Metastasis in Patients With Hepatocellular Carcinoma

Prevalence, Determinants, Prognostic Impact and Ability to Improve the Barcelona Clinic Liver Cancer System

Chia-Yang Hsu; Po-Hong Liu; Shu-Yein Ho; Yi-Hsiang Huang; Yun-Hsuan Lee; Rheun-Chuan Lee; Teddy S. Nagaria; Ming-Chih Hou; Teh-Ia Huo


Liver International. 2018;38(10):1803-1811. 

In This Article

Patients and Methods


During a 14-year period between 2002 and 2016, 3414 newly diagnosed HCC patients in Taipei Veterans General Hospital, Taiwan, were prospectively identified and retrospectively analysed. Underlying liver diseases, number and size of tumor(s), cirrhosis, serum biochemistry and PS were comprehensively documented at the time of diagnosis. The survival status was reviewed every 3-4 months and was confirmed by using the database of National Cancer Registry, Taiwan. This study complies with current ethical guidelines and has been approved by the institutional review board (IRB) of Taipei Veterans General Hospital, Taiwan. The waiver of consent was obtained as justified by the IRB committee, and patient records/information was anonymized and de-identified before analysis.

Diagnosis and Definitions

Findings of typical radiological features in at least 2 imaging modalities including magnetic resonance imaging (MRI), contrast-enhanced dynamic computed tomography (CT), ultrasound and hepatic arterial angiography or by a single positive imaging study associated with serum α-foetoprotein (AFP) level ≥400 ng/mL or histological confirmation were used to diagnose HCC as described previously.[1,10,11] Hepatitis B and C were diagnosed with positive hepatitis B surface antigen and anti-hepatitis C antibody respectively. Daily consumption of 40 g of alcohol for 5 years or more was considered alcoholic liver disease.[12] The presence of thrombus adjacent to the tumour in the portal system by at least 2 imaging modalities confirmed vascular invasion. Metastatic lymph nodes were diagnosed by radiographic evidence of enlarged nodes (>1 cm) or histological confirmation. Total tumour volume (TTV) is a marker of tumour burden and was calculated based on tumour diameter of every HCC nodule as previously reported.[13] The Eastern Cooperative Oncology Group (ECOG) PS criteria were used to evaluate the overall physical status.[14] The estimated glomerular filtration rate (eGFR) was calculated with the Modification of Diet in Renal Disease (MDRD) equation.[15] Chest CT scan was performed to detect metastatic lesion(s) and lymph node involvement. Other metastatic lesions were surveyed and confirmed by bone scan, positron emission tomography or MRI if indicated. All clinical data analysed in this study were recorded at the time of diagnosis.


Continuous characteristics were compared with the Mann-Whitney ranked sum test. Categorical data were compared with the Chi-squared or Fisher exact tests. The comparison of survival distributions was performed by using the Kaplan-Meier method with a log-rank test. All associated clinical and pathological variables were examined by the univariate survival analysis. Variables with a significant survival difference were introduced into the multivariate Cox proportional regression model to calculate hazard ratios (HR) and confidence intervals (CI). The prognostic accuracy of modified and original BCLC systems was compared by using Akaike information criterion (AIC). A P value less than .05 was considered statistically significant. All statistical analyses were conducted with the SPSS 21 software (SPSS Inc., Chicago, IL, USA).