Prognostic Value of the Fibrosis-4 Index in Human Immunodeficiency Virus Type-1 Infected Patients Initiating Antiretroviral Therapy with or without Hepatitis C Virus

Cristina Mussini, Patrizia Lorenzini, Massimo Puoti, Miriam Lichtner, Giuseppe Lapadula, Simona Di Giambenedetto, Andrea Antinori, Giordano Madeddu, Alessandro Cozzi-Lepri, Antonella D'Arminio Monforte, Andrea De Luca, M. Moroni, M. Andreoni, G. Angarano, A. Antinori, A. D'Arminio Monforte, F. Castelli, R. Cauda, G. Di Perri, M. GalliR. Iardino, G. Ippolito, A. Lazzarin, C. F. Perno, F. Von Schloesser, P. Viale, A. D'Arminio Monforte, A. Antinori, A. Castagna, F. Ceccherini-Silberstein, A. Cozzi-Lepri, E. Girardi, S. Lo Caputo, C. Mussini, M. Puoti, M. Andreoni, A. Ammassari, A. Antinori, C. Balotta, A. Bandera, P. Bonfanti, S. Bonora, M. Borderi, A. Calcagno, L. Calza, M. R. Capobianchi, A. Castagna, F. Ceccherini-Silberstein, A. Cingolani, P. Cinque, A. Cozzi-Lepri, A. D'Arminio Monforte, A. De Luca, A. Di Biagio, E. Girardi, N. Gianotti, A. Gori, G. Guaraldi, G. Lapadula, M. Lichtner, S. Lo Caputo, G. Madeddu, F. Maggiolo, G. Marchetti, S. Marcotullio, L. Monno, C. Mussini, S. Nozza, M. Puoti, E. Quiros Roldan, R. Rossotti, S. Rusconi, M. M. Santoro, A. Saracino, M. Zaccarelli, A. Cozzi-Lepri, I. Fanti, L. Galli, P. Lorenzini, A. Rodano, M. Shanyinde, A. Tavelli

Research output: Contribution to journalArticle

Abstract

Objective: To evaluate the Fibrosis (FIB)-4 index as a predictor of major liver-related events (LRE) and liver-related death (LRD) in human immunodeficiency virus (HIV) type-1 patients initiating combination antiretroviral therapy (cART). Design: Retrospective analysis of a prospective cohort study. Setting: Italian HIV care centers participating to the ICONA Foundation cohort. Participants: Treatment-naive patients enrolled in ICONA were selected who: initiated cART, had hepatitis C virus (HCV) serology results, were HBsAg negative, had an available FIB-4 index at cART start and during follow up. Methods: Cox regression models were used to determine the association of FIB4 with the risk of major LRE (gastrointestinal bleeding, ascites, hepatic encephalopathy, hepato-renal syndrome or hepatocellular carcinoma) or LRD. Results: Three-thousand four-hundred seventy-five patients were enrolled: 73.3% were males, 27.2% HCV seropositive. At baseline (time of cART initiation) their median age was 39 years, had a median CD4+ T cell count of 260 cells/uL, and median HIV RNA 4.9 log copies/ mL, 65.9% had a FIB-4 <1.45, 26.4% 1.45-3.25 and 7.7% > 3.25. Over a follow up of 18,662 person-years, 41 events were observed: 25 major LRE and 16 LRD (incidence rate, IR, 2.2 per 1,000 PYFU [95% confidence interval, CI 1.6-3.0]). IR was higher in HCV seropositives as compared to negatives (5.9 vs 0.5 per 1,000 PYFU). Higher baseline FIB-4 category as compared to <1.45 (FIB-4 1.45-3.25: HR 3.55, 95% CI 1.09-11.58; FIB-4 > 3.25: HR 4.25, 1.21-14.92) and time-updated FIB-4 (FIB-4 1.45-3.25: HR 3.40, 1.02-11.40; FIB- 4> 3.25: HR 21.24, 6.75-66.84) were independently predictive of major LRE/LRD, after adjusting for HIV- and HCV-related variables, alcohol consumption and type of cART. Conclusions: The FIB-4 index at cART initiation, and its modification over time are risk factors for major LRE or LRD, independently of infection with HCV and could be used to monitor patients on cART.

