Liver Disease State and Antiretroviral Therapy in Patients with HIV/HCV
According to researchers, individuals infected with HIV often experience hepatitis C virus (HCV) coinfection. Among patients treated with effective HIV antiretroviral therapy (ART), the presence of HCV infection has been associated with an increased risk of death compared with patients with HIV monoinfection. In the North American AIDS Cohort Collaboration on Research and Design, for example, patients coinfected with HCV had an 85% greater risk of death.
In other studies, HCV-related liver disease has been shown to be a leading cause of morbidity and mortality in coinfected persons. This association is due, in part, to more rapid progression of liver disease with concurrent HIV infection. However, the researchers noted, is it unknown whether the risk of clinical outcomes differs by the liver fibrosis stage.
The researchers recently conducted a prospective cohort study to determine the incidence rates of end-stage liver disease (ESLD), hepatocellular carcinoma (HCC), or death (all-cause and liver-related mortality) among HIV/HCV coinfected adults according to their baseline histologic disease stage and their exposure to effective treatment for HIV and HCV. They reported results of the study in JAMA [2013;308(4):370-378].
The primary outcome measure was the incidence of composite outcome of ESLD, HCC, or death. Two main composite outcomes were analyzed: (1) any clinical outcome, defined as ESLD, HCC, or death (all-cause) and (2) liver-related outcomes, defined as ESLD, HCC, or liver-related death.
The participants were 638 coinfected adults being treated at the Moore Clinic for HIV Care at Johns Hopkins Hospital. They had received a liver biopsy and were prospectively monitored for clinical events between July 1993 and August 2011. Median age was 45.6 years, 80% were black, 66% were male, 75% were former or active injection drug users, and 47% were alcohol abusers. At the time of initial biopsy, 69% of participants were taking ART. Median cumulative exposure to ART prior to biopsy was 1.6 years.
On initial staging, 73% (n=467) of the patients had a METAVIR fibrosis stage consistent with no fibrosis (F0, n=208) or minimal portal fibrosis (F1, n=259). Sixty patients with portal fibrosis with few septa were staged at F2 and 41 patients with portal fibrosis with many septa were staged at F3. The remaining 70 patients with cirrhosis were staged at F4.
Overall, 150 clinical events were observed during 3888.3 person-years (5 cases HCC; 14 cases ESLD; 131 cases all-cause death). The overall incidence rate per 1000 person-years was 38.58 (95% confidence interval [CI], 32.87-45.27). Of the 150 events, 51 were designated as liver-related.
Patients experienced a graded increased risk in incidence of clinical outcomes based on baseline hepatic fibrosis stage: 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).
After adjustment for confounders by multivariable negative binomial regression, liver fibrosis greater than METAVIR stage F1 remained independently associated with ESLD, HCC, or all-cause mortality, as well as liver-related mortality. Compared with F0, the incidence rate ratio (RR) for F2 was 2.31 (95% CI, 1.23-4.32; 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).
Treatment for HIV was associated with fewer clinical events: for patients who underwent HIV treatment (n=226), the incidence of clinical events did not differ significantly between treatment nonresponders and untreated patients (incidence RR, 1.27; 95% CI, 0.86-1.86; P=.23). No events were observed in the 51 patients with sustained virologic response (n=36) and relapse (n=15), including 19 with significant fibrosis.
In summary, the researchers said, “In this cohort of patients with HIV/HCV coinfection, hepatic fibrosis state was independently associated with a composite outcome of ESLD, HCC, or death.”
