Impact of Liver Fibrosis Severity on Oncological Prognosis in Hepatocellular Carcinoma

Abstract

<b><i>Introduction:</i></b> Cirrhosis is deemed to be a contributing factor to the postoperative recurrence of hepatocellular carcinoma (HCC); however, the precise impact of liver fibrosis on both cancer-specific prognoses remains unclear. This investigation sought to elucidate the effect of liver fibrosis severity on the cancer-specific prognosis. <b><i>Methods:</i></b> A total of 524 consecutive patients were included. Recurrence-free survival (RFS) and disease-specific survival (DSS) were compared according to fibrosis stage. Moreover, postoperative outcomes were subjected to analysis in cohorts of patients with F0 and F1–3, as well as in those with F1–3 and F4, who were carefully matched for background factors. <b><i>Results:</i></b> The 5-year RFS exhibited a significantly worse outcome in the F4 group compared to other stages of fibrosis: 5-year RFS – F0 (46.6%), F1–3 (33.1%), and F4 (23.5%), <i>p</i> = 0.03 (F0 vs. F1–3) and <i>p</i> &lt; 0.01 (F1–3 vs. F4). Additionally, the 5-year DSS also presented a significantly worse prognosis in the F4 group: 5-year DSS – F0 (82.9%), F1–3 (73.6%), and F4 (57.4%), <i>p</i> = 0.04 (F0 vs. F1–3) and <i>p</i> &lt; 0.01 (F1–3 vs. F4). In multivariate analysis, fibrosis 1, 2, 3, and 4 stage (compared with F0) (HR: 1.70, 1.81, 1.89, and 3.99, 95% confidence interval: 1.10–1.99, 1.39–2.22, 1.41–2.55, and 2.25–5.01, <i>p</i> = 0.022, <i>p</i> = 0.008, <i>p</i> &lt; 0.001, and <i>p</i> &lt; 0.001, respectively) was independent risk factor for RFS. After matched analysis, both RFS and DSS exhibited significantly worse prognoses in the presence of more advanced fibrosis. There was a significantly higher incidence of multiple recurrences in the F4 group than the F1–3 group, and a number of recurrences were observed both in the same hepatic segment as the resected side and in the contralateral lobe in F4 group. <b><i>Discussion/Conclusion:</i></b> The hazard and recurrence pattern of HCC signifies that the prognosis could potentially be poor, as the hepatic fibrosis likely owing to a higher hepatocarcinogenic potential, even in the absence of progression to cirrhotic condition. The risk of de novo recurrence may also increase with the progression of this fibrosis.