title: Relationship of liver disease stage and antiviral therapy with liver-related events and death in adults coinfected with HIV/HCV.
abstract: BACKGROUND
  Human immunodeficiency virus (HIV) accelerates hepatitis C virus (HCV) disease progression; however, the effect of liver disease stage and antiviral therapy on the risk of clinical outcomes is incompletely understood.
  
  
  OBJECTIVE
  To determine the incidence of end-stage liver disease (ESLD), hepatocellular carcinoma (HCC), or death according to baseline hepatic fibrosis and antiviral treatment for HIV/HCV coinfected individuals.
  
  
  METHODS
  Prospective cohort of 638 coinfected adults (80% black, 66% men) receiving care at the Johns Hopkins HIV clinic and receiving a liver biopsy and who were prospectively monitored for clinical events between July 1993 and August 2011 (median follow-up, 5.82 years; interquartile range, 3.42-8.85 years). Histological specimens were scored for hepatic fibrosis stage according to the METAVIR scoring system.
  
  
  METHODS
  Incidence of composite outcome of ESLD, HCC, or death.
  
  
  RESULTS
  Patients experienced a graded increased risk in incidence of clinical outcomes based on baseline hepatic fibrosis stage (classification range, F0-F4): F0, 23.63 (95% CI, 16.80-33.24); F1, 36.33 (95% CI, 28.03-47.10); F2, 53.40 (95% CI, 33.65-84.76); F3, 56.14 (95% CI, 31.09-101.38); and F4, 79.43 (95% CI, 55.86-112.95) per 1000 person-years (P < .001). In multivariable negative binomial regression, fibrosis stages F2 through F4 and antiretroviral therapy were independently associated with composite ESLD, HCC, or all-cause mortality after adjustment for demographic characteristics, injection drug use, and CD4 cell count. Compared with F0, the incidence rate ratio (RR) for F2 was 2.31 (95% CI, 1.23-4.34; P = .009); F3, 3.18 (95% CI, 1.47-6.88; P = .003); and F4, 3.57 (95% CI, 2.06-6.19; P < .001). Human immunodeficiency virus treatment was associated with fewer clinical events (incidence RR, 0.27; 95% CI, 0.19-0.38; P < .001). For the 226 patients who underwent HCV treatment, the incidence of clinical events did not significantly differ between treatment nonresponders and untreated patients (incidence RR, 1.27; 95% CI, 0.86-1.86; P = .23). In contrast, no events were observed in the 51 patients with sustained virologic response (n = 36) and relapse (n = 15), including 19 with significant fibrosis.
  
  
  CONCLUSIONS
  In this cohort of patients with HIV/HCV coinfection, hepatic fibrosis stage was independently associated with a composite outcome of ESLD, HCC, or death.
authors: Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors: Berkeley N
authors: BN
authors: Limketkai
authors: Shruti H
authors: SH
authors: Mehta
authors: Catherine G
authors: CG
authors: Sutcliffe
authors: Yvonne M
authors: YM
authors: Higgins
authors: Michael S
authors: MS
authors: Torbenson
authors: Sherilyn C
authors: SC
authors: Brinkley
authors: Richard D
authors: RD
authors: Moore
authors: David L
authors: DL
authors: Thomas
authors: Mark S
authors: MS
authors: Sulkowski
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use; D015142:Baltimore / Q000453:epidemiology; D001706:Biopsy; D006528:Carcinoma, Hepatocellular / Q000401:mortality; D060085:Coinfection; D018450:Disease Progression; D058625:End Stage Liver Disease / Q000401:mortality*; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy* / Q000401:mortality*; D006526:Hepatitis C / Q000150:complications*; D006801:Humans; D015994:Incidence; D008099:Liver / Q000473:pathology; D008103:Liver Cirrhosis / Q000145:classification* / Q000401:mortality; D008113:Liver Neoplasms / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents