Abstract
BackgroundIn vitro, gp120 of both X4 and R5 HIV-1 strains activates human hepatic stellate cells, but if it can promote liver fibrosis in vivo is unknown. We aimed to evaluate if patients carrying X4 or R5 strains have a different liver fibrosis (LF) progression over time.MethodsA total of 1,137 HIV-infected patients in ICONA cohort (21% females, 7% HCV co-infected) with an available determination of HIV-1 co-receptor tropism (CRT), a Fibrosis-4 Index for Liver Fibrosis (FIB-4) <3.25 and at least one-year follow-up were included. CRT was assessed by gp120 sequencing on plasma RNA and geno2pheno algorithm (10% false positive rate) or by Trofile. LF was assessed by means of FIB-4. LF progression was defined as an absolute score increase or a transition to higher fibrosis stratum and/or occurrence of liver-related clinical events.ResultsA total of 249 (22%) patients carried X4 strains, which were associated with older age, lower CD4 count, lower nadir CD4, and intravenous drug use. Overall, X4 and R5 patients had similar baseline FIB-4 scores and similar mean FIB-4 slope after a median follow-up of 35 months. There was no difference between X4 and R5 for time to LF progression (p = 0.925). Estimated risk of LF at 24 months (95% CI) after baseline in X4 and R5 was 10.6% (8.3–12.9) and 9.9% (5.9–14.0), respectively. Age, HCV co-infection, diabetes, HIV-duration, HIV-RNA>100.000 cp/mL, antiretroviral therapy exposure were associated with LF progression at multivariate analysis.ConclusionsA slight LF progression over time was observed in HIV-infected patients. No difference was demonstrated for X4 and R5 HIV-1 strains in accelerating LF evolution.
Highlights
A significant risk of liver fibrosis (LF) has been described in HIV infected patients, even in the absence of other common causes of liver disease, such as HBV or HCV co-infections, drugs use, alcohol abuse, metabolic diseases, and immune-suppression [1,2,3,4,5], thereby suggesting a potential role of HIV itself as a cause of liver damage in vivo
No difference was demonstrated for X4 and R5 HIV-1 strains in accelerating LF evolution
HIV-1 co-receptor tropism and liver fibrosis behavioral data, initiation and discontinuation dates of each antiretroviral drug, HIV-viral load and CD4 cell count every 3–6 months, AIDS defining diseases according to Centers for Disease Control and Prevention (CDC) criteria as well as non-HIV related diseases and death are recorded for all enrolled patients
Summary
A significant risk of liver fibrosis (LF) has been described in HIV infected patients, even in the absence of other common causes of liver disease, such as HBV or HCV co-infections, drugs use, alcohol abuse, metabolic diseases, and immune-suppression [1,2,3,4,5], thereby suggesting a potential role of HIV itself as a cause of liver damage in vivo. HIV infection in the gastrointestinal tract amplifies microbial translocation, which can stimulate hepatocytes, Kuppfer cells and Hepatic Stellate Cells (HSC) to produce proinflammatory cytokines and chemokines [8,9]. These mediators attract activated lymphocytes and monocytes to the liver further inducing fibrosis [8,9]. The state of HIV-associated chronic immune activation associated with CD4 cell loss could induce intra-hepatic inflammation, enhancing liver disease progression [4]. We aimed to evaluate if patients carrying X4 or R5 strains have a different liver fibrosis (LF) progression over time.
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