ArticlesHIV-1, hepatitis B virus, and risk of liver-related mortality in the Multicenter Cohort Study (MACS)
Introduction
Coinfection with hepatitis B virus (HBV) and HIV-1 is common, because of shared modes of transmission.1 However, liver-related mortality in individuals with chronic hepatitis B and HIV-1 infection is not well characterised.
More than 95% of adults spontaneously recover from an acute HBV infection,2 an outcome that is defined by clearance of the hepatitis B surface antigen (HBsAg) from blood. Those persistently infected with HBV are at increased risk of development of cirrhosis and hepatocellular carcinoma over the ensuing decades.3, 4 HIV-1 causes multidimensional immunosuppression, associated with reduced frequency of spontaneous recovery from HBV infection.5, 6 The effect of HIV-1 infection on those infected with HBV is not well understood. Results of some studies7 suggest that the progression of liver disease is diminished, which might be expected since the pathogenesis of hepatitis B is believed to be immunologically mediated.8 Findings of other studies, however, suggest that progression of liver disease is increased,5, 9 as is the case for hepatitis C virus (HCV).10, 11
The effect of HIV-1 infection on the natural history of hepatitis B could also be modified by highly active antiretroviral therapy (HAART), which has increased the life expectancy of people infected with HIV-1 and decreased the incidence of AIDS.12 Since the introduction of HAART, the proportion of deaths attributable to liver disease has risen.13, 14 A longer life expectancy might allow greater time for cirrhosis to develop, and both HAART-associated liver toxicity15 and immune restoration16, 17 could accelerate liver damage. Studies on people coinfected with HIV-1 and HBV have been limited by small size, cross-sectional design, confounding with HCV, or selection bias of a referral clinic population, which sees more severe cases.5, 9, 18, 19, 20 Our aim was to investigate the inter-relation of HIV-1 and HBV infection with liver-related mortality.
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Participants
We prospectively recruited men who reported having had sex with men into the Multicenter AIDS Cohort Study (MACS) from four metropolitan areas in the USA (Baltimore, MD; Chicago, IL; Pittsburgh, PA; and Los Angeles, CA) between April, 1984, and March, 1985, and during a second recruitment period designed to increase minority representation in the cohort between 1987 and 1991.21, 22 We included all men who had been tested for HBsAg and hepatitis B core antibody, and HIV-1 by enzyme immunoassay
Results
We recruited 5622 men, of whom 5293 (94%) had appropriate HBV and HIV-1 testing to be included in these analyses. 3356 (64%) men had been exposed to HBV and were seropositive for hepatitis B core antibody. Table 1 shows the characteristics of individuals, according to HBsAg and HIV-1 status. The groups were similar with respect to age, ethnic origin, number of sexual partners, and amount of alcohol consumed per week. However, HIV-1 seropositive men were more likely to have ever used injection
Discussion
Our results show an increased risk of death from liver disease in persons infected with either HIV-1 or HBV, but this risk was highest in men coinfected with both viruses. Rates of liver-related deaths were higher in men with the lowest CD4 nadir and seemed to increase after 1996, when HAART was introduced. These findings suggest that although HAART is effective against HIV-1, identification and comprehensive management of individuals coinfected with HIV-1 and HBV is important, especially in
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