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Hepatitis Viruses and Liver Cancer

Hepatocellular carcinoma (HCC) is the third leading cause of cancer mortality worldwide; most cases result from chronic hepatitis virus infection. To address scientific questions concerning these infections, DCEG investigators conduct interdisciplinary collaborative studies that integrate epidemiology, virology and human genetics. One such effort led to the discovery of the interferon lambda 4 (IFNL4) gene [1]. The IFNL4 genotype plays a key role in hepatitis C virus (HCV) infection, as well as in other conditions (IFNL4 Phenotypes Research Area). Investigators in the Infections and Immunoepidemiology Branch (IIB) attempt to translate our scientific findings for clinical and public health benefits. Currently, they are examining the role of IFNL4 genotype in response to treatment with highly effective, but costly, direct-acting antiviral agents for treatment of HCV.

Hepatitis D virus (HDV) is the most pathogenic hepatitis virus and it requires hepatitis B virus (HBV) for its life cycle. Compared to individuals infected with HBV alone, HBV/HDV coinfected people have an even higher incidence of HCC. New therapeutic agents are in clinical trials for treatment of chronic hepatitis D, therefore, studies of HDV infection are timely. IIB investigators conduct studies of HDV infection in the United States [2] and Africa [3].

Both host genetics and HBV genetics play a role in the development of liver cancer related to HBV. IIB investigators perform genome-to-genome analysis to understand the impact of the human immune system on HBV and its associated outcomes.

In addition to these activities, IIB investigators conduct surveillance studies of the effect of hepatitis virus infection on HCC rates in the United States.

For more information, contact Thomas O’Brien and Zhiwei Liu.
Infections and Immunoepidemiology Branch - Research Areas


  1. Prokunina-Olsson L, Muchmore B, Tang W, et al. A variant upstream of IFNL3 (IL28B) creating a new interferon gene IFNL4 is associated with impaired clearance of hepatitis C virus. Nat Genet 2013 Feb; doi: 10.1038/ng.2521. Epub 2013 Jan 6.
  2. Mahale P, Aka PV,2, Chen X, et al. Hepatitis D viremia among injection drug users in San Francisco. J Infect Dis 2018 May 25; doi: 10.1093/infdis/jiy157.
  3. Mahale, P, P Aka, X Chen, et al. Hepatitis D virus infection and hepatocellular carcinoma in The Gambia. J Viral Hepat 2019 Jan 20. doi: 10.1111/jvh.13065. Epub ahead of print.