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

Berkeley N. Limketkai, Shruti H. Mehta, Catherine G. Sutcliffe, Yvonne M. Higgins, Michael S. Torbenson, Sherilyn C. Brinkley, Richard D. Moore, David L. Thomas, Mark S. Sulkowski

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)370-378
Number of pages9
JournalJAMA - Journal of the American Medical Association
Volume308
Issue number4
DOIs
StatePublished - Jul 25 2012

ASJC Scopus subject areas

  • Medicine(all)

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    Limketkai, B. N., Mehta, S. H., Sutcliffe, C. G., Higgins, Y. M., Torbenson, M. S., Brinkley, S. C., Moore, R. D., Thomas, D. L., & Sulkowski, M. S. (2012). Relationship of liver disease stage and antiviral therapy with liver-related events and death in adults coinfected with HIV/HCV. JAMA - Journal of the American Medical Association, 308(4), 370-378. https://doi.org/10.1001/jama.2012.7844