Incidence of Extrahepatic Cancers Among Individuals With Chronic Hepatitis B or C Virus Infection

A Nationwide Cohort Study

Chai Yeong Hong; Dong Hyun Sinn; Danbee Kang; Seung Woon Paik; Eliseo Guallar; Juhee Cho; Geum-Youn Gwak


J Viral Hepat. 2020;27(9):896-903. 

In This Article

Abstract and Introduction


This study examined the association between chronic HBV or HCV infection and the risk of extrahepatic cancers. A total of 537 103 adults aged ≥20 years without history of cancer were identified from the Korean National Health Insurance Service-National Sample Cohort between 2003 and 2013. The difference in cancer incidence was compared between those with and without chronic HBV or HCV infection. During 3 854 130 person-years of follow-up (median follow-up: 8.0 years), 19 089 participants developed cancer. After adjusting for sex, body mass index, smoking, drinking, income percentile, residential area and comorbidities, hazard ratios (HRs) for incident extrahepatic cancer were significantly higher in participants with chronic HBV infection (HR: 1.27, 95% confidence interval [CI]: 1.20–1.35), HCV infection (HR: 1.31, 95% CI: 1.16–1.48) or HBV/HCV dual infection (HR: 1.41, 95% CI: 1.31–1.72) compared to participants without HBV or HCV infection. In chronic HBV infection, the cancer risk was higher for haematologic malignancy [HR (95% CI) = 2.46 (1.92–3.15)], gallbladder [1.55 (1.05–2.29)], pancreas [1.52 (1.07–2.15)], stomach [1.39 (1.22–1.58)], lung [1.27 (1.04–1.55)], colorectum [1.21 (1.03–1.42)] and thyroid cancer [1.20 (1.05–1.36)]. In chronic HCV infection, the cancer risk was higher for testis [10.34 (1.35–79.78)], gallbladder [2.90 (1.62–5.18)], prostate [2.51 (1.65–3.82)] and thyroid cancer [1.46 (1.10–1.93)]. In conclusion, chronic HBV or HCV infection was not only associated with an increased risk of liver cancer, but also associated with an increased risk of multiple extrahepatic cancers.


Viral hepatitis is a leading cause of death and disability worldwide, with increases in both absolute burden and relative rank.[1] Between 1990 and 2013, global death from viral hepatitis increased by 63%.[1] Hepatitis B virus (HBV) and hepatitis C virus (HCV) accounted for the majority of viral hepatitis-related mortality, with most mortality attributable to cirrhosis and liver cancer.[1,2] However, the burden of viral hepatitis may not be limited to liver.

In addition to hepatocellular carcinoma (HCC), several epidemiologic studies have revealed an association between HBV or HCV infection and the development of extrahepatic cancers such as pancreatic cancer, gallbladder and extrahepatic bile duct cancer, and non-Hodgkin's lymphoma.[3–7] However, the association between HBV or HCV infection and extrahepatic cancers varies among studies and, thus, is not very conclusive.[8] Large and comprehensive data on the incidence of extrahepatic cancers among patients with HBV or HCV infection are still lacking.

HBV and HCV are major causes of chronic liver disease in Korea.[9] Korea is an endemic area for HBV infection. In the 1990s, the prevalence of HBsAg positivity was 8–10% in Korea.[10] Due to several government programmes including universal HBV vaccination for newborns, a vertical transmission prevention programme and a mandatory surveillance system for acute hepatitis B cases, the prevalence of HBsAg positivity had decreased to 2.9% in 2013.[10] However, the prevalence of HBsAg positivity is still 4~6% in middle-aged men.[10] Anti-HCV prevalence in Korea was 0.6% in 2015.[11] Unlike in Western countries where HCV is prevalent in drug users, the prevalence of HCV infection in Korea is high in the elderly population.[12] Frequencies of a history of acupuncture, moxibustion and tattooing were high in patients with HCV infection.[12] Recent regional outbreaks of HCV infection related to unsafe healthcare injection have brought great concerns to increasing HCV infection in Korea.[13] In addition, malignancy is the most common cause of death in Korea, followed by cardiovascular diseases and respiratory diseases ( Thus, there is a crucial need to clarify the influence of HBV or HCV infection on the development of all types of malignancy including HCC and extrahepatic cancers. Therefore, the present study aimed to examine the association between chronic HBV or HCV infection and the risk of extrahepatic cancers.