A Systematic Review of Microvascular Invasion in Hepatocellular Carcinoma: Diagnostic and Prognostic Variability

Abstract

Selected patients with hepatocellular carcinoma are candidates to receive potentially curative treatments, such as hepatic resection or liver transplantation, but nevertheless there is a high risk of tumor recurrence. Microvascular invasion is a histological feature of hepatocellular carcinoma related to aggressive biological behavior. We systematically reviewed 20 observational studies that addressed the prognostic impact of microvascular invasion, either after liver transplantation or resection. Outcomes were disease-free survival and overall survival. In liver transplantation, the presence of microvascular invasion shortened disease-free survival at 3 years (relative risk (RR)=3.41 [2.05-5.7]; five studies, n=651) and overall survival both at 3 years (RR=2.41 [1.72-3.37]; five studies, n=1,938) and 5 years (RR=2.29 [1.85-2.83]; six studies, n=2,003). After liver resection, microvascular invasion impacted disease-free survival at 3 and 5 years (RR=1.82 [1.61-2.07] and RR=1.51 [1.29-1.77]; four studies, n=1,501 for both comparisons). However inter/intraobserver variability in reporting and the lack of definition and grading of microvascular invasion has led to great heterogeneity in evaluating this histological feature in hepatocellular carcinoma. Thus, there is an urgent need to clarify this issue, because determining prognosis and response to therapy have become important in the current management of hepatocellular carcinoma. In this systematic review, we summarize the diagnostic and prognostic data concerning microvascular invasion in hepatocellular carcinoma and present a basis for consensus on its definition.

Predictors of Recurrence in Hepatitis C Virus Related Hepatocellular Carcinoma after Hepatic Resection: A Retrospective Cohort Study

“…In our study, AFP was a significant predictor of HCC recurrence; similar to other studies evaluating HCV related HCCs [3,21] and hepatitis B virus (HBV) related HCCs [13,22]. Hepatocellular carcinoma (HCC) is characterized by its high affinity for vascular invasion (microvascular or microvascular invasion), which indicates aggressive biological manner of the tumour and is currently one of the most grave predictors of HCC recurrence [23]. The presence of vascular invasion is a reported risk factor for HCC recurrence after hepatic resection for both HCV related HCCs [3,24] and HBV related HCCs [10,13,19].…”

Strategies to improve outcome of patients with hepatocellular carcinoma receiving a liver transplantation

“…Thus mVI is a critical hallmark in HCC progression, and the strongest prognostic factor as demonstrated in a metaanalysis of observational studies (RR = 3.41 for tumour recurrence and RR = 2.41 for mortality at 3 years) [17] . However the diagnosis of mVI has proven to be difficult even for experienced pathologists with the whole HCC specimen [33] .…”

“…The tumour was evaluated in the explanted liver rather than by using radiological techniques, and a certain grade of disagreement between both approaches is expected in clinical practice. Most importantly, the favorable outcome showed by patients within the up-toseven criteria was only present after excluding patients with microvascular invasion, which cannot be assessed pre-LT [17] . Thus the up-to-seven criteria cannot be considered a safe approach to expand Milan criteria.…”

Guidelines for Diagnosis and Treatment of Primary Liver Cancer in China (2017 Edition)

“…The simple Scheuer score system and Chinese Criteria for Histological Grading and Staging of Chronic Virus Hepatitis [29, 30] should also be used. MVI refers to the presence of cancer cell clusters in the blood vessels lined with endothelial cells, which are most pronounced in the branch of portal vein (including the intracapsular blood vessels) under microscopic observation [31] (evidence level 1). MVI is an important factor for the evaluation of invasiveness and recurrence risk of liver cancer and for the selection of treatment plan; it should be used as a routine parameter for pathological examination [32-34] (evidence level 2).…”