Hepatitis A Among Homosexual Men and Injection Drug Users: More Evidence for Vaccination

As agencies develop guidelines for administering the newly developed hepatitis A virus (HAV) vaccine, information is needed regarding the occurrence of HAV infection in groups putatively at risk for the infection. We tested serum samples from 300 injection drug users (IDUs), 300 homosexual males, and 300 blood donors for the presence of total antibody to HAV (anti-HA V). Anti-HAV was detected in 66% of IDUs, 32% of homosexual males, and 14% of blood donors. Anti-HAV was not significantly associated (P > .10) with high-risk drug-using behaviors but was more prevalent among IDUs with annual incomes of <$5,000 (P = .018). The occurrence of anti-HAV increased among homosexual males as the number of sexual partners increased (P < .001) but was similar to the age-adjusted prevalence (30.6%) estimated for the general United States population. IDUs are at increased risk for HAV infection; however, our data suggest that factors related to low socioeconomic status contribute more to the occurrence of HAV infection among IDUs than does injection drug use. IDUs and persons at risk for injection drug use should receive HAV vaccine.

Hepatitis A virus (HAV) is the leading cause of acute viral hepatitis in the United States; HA V infection results in significant morbidity and annual economic losses that exceed $200,000,000 [1]. HAV is a nonenveloped RNA virus that is excreted in stool and is primarily transmitted by fecal-oral contact.

Several outbreaks of HAV infection have occurred among homosexual males, especially those who have acknowledged high-risk sexual practices such as oral-anal intercourse [2, 3]. However, with increased adherence to safer sexual practices, the risk for HAV infection among homosexual males may have declined. Hepatitis A outbreaks have also been reported among injection drug users (IDUs) [4], and during the mid-1980s, drug use contributed to > 20% of acute hepatitis A cases reported to the Centers for Disease Control and Prevention (CDC) [5]. Although blood-borne transmission of HAV occurs, the increased risk for HAV infection among IDUs may be due to factors other than parenteral transmission.

Safe and effective vaccines for preventing HAV infection have recently been licensed for use in the United States [6]. As agencies formulate recommendations for vaccine use, more information is needed to project the anticipated benefit of immunizing putative risk groups such as homosexual men and IDUs.

Patients and Methods

Cohorts of IDUs and homosexual men have been followed up at The Johns Hopkins University School of Hygiene and Public Health (Baltimore) in two distinct studies of the natural history of HIV. The IDUs were enrolled in the AIDS Link to Intravenous Experiences (ALIVE) study [7], and the homosexual men participated in the Baltimore arm of the Multicenter AIDS Cohort Study (MACS) [8]. Demographic and risk factor information was collected via questionnaires administered on enrollment and during semiannual visits, at which time serum samples were obtained and stored at -70°C. One hundred fifty HIV -seropositive participants and 150 HIV -seronegative participants were randomly selected from each cohort, and, when available, serum samples that were collected on visits during the years 1993-1994 were obtained. Contemporary specimens from 300 consecutive blood donors at the New York Blood Center (New York) were also tested without identifying information.

All samples were tested for total antibodies to HAV (anti- HAV) by using a commercially available assay (Abbott Laboratories, Chicago). For the 600 participants in research protocols, sexual and drug-use factors were considered as possible correlates of HAV infection. After frequency distributions were examined, continuous variates were categorized into quartiles. The X2 test or Fisher's exact test was used to evaluate the significance of associations.

Results

Anti-HAV was found in 95 (32.3%) of 294 homosexual men, 194 (66.4%) of 292 IDUs, and 41 (13.7%) of 300 blood donors. The HAV infection rates were then age-adjusted according to the 1980 population distribution, for which an HAV prevalence of 30.6% had been calculated with use of data from the Third National Health and Nutrition Examination Survey (Craig Shapiro, personal communication). In the present study, the age-adjusted anti-HAV prevalences were 27.3% for homosexual men and 67.6% for IDUs.

