Hepatic fibrosis stage at the start of follow-up independently predicted a composite outcome of end-stage liver disease (ESLD), hepatocellular carcinoma (HCC), or death in people infected with HIV and hepatitis C virus (HCV) at the Johns Hopkins HIV clinic in Baltimore, Maryland.
HIV infection speeds progression of HCV disease, but the impact of liver disease stage and antiviral therapy on clinical outcome risk remains incompletely understood. To address these questions, researchers at Johns Hopkins University conducted a prospective cohort study of 638 HIV/HCV-infected adults.
Of the 638 cohort members, 80% were black and 66% were men. All had a liver biopsy and were prospectively monitored for HCV disease progression between July 1993 and August 2011. Median follow-up was 5.82 years (interquartile range 3.42 to 8.85). The Hopkins team used the METAVIR scoring system to grade liver fibrosis stage.
Incidence of clinical outcomes increased significantly (P < 0.001) with each higher baseline hepatic fibrosis stage:
• F0: 23.63 per 1000 person-years (P-Y) (95% confidence interval [CI] 16.80 to 33.24)
• F1: 36.33 per 1000 P-Y (95% CI 28.03 to 47.10)
• F2: 53.40 per 1000 P-Y (95% CI 33.65 to 84.76)
• F3: 56.14 per 1000 P-Y (95% CI 31.09 to 101.38)
• F4: 79.43 per 1000 P-Y (95% CI 55.86 to 112.95)
Multivariate analysis that adjusted for demographic characteristics, injection drug use, and CD4 count determined that, compared with stage F0, stages F2 through F4 independently raised the risk of a composite endpoint including ESLD, HCC, and all-cause mortality by the following incidence rate ratios (IRR)
• F2 vs F0: IRR 2.31 (95% CI 1.23 to 4.34), P = 0.009
• F3 vs F0: IRR 3.18 (95% CI 1.47 to 6.88), P = 0.003
• F4 vs F0: IRR 3.57 (95% CI 2.06 to 6.19), P < 0.001
Antiretroviral therapy lowered the risk of clinical events almost 75% (IRR 0.27, 95% CI 0.19 to 0.38, P < 0.001).
Among 226 people treated for HCV, clinical event incidence did not differ significantly between nonresponders and untreated patients (IRR 1.27, 95% CI 0.86 to 1.86, P = 0.23). Thirty-six people with sustained virologic response to anti-HCV therapy and 15 people with relapse after anti-HCV therapy had no clinical events, including 19 people with significant fibrosis.
The Johns Hopkins researchers believe their data “support recent guidelines that recommend HIV treatment for most coinfected persons who are willing and able to adhere to therapy, including those with high CD4 cell counts.”
However, they add, the progression rates observed “highlight the need for more effective HCV treatment regimens for this population,” and they call for “clinical trials of novel combinations of direct-acting antivirals for HCV . . . as soon as possible.”