Original languageEnglish
Article numbere0140877
JournalPLoS One
Volume10
Issue number12
DOIs
Publication statusPublished - Dec 1 2015

Fingerprint

Hepatitis C virus
Human immunodeficiency virus 1
fibrosis
Viruses
Hepacivirus
Liver
HIV-1
Fibrosis
therapeutics
liver
death
Human immunodeficiency virus
Therapeutics
HIV
Patient treatment
T-cells
Hepatic Encephalopathy
encephalopathy
Serology
CD4 Lymphocyte Count

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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Prognostic Value of the Fibrosis-4 Index in Human Immunodeficiency Virus Type-1 Infected Patients Initiating Antiretroviral Therapy with or without Hepatitis C Virus. / Mussini, Cristina; Lorenzini, Patrizia; Puoti, Massimo; Lichtner, Miriam; Lapadula, Giuseppe; Di Giambenedetto, Simona; Antinori, Andrea; Madeddu, Giordano; Cozzi-Lepri, Alessandro; D'Arminio Monforte, Antonella; De Luca, Andrea; Moroni, M.; Andreoni, M.; Angarano, G.; Antinori, A.; D'Arminio Monforte, A.; Castelli, F.; Cauda, R.; Di Perri, G.; Galli, M.; Iardino, R.; Ippolito, G.; Lazzarin, A.; Perno, C. F.; Von Schloesser, F.; Viale, P.; D'Arminio Monforte, A.; Antinori, A.; Castagna, A.; Ceccherini-Silberstein, F.; Cozzi-Lepri, A.; Girardi, E.; Lo Caputo, S.; Mussini, C.; Puoti, M.; Andreoni, M.; Ammassari, A.; Antinori, A.; Balotta, C.; Bandera, A.; Bonfanti, P.; Bonora, S.; Borderi, M.; Calcagno, A.; Calza, L.; Capobianchi, M. R.; Castagna, A.; Ceccherini-Silberstein, F.; Cingolani, A.; Cinque, P.; Cozzi-Lepri, A.; D'Arminio Monforte, A.; De Luca, A.; Di Biagio, A.; Girardi, E.; Gianotti, N.; Gori, A.; Guaraldi, G.; Lapadula, G.; Lichtner, M.; Lo Caputo, S.; Madeddu, G.; Maggiolo, F.; Marchetti, G.; Marcotullio, S.; Monno, L.; Mussini, C.; Nozza, S.; Puoti, M.; Quiros Roldan, E.; Rossotti, R.; Rusconi, S.; Santoro, M. M.; Saracino, A.; Zaccarelli, M.; Cozzi-Lepri, A.; Fanti, I.; Galli, L.; Lorenzini, P.; Rodano, A.; Shanyinde, M.; Tavelli, A.

In: PLoS One, Vol. 10, No. 12, e0140877, 01.12.2015.

