International Journal of Infectious Diseases 65 (2017) 15–21
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Contribution of hepatitis B virus and hepatitis C virus to liver cancer in China north areas: Experience of the Chinese National Cancer Center Minjie Wang1, Yuting Wang1, Xiaoshuang Feng1, Ruijun Wang, Yanmei Wang, Hongmei Zeng, Jun Qi, Hong Zhao, Ni Li*** , Jianqiang Cai** , Chunfeng Qu* National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
A R T I C L E I N F O
A B S T R A C T
Article history: Received 7 July 2017 Received in revised form 7 September 2017 Accepted 8 September 2017 Corresponding Editor: Eskild Petersen, Aarhus, Denmark
Introduction: The aim of this study was to determine the impact of hepatitis B virus (HBV) and/or hepatitis C virus (HCV) on primary liver cancer (PLC) in China north areas. Methods: A total of 2172 histologically confirmed PLC patients attending the National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences during the period January 1, 2003 to December 31, 2014 were enrolled. Details of hepatitis B surface antigen (HBsAg), antibodies against HBV core antigen (anti-HBc), and antibodies against HCV (anti-HCV) status were recorded. Sequencing of the HBV PreS-S gene and the C/E1 and NS5B fragments of HCV was performed and the genotypes were analyzed for some of the patients with hepatocellular carcinoma (HCC). Results: Among the 2172 histologically confirmed PLC cases, 1823 (83.9%) had HCC and 238 (11.0%) had intrahepatic cholangiocarcinoma (iCCA). Among HCC cases, HBV infection alone, indicated by HBsAg-neg/pos + anti-HBc-pos, was found in 1567 (86.0%) cases; of these, 18.2% (331/1823) were HBsAg-neg + anti-HBc-pos. Serum HBV-DNA was detectable in 70% of HBsAg-neg + anti-HBc-pos HCC cases. The dominant HBV genotype was HBV-C2 (94.4%). HCV infection alone, indicated by anti-HCV-pos, was found in 2.5% (46/1823) of cases; HCV-1b (72.1%) was the dominant genotype. HBV + HCV co-infection markers were found in 6.7% (122/1823) of cases. Only 88 (4.8%) cases had no HBV and no HCV markers. Among the 238 iCCA cases, 54 (22.7%) were HBsAg-pos + anti-HBc-pos; none was anti-HCV-pos alone. Conclusions: HBV remains the major contributor to PLC in China north areas Individuals with occult HBV infection should not be ignored in liver cancer screening. © 2017 The Authors. Published by Elsevier Ltd on behalf of International Society for Infectious Diseases. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/bync-nd/4.0/).
Keywords: Hepatocellular carcinoma Intrahepatic cholangiocarcinoma Hepatitis B virus Hepatitis C virus Etiology Serum alpha-fetoprotein
Introduction Primary liver cancer (PLC) is the seventh most commonly diagnosed cancer, but the third leading cause of cancer death (Ferlay et al., 2013). Worldwide, hepatocellular carcinoma (HCC) represents the major histological type of PLC and likely accounts for 70–85% of cases; this is followed by intrahepatic
cholangiocarcinoma (iCCA), which accounts for approximately 10–25% of all hepatobiliary malignancies (Tyson and El-Serag, 2011). It has been estimated that approximately 80% of HCC worldwide is associated with chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections (El-Serag, 2012). Some studies have also found a relationship between iCCA and HBV or HCV (Ralphs and Khan, 2013), although their causal effects need to be
* Corresponding author at: State Key Lab of Molecular Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 17 Panjiayuan Nanli, Beijing 100021, China. ** Corresponding author at: Department of Hepatobiliary Surgery, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 17 Panjiayuan Nanli, Beijing 100021, China. *** Corresponding author at: Program Office for Cancer Screening in Urban China, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 17 Panjiayuan Nanli, Beijing 100021, China. E-mail addresses:
[email protected] (M. Wang),
[email protected] (Y. Wang),
[email protected] (X. Feng),
[email protected] (R. Wang),
[email protected] (Y. Wang),
[email protected] (H. Zeng),
[email protected] (J. Qi),
[email protected] (H. Zhao),
[email protected] (N. Li),
[email protected] (J. Cai),
[email protected] (C. Qu). 1 Minjie Wang, Yuting Wang, and Xiaoshuang Feng contributed equally to this work. http://dx.doi.org/10.1016/j.ijid.2017.09.003 1201-9712/© 2017 The Authors. Published by Elsevier Ltd on behalf of International Society for Infectious Diseases. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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confirmed. The contributions of HBV and HCV to PLC have been found to differ by area, mainly due to the varying prevalence of HBV and HCV in different populations (de Martel et al., 2015; El-Serag, 2012). High liver cancer incidence rates have been reported for East and Southeast Asia, including China, which largely reflect the elevated prevalence of HBV infection (McMahon, 2009; Poon et al., 2009). A meta-analysis that included 39 studies performed in China during the years 1954 to 2010, based on the seroprevalence of HBV surface antigen (HBsAg) and antibodies against HCV (antiHCV) in HCC patients, reported that about 70% of HCC was associated with HBV infection, 5% with HCV infection, and 6% with HBV + HCV co-infection. Up to 19% of HCC cases showed no relationship with HBV or HCV (de Martel et al., 2015). In the last decade, with the use of nucleic acid tests to detect HBV infection, a substantial proportion of HBsAg-negative HCC patients have been found to be serum HBV-DNA-positive (Chen et al., 2009; Fang et al., 2009; Reddy et al., 2013). Hence, determining the contribution of HBV infection on the basis of HBsAg positivity may have led to underestimations. To develop practical strategies for the control of PLC, it is important to understand the contributions of HBV and/or HCV to the development PLC in a particular population. HBV vaccination has been demonstrated to be efficacious in decreasing the prevalence of HBsAg and therefore to reduce the incidence of PLC in young adults in endemic areas (Chiang et al., 2013; Qu et al., 2014). Universal HBV vaccination has been implemented in China since 2002 (Sun et al., 2002), and HBsAg prevalence decreased to
