Herpes and syphilis found to be important risk factors for women acquiring hepatitis B

The largest-ever study examining risk factors for acquiring hepatitis B virus (HBV) in women with, and at risk for, HIV infection, has found that infection with herpes simplex virus (HSV-2) and/or syphilis are important correlates of HBV infection. The results were published in the November 1^st issue of Clinical Infectious Diseases.

Liver disease has become a major cause of illness and death in people with HIV in recent years. Infection with hepatitis C, alcohol abuse and use of liver-toxic medications account for much of this, but there is also a role for hepatitis B infection. Few, if any, studies have explored the prevalence and predictors of HBV infection in a group of predominantly HIV-positive women, and so investigators analysed data from the US Women’s Interagency HIV Study (WIHS), which includes 3781 women; 2132 had data available for this study, of whom 1606 were HIV-positive and 526 were HIV-negative.

The study found that HIV-positive women had a higher prevalence of hepatitis B surface antigen, higher prevalence of natural immunity to HBV, higher prevalence of an isolated anti-HBc pattern and a lower prevalence of vaccine immunity compared with HIV-negative women. Of note, 37% of HIV-positive women with hepatitis B antibodies had an isolated anti-HBc pattern, which makes them more likely to have detectable HBV virus, leading to an increased risk of cirrhosis and a shorter survival time. The investigators were also concerned that over half of the HIV-positive women who remained uninfected with HBV had not been successfully vaccinated. This, they suggest, could be due to lack of access to routine HBV vaccination or the inability to develop an adequate immune response.

A number of statistically significant risk factors were found to be associated with evidence of HBV infection.

• Forty-three percent of HIV-positive women were found to have evidence of HBV infection, whereas evidence of HBV infection was found in 22% of HIV-negative women.
• Of the 593 women with hepatitis C (HCV) in the study, 442 (75%) were found to have evidence of HBV infection.
• Almost half (48%) of the women who stated that they had more than ten lifetime sexual partners were found to have evidence of HBV infection compared with 28% of those who said they had fewer than ten sexual partners in their lifetime.
• Women who were older, of black ethnicity and/or had a lower education level were more likely to have evidence of HBV infection.

The women were stratified into three groups according to their stated drug use. The IDU group (n=581) were women who had injected heroin, crack or cocaine; the non-IDU group (n=512) were women who had used heroin, crack or cocaine but not injected them; and the no drug use group (n=850) were women who reported that they didn’t use these hard drugs at all. Evidence of hepatitis B infection was significantly different in the three groups: 76% of the IDU group, 30% of the non-IDU group and 17% of the no drug use group were found to have evidence of HBV infection.

Multivariate analysis found that the following factors were associated with HBV infection:

• Evidence of herpes (HSV-2) infection was strongly associated with evidence of HBV infection in the IDU group, after adjustment for other factors.
• Syphilis was strongly associated with evidence of HBV infection in both non-IDU and no drug use groups.
• Other sexually transmitted infections (STIs) were not found to be associated with evidence of HBV infection. The authors note that genital ulcer-causing STIs are more likely to facilitate sexually transmission of, and infection with, both HIV and HBV.
• HIV and HCV infection were strongly correlated to HBV infection, especially in the IDU and no drug use groups.

The authors concede that despite the large numbers of women in this study, there are still some major limitations due to its cross-sectional design. In particular, the study was unable to distinguish whether infection with HIV, HBV and/or HVC occurred prior to, or after infection with these and/or the herpes virus or the Treponema pallidum bacteria that causes syphilis infection. Therefore no cause and effect can be established. However, since there appears to be a strong correlation between ulcer-causing STIs and HBV infection, “preventing sexual transmission of HBV should be a major focus for all high-risk groups,” they conclude, “and HBV vaccination should be routinely offered to those presenting with sexually transmitted disease, especially genital ulcer disease.”