Abstract
Introduction Evidence of biliary invasion as a prognostic factor in patients with hepatocellular carcinoma is unclear. We aimed to verify the significance of clinically diagnosed biliary involvement in patients with Barcelona Clinic Liver Cancer stage B-C (BCLC B-C) hepatocellular carcinoma. Methods The Korean Liver Cancer Study Group randomly extracted data of patients with hepatocellular carcinoma enrolled in the Korean Central Cancer Registry between 2011–2016 from approximately 50 hospitals nationwide. After excluding records without information regarding serum bilirubin level, alpha-fetoprotein level, and Child-Pugh class, a pre-propensity score matching cohort comprising 4077 patients was included. Considering age, sex, body mass index, viral cause, serum bilirubin level, alpha-fetoprotein level, Child-Pugh class, tumor size, multiplicity, portal invasion, and extrahepatic metastasis, patients with and without bile duct invasion at initial imaging diagnosis were matched at a ratio of 1:2 from the pre- propensity score matching cohort to form a matched cohort (propensity score matching cohort). Results The pre-propensity score matching cohort included 4077 patients with BCLC B-C and 165 (4.0%) with biliary invasion at diagnosis. Regarding biliary invasion at diagnosis, one- and two-year overall survival rates were 41.2% and 29.1% (with invasion) and 54% and 40.9% (without invasion), respectively (p<0.0001). Corresponding cancer-specific survival rates at one and two years were 43.4% and 30.7% (with invasion) and 56.6% and 44% (without invasion), respectively (p<0.0001). Although biliary invasion was a significant factor affecting overall and cancer-specific survival rates in a univariate analysis, it was not statistically significant in multivariate analyses for overall (p=0.153) and cancer-specific (p=0.198) survival rates. The propensity score matching cohort included 165 patients with biliary invasion at diagnosis and 330 without biliary invasion. In the propensity score matching cohort, biliary invasion at diagnosis was not a significant factor affecting overall (p=0.603) or cancer-specific (p=0.960) survival rates in the univariate analyses. One- and two-year overall survival were 41.2% and 29.1% (with invasion) and 36.1% and 28.2% (without invasion), respectively. The corresponding cancer-specific survival at one and two years were 43.4% and 30.7% (with invasion) and 39.8% and 31.4% (without invasion), respectively. Multivariate analyses revealed that alpha-fetoprotein levels, Child-Pugh class, tumor singularity, tumor size, portal invasion, lymph node metastases, and distant metastases significantly affected both overall and cancer-specific survival rates. Conclusion Biliary invasion at diagnosis in patients with BCLC B-C does not affect overall or cancer-specific survival rates; however, other prognostic factors associated with biliary invasion could have a greater impact.