Persistently low CD4 cell counts are associated with hepatic events in HCV/HIV coinfected patients: data from the national free antiretroviral treatment program of China

Abstract

Background: Chronic liver disease has emerged as a leading cause of non-acquired immune deficiency syndrome (AIDS)-related mortality in hepatitis C virus (HCV)/human immunodeficiency virus (HIV)-coinfected patients. The relationship between CD4 cell count and HIV-related opportunistic infections and tumors has been well characterized; however, it is unclear whether CD4 cell count is associated with HCV-related hepatic events.

Methods: This observational cohort study enrolled HCV/HIV-coinfected patients from the National Free Antiretroviral Treatment Program of China from 2004 to 2019 in Guangzhou. The primary outcome was a composite of hepatic events, including cirrhosis complications, hepatocellular carcinoma (HCC), and liver-related mortality. Kaplan-Meier survival and multivariate logistic regression analyses were performed.

Results: Among the 793 patients, 43 developed hepatic events during a median follow-up of 6.7 years, including 35 cirrhosis complications, 13 HCC cases, and 14 cases of liver-related mortality. The 5-year and 10-year cumulative incidences of hepatic events were 4.2% and 9.3%, respectively. Patients who developed hepatic events had a less satisfactory increase in CD4 cell count, lower peak CD4 (354.5 cells/μL vs. 560.0 cells/μL, P < 0.001), and lower percentage of peak CD4 > 500 cells/μL (30.2% vs. 60.7%, P < 0.001) after the initiation of antiretroviral therapy (ART) than those who did not. The cumulative incidences of hepatic events were higher in patients with lower peak CD4 levels with adjusted odds ratios of 3.96 (95% confidence interval [CI]: 1.51-10.40), 2.25 (95% CI: 0.87-5.86), and 0.98 (95% CI: 0.35-2.74) for patients with peak CD4 at <200 cells/μL, 200-350 cells/μL, and 351 to 500 cells/μL, respectively, relative to those with peak CD4 > 500 cells/μL. Peak CD4 was negatively associated with the risk of hepatic events in a dose-response manner ( P -value for trend = 0.004).

Conclusion: Persistently low CD4 cell counts after ART are independently associated with a high risk of hepatic events in HCV/HIV-coinfected patients, highlighting the important role of immune reconstitution in improving liver outcomes.