title: Association of noncirrhotic portal hypertension in HIV-infected persons and antiretroviral therapy with didanosine: a nested case-control study.
abstract: BACKGROUND
  Noncirrhotic portal hypertension (NCPH) is a newly described life-threatening liver disease of unknown cause in human immunodeficiency virus (HIV)-infected persons. Postulated pathogenesis includes prolonged exposure to antiretroviral therapy, particularly didanosine.
  
  
  METHODS
  We performed a nested case-control study including 15 patients with NCPH and 75 matched control subjects of the Swiss HIV Cohort Study to investigate risk factors for the development of NCPH. Matching criteria were similar duration of HIV infection, absence of viral hepatitis, and follow-up to at least the date of NCPH diagnosis in the respective case.
  
  
  RESULTS
  All 15 case patients had endoscopically documented esophageal varices and absence of liver cirrhosis on biopsies; 4 died because of hepatic complications. At NCPH diagnosis, case patients and control subjects were similar concerning sex; race; Centers for Disease Control and Prevention stage; HIV-RNA level; CD4 cell count nadir; and lipids and lipodystrophy. Differences were found in age (conditional logistic regression odds ratio [OR] for 10 years older, 2.9; 95% confidence interval [CI], 1.4-6.1); homosexuality (OR, 4.5; 95% CI, 1.2-17); current CD4 cell count <200 cells/microL (OR, 34.3; 95% CI, 4.3-277); diabetes mellitus (OR, 8.8; 95% CI, 1.6-49); alanine aminotransferase level higher than normal (OR, 13.0; 95% CI, 2.7-63); alkaline phosphatase higher than normal (OR, 18.3; 95% CI, 4.0-85); and platelets lower than normal (OR, 20.5; 95% CI, 2.4-178). Cumulative exposure to antiretroviral therapy (OR per year, 1.3; 95% CI, 1.0-1.6), nucleoside reverse-transcriptase inhibitor (OR, 1.3; 95% CI, 1.1-1.7), didanosine (OR, 3.4; 95% CI, 1.5-8.1), ritonavir (OR, 1.4; 95% CI, 1.0-1.9), and nelfinavir (OR, 1.4; 95% CI, 1.0-1.9) were longer in case patients. Exposure to nonnucleoside reverse-transcriptase inhibitor and other protease inhibitors were not different between groups. In bivariable models, only the association of NCPH with didanosine exposure was robust; other covariables were not independent risk factors.
  
  
  CONCLUSIONS
  We found a strong association between prolonged exposure to didanosine and the development of NCPH.
authors: Divisions of Infectious Diseases and Hospital Epidemiology, University Hospital, Zurich CH-8091, Switzerland. helen.kovari@usz.ch
authors: Helen
authors: H
authors: Kovari
authors: Bruno
authors: B
authors: Ledergerber
authors: Ulrich
authors: U
authors: Peter
authors: Markus
authors: M
authors: Flepp
authors: Josef
authors: J
authors: Jost
authors: Patrick
authors: P
authors: Schmid
authors: Alexandra
authors: A
authors: Calmy
authors: Nicolas J
authors: NJ
authors: Mueller
authors: Beat
authors: B
authors: Muellhaupt
authors: Rainer
authors: R
authors: Weber
mesh_terms: D019380:Anti-HIV Agents / Q000009:adverse effects* / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects*; D016022:Case-Control Studies; D016049:Didanosine / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy*; D006801:Humans; D006975:Hypertension, Portal / Q000139:chemically induced* / Q000453:epidemiology*; D008297:Male; D008875:Middle Aged
chemical_list: D019380:Anti-HIV Agents; D016049:Didanosine