Elsevier

The Lancet

Volume 360, Issue 9349, 14 December 2002, Pages 1921-1926
The Lancet

Articles
HIV-1, hepatitis B virus, and risk of liver-related mortality in the Multicenter Cohort Study (MACS)

https://doi.org/10.1016/S0140-6736(02)11913-1Get rights and content

Summary

Background

Although coinfection with HIV-1 and hepatitis B virus (HBV) is common, few long-term studies on liver-disease mortality in coinfected people have been undertaken. Our aim was to examine liver-related mortality among people at risk for HIV-1 and HBV infections.

Methods

We used data from a multicentre, prospective cohort study to classify 5293 men who had sex with men, according to their HIV-1 antibody status, ascertained semiannually, and their hepatitis-B surface antigen status (HBsAg), which we ascertained at baseline. Mortality rates were estimated in terms of person-years and Poisson regression methods were used to test for signifiance of relative risks.

Findings

326 (6%) men were HBsAg positive, of whom 213 (65%) were HIV-1 positive. Of the 4967 HBsAg negative men, 2346 (47%) were infected with HIV-1. The liver-related mortality rate was 1·1/1000 person years, and was higher in men with HIV-1 and HBsAg (14·2/1000) than in those with only HIV-1 infection (1·7/1000, p<0·001) or only HBsAg (0·8/1000, p<0·001). In coinfected individuals, the liver-related mortality rate was highest with lower nadir CD4+ cell counts and was twice as high after 1996, when highly active antiretroviral therapy (HAART) was introduced.

Interpretation

Individuals coinfected with HIV-1 and HBV, especially those with low CD4+ nadir counts, are at increased risk for liver-related mortality, underscoring the importance of prevention, identification, and comprehensive management of hepatitis B in people infected with HIV-1.

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.

Section snippets

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

References (38)

  • MW Yu et al.

    Prospective study of hepatocellular carcinoma and liver cirrhosis in asymptomatic chronic hepatitis B virus carriers

    Am J Epidemiol

    (1997)
  • BJ McMahon et al.

    Hepatitis B-related sequelae. Prospective study in 1400 hepatitis B surface antigen-positive Alaska native carriers

    Arch Intern Med

    (1990)
  • JF Colin et al.

    Influence of human immunodeficiency virus infection on chronic hepatitis B in homosexual men

    Hepatology

    (1999)
  • SC Hadler et al.

    Outcome of hepatitis B virus infection in homosexual men and its relation to prior human immunodeficiency virus infection

    J Infect Dis

    (1991)
  • WG Rector et al.

    Hepatic inflammation, hepatitis B replication, and cellular immune function in homosexual males with chronic hepatitis B and antibody to human immunodeficiency virus

    Am J Gastroenterol

    (1988)
  • M Puoti et al.

    Mortality for liver disease in patients with HIV infection: a cohort study

    JAcquir Immune Defic Sy®/r

    (2000)
  • Y Benhamou et al.

    Liver fibrosis progression in human immunodeficiency virus and hepatitis C virus coinfected patients

    Hepatology

    (1999)
  • DM Forrest et al.

    The incidence and spectrum of AIDS-defining illnesses in persons treated with antiretroviral drugs

    Clin Infect Dis

    (1998)
  • JE Kaplan et al.

    Epidemiology of human immunodeficiency virus-associated opportunistic infections in the United States in the era of highly active antiretroviral therapy

    Clin Infect Dis

    (2000)
  • Cited by (943)

    • HIV: hepatic manifestations of HIV and antiretroviral therapy

      2023, Comprehensive Guide to Hepatitis Advances
    View all citing articles on Scopus
    View full text