title: Influence of genotype 3 hepatitis C coinfection on liver enzyme elevation in HIV-1-positive patients after commencement of a new highly active antiretroviral regimen: results from the EPOKA-MASTER Cohort.
abstract: BACKGROUND
  The independent role of hepatitis C virus (HCV) genotype 3 in liver transaminase elevation following highly active antiretroviral regimens is still controversial.
  
  
  METHODS
  Analysis of data from a cohort of 492 HIV/HCV-coinfected patients was conducted using an intention-to-treat approach. Incidence of grade > or = III liver transaminase elevation was estimated per 100 patient-years of follow-up. Univariate and multiple proportional hazards regression analysis of factors that may predict liver enzyme elevation was performed.
  
  
  RESULTS
  The incidence of grade > or = III hepatotoxicity was 25 per 100 patient-years among patients coinfected with HCV genotype 3 and 11 per 100 patient-years among those with other genotypes. On multiple proportional hazard regression analysis, time-to-grade > or = III liver enzyme elevation was directly correlated with HCV genotype 3 (hazards ratio [HR]: 2.0, 95% CI: 1.3 to 2.9; P = 0.001), male gender (HR: 2.7; 95% CI: 1.3 to 5.7; P = 0.007), chronic hepatitis B virus infection (HR: 2.9, 95% CI: 1.5 to 5.9; P = 0.002), and alanine aminotransferase level at baseline (per 10 IU/L HR: 1.10; 95% CI: 1.06 to 1.15; P < 0.001). In the same model, higher CD4 T-cell counts at baseline were inversely correlated with risk of hepatotoxicity (HR: 0.998; 95% CI: 0.997 to 0.999; P = 0.036). Moreover, among patients experienced to antiretroviral drugs, previous grade > or = III hepatotoxicity (HR: 2.8; 95% CI: 1.8 to 4.3; P < 0.001) was an adjunctive independent risk factor.
  
  
  CONCLUSIONS
  HIV-positive patients coinfected with HCV genotype 3 displayed a higher risk of relevant hepatotoxicity, independently from other clinical variables. The impact of HCV genotype outweighed the role of drugs in determining hepatotoxicity.
authors.affiliation: Istituto di Malattie Infettive e Tropicali, Università di Brescia, Brescia, Italy. torti.carlo@libero.it
authors.forename: Carlo
authors.initials: C
authors.lastname: Torti
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Lapadula
authors.forename: Massimo
authors.initials: M
authors.lastname: Puoti
authors.forename: Salvatore
authors.initials: S
authors.lastname: Casari
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Uccelli
authors.forename: Graziella
authors.initials: G
authors.lastname: Cristini
authors.forename: Daniele
authors.initials: D
authors.lastname: Bella
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Pastore
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Ladisa
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Minoli
authors.forename: Giovanni
authors.initials: G
authors.lastname: Sotgiu
authors.forename: Sergio Lo
authors.initials: SL
authors.lastname: Caputo
authors.forename: Stefano
authors.initials: S
authors.lastname: Bonora
authors.forename: Giampiero
authors.initials: G
authors.lastname: Carosi
mesh_terms: D000328:Adult; D000410:Alanine Transaminase / Q000097:blood*; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood / Q000209:etiology; D015331:Cohort Studies; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D015497:HIV-1; D016174:Hepacivirus / Q000235:genetics*; D006526:Hepatitis C / Q000097:blood / Q000150:complications / Q000821:virology*; D006801:Humans; D008297:Male; D016016:Proportional Hazards Models; D013045:Species Specificity
chemical_list: D019380:Anti-HIV Agents; D000410:Alanine Transaminase