Liver enzymes elevation and immune reconstitution among treatment-naïve HIV-infected patients instituting antiretroviral therapy

Am J Med Sci. 2007 Nov;334(5):334-41. doi: 10.1097/MAJ.0b013e31811ec780.


Objectives: Because liver enzymes elevation (LEE) complicates antiretroviral (ARV) therapy, and because the strongest risk factor for ARV-related LEE is HBV/HCV coinfection, it is speculated that ARV-related LEE may be a form of immune reconstitution disease. This study summarizes the relation between immune reconstitution, ARV-induced LEE, and HBV/HCV coinfection.

Methods: Medical records of ARV-naïve HIV-infected patients initiating ARV were reviewed for hepatitis coinfection, LEE (grade > or =2 AST/ALT) and changes in CD4 T-cell counts over time in an urban HIV clinic. Risk factors for LEE were statistically evaluated, and changes in CD4 T-cell counts were estimated by a mixed-effects linear model.

Results: Predictors of LEE included HBV/HCV coinfection (OR = 6.44) and stavudine use (OR = 2.33). Nelfinavir use was protective (OR = 0.45). The mean rate of change in CD4 T-cell counts was higher in HBV/HCV coinfected subjects who developed LEE (99 cells/microL per month) compared with non-coinfected subjects who did not develop LEE (59 cells/microL per month, P = 0.03), non-coinfected subjects who developed LEE (36 cells/microL per month, P =0.01), and coinfected subjects who did not develop LEE, 38% higher (62 cells/microL per month; P =0.11)

Conclusions: A more robust immune restoration was observed among HBV/HCV coinfected subjects who developed liver enzyme elevation after antiretroviral initiation compared with other groups. This finding suggests that ARV-related liver enzyme elevation may be related in part to immune reconstitution, as measured by changes in CD4 T-cell counts.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alanine Transaminase / blood*
  • Anti-HIV Agents / adverse effects
  • Anti-HIV Agents / therapeutic use
  • Anti-Retroviral Agents / adverse effects*
  • Anti-Retroviral Agents / therapeutic use
  • Aspartate Aminotransferases / blood*
  • Benzoxazines / adverse effects
  • CD4-Positive T-Lymphocytes / pathology
  • Drug Therapy, Combination
  • Female
  • HIV Infections / blood
  • HIV Infections / complications
  • HIV Infections / drug therapy*
  • HIV Infections / enzymology
  • Hepatitis B / blood
  • Hepatitis B / complications
  • Hepatitis B / pathology
  • Hepatitis C / blood
  • Hepatitis C / complications
  • Hepatitis C / pathology
  • Humans
  • Immune Reconstitution Inflammatory Syndrome / blood
  • Immune Reconstitution Inflammatory Syndrome / chemically induced*
  • Immune Reconstitution Inflammatory Syndrome / pathology
  • Lamivudine / adverse effects
  • Lamivudine / therapeutic use
  • Linear Models
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Retrospective Studies
  • Risk Factors
  • Stavudine / adverse effects
  • Stavudine / therapeutic use
  • Zidovudine / adverse effects
  • Zidovudine / therapeutic use


  • Anti-HIV Agents
  • Anti-Retroviral Agents
  • Benzoxazines
  • Lamivudine
  • Zidovudine
  • Stavudine
  • Aspartate Aminotransferases
  • Alanine Transaminase
  • efavirenz