Combined antiretroviral therapy attenuates hepatic extracellular matrix remodeling in HIV patients assessed by novel protein fingerprint markers

TY - JOUR

T1 - Combined antiretroviral therapy attenuates hepatic extracellular matrix remodeling in HIV patients assessed by novel protein fingerprint markers

AU - Leeming, Diana J

AU - Anadol, Evrim

AU - Schierwagen, Robert

AU - Karsdal, Morten A

AU - Byrjalsen, Inger

AU - Nielsen, Mette Juul

AU - Schwarzer-Zander, Carolyn

AU - Boesecke, Christoph

AU - Bendtsen, Flemming

AU - Møller, Søren

AU - Strassburg, Christian P

AU - Spengler, Ulrich

AU - Krag, Aleksander

AU - Rockstroh, Jürgen

AU - Trebicka, Jonel K

PY - 2014/9/10

Y1 - 2014/9/10

N2 - OBJECTIVES: Combined antiretroviral therapy (cART) attenuates hepatic fibrosis in hepatitis C virus and HIV coinfected patients. However, the role of HIV or cART on hepatic fibrosis in HIV monoinfection is discussed controversially. During liver fibrosis, matrix metalloproteinases (MMPs) degrade extracellular matrix (ECM) proteins into small soluble fragments, which reflect hepatic remodeling processes. This study used these novel biomarkers to investigate the effect of HIV and cART on hepatic fibrosis remodeling.DESIGN: In 249 patients with HIV monoinfection and 55 healthy controls, the serum levels of MMP-degraded collagen type III (C3M), biglycan (BGM), elastin (ELM), as well as the formation marker 7S (P4NP 7S), and MMP-degraded collagen type IV (C4M) were determined using specific ELISAs. Sixty-eight patients underwent a follow-up visit 3 years later including assessment of ECM markers and fibrosis using transient elastography (Fibroscan).RESULTS: C3M, BGM, C4M and P4NP 7S were significantly elevated in HIV patients compared to controls and correlated to HIV viral loads and inversely to cART duration. C4M, P4NP 7S and ELM were lower in patients under cART therapy and in patients without HIV viremia, indicating that lowering of the HIV load by cART attenuates remodeling of ECM. The levels of C3M, C4M, P4NP 7S and ELM correlated significantly with the progression of fibrosis in these patients.CONCLUSION: Specific therapy of patients with HIV monoinfection also beneficially influences liver fibrosis. These novel markers of liver fibrosis remodeling may help to monitor the hepatic effects by HIV therapy.

AB - OBJECTIVES: Combined antiretroviral therapy (cART) attenuates hepatic fibrosis in hepatitis C virus and HIV coinfected patients. However, the role of HIV or cART on hepatic fibrosis in HIV monoinfection is discussed controversially. During liver fibrosis, matrix metalloproteinases (MMPs) degrade extracellular matrix (ECM) proteins into small soluble fragments, which reflect hepatic remodeling processes. This study used these novel biomarkers to investigate the effect of HIV and cART on hepatic fibrosis remodeling.DESIGN: In 249 patients with HIV monoinfection and 55 healthy controls, the serum levels of MMP-degraded collagen type III (C3M), biglycan (BGM), elastin (ELM), as well as the formation marker 7S (P4NP 7S), and MMP-degraded collagen type IV (C4M) were determined using specific ELISAs. Sixty-eight patients underwent a follow-up visit 3 years later including assessment of ECM markers and fibrosis using transient elastography (Fibroscan).RESULTS: C3M, BGM, C4M and P4NP 7S were significantly elevated in HIV patients compared to controls and correlated to HIV viral loads and inversely to cART duration. C4M, P4NP 7S and ELM were lower in patients under cART therapy and in patients without HIV viremia, indicating that lowering of the HIV load by cART attenuates remodeling of ECM. The levels of C3M, C4M, P4NP 7S and ELM correlated significantly with the progression of fibrosis in these patients.CONCLUSION: Specific therapy of patients with HIV monoinfection also beneficially influences liver fibrosis. These novel markers of liver fibrosis remodeling may help to monitor the hepatic effects by HIV therapy.

U2 - 10.1097/qad.0000000000000388

DO - 10.1097/qad.0000000000000388

M3 - Journal article

C2 - 25136933

SN - 0269-9370

VL - 28

SP - 2081

EP - 2090

JO - AIDS

JF - AIDS

IS - 14

ER -