Decreases in markers of monocyte/macrophage activation after hepatitis C eradication in HIV/hepatitis C virus coinfected women

Abstract

Objective: Eradication of hepatitis C virus (HCV) in HIV disease decreases liver and non-liver-related morbidity and mortality. Elevated markers of monocyte/macrophage activation (soluble CD163 and sCD14) are associated with excess non-AIDS morbidity and mortality in HIV. We examined the effect of HCV eradication on these markers in relation to change in hepatic fibrosis.Design: A nested substudy within a longitudinal observational cohort Methods: We studied 126 HIV/HCV-coinfected women successfully treated for HCV, with undetectable HCV RNA at least 12 weeks after therapy completion. sCD163 and sCD14 were measured in serum collected before and after HCV eradication. Results were correlated with changes in markers of hepatic fibrosis.Results: Mean age of participants was 56.3 years, mean CD4 þ cell count was 615, and 72% had suppressed HIV RNA. After treatment, sCD163 and sCD14 levels significantly decreased from pre-treatment levels in unadjusted analyses. After adjusting for age, race, hepatic fibrosis status, baseline HCV RNA, CD4 count and HIV RNA status, cigarette smoking, and alcohol use, the decreases in sCD163 and sCD14 remained significant. Decrease in pre-treatment to post-treatment sCD163 were significantly positively correlated with changes in FIB-4 (r ¼ 0.250, P ¼ 0.005) and APRI (r ¼ 0.262, P ¼ 0.003); similarly decrease in sCD14 was significantly positively correlated with changes in FIB-4 (r ¼ 0.333, P ¼ 0.0001) and APRI (r ¼ 0.457, P < 0.0001). Conclusion:HCV eradication is associated with significant reductions in monocyte/ macrophage activation markers that correlate with reductions in markers of hepatic

Longitudinal Assessment of the Enhanced Liver Fibrosis Score in the Era of Contemporary HIV and Hepatitis C Virus Treatment

“…Consistent with prior studies that have evaluated mostly short-term changes in liver fibrosis post-SVR, we also found declines post-HCV treatment [15,17,18,20]. The declines in APRI and FIB-4, however, were substantial and significant both in the peri-and immediate post-HCV treatment period, whereas the declines in ELF were significant only in the immediate post-HCV treatment period.…”

“…Most HCV treatment studies prior to DAA therapy found significant decreases in liver fibrosis as well as in clinical end points such as hepatic decompensation and liver-related deaths after achievement of sustained virologic response (SVR) [10][11][12]. In the DAA era, most liver fibrosis studies in persons with HCV monoinfection [13][14][15] and HIV/HCV coinfection [16][17][18] have limited follow-up of less than 1 year after SVR. These studies assessed fibrosis change using noninvasive serum markers, aspartate transaminase-to-platelet ratio index (APRI) and Fibrosis-4 (FIB-4), as well as transient elastography (TE), but whether the short-term declines observed may be more a result of decreases in liver inflammation than regression of liver fibrosis is unclear, because liver inflammation can affect APRI, FIB-4, and TE-measured liver stiffness values [19,20].…”

Important Risk Factors of Liver Cirrhosis in HIV and Hepatitis C Coinfected Patients: A Systematic Review

“…190 HIV/HCV-coinfected, 25 did not develop fibrosis (F0) (non-progressor), 165 patients developed fibrosis(F≥1] (progressors) Ferreira [34] Cross sectional 354 HIV-infected, 93 monoinfected, 261 coinfected: 40.1% HIV/HBV, 19.5% HIV/HCV and 14.1% HIV/HBV/HCV Feuth [19] Cross-sectional 89 subjects, including 18 chronic HCV monoinfected patients, 10 HIV-1 monoinfected patients, 14 HIV/ HCV coinfected patients, 18 HBV infected patients, 14 PBC patients and 15 healthy controls Foca [30] Cohort 1433 HIV/HCV coinfected Franco [20] Cross-sectional 46 HIV-1/HCV coinfections, 20 Non progressing, 26 progressing in mean of 10.3 years And 21 uninfected Medrano [51] cross-sectional study 220 HIV/HCV-coinfected Medrano [52] cross-sectional study 238 HIV/HCV-coinfected patients, 32 healthy controls, 39 HIV-monoinfected Merchante [53] prospective cohort 239 HIV/HCV-coinfected Molina-Carrión [28] prospective cohort 44 HIV/HCV-coinfected, 9 HCV-monoinfected Moqueet [54] prospective cohort 485 HIV/HCV-coinfected Moqueet [45] case-cohort study 679 HIV-HCV coinfected Nguyen Truong [37] cross-sectional study 104 HIV-HCV coinfected Nunez-Torres [44] cross-sectional and longitudinal 337 HIV-HCV coinfected Márquez-Coello [55] Cohort study HCV monoinfected:20, HCV/HIV co-infected:66, Control:15 Matas [56] Cohort study 63 Giovanni Mazzola [57] observational, retrospective study HCV mono-infected (n=1937], HIV/HCV co-infected (n=238] José A. Mira [58] Prospective cohort 166 HIV-HCV coinfected, 43 SVR, 123 non-SVR Marco Merli [59] n observational retrospective 646 coinfected, LS<13kpa n=474, LS>=13kpa n=172 French [60] Cross-sectional HIV/HCV coinfected patients (n=44] French [61] Prospective cohort HIV/HCV coinfected patients (n=126] Garcia-Broncano [40] Cross-Sectional 238 HIV/HCV co-infected patients, 39 HIV monoinfected patients, 32 healthy donors negative for HIV, HCV and HBV Frias [46] Retrospective and longitudinal cohort HIV/HCV coinfected (n=104] Fuster [47] Cross-Sectional 308 Gad [35] Cross-Sectional HIV-monoinfected (n=169], HIV/HBV coinfected (n=20], HIV/HCV coinfected (n=39], HIV/HBV/HCV, Triplet infection (n=13] Mandorfer, Mattias [62] 86 HIV/HCV Shmagel [39] Case-control Study [1] HIV/HCV coinfected patients (n = 42]; Soldevila [42] Cross-Sectional 115 HIV/HCV-coinfected patients S...…”

Recent advances in poor HIV immune reconstitution: what will the future look like?

“…Moreover, several studies have affirmed that HIV-1/HCV-coinfected individuals presented a remarkable reduction in the median expression of HLA-DR and CD38 on CD4 and CD8 T cells, as HCV is controlled. Meanwhile, after HCV eradication, significantly lower levels of innate immune activation markers (sCD163, sCD14), HIV-1 proviral load and LPS ( López-Cortés et al, 2018 ; French et al, 2021 ). Furthermore, the coexistence of CMV or EBV with HIV-1 in PLHIV also contributes to elevated plasma inflammatory factors and promotes chronic immune activation, which is a key element for T cell activation and incomplete immune reconstitution after cART ( Hernandez et al, 2018 ).…”