al. published in Clinical and Molecular Hepatology [1], which explored the classification of microvascular invasion (MVI) of hepatocellular carcinoma (HCC) associated with prognosis and magnetic resonance imaging (MRI). In this study, they reported that the presence of severe MVI was significantly associated with worse prognosis, while no significant difference in survival was evident between cases of mild MVI and no MVI. Additionally, the study underlined that non-smooth tumor margin and satellite nodules on MRI were significantly associated with severe MVI and poor survival outcomes. Considering important implications in clinical practice for new MVI grading, the novelty of this result should be highlighted. Based on the above, we would like to raise the following comment.

First, it is vital to provide more detailed pathological information on MVI. The key limitation is significant heterogeneity for pathological diagnostic criteria and tissue sampling standards. The presence of MVI (severe or mild) in this study was considered when they identified at intervals of 1 cm at planes perpendicular to the parenchymal resection margin, especially for the most representative sections and additional foci of interest. However, a widely used pathological diagnosis for evaluating MVI of HCC in China based on the seven-point sampling protocol are graded as M0, M1 or M2 (three-tiered MVI grading), and was a practical method to balance the efficacy of sampling numbers and MVI detection rates [2]. Further, another grading system of MVI classified into 4 groups [3]: M0: no MVI; M1: 1–5 proximal MVIs (≤1 cm from tumor boundary); M2a: >5 proximal MVIs (≤1 cm from tumor boundary); M2b: ≥1 distal MVIs (>1 cm from tumor boundary), and the severity of MVI from both adjacent and distant from tumor boundary should be stated, which echoes with an early system of classifying MVI. Additionally, a novel pathological examination method called image-matching digital macro-slide could help enhance the detection rate of MVI in HCC and refine the prediction of HCC prognosis [4]. Thus, the MVI grading combined with the severity of MVI from both adjacent and distant from tumor boundary and the number of invaded microvessels may be a better prognostic predictor than the only severe or mild MVI scheme.

Second, the present study reported that satellite nodules (specificity, 88.9%) on MRI were significantly associated with severe MVI, and were associated with decreased survival. Interestingly, a recent study [5] demonstrated that the presence of microinvasion and/or satellite nodules (MVI/S) was the only independent risk factor for aggressive recurrence (defined as patients that exceeded the Milan criteria at 1st recurrence) and mortality in patients with BCLC-0/A HCC. In the fact, MVI may mark the gain of metastatic traits in HCC, and mostly happens on portal venous, which may reflect very early intrahepatic metastasis compared with satellite nodules. Although these is significant tumor biological and pathological heterogeneity between MVI and satellite nodules, MVI may develop into a satellite nodules with the progression of HCC [6]. Our previous study [7] indicated that satellite nodules were also a risk factor for patients with HCC and macrovascular invasion. In addition to nonsmooth tumor margins and satellite nodules on MRI, lots of recent studies [8,9] established MRI radiomics model and nomogram to predict MVI, which may provide more detailed MRI information. Accurate preoperative prediction of MVI has always been a hot and difficult topic in HCC research.

Finally, from January 2011 to December 2017, selection bias is highly apparent in flow and timing and patients’ selection. Recent advances in surgical techniques, perioperative management and postoperative adjuvant therapy also contribute to reduce postoperative recurrence rate and prolong survival outcomes in patients with HCC and MVI. In our previous studies [10,11], we found that patients with preoperative diabetes and hypercoagulability was associated with poor long-term prognosis in patients with HCC and MVI. Anatomical resection combined with wide resection margin should be the recommended therapeutic strategy for HCC patients who are estimated preoperatively with a high risk of MVI [12], and postoperative adjuvant transarterial chemoembolization were associated with significantly better survival outcomes than liver resection alone in patients with HCC and MVI [13]. A recent multicenter, open-label, randomized, controlled, phase 2 trial demonstrated that sintilimab significantly prolonged recurrence-free survival compared to active surveillance in eligible patients with HCC with MVI [14]. Thus, increasing use of postoperative adjuvant therapy for HCC with high-risk recurrence in clinical practice should also be paid attention to.

In summary, the study by Hwang et al. is a great work focusing on classification of MVI in HCC and correlation with prognosis. It may be significant to developing robust tools and biomarkers for accurately predicting MVI and tumor early recurrence, and be performed postoperative adjuvant therapy to reduce recurrence rate and prolong survival outcomes.