Clinically Evident Portal Hypertension Is an Independent Risk Factor of Hepatocellular Carcinoma Recurrence Following Liver Transplantation

<b>Background/Objectives</b>: Clinically evident portal hypertension (CEPH) is a major risk factor for the development and poor outcomes of hepatocellular carcinoma (HCC). The aim of this study was to determine the impact of CEPH on the risk of HCC recurrence following liver transplantation (LT). <b>Methods</b>: A total of 129 HCC patients were included in this retrospective analysis. The definition of CEPH was based on indirect clinical features without hepatic venous pressure gradient measurement. The impact of CEPH on the post-LT risk of HCC recurrence was determined by uni- and multivariate analysis. <b>Results:</b> Evidence of manifest portal hypertension (PH) was associated with a higher ¹⁸F-fluorodeoxy-glucose (FDG) uptake of HCC on positron emission tomography (PET; <i>p</i> < 0.001) and increased serum levels of C-reactive protein (<i>p</i> = 0.008) and interleukin-6 (IL-6; <i>p</i> = 0.001). The cumulative risk of HCC recurrence at 5 years post-LT was significantly higher in the CEPH group (38.1% vs. 10.6%, <i>p</i> < 0.001). The eligibility for neoadjuvant transarterial chemoembolization (TACE) was comparable between both study cohorts (71.4% vs. 74.2%; <i>p</i> = 0.719). However, the post-interventional pathologic response rate was significantly lower in the case of PH (15.6% vs. 53.1%; <i>p</i> < 0.001). In addition to the Milan criteria (MC), ¹⁸F-FDG avidity on PET and serum values of IL-6 and alfa-fetoprotein, we identified CEPH as another significant and independent predictor of HCC recurrence (<i>p</i> = 0.008). <b>Conclusions</b>: CEPH correlates with an unfavorable tumor phenotype, TACE refractoriness and a risk of post-LT HCC recurrence. Therefore, the clinical features of PH should be implemented in pre-transplant risk assessment and decision-making processes.