Extrahepatic Cancers in Patients With Chronic Hepatitis B or C Infections

Chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infection was associated with increased risk for liver cancer and an increased risk for multiple extrahepatic cancers, according to data published in the Journal of Viral Hepatitis.

Using a nationwide Korean cohort identified from the Korean National Health Insurance Service-National Sample Cohort between 2003 and 2013, investigators compared cancer incidence between patients with and without chronic HBV or HBC infection. In total, 537,103 adults aged ≥20 years without history of cancer were identified.

The study found that throughout 3,854,130 person-years of follow-up (median follow-up 8.0 years), 19,089 participants developed cancer. For liver cancer, the hazard ratio was remarkably higher in participants with chronic HBV infection (HR, 32.05; 95% CI, 28.42-36.14), chronic HCV infection (HR, 9.51; 95% CI, 7.15-12.65), or chronic HBV/HCV coinfection (HR, 46.14; 95% CI, 36.68-58.04) compared with people without such infection. After adjustments for sex, body mass index, smoking, drinking, income percentile, residential area and comorbidities were made, the HR for incident extrahepatic cancer was also significantly higher in patients with chronic HBV (HR, 1.27; 95% CI, 1.20-1.35), HCV (HR, 1.31; 95% CI, 1.16-1.48) or coinfection (HR, 1.41; 95% CI, 1.31-1.72).

Among patients with chronic HBV, the risk for hematologic malignancy (HR, 2.46; 95% CI, 1.92-3.15), and for cancer of the gallbladder (HR, 1.55; 95% CI, 1.05-2.29), pancreas (HR, 1.52; 95% CI, 1.07-2.15), stomach (HR, 1.39; 95% CI, 1.22-1.58), lung (HR, 1.27; 95%CI, 1.04-1.55), colorectum (HR, 1.21; 95% CI, 1.03-1.42) and thyroid (HR, 1.20; 95% CI, 1.05-1.36) was higher compared with patients without HBV.

Among patients with HCV infection, cancer risks were higher for testicular (HR, 10.34; 95% CI, 1.35-79.78), gallbladder (HR, 2.90; 95%CI, 1.62-5.18), prostate (HR, 2.51; 95% CI, 1.65-3.82) and thyroid cancer (HR, 1.46; 95% CI, 1.10-1.93).

The cohort data did not contain factors that may be related to the development of a specific type of cancer; this was one of several study limitations. The study also used the presence of any International Classification of Disease codes representing HBV infection during the study period to define infection. This assumes vertical transmission, which is a major mode of infection in Korea; however some patients may have been infected during adulthood and lacked detailed information. Because chronic viral hepatitis is a dynamic infection, different phases of infection may also affect risk for cancer development, therefore additional studies with detailed information on the phase of infection are needed. Furthermore, the use of claims data means it was possible that unscreened or undiagnosed individuals were missed and misclassified as uninfected. Finally, the small number of events for some cancers might reduce the studies statistical power but the large sample size and availability of data over time are notable study strengths.

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Overall, investigators concluded that HBV or HCV infection was not only associated with an increased risk for liver cancer, but also with increased risk for multiple extrahepatic cancers. Therefore, they recommended that physicians, “pay attention to the development of extrahepatic cancers as well as liver cancer in these patients.”


Hong CY, Sinn DH, Kang D, et al. Incidence of extrahepatic cancers among individuals with chronic hepatitis B or C virus infection: A nationwide cohort study [published online April 27 2020]. J Viral Hepat. doi:10.1111/jvh.13304