Research output: Contribution to journalArticle

Mussini, C, Lorenzini, P, Puoti, M, Lichtner, M, Lapadula, G, Di Giambenedetto, S, Antinori, A, Madeddu, G, Cozzi-Lepri, A, D'Arminio Monforte, A, De Luca, A, Moroni, M, Andreoni, M, Angarano, G, Antinori, A, D'Arminio Monforte, A, Castelli, F, Cauda, R, Di Perri, G, Galli, M, Iardino, R, Ippolito, G, Lazzarin, A, Perno, CF, Von Schloesser, F, Viale, P, D'Arminio Monforte, A, Antinori, A, Castagna, A, Ceccherini-Silberstein, F, Cozzi-Lepri, A, Girardi, E, Lo Caputo, S, Mussini, C, Puoti, M, Andreoni, M, Ammassari, A, Antinori, A, Balotta, C, Bandera, A, Bonfanti, P, Bonora, S, Borderi, M, Calcagno, A, Calza, L, Capobianchi, MR, Castagna, A, Ceccherini-Silberstein, F, Cingolani, A, Cinque, P, Cozzi-Lepri, A, D'Arminio Monforte, A, De Luca, A, Di Biagio, A, Girardi, E, Gianotti, N, Gori, A, Guaraldi, G, Lapadula, G, Lichtner, M, Lo Caputo, S, Madeddu, G, Maggiolo, F, Marchetti, G, Marcotullio, S, Monno, L, Mussini, C, Nozza, S, Puoti, M, Quiros Roldan, E, Rossotti, R, Rusconi, S, Santoro, MM, Saracino, A, Zaccarelli, M, Cozzi-Lepri, A, Fanti, I, Galli, L, Lorenzini, P, Rodano, A, Shanyinde, M & Tavelli, A 2015, 'Prognostic Value of the Fibrosis-4 Index in Human Immunodeficiency Virus Type-1 Infected Patients Initiating Antiretroviral Therapy with or without Hepatitis C Virus', PLoS One, vol. 10, no. 12, e0140877. https://doi.org/10.1371/journal.pone.0140877
Mussini, Cristina ; Lorenzini, Patrizia ; Puoti, Massimo ; Lichtner, Miriam ; Lapadula, Giuseppe ; Di Giambenedetto, Simona ; Antinori, Andrea ; Madeddu, Giordano ; Cozzi-Lepri, Alessandro ; D'Arminio Monforte, Antonella ; De Luca, Andrea ; Moroni, M. ; Andreoni, M. ; Angarano, G. ; Antinori, A. ; D'Arminio Monforte, A. ; Castelli, F. ; Cauda, R. ; Di Perri, G. ; Galli, M. ; Iardino, R. ; Ippolito, G. ; Lazzarin, A. ; Perno, C. F. ; Von Schloesser, F. ; Viale, P. ; D'Arminio Monforte, A. ; Antinori, A. ; Castagna, A. ; Ceccherini-Silberstein, F. ; Cozzi-Lepri, A. ; Girardi, E. ; Lo Caputo, S. ; Mussini, C. ; Puoti, M. ; Andreoni, M. ; Ammassari, A. ; Antinori, A. ; Balotta, C. ; Bandera, A. ; Bonfanti, P. ; Bonora, S. ; Borderi, M. ; Calcagno, A. ; Calza, L. ; Capobianchi, M. R. ; Castagna, A. ; Ceccherini-Silberstein, F. ; Cingolani, A. ; Cinque, P. ; Cozzi-Lepri, A. ; D'Arminio Monforte, A. ; De Luca, A. ; Di Biagio, A. ; Girardi, E. ; Gianotti, N. ; Gori, A. ; Guaraldi, G. ; Lapadula, G. ; Lichtner, M. ; Lo Caputo, S. ; Madeddu, G. ; Maggiolo, F. ; Marchetti, G. ; Marcotullio, S. ; Monno, L. ; Mussini, C. ; Nozza, S. ; Puoti, M. ; Quiros Roldan, E. ; Rossotti, R. ; Rusconi, S. ; Santoro, M. M. ; Saracino, A. ; Zaccarelli, M. ; Cozzi-Lepri, A. ; Fanti, I. ; Galli, L. ; Lorenzini, P. ; Rodano, A. ; Shanyinde, M. ; Tavelli, A. / Prognostic Value of the Fibrosis-4 Index in Human Immunodeficiency Virus Type-1 Infected Patients Initiating Antiretroviral Therapy with or without Hepatitis C Virus. In: PLoS One. 2015 ; Vol. 10, No. 12.
@article{958ef12101d2419dab318f5e8a201a39,
title = "Prognostic Value of the Fibrosis-4 Index in Human Immunodeficiency Virus Type-1 Infected Patients Initiating Antiretroviral Therapy with or without Hepatitis C Virus",
