The impact of chronic hepatitis B infection, antiviral treatment and HIV coinfection on the occurrence of cancer outcomes among U.S. veterans: A retrospective cohort study

Hepatitis B infection is one of the most common viral infections. It is estimated that more than 2 billion people or one third of the world’s population have been infected with hepatitis B virus (HBV). There are around 240 million HBV chronic infected carriers worldwide with more than 780,000 deaths occurring every year. In the United States, there is estimated 12 million infected with HBV and around 1 million are chronically infected. Chronic hepatitis B infection (CHB) is the leading risk factor for liver cirrhosis and hepatocellular carcinoma (HCC). Besides liver-related outcomes, studies suggest that CHB infection is also associated with increased risk of pancreatic cancer, kidney cancer, bile duct cancer, and non-Hodgkin lymphoma. By utilizing automated clinical data from the U.S. Department of Veteran Affairs (VA), which comprises more than 120 medical facilities and serves 5.5 million veterans around the country, my goal is to examine the impact of CHB, antiviral treatment and HIV coinfection on the occurrence of cancer outcomes in the U.S. veteran population. The specific aims are: 1. To compare the incidence rates of HCC, pancreatic cancer, kidney cancer, bile duct cancer, and non-Hodgkin lymphoma between CHB infected patients in the VA and the U.S. general population in Surveillance, Epidemiology, and End Results Program (SEER) regions; 2. To determine the effect of nucleotide analogues on risk of HCC, pancreatic cancer, kidney cancer, bile duct cancer, and non-Hodgkin lymphoma in chronic hepatitis B infected patients eligible for treatment and 3. To determine the effect of HIV coinfection on the risk of developing HBV-related malignancies (HCC, pancreatic cancer, kidney cancer and bile duct cancer and non-Hodgkin lymphoma) in HBV/HIV coinfected patients compared with HBV monoinfected patients. Overall, we found non-Asian CHB patients in VA population had significantly more incident cancer cases (SIR 2.30) than the general population of SEER region regardless of cancer categories except for female breast cancer. Our study also demonstrated that the newer generation of NA has a significant effect on prolonging chronic HBV patient overall survival. However, we did not observe that new NA had a significant protective effect against the risk for getting cancers. As for the effect of HIV/HBV coinfection, we found HIV coinfection is related to reduced overall survival and, therefore, reduced chance of developing cancer because their mean duration to cancer is longer than their mean duration of survival. This study not only helps us to understand the natural history of CHB and additional effects of HIV coinfection on cancer outcomes in a U.S. population but also provides insights into future treatment and control of HBV chronic infection and its associated cancers