1. Immune activation and microbial translocation in liver disease progression in HIV/hepatitis co-infected patients: results from the Icona Foundation study
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Marchetti, Giulia, Cozzi Lepri, Alessandro, Tincati, Camilla, Calcagno, Andrea, Ceccherini Silberstein, Francesca, De Luca, Andrea, Antinori, Andrea, Castagna, Antonella, Puoti, Massimo, Monforte, Antonella d'Arminio, for the Icona Foundation Study Group […, Moroni M, Angarano G, Antinori A, Carosi G, Cauda R, Monforte A, Di Perri G, Galli M, Iardino R, Ippolito G, Lazzarin A, Perno CF, Viale PL, Von Schlosser F, Monforte Ad, Ammassari A, Andreoni M, Balotta C, Bonfanti P, Bonora S, Borderi M, Capobianchi MR, Castagna A, Ceccherini Silberstein F, Cozzi Lepri A, De Luca A, Gargiulo M, Gervasoni C, Girardi E, Lichtner M, Lo Caputo S, Madeddu G, Maggiolo F, Marcotullio S, Monno L, Murri R, Mussini C, Puoti M, Torti C, Fanti I, Formenti T, Montroni M, Giacometti A, Costantini A, Riva A, Tirelli U, Martellotta F, Ladisa N, Suter F, Piergentili B, Cristini G, Minardi C, Bertelli D, Quirino T, Abeli C, Manconi PE, Piano P, Vecchiet J, Falasca K, Carnevale G, Lorenzotti S, Sighinolfi L, Leoncini F, Mazzotta F, Pozzi M, Cassola G, Viscoli G, Alessandrini A, Piscopo R, Mazzarello G, Mastroianni C, Belvisi V, Molteni C, Chiodera A, Castelli P, Rizzardini G, Ridolfo AL, Foschi A, Salpietro S, Merli S, Carenzi L, Moioli MC, Cicconi P, Esposito R, Gori A, Pastore V, Abrescia N, Chirianni A, De Marco M, Ferrari C, Borghi R, Baldelli F, Belfiori B, Parruti G, Sozio F, Magnani G, Ursitti MA, Arlotti M, Ortolani P, Antonucci G, Narciso P, Tozzi V, Vullo V, Zaccarelli M, Gallo L, Acinapura R, De Longis P, Ceccarelli L, Libertone R, Trotta MP, Miccoli A, Cattelan AM, Mura MS, Caramello P, Orofino GC, Sciandra M, Raise E, Ebo F, Pellizzer G, Buonfrate D, VERUCCHI, GABRIELLA, Marchetti, G, Cozzi Lepri, A, Tincati, C, Calcagno, A, Ceccherini Silberstein, F, DE LUCA, A, Antinori, A, Castagna, A, Puoti, M, Monforte, A, Marchetti, Giulia, Cozzi Lepri, Alessandro, Tincati, Camilla, Calcagno, Andrea, Ceccherini Silberstein, Francesca, De Luca, Andrea, Antinori, Andrea, Castagna, Antonella, Puoti, Massimo, Monforte Antonella, D'Arminio, Cozzi-Lepri, Alessandro, Ceccherini-Silberstein, Francesca, Monforte, Antonella d'Arminio, and for the Icona Foundation Study Group […, Moroni M, Angarano G, Antinori A, Carosi G, Cauda R, Monforte A, Di Perri G, Galli M, Iardino R, Ippolito G, Lazzarin A, Perno CF, Viale PL, Von Schlosser F, Monforte Ad, Ammassari A, Andreoni M, Balotta C, Bonfanti P, Bonora S, Borderi M, Capobianchi MR, Castagna A, Ceccherini-Silberstein F, Cozzi-Lepri A, De Luca A, Gargiulo M, Gervasoni C, Girardi E, Lichtner M, Lo Caputo S, Madeddu G, Maggiolo F, Marcotullio S, Monno L, Murri R, Mussini C, Puoti M, Torti C, Fanti I, Formenti T, Montroni M, Giacometti A, Costantini A, Riva A, Tirelli U, Martellotta F, Ladisa N, Suter F, Verucchi G, Piergentili B, Cristini G, Minardi C, Bertelli D, Quirino T, Abeli C, Manconi PE, Piano P, Vecchiet J, Falasca K, Carnevale G, Lorenzotti S, Sighinolfi L, Leoncini F, Mazzotta F, Pozzi M, Cassola G, Viscoli G, Alessandrini A, Piscopo R, Mazzarello G, Mastroianni C, Belvisi V, Molteni C, Chiodera A, Castelli P, Rizzardini G, Ridolfo AL, Foschi A, Salpietro S, Merli S, Carenzi L, Moioli MC, Cicconi P, Esposito R, Gori A, Pastore V, Abrescia N, Chirianni A, De Marco M, Ferrari C, Borghi R, Baldelli F, Belfiori B, Parruti G, Sozio F, Magnani G, Ursitti MA, Arlotti M, Ortolani P, Antonucci G, Narciso P, Tozzi V, Vullo V, Zaccarelli M, Gallo L, Acinapura R, De Longis P, Ceccarelli L, Libertone R, Trotta MP, Miccoli A, Cattelan AM, Mura MS, Caramello P, Orofino GC, Sciandra M, Raise E, Ebo F, Pellizzer G, Buonfrate D, …], DIPARTIMENTO DI SCIENZE MEDICHE E CHIRURGICHE, Facolta' di MEDICINA e CHIRURGIA, and AREA MIN. 06 - Scienze mediche
