Predicting Microvascular Invasion in Liver Transplant Recipients for Hepatocellular Carcinoma

Background: Among primary liver tumors, hepatocellular carcinoma (HCC) is considered the most common hepatic tumor. Liver transplantation is one of the curative treatment options for HCC. However, the risk of HCC recurrence after liver transplantation varies and is influenced by various factors. Microvascular invasion (MVI) is a major factor associated with HCC recurrence after a liver transplant (LT). The study assessed the pre-transplant factors to predict MVI on explant liver specimens.

Methods: The retrospective study included adult LT recipients with HCC on explant specimens to identify pre-transplant predictors of MVI. Univariate analyses, including Mann-Whitney U tests and chi-square tests, were conducted to assess associations between variables and MVI. Logistic regression was employed for multivariate analysis, including variables significant in univariate analysis. Pearson or Spearman correlation coefficients were calculated to examine correlations between continuous variables. Cohen's kappa coefficient was used to measure inter-rater reliability.

Results: Out of 523 LT recipients, 136 (26%) were diagnosed with HCC based on pre-transplant imaging and histopathological analysis of the explanted liver. Descriptive data showed an average age of 54.06 ± 8.16 years (range: 15-70), with a majority being male (76.47%). Hepatitis C (HCV) was the leading etiology (72.8%). Most patients had moderately differentiated grade-II tumors (75.7%) and met the Milan criteria (74.3%). Mean pre-operative alpha-fetoprotein (pre-op AFP) levels were 104.42 ± 308.38 ng/ml. 74.3% were within the Milan criteria. MVI was present in 28.7%. The frequency of MVI among HCCs within vs. outside Milan criteria was not statistically significant (26.73% vs. 34.28% (p = 0.395)). Univariate analysis revealed that pre-op AFP levels (p = 0.001), Child-Turcotte Pugh class (p=0.05), and body mass index (p=0.02) were significantly associated with MVI. Multivariate logistic regression analysis showed that pre-op AFP was the only independent predictor of MVI (OR: 1.006, 95% CI: 1.003-1.008, p < 0.001).

Conclusion: This study not only reinforces the clinical significance of pre-op AFP levels as a simple pre-transplant predictor of MVI in patients with HCC but also advocates for the safety of liver transplantation beyond conventional Milan criteria, promoting extended LT protocols.