Multiple Pregnancies May Reduce the Risk of Liver Cancer Among Women with Hepatitis B Virus (web article)

Women with Hepatitis B Virus (HBV) infection who experience multiple pregnancies have a reduced risk of developing hepatocellular carcinoma, according to a study led by researchers at the Johns Hopkins Bloomberg School of Public Health. Researchers evaluated the incidence and risk factors for hepatocellular carcinoma among pregnant women in Taiwan who were screened for HBV infection to prevent transmission of the virus to their infants.  They found that markers of active HBC viral replication were associated with a greater risk of later developing hepatocellular carcinoma than those who had inactive chronic HBV infection. The results are published in the July 15, 2009, issue of the Journal of the National Cancer Institute.

“Previous studies have primarily focused on the relationship between HBV and hepatocellular carcinoma in men, since the rate of hepatocellular carcinoma among men infected with HBV is 2 to 6 times higher than among HBV-infected women. This is the largest published study that examines the association of HBV infection with liver cancer among women,” said Kenrad Nelson, MD, author of the study and professor with the Bloomberg School’s Department of Epidemiology. “Although chronic HBV- infected women are at increased risk of developing hepatocellular carcinoma, we found that the more pregnancies an HBV-infected woman experienced, the lower her risk of developing liver cancer within the next 12 years. Thus leading us to question of whether estrogen and progesterone secretion during pregnancy may have provided some protection from HBV-induced liver cancer. These data help explain why the rates of hepatocellular carcinoma have been significantly higher among men than women in every population that has been studied.”

Nelson, along with colleagues from the Bloomberg School of Public Health, Academia Sinica, the National Taiwan University and the Centers for Disease Control of Taiwan, used data from four population based registries and examined information about pregnant women who were tested for hepatitis B surface antigen and e antigen between 1983 and 2000 and subsequent diagnoses of hepatocellular carcinoma. Researchers found that risk for hepatocellular carcinoma during follow-up was statistically significantly higher among pregnant women with chronic, active or persistent HBC infections or who underwent hepatitis B surface antigen seroclearance, than among HBV-unexposed women. Risk decreased as parity increased, independent of hepatitis B surface antigen status and age.  

Hepatocellular carcinoma is the most common form of liver cancer in adults that stems from the major cell type of the liver, hepatocytes. Hepatocellular carcinoma is not as common in the U.S. as it is in Asia, however it has increased significantly in the U.S. during the past two decades. The recent increased incidence is thought to be related to an increased number of persons with chronic infections with hepatitis C and B viruses. Worldwide, liver cancer is a leading cause of cancer death, especially among men, and is especially prevalent in parts of Asia and Africa where chronic HBV infections that have been acquired at birth or in early childhood are common.

“Although women who were persistently hepatitis B surface antigen-positive had an approximately threefold increase in hepatocellular carcinoma risk compared with those who cleared hepatitis B surface antigen, the loss of hepatitis B surface antigen was still associated with an approximately eightfold increased risk for hepatocellular carcinoma compared with those with no evidence for chronic HBV infection. This suggests that the initiation of cacinogenesis by HBV may proceed independent of the degree of activity of the HBV infection in many persons with chronic HBV infection,” said lead author and Bloomberg School graduate Chyng-Wen Fwu, PhD.

“Hepatitis B Virus Infection and Hepatocellular Carcinoma Among Parous Taiwanese Women: Nationwide Cohort Study” was written by Chyng-Wen Fwu, Yin-Chu Chien, Gregory D. Kirk, Kenrad E. Nelson, San-Lin You, Hsu-Sung Kuo, Manning Feinleib and Chien-Jen Chen.

The research was supported in part by the Department of Health, Executive Yuan, Taiwan.