Aims: The intent of this analysis is to assess clinico-pathologic and prognostic characteristics of HCC in patients with minimal liver fibrosis (Ishak stage 1-2) after primary surgical liver resection as compared to patients with moderate to severe fibrosis (Ishak stage 3-6) in order to improve screening and treatment of HCC.
Methods: Data were obtained from 200 patients with HBV-related HCC who underwent primary surgical liver resection at a single North American medical institution between 1988 and 2012. A dedicated liver pathologist performed fibrosis staging for each resection specimen using the modified Ishak method. Univariate and multivariate analyses of clinico-pathologic variables were performed to determine those associated with prognosis.
Results: Twenty-two percent of patients had minimal fibrosis defined as Ishak stage 1 or 2. Kaplan-Meier analysis of 5-year survival showed a non-significant trend toward better outcome among Ishak 1-2 patients compared to Ishak 3-6 (p = 0.09). Ishak 1-2 was associated with lower hazard of death compared to Ishak 3-6 (adjusted HR = 0.38, 95% CI = 0.15-0.99). Ishak 1-2 retained statistical significance after multivariate analysis for overall survival (p = 0.05), but not recurrence-free survival.
Conclusions: A significant proportion of HBV-HCC cases arise in the minimally fibrotic liver. Patients with Ishak 1-2 fibrosis have better overall survival compared to those with Ishak 3-6, indicating that minimally fibrotic patients should be treated as a separate cohort. There is a need to better understand the mechanisms underlying hepatocarcinogenesis and to formulate unique diagnostic and therapeutic algorithms for minimally fibrotic HCC patients.
Keywords: Cirrhosis; HBV; HCC; Ishak fibrosis stage; Liver resection.
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