abstract = "Objective: To evaluate the Fibrosis (FIB)-4 index as a predictor of major liver-related events (LRE) and liver-related death (LRD) in human immunodeficiency virus (HIV) type-1 patients initiating combination antiretroviral therapy (cART). Design: Retrospective analysis of a prospective cohort study. Setting: Italian HIV care centers participating to the ICONA Foundation cohort. Participants: Treatment-naive patients enrolled in ICONA were selected who: initiated cART, had hepatitis C virus (HCV) serology results, were HBsAg negative, had an available FIB-4 index at cART start and during follow up. Methods: Cox regression models were used to determine the association of FIB4 with the risk of major LRE (gastrointestinal bleeding, ascites, hepatic encephalopathy, hepato-renal syndrome or hepatocellular carcinoma) or LRD. Results: Three-thousand four-hundred seventy-five patients were enrolled: 73.3{\%} were males, 27.2{\%} HCV seropositive. At baseline (time of cART initiation) their median age was 39 years, had a median CD4+ T cell count of 260 cells/uL, and median HIV RNA 4.9 log copies/ mL, 65.9{\%} had a FIB-4 <1.45, 26.4{\%} 1.45-3.25 and 7.7{\%} > 3.25. Over a follow up of 18,662 person-years, 41 events were observed: 25 major LRE and 16 LRD (incidence rate, IR, 2.2 per 1,000 PYFU [95{\%} confidence interval, CI 1.6-3.0]). IR was higher in HCV seropositives as compared to negatives (5.9 vs 0.5 per 1,000 PYFU). Higher baseline FIB-4 category as compared to <1.45 (FIB-4 1.45-3.25: HR 3.55, 95{\%} CI 1.09-11.58; FIB-4 > 3.25: HR 4.25, 1.21-14.92) and time-updated FIB-4 (FIB-4 1.45-3.25: HR 3.40, 1.02-11.40; FIB- 4> 3.25: HR 21.24, 6.75-66.84) were independently predictive of major LRE/LRD, after adjusting for HIV- and HCV-related variables, alcohol consumption and type of cART. Conclusions: The FIB-4 index at cART initiation, and its modification over time are risk factors for major LRE or LRD, independently of infection with HCV and could be used to monitor patients on cART.",
author = "Cristina Mussini and Patrizia Lorenzini and Massimo Puoti and Miriam Lichtner and Giuseppe Lapadula and {Di Giambenedetto}, Simona and Andrea Antinori and Giordano Madeddu and Alessandro Cozzi-Lepri and {D'Arminio Monforte}, Antonella and {De Luca}, Andrea and M. Moroni and M. Andreoni and G. Angarano and A. Antinori and {D'Arminio Monforte}, A. and F. Castelli and R. Cauda and {Di Perri}, G. and M. Galli and R. Iardino and G. Ippolito and A. Lazzarin and Perno, {C. F.} and {Von Schloesser}, F. and P. Viale and {D'Arminio Monforte}, A. and A. Antinori and A. Castagna and F. Ceccherini-Silberstein and A. Cozzi-Lepri and E. Girardi and {Lo Caputo}, S. and C. Mussini and M. Puoti and M. Andreoni and A. Ammassari and A. Antinori and C. Balotta and A. Bandera and P. Bonfanti and S. Bonora and M. Borderi and A. Calcagno and L. Calza and Capobianchi, {M. R.} and A. Castagna and F. Ceccherini-Silberstein and A. Cingolani and P. Cinque and A. Cozzi-Lepri and {D'Arminio Monforte}, A. and {De Luca}, A. and {Di Biagio}, A. and E. Girardi and N. Gianotti and A. Gori and G. Guaraldi and G. Lapadula and M. Lichtner and {Lo Caputo}, S. and G. Madeddu and F. Maggiolo and G. Marchetti and S. Marcotullio and L. Monno and C. Mussini and S. Nozza and M. Puoti and {Quiros Roldan}, E. and R. Rossotti and S. Rusconi and Santoro, {M. M.} and A. Saracino and M. Zaccarelli and A. Cozzi-Lepri and I. Fanti and L. Galli and P. Lorenzini and A. Rodano and M. Shanyinde and A. Tavelli",
year = "2015",
month = "12",
day = "1",
doi = "10.1371/journal.pone.0140877",
language = "English",
volume = "10",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
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TY - JOUR