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microbial ,Male ,Fibrosi ,Lipopolysaccharide Receptors ,HIV Infections ,Kaplan-Meier Estimate ,Liver disease ,Medical microbiology ,Risk Factors ,HIV Infection ,Fib-4 ,Coinfection ,Liver Disease ,Medicine (all) ,Liver Diseases ,virus diseases ,Hepatitis A ,Hepatitis C ,Hepatitis B ,Middle Aged ,sCD14 ,Settore MED/07 - Microbiologia e Microbiologia Clinica ,Infectious Diseases ,Treatment Outcome ,HIV/hepatitis co-infection ,traslocation ,HCV ,HIV ,liver ,Disease Progression ,Biological Markers ,Female ,medicine.symptom ,Adult ,Antigens, CD14 ,CD4 Lymphocyte Count ,Enzyme-Linked Immunosorbent Assay ,Fibrosis ,Humans ,Inflammation ,CD14 ,Microbial translocation ,Research Article ,Human ,medicine.medical_specialty ,Infectious Disease ,Settore MED/17 - MALATTIE INFETTIVE ,Biomarkers ,medicine ,Antigens ,Hepatitis ,business.industry ,Risk Factor ,Biomarker ,medicine.disease ,Virology ,digestive system diseases ,Immunology ,business - Abstract
none 157 no Abstract BACKGROUND: We evaluated whether immune activation (IA) and microbial translocation (MT) might play a role in accelerating liver disease progression in HIV-HBV/HCV co-infected patients. METHODS: ART-naïve HIV/viral hepatitis co-infected patients from Icona with a CD4 cell count >200/μl and with a known date of prior HIV neg/pos tests and ≥1 plasma sample stored were included in the study. Plasma MT (LPS, sCD14) and IA (IL-6,TNFα) were measured using ELISA while activated CD8 + CD38 + HLA-DR + were measured by flow cytometry, with one measurement being performed for all patients and two measurements for a smaller group of subjects. The association between these biomarkers and the time to i) a single ALT >200 IU/l and ii) a Fib-4 >1.45 was also investigated. A standard survival analysis with robust standard errors was used for all evaluations. Follow-up was censored at patients' last clinical follow-up. RESULTS: We studied 127 HIV-infected hepatitis viruses co-infected patients (118 HCV, 9 HBV). Overall median (IQR) CD4, VL, age were 596/μl (208-1303), 3.8 log10cp/mL (3-4.3), 34 years (22-56). While heightened TNF-α was associated with a 13-fold increased risk of Fib-4 > 1.45 (RH 13.05, 95% CI 2.43-70; p = 0.003), markers of MT did not show an association with liver illness. Interestingly, higher sCD14 was associated with a decreased risk of Fib-4 > 1.45, independently of other biomarkers considered (RH 0.20, 95% CI 0.04-0,9; p = 0.04). CONCLUSIONS: In HIV/hepatitis virus co-infected ART-naive patients, higher TNF-α plasma levels were associated with a 13-fold increase in the risk of progression to a Fib-4 >1.45, suggesting that the pro-inflammatory status in HIV infection might hasten the course of HCV. In view of the fact that sCD14 may hinder the interaction between LPS and the phagocyte membrane CD14, we herewith propose a model which aims to demonstrate that high sCD14 levels might contribute to shelter liver function through the down-regulation of the inflammatory cascade. Marchetti, Giulia; Cozzi-Lepri, Alessandro; Tincati, Camilla; Calcagno, Andrea; Ceccherini-Silberstein, Francesca; De Luca, Andrea; Antinori, Andrea; Castagna, Antonella; Puoti, Massimo; Monforte, Antonella d'Arminio; and for the Icona Foundation Study Group […; Moroni M; Angarano G; Antinori