Epidemiology of cholangiocarcinoma: an update focusing on risk factors

Abstract

Cholangiocarcinoma is relatively rare, but high incidence rates have been reported in Eastern Asia, especially in Thailand. The etiology of this cancer of the bile ducts appears to be mostly due to specific infectious agents. In 2009, infections with the liver flukes, Clonorchis sinensis or Opistorchis viverrini, were both classified as carcinogenic to humans by the International Agency for Research on Cancer for cholangiocarcinoma. In addition, a possible association between chronic infection with hepatitis B and C viruses and cholangiocarcinoma was also noted. The meta-analysis of published literature revealed the summary relative risks of infection with liver fluke (both Opistorchis viverrini and Clonorchis sinensis), hepatitis B virus, and hepatitis C virus to be 4.8 (95% confidence interval [95% CI]: 2.8-8.4), 2.6 (95% CI: 1.5-4.6), and 1.8 (95% CI: 1.4-2.4), respectively - liver fluke infection being the strongest risk factor for cholangiocarcinoma. Countries where human liver fluke infection is endemic include China, Korea, Vietnam, Laos, and Cambodia. The number of infected persons with Clonorchis sinensis in China has been estimated at 12.5 million with considerable variations among different regions. A significant regional variation in Opistorchis viverrini prevalence was also noted in Thailand (average 9.6% or 6 million people). The implementation of a more intensive preventive and therapeutic program for liver fluke infection may reduce incidence rates of cholangiocarcinoma in endemic areas. Recently, advances have been made in the diagnosis and management of cholangiocarcinoma. Although progress on cholangiocarcinoma prevention and treatment has been steady, more studies related to classification and risk factors will be helpful to develop an advanced strategy to cure and prevent cholangiocarcinoma.

Figure 1

Test for heterogeneity: Q = 27.163 on 9 degrees of freedom (P = 0.001). Moment‐based estimate of between‐studies variance = 0.481. 95% CI, 95% confidence interval.
 Risk estimates for cholangiocarcinoma according to Clonorchis sinensis or Opisthorchis viverrini infection.

Figure 2

Test for heterogeneity: Q = 40.722 on 9 degrees of freedom (P = 0.000). Moment‐based estimate of between‐studies variance = 0.498. 95% CI, 95% confidence interval.
 Risk estimates for cholangiocarcinoma according to hepatitis B virus (HBV) infection (overall).

Figure 3

Test for heterogeneity: Q = 17.296 on 10 degrees of freedom (P = 0.068). Moment‐based estimate of between‐studies variance = 0.188.
 Risk estimates for cholangiocarcinoma according to hepatitis C virus (HCV) infection (overall).