Homosexual men. Anti-HAV-positive homosexual men were older (P = .001), more likely to have a history of hepatitis (P < .001), and reported more sexual partners (P = .001) than anti-HAV-negative homosexual men. HAV-seropositive homosexual males also more frequently had serological evidence of infection with hepatitis B (P < .001), syphilis (P = .02), and HIV (P = .022). Anti-HAV status was not correlated with race, income, or smoking history (P > .10).

IDUs. Anti-HAV was more prevalent among IDUs with an annual legal income of <$5,000 (P = .018). However, the presence of anti-HAV did not correlate with a history of hepatitis or transfusions, the number of sexual partners, or a history of a sexually transmitted disease (P > .10). We found no association between anti-HAV status and any specific drug-use practice, including the duration of injection drug use, the frequency of injection drug use, the sharing of needles, or injecting at a shooting gallery (P > .10). Similarly, exposure to HAV did not correlate with serological evidence of hepatitis B, hepatitis C, syphilis, or HIV infection (P > .05).

Discussion

HAV transmission through transfusion of blood products has been well documented [9]. In addition, the infectivity of HAV suspensions in a primate model was markedly higher after percutaneous injection than after oral inoculation [10]. These factors and the viremia that occurs during HAV infection (albeit brief) make it plausible that the high frequency of anti-HAV found among IDUs is due to the use of needles contaminated with HAV-tainted blood. However, the results of the present study do not support this hypothesis. We found no correlation between the presence of anti-HAV and the duration of drug use or high-risk drug-use practices. Moreover, the presence of anti-HAV was not correlated with hepatitis B or hepatitis C infections, both of which are associated with such practices. Thus, for this cohort of IDUs, there was no evidence that percutaneous injecting of drugs contributed substantially to the high prevalence of anti-HAV.

An alternative explanation for the high prevalence of anti-HAV among IDUs is the increased occurrence of direct person-to-person transmission, which is related to factors such as crowding and poor hygiene [4]. Although there was no direct evidence, the higher prevalence of anti-HAV among IDUs in this study who had annual incomes of <$5,000 suggests that low socioeconomic status may play an important role. Additional studies are needed to characterize the magnitude of the risk of HAV infection among non-drug-using inner-city residents of low socioeconomic status and to project the benefit of vaccination in this setting.

The high rate of HAV infection observed in this study suggests that IDUs are an important reservoir of HAV infection. HAV infection is also more severe in persons with chronic hepatitis, which has been found in >80% of the IDUs in this cohort [11, 12]. Thus, HAV vaccination of IDUs and persons at risk for illicit drug use is indicated to protect the vaccinee from a potentially fatal condition and to reduce HAV transmission in the general population.

We found that homosexual males with greater numbers of sexual partners and serological evidence of other sexually transmitted diseases were more likely to have HAV infection, suggesting that sexual transmission of HAV did occur. However, the overall prevalence of anti-HAV among this cohort of homosexual males was similar to the prevalence that the CDC has projected for the general United States population. Similarly, although studies of HAV infection in homosexual men have revealed anti-HAV rates ranging from 30% to 43.4% [13], the prevalence of anti-HAV was not higher among these men than among heterosexual controls. Thus, while male homosexual HAV transmission appears to occur, in some settings the frequency may be low.

In summary, we found that the risk of HAV infection was markedly increased among IDUs in Baltimore, which emphasizes the importance of providing the HAV vaccine to this population. More studies are needed to demonstrate conclusively the routes of HAV transmission among IDUs, the usefulness of screening for anti-HAV before vaccination, and the cost-benefit of specific approaches to vaccination. We also noted indirect evidence of homosexual transmission of HAV infection. However, it remains to be proven that the risk of HAV infection for most homosexual males is substantially greater than that for the general population.

Acknowledgment

The authors thank Cladd Stevens for generously providing anonymous specimens from blood donors at the New York Blood Center.

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From the Division of Infectious Diseases, Johns Hopkins School of Medicine, and the Department of Epidemiology, Johns Hopkins School of Hygiene and Public Health, Baltimore; and the Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.

Grant support. This study was supported in part by the U.S. Public Health Service (DA-04334, DA-05911, UOI-AI-35042, 5-MOI-RR-OO722, and DA- 023201)