A; Carosi G; Cauda R; Monforte A; Di Perri G; Galli M; Iardino R; Ippolito G; Lazzarin A; Perno CF; Viale PL; Von Schlosser F; Monforte Ad; Ammassari A; Andreoni M; Antinori A; Balotta C; Bonfanti P; Bonora S; Borderi M; Capobianchi MR; Castagna A; Ceccherini-Silberstein F; Cozzi-Lepri A; Monforte A; De Luca A; Gargiulo M; Gervasoni C; Girardi E; Lichtner M; Lo Caputo S; Madeddu G; Maggiolo F; Marcotullio S; Monno L; Murri R; Mussini C; Puoti M; Torti C; Cozzi-Lepri A; Fanti I; Formenti T; Montroni M; Giacometti A; Costantini A; Riva A; Tirelli U; Martellotta F; Angarano G; Monno L; Ladisa N; Suter F; Maggiolo F; Viale PL; Verucchi G; Piergentili B; Carosi G; Cristini G; Torti C; Minardi C; Bertelli D; Quirino T; Abeli C; Manconi PE; Piano P; Vecchiet J; Falasca K; Carnevale G; Lorenzotti S; Sighinolfi L; Leoncini F; Mazzotta F; Pozzi M; Lo Caputo S; Cassola G; Viscoli G; Alessandrini A; Piscopo R; Mazzarello G; Mastroianni C; Belvisi V; Bonfanti P; Molteni C; Chiodera A; Castelli P; Galli M; Lazzarin A; Rizzardini G; Puoti M; Monforte A; Ridolfo AL; Foschi A; Castagna A; Salpietro S; Merli S; Carenzi L; Moioli MC; Cicconi P; Formenti T; Esposito R; Mussini C; Gori A; Pastore V; Abrescia N; Chirianni A; De Marco M; Ferrari C; Borghi R; Baldelli F; Belfiori B; Parruti G; Sozio F; Magnani G; Ursitti MA; Arlotti M; Ortolani P; Cauda R; Andreoni M; Antinori A; Antonucci G; Narciso P; Tozzi V; Vullo V; De Luca A; Zaccarelli M; Gallo L; Acinapura R; De Longis P; Ceccarelli L; Libertone R; Trotta MP; Miccoli A; Cattelan AM; Mura MS; Madeddu G; Caramello P; Di Perri G; Orofino GC; Sciandra M; Raise E; Ebo F; Pellizzer G; Buonfrate D; …] Marchetti, Giulia; Cozzi-Lepri, Alessandro; Tincati, Camilla; Calcagno, Andrea; Ceccherini-Silberstein, Francesca; De Luca, Andrea; Antinori, Andrea; Castagna, Antonella; Puoti, Massimo; Monforte, Antonella d'Arminio; and for the Icona Foundation Study Group […; Moroni M; Angarano G; Antinori A; Carosi G; Cauda R; Monforte A; Di Perri G; Galli M; Iardino R; Ippolito G; Lazzarin A; Perno CF; Viale PL; Von Schlosser F; Monforte Ad; Ammassari A; Andreoni M; Antinori A; Balotta C; Bonfanti P; Bonora S; Borderi M; Capobianchi MR; Castagna A; Ceccherini-Silberstein F; Cozzi-Lepri A; Monforte A; De Luca A; Gargiulo M; Gervasoni C; Girardi E; Lichtner M; Lo Caputo S; Madeddu G; Maggiolo F; Marcotullio S; Monno L; Murri R; Mussini C; Puoti M; Torti C; Cozzi-Lepri A; Fanti I; Formenti T; Montroni M; Giacometti A; Costantini A; Riva A; Tirelli U; Martellotta F; Angarano G; Monno L; Ladisa N; Suter F; Maggiolo F; Viale PL; Verucchi G; Piergentili B; Carosi G; Cristini G; Torti C; Minardi C; Bertelli D; Quirino T; Abeli C; Manconi PE; Piano P; Vecchiet J; Falasca K; Carnevale G; Lorenzotti S; Sighinolfi L; Leoncini F; Mazzotta F; Pozzi M; Lo Caputo S; Cassola G; Viscoli G; Alessandrini A; Piscopo R; Mazzarello G; Mastroianni C; Belvisi V; Bonfanti P; Molteni C; Chiodera A; Castelli P; Galli M; Lazzarin A; Rizzardini G; Puoti M; Monforte A; Ridolfo AL; Foschi A; Castagna A; Salpietro S; Merli S; Carenzi L; Moioli MC; Cicconi P; Formenti T; Esposito R; Mussini C; Gori A; Pastore V; Abrescia N; Chirianni A; De Marco M; Ferrari C; Borghi R; Baldelli F; Belfiori B; Parruti G; Sozio F; Magnani G; Ursitti MA; Arlotti M; Ortolani P; Cauda R; Andreoni M; Antinori A; Antonucci G; Narciso P; Tozzi V; Vullo V; De Luca A; Zaccarelli M; Gallo L; Acinapura R; De Longis P; Ceccarelli L; Libertone R; Trotta MP; Miccoli A; Cattelan AM; Mura MS; Madeddu G; Caramello P; Di Perri G; Orofino GC; Sciandra M; Raise E; Ebo F; Pellizzer G; Buonfrate D; …]
- Published
- 2014