• hepatocellular carcinoma;
  • multiple primary malignancy;
  • second primary cancer



There has been no large-scale population-based study on the incidence and clinical manifestations of second primary cancer (SPC) after diagnosis of hepatocellular carcinoma (HCC).


This study aimed to evaluate the incidence and the risk factors of SPC following HCC diagnosis.


This study used data from the National Health Insurance Research Database of Taiwan to identify all HCC patients from 1 January 1997 to 31 December 2006. Cases of SPC were gathered using the ICD9-CM codes of 140–208.91. Standardized incidence ratios (SIRs) were conducted for incidence of SPC in HCC survivors. Competing-risks regression with adjustment of death was used to analyse the risk factors of SPC.


From 45 976 HCC patients, 749 (1.6%) developed SPC after 90 days of HCC diagnosis. Male HCC patients had higher risks of gastric, biliary, urinary bladder, kidney and haematological cancers compared to the general male population. Female patients had higher incidences of biliary tract, kidney and bone and soft tissue cancers. Older age and chronic kidney disease (CKD) were independent factors predicting SPC.


SPC in patients with HCC is not rare in Taiwan. Urinary bladder cancer and renal cancer are more specific SPC for HCC patients. Better surveillance strategies for SPC should be established for HCC survivors, especially in the elderly or those with CKD.