title: Incidence and risk factors for chronic elevation of alanine aminotransferase levels in HIV-infected persons without hepatitis b or c virus co-infection.
abstract: BACKGROUND
  Chronic liver disease in human immunodeficiency virus (HIV)-infected patients is mostly caused by hepatitis virus co-infection. Other reasons for chronic alanine aminotransferase (ALT) elevation are more difficult to diagnose.
  
  
  METHODS
  We studied the incidence of and risk factors for chronic elevation of ALT levels (greater than the upper limit of normal at 2 consecutive semi-annual visits) in participants of the Swiss HIV Cohort Study without hepatitis B virus (HBV) or hepatitis C virus (HCV) infection who were seen during the period 2002-2008. Poisson regression analysis was used.
  
  
  RESULTS
  A total of 2365 participants were followed up for 9972 person-years (median age, 38 years; male sex, 66%; median CD4+ cell count, 426/microL; receipt of antiretroviral therapy [ART], 56%). A total of 385 participants (16%) developed chronic elevated ALT levels, with an incidence of 3.9 cases per 100 person-years (95% confidence interval [CI], 3.5-4.3 cases per 100 person-years). In multivariable analysis, chronic elevated ALT levels were associated with HIV RNA level >100,000 copies/mL (incidence rate ratio [IRR], 2.23; 95% CI, 1.45-3.43), increased body mass index (BMI, defined as weight in kilograms divided by the square of height in meters) (BMI of 25-29.9 was associated with an IRR of 1.56 [95% CI, 1.24-1.96]; a BMI 30 was associated with an IRR of 1.70 [95% CI, 1.16-2.51]), severe alcohol use (1.83 [1.19-2.80]), exposure to stavudine (IRR per year exposure, 1.12 [95% CI, 1.07-1.17]) and zidovudine (IRR per years of exposure, 1.04 [95% CI, 1.00-1.08]). Associations with cumulative exposure to combination ART, nucleoside reverse-transcriptase inhibitors, and unboosted protease inhibitors did not remain statistically significant after adjustment for exposure to stavudine. Black ethnicity was inversely correlated (IRR, 0.52 [95% CI, 0.33-0.82]). Treatment outcome and mortality did not differ between groups with and groups without elevated ALT levels.
  
  
  CONCLUSIONS
  Among patients without hepatitis virus co-infection, the incidence of chronic elevated ALT levels was 3.9 cases per 100 person-years, which was associated with high HIV RNA levels, increased BMI, severe alcohol use, and prolonged stavudine and zidovudine exposure. Long-term follow-up is needed to assess whether chronic elevation of ALT levels will result in increased morbidity or mortality.
authors.affiliation: Division of Infectious Diseases and Hospital Epidemiology, University Hospital, Zurich, Switzerland. helen.kovari@usz.ch
authors.forename: Helen
authors.initials: H
authors.lastname: Kovari
authors.forename: Bruno
authors.initials: B
authors.lastname: Ledergerber
authors.forename: Manuel
authors.initials: M
authors.lastname: Battegay
authors.forename: Andri
authors.initials: A
authors.lastname: Rauch
authors.forename: Bernard
authors.initials: B
authors.lastname: Hirschel
authors.forename: Alain Kenfak
authors.initials: AK
authors.lastname: Foguena
authors.forename: Pietro
authors.initials: P
authors.lastname: Vernazza
authors.forename: Enos
authors.initials: E
authors.lastname: Bernasconi
authors.forename: Nicolas J
authors.initials: NJ
authors.lastname: Mueller
authors.forename: Rainer
authors.initials: R
authors.lastname: Weber
mesh_terms: D000328:Adult; D000410:Alanine Transaminase / Q000097:blood / Q000378:metabolism*; D000428:Alcohol Drinking / Q000378:metabolism; D044966:Anti-Retroviral Agents / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000201:enzymology* / Q000821:virology; D006509:Hepatitis B / Q000201:enzymology / Q000821:virology; D006526:Hepatitis C / Q000201:enzymology / Q000821:virology; D006801:Humans; D008099:Liver / Q000201:enzymology; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016012:Poisson Distribution; D011446:Prospective Studies; D012307:Risk Factors; D012680:Sensitivity and Specificity; D019562:Viral Load
chemical_list: D044966:Anti-Retroviral Agents; D000410:Alanine Transaminase