Liver disease in the era of highly active antiretroviral therapy

Several studies done since the advent of protease inhibitors indicate that the prevalence of ESLD among HIV-positive individuals increased in the late 1990s. For example, a clinic in Boston reported that deaths among HIV-positive people due to liver disease rose from 12% in 1991 to 50% in 1998 and 1999.1 Fifty-five per cent of deaths in this cohort occurred among people with undetectable HIV viral load and CD4 cell counts above 200 cells/mm3.

In countries where combination antiretroviral therapy is widely available, liver disease has become more prevalent among HIV-positive people and is now a major cause of hospital admissions and death in this population.2,3,4,5,6,7,8,9,10,11,12  A majority of these deaths are in people co-infected with hepatitis C. Individuals with both HCV and HBV in addition to HIV have a higher risk of death than HIV-positive people co-infected with only one hepatitis virus.13,11

Prior to highly active antiretroviral therapy (HAART), people co-infected with HCV and HIV had a similar prognosis to those infected with HIV alone. After the introduction of HAART, however, co-infected people did not benefit to the same extent. One researcher found that in the HAART era, HIV/HCV co-infected individuals were approximately twice as likely to be hospitalised and three times more likely to die compared to individuals with HIV alone.14,15 Another study found that HCV co-infection increased the risk of death amongst HIV-positive US veterans by between 30% and 80%.16 It has been estimated that a 35-year-old HIV/HCV co-infected man with a CD4 cell count between 200 and 350 cells/mm3 and stage 2 liver fibrosis has a 21% chance of developing cirrhosis and a 16% chance of death due to liver disease over 20 years.17

The increase in morbidity and mortality related to liver disease among HIV-positive people since the advent of HAART is partly due to the fact that individuals receiving effective anti-HIV treatment are much less likely to die from other causes such as opportunistic infections (OIs). As co-infected individuals live longer, there is more time for progressive liver damage due to chronic hepatitis B or C to develop. Nevertheless, reductions in mortality have been seen in HCV/HIV co-infected patients since the introduction of HAART.18

Finally, a small proportion of liver-related deaths in people with HIV may be due to hepatotoxicity associated with antiretroviral drugs.

References

  1. Bica I et al. Increasing mortality due to end-stage liver disease in patients with human immunodeficiency virus infection. Clin Infect Dis 32: 492-497, 2001
  2. Ahmad S et al. Death in HIV-infected inpatients in the HAART era: an evaluation of mortality in an inner city hospital. Eighth Conference on Retroviruses and Opportunistic Infections, Chicago, abstract 300, 2001
  3. Bonnet F et al. Causes of death among HIV-infected patients in the era of highly active antiretroviral therapy (HAART). Aquitaine Cohort (France), 1998-1999. Eighth Conference on Retroviruses and Opportunistic Infections, Chicago, abstract 299, 2001
  4. Cacoub P et al. Mortality among human immunodeficiency virus infected patients with cirrhosis or hepatocellular carcinoma due to hepatitis C virus in French departments of internal medicine/infectious diseases, in 1995 and 1997. Clin Infect Dis 32: 1207-1214, 2001
  5. Martin-Carbonero L et al. Increasing impact of chronic viral hepatitis on hospital admissions and mortality among HIV-infected patients. AIDS Res Hum Retroviruses 17: 1467-1471, 2001
  6. Monga HK et al. Hepatitis C virus infection-related morbidity and mortality among patients with human immunodeficiency virus infection. Clin Infect Dis 33: 240-247, 2001
  7. Puoti M et al. Hepatitis viruses coinfections, antiretrovirals hepatotoxicity and risk of death in HIV-infected patients: prospective cohort study. Eighth Conference on Retroviruses and Opportunistic Infections, Chicago, abstract 576, 2001
  8. Ragni MV et al. Impact of human immunodeficiency virus infection on progression to end-stage liver disease in individuals with hemophilia and hepatitis C virus infection. J Infect Dis 183: 1112-1115, 2001
  9. Rancinan C et al. Does hepatitis C virus (HCV) coinfection modify survival in HIV patients on combination of antiretrovirals? Eighth Conference on Retroviruses and Opportunistic Infections, Chicago, abstract 570, 2001
  10. Rosenthal E et al. Mortality due to hepatitis C-related liver disease in HIV-infected patients in France in 2001 (Mortavic 2001 study). Second International AIDS Society Conference on HIV Pathogenesis and Treatment, Paris, abstract 87, 2003
  11. Salmon-Ceron D et al. Liver disease as a major cause of death among HIV infected patients: role of hepatitis C and B viruses and alcohol. J Hepatol 42: 799-805, 2005
  12. Soriano V et al. Impact of chronic liver disease due to hepatitis viruses as cause of hospital admission and death in HIV-infected drug users. Eur J Epidemiol 15: 1-4, 1999
  13. Bonacini M et al. Survival in patients with HIV infection and viral hepatitis B or C: a cohort study. AIDS 18: 2039-2045, 2004
  14. Klein MB et al. Hepatitis C (HCV) co-infection is associated with increased morbidity and mortality among HIV-infected patients. Eighth Conference on Retroviruses and Opportunistic Infections, Chicago, abstract 308, 2001
  15. Klein MB et al. The impact of hepatitis C virus coinfection on HIV progression before and after highly active antiretroviral therapy. J Acquir Immune Defic Syndr 33: 365-372, 2003
  16. Backus LI et al. Effects of hepatitis C virus coinfection on survival in veterans with HIV treated with highly active antiretroviral therapy. J Acquir Immune Defic Syndr 39: 613-619, 2005
  17. Wong JB et al. Projecting the prognosis of hepatitis fibrosis in HIC-HCV co-infection. Hepatology 38: S425A, abstract 551, 2003
  18. Lumbreras B et al. Impact of hepatitis C infection on long-term mortality of injecting drug users from 1990 to 2002: differences before and after HAART. AIDS 20: 111 – 116, 2006
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