title: Hepatotoxicity and nelfinavir: a meta-analysis.
abstract: OBJECTIVE
  The inclusion of protease inhibitors in 3-drug highly active antiretroviral regimens for treating patients who are infected with human immunodeficiency virus-1 has had a significant impact in increasing survival and decreasing morbidity. However, the effectiveness of this class of drugs may be compromised by the occurrence of drug-related hepatotoxicity, which is problematic especially in individuals co-infected with hepatitis viruses. Based on its clinical and pharmacologic profile, especially its unique pattern of resistance, nelfinavir has been used frequently as a first-line protease-inhibitor therapy for human immunodeficiency virus-1-infected patients. The aim of this study was to identify the relative potential for developing hepatotoxicity for nelfinavir vs other protease inhibitors.
  
  
  METHODS
  An exploratory meta-analysis of liver enzyme level increases was conducted in a combined total of 4268 patients derived from 3 large recently conducted prospective and retrospective clinical trials and a prospective cohort study.
  
  
  RESULTS
  The results indicate that among 4 commercially available protease inhibitors and a 2-protease inhibitor combination, nelfinavir and indinavir are associated with the lowest rates of occurrence of severe hepatotoxicity (ie, combined estimates of liver enzyme level increases of 2.9% and 3.1%, respectively). The low rate of occurrence of severe hepatotoxicity for nelfinavir was shown even among patients co-infected with hepatitis viruses.
  
  
  CONCLUSIONS
  In conclusion, these data provide support for the conclusion that differences in the potential for hepatotoxicity do exist among the commercially available protease inhibitors.
authors.affiliation: Division of Infectious and Tropical Diseases, Istituto di Ricovero e Cura a Carattere Scientifico San Mateo Hospital--University of Pavia, Italy.
authors.forename: Raffaele
authors.initials: R
authors.lastname: Bruno
authors.forename: Paolo
authors.initials: P
authors.lastname: Sacchi
authors.forename: Laura
authors.initials: L
authors.lastname: Maiocchi
authors.forename: Cristina
authors.initials: C
authors.lastname: Zocchetti
authors.forename: Gaetano
authors.initials: G
authors.lastname: Filice
mesh_terms: D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology*; D004359:Drug Therapy, Combination; D015658:HIV Infections / Q000188:drug therapy; D017320:HIV Protease Inhibitors / Q000009:adverse effects*; D006801:Humans; D019469:Indinavir / Q000009:adverse effects; D008099:Liver / Q000201:enzymology; D019888:Nelfinavir / Q000009:adverse effects*
chemical_list: D017320:HIV Protease Inhibitors; D019469:Indinavir; D019888:Nelfinavir