Medscape coverage of: XIV International AIDS Conference

Liver Function Tests Independently Predict Survival

Mike Youle, MBBS

Barcelona, Spain; Monday, July 8, 2002 -- The role of surrogate markers to predict survival or other outcomes in HIV disease has been an area of interest for many groups, especially as the epidemic has advanced and the range of potential markers has increased. When quantitation of viral load became possible in the mid-1990s, it was widely believed that this would provide the ultimate marker of the risk of HIV progression and death. In fact, this has not proved to be the case, and there has therefore been renewed attention to other, perhaps simpler and cheaper measures of risk. The laboratory measures that are routinely evaluated in HIV-infected patients include hemoglobin levels as a marker of anemia and liver function tests such as the transaminases ALT and AST. The European EuroSIDA cohort has noted anemia to be a predictor of clinical progression.[1]

In a study presented by Justice and coworkers,[2] 2 large US cohorts were examined, the CHORUS and VAC 3 groups. The former is a cohort of 5985 subjects, mainly comprising white men who have sex with men (87%), while the VAC 3 patients are predominantly male (99%), black (55%), and contracted HIV via injection-drug use or heterosexual exposure (53%). At the time of analysis, 400 members of the CHORUS cohort and 71 members of the VAC 3 cohort had died. Cox proportional hazard models were constructed to examine the factors involved in survival when either liver function tests or anemia were considered.

When the analyses were unadjusted for CD4+ cell count, viral load and AST were significant predictors of survival in both cohorts. When adjusted for CD4+ cell count, however, both AST and ALT predicted survival, with elevated levels associated with a 2- to 6-fold increased risk of death. A raised AST was associated with hepatitis C virus (HCV) infection (hazard ratio [HR], 15.4), hepatitis B virus (HBV) infection (HR, 4.3), and alcohol use, and was negatively associated with CD4+ cell count increase; however, hepatitis virus confection did not independently predict death in either cohort. Hemoglobin was negatively correlated with survival, with a 6-fold increase in death at low levels (< 11 mg/dL). In a model that linked AST and ALT elevations with lowered hemoglobin, there was a 37-fold risk of death among patients in the lowest hemoglobin stratum and the highest liver function test stratum.

The authors concluded that "even mild elevation of AST or mild anemia requires clinical attention," because they had predictive value for survival after adjustment for age, sex, alcohol use, viral load and CD4+ cell count changes, and coinfection with HBV and HCV. They pointed out that HCV had no direct association with death in this study, presumably because elevations in AST were associated with different etiologies. Andrew Carr from the University of New South Wales, Australia, asked whether the cumulative length of treatment with nucleoside reverse transcriptase inhibitors had been considered as a variable; the authors noted that it had not but thought that it would be a good idea to include this in further analyses.

Whether these findings are of relevance to clinical practice remains to be seen. However, the correction of minor metabolic abnormalities is a relatively easy undertaking, and prospective studies of interventions to normalize these markers may be warranted, as the benefits may be tangible and significant.

References

1. Mocroft A, Kirk O, Barton SE, et al. Anaemia is an independent predictive marker for clinical prognosis in HIV-infected patients from across Europe. AIDS. 1999;13:943-950.

2. Justice AC, Wagner JH, Fusco GP, et al. HIV survival: liver function tests independently predict survival. Program and abstracts of the XIV International AIDS Conference; July 7-12, 2002; Barcelona, Spain. Abstract MoOrB1058.