Relationship of liver disease stage and antiviral therapy with liver-related events and death in adults coinfected with HIV/HCV.

Publication Type:

Journal Article


JAMA : the journal of the American Medical Association, Volume 308, Issue 4, p.370-8 (2012)


Adultdigestive disease, digestive deseases Antiviral Agentsdigestive disease, digestive deseases Baltimoredigestive disease, digestive deseases Biopsydigestive disease, digestive deseases Carcinoma, Hepatocellulardigestive disease, digestive deseases Coinfectiondigestive disease, digestive deseases Disease Progressiondigestive disease, digestive deseases End Stage Liver Diseasedigestive disease, digestive deseases Femaledigestive disease, digestive deseases Hepatitis Cdigestive disease, digestive deseases HIV Infectionsdigestive disease, digestive deseases Humansdigestive disease, digestive deseases Incidencedigestive disease, digestive deseases Liverdigestive disease, digestive deseases Liver Cirrhosisdigestive disease, digestive deseases Liver Neoplasmsdigestive disease, digestive deseases Maledigestive disease, digestive deseases Middle Ageddigestive disease, digestive deseases Prospective Studiesdigestive disease, digestive deseases Treatment Outcome


CONTEXT: 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.

DESIGN, SETTING, AND PARTICIPANTS: 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.

MAIN OUTCOME MEASURE: 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.

CONCLUSION: In this cohort of patients with HIV/HCV coinfection, hepatic fibrosis stage was independently associated with a composite outcome of ESLD, HCC, or death.