| |
|
HCV Cure Reduced End Stage Liver Disease
|
| |
| |
Download the PDF here
HCV-negative individuals (adjusted incidence rate ratio [aIRR] 0.22, 95% CI 0.14-0.34) and those with spontaneous clearance (aIRR 0.61, 95% CI 0.36-1.02) had reduced rates of ESLD compared to cured individuals. Persons with chronic, untreated HCV infections (aIRR 1.47, 95% CI 1.02-2.13) or treatment failure (aIRR 1.80, 95% CI 1.22-2.66) had significantly raised rates of ESLD, compared to those who were cured.
Although there were a number of ESLD events in those HCV-negative (Group 1), there was a low incidence of ESLD in those with chronic, untreated infections (Group 3), while those with treatment failure (Group 5) had the highest rates of ESLD (9.6 [95% CI 8.2-10.9] and 9.9 [95% CI 7.7-12.1] per 1000 PYFU, respectively; global P < .0001).
Compared to those cured (Group 4), there were few differences in the adjusted IR ratios for CVD or NADM across the 5 groups (Figure 3). Consistent results and no differences between the groups were seen when considering MI or stroke individually. Unsurprisingly, those who were HCV-negative (Group 1) had significantly reduced rates of ESLD (adjusted IR ratio [aIRR] 0.22, 95% CI 0.14-0.34), while persons with chronic, untreated infections (Group 3; aIRR 1.47, 95% CI 1.02-2.13; P = .041) or treatment failure (Group 5; aIRR 1.80, 95% CI 1.22-2.66; P = .0033) had significantly higher IRs of ESLD compared to those cured (Group 4). Spontaneous clearers (Group 3) had a marginally significantly lower IR of ESLD, compared to those cured (Group 4; aIRR 0.61, 95% CI 0.36-1.02 ; p = .058). There was no evidence that the associations between HCV strata and each of the clinical events differed according to age (above or below 50, all P interactions > 0.15).
those cured had substantially lower incidences of ESLD, underlining the importance of successful HCV treatment for reducing ESLD.
This raises the question of whether people living with HIV but cured of HCV have a lower rate of long-term, non-liver related clinical outcomes compared to those who are untreated or failing treatment, or compared to those who are HCV antibody-positive and HCV RNA-negative without treatment (spontaneous clearers).
Persons were included from the EuroSIDA study, a large, prospective, observational cohort of almost 23 000 patients living with HIV-1 who were followed in 100 hospitals in 35 European countries, plus Israel and Argentina.
As expected, the baseline fibrosis stage was strongly associated with an increased IR of ESLD (global P < .0001). Compared to those with F0/F1 fibrosis, those with F2 fibrosis had a 2.5-fold increased IR of ESLD (aIRR 2.51, 95% CI 1.66-3.80; p <.0001) increasing to a >5-fold increase in those with F4 fibrosis (aIRR 5.80, 95% CI 4.12-8.19; p <.0001). Analyses were repeated including fibrosis as time-updated, with consistent results (data not shown).
In this large study of more than 16 000 people living with HIV, with a median follow-up of over 8 years, we found no differences in CVD or NADM between those without HCV; spontaneous HCV clearers; those with chronic, untreated HCV infections; those cured; or treatment failures. As expected, we found large differences in ESLD depending on HCV serostatus and HCV RNA replication. To our knowledge, this is among the largest studies to date including HIV and HCV coinfected persons with clinical endpoints and comparing outcomes to persons who have been cured of HCV.
Although an HCV cure has been shown to perturb levels of lipid and inflammatory biomarkers, studies of HIV/HCV-coinfected persons have lacked the power to focus on clinical events. Our study shows similar IRs of CVD and NADM across 5 well-defined HCV strata and underlines the importance of early treatment and HCV cures for reducing ESLD.
------------------
Clinical Outcomes in Persons Coinfected With Human Immunodeficiency Virus and Hepatitis C Virus: Impact of Hepatitis C Virus Treatment
Abstract
Background
A hepatitis C (HCV) cure is associated with changes in lipids and inflammatory biomarkers, but its impact on clinical endpoints among treated human immunodeficiency virus (HIV)/HCV coinfected persons is unclear.
Methods
People living with HIV from EuroSIDA with a known HCV status after January 2001 were classified into strata based on time-updated HCV RNA measurements and HCV treatment, as either HCV antibody-negative; spontaneously resolved HCV; chronic, untreated HCV; cured HCV (HCV RNA-negative); or HCV treatment failures (HCV RNA-positive). Poisson regression was used to compare incidence rates between HCV groups for end-stage liver disease (ESLD; including hepatocellular carcinoma [HCC]), non-acquired immunodeficiency virus defining malignancy (NADM; excluding HCC), and cardiovascular disease (CVD).
Results
There were 16 618 persons included (median follow-up 8.3 years, interquartile range 3.1-13.7). There were 887 CVD, 902 NADM, and 436 ESLD events; crude incidence rates/1000 person-years follow-up were 6.4 (95% confidence interval [CI] 6.0-6.9) for CVD, 6.5 (95% CI 6.1-6.9) for NADM, and 3.1 (95% CI 2.8-3.4) for ESLD. After adjustment, there were no differences in incidence rates of NADM or CVD across the 5 groups. HCV-negative individuals (adjusted incidence rate ratio [aIRR] 0.22, 95% CI 0.14-0.34) and those with spontaneous clearance (aIRR 0.61, 95% CI 0.36-1.02) had reduced rates of ESLD compared to cured individuals. Persons with chronic, untreated HCV infections (aIRR 1.47, 95% CI 1.02-2.13) or treatment failure (aIRR 1.80, 95% CI 1.22-2.66) had significantly raised rates of ESLD, compared to those who were cured.
Conclusions
Incidences of NADM or CVD were independent of HCV group, whereas those cured had substantially lower incidences of ESLD, underlining the importance of successful HCV treatment for reducing ESLD.
| |
| |
| |
|
|
|