T1 - Prognostic Value of the Fibrosis-4 Index in Human Immunodeficiency Virus Type-1 Infected Patients Initiating Antiretroviral Therapy with or without Hepatitis C Virus

AU - Mussini, Cristina

AU - Lorenzini, Patrizia

AU - Puoti, Massimo

AU - Lichtner, Miriam

AU - Lapadula, Giuseppe

AU - Di Giambenedetto, Simona

AU - Antinori, Andrea

AU - Madeddu, Giordano

AU - Cozzi-Lepri, Alessandro

AU - D'Arminio Monforte, Antonella

AU - De Luca, Andrea

AU - Moroni, M.

AU - Andreoni, M.

AU - Angarano, G.

AU - Antinori, A.

AU - D'Arminio Monforte, A.

AU - Castelli, F.

AU - Cauda, R.

AU - Di Perri, G.

AU - Galli, M.

AU - Iardino, R.

AU - Ippolito, G.

AU - Lazzarin, A.

AU - Perno, C. F.

AU - Von Schloesser, F.

AU - Viale, P.

AU - D'Arminio Monforte, A.

AU - Antinori, A.

AU - Castagna, A.

AU - Ceccherini-Silberstein, F.

AU - Cozzi-Lepri, A.

AU - Girardi, E.

AU - Lo Caputo, S.

AU - Mussini, C.

AU - Puoti, M.

AU - Andreoni, M.

AU - Ammassari, A.

AU - Antinori, A.

AU - Balotta, C.

AU - Bandera, A.

AU - Bonfanti, P.

AU - Bonora, S.

AU - Borderi, M.

AU - Calcagno, A.

AU - Calza, L.

AU - Capobianchi, M. R.

AU - Castagna, A.

AU - Ceccherini-Silberstein, F.

AU - Cingolani, A.

AU - Cinque, P.

AU - Cozzi-Lepri, A.

AU - D'Arminio Monforte, A.

AU - De Luca, A.

AU - Di Biagio, A.

AU - Girardi, E.

AU - Gianotti, N.

AU - Gori, A.

AU - Guaraldi, G.

AU - Lapadula, G.

AU - Lichtner, M.

AU - Lo Caputo, S.

AU - Madeddu, G.

AU - Maggiolo, F.

AU - Marchetti, G.

AU - Marcotullio, S.

AU - Monno, L.

AU - Mussini, C.

AU - Nozza, S.

AU - Puoti, M.

AU - Quiros Roldan, E.

AU - Rossotti, R.

AU - Rusconi, S.

AU - Santoro, M. M.

AU - Saracino, A.

AU - Zaccarelli, M.

AU - Cozzi-Lepri, A.

AU - Fanti, I.

AU - Galli, L.

AU - Lorenzini, P.

AU - Rodano, A.

AU - Shanyinde, M.

AU - Tavelli, A.

PY - 2015/12/1

Y1 - 2015/12/1

N2 - Objective: To evaluate the Fibrosis (FIB)-4 index as a predictor of major liver-related events (LRE) and liver-related death (LRD) in human immunodeficiency virus (HIV) type-1 patients initiating combination antiretroviral therapy (cART). Design: Retrospective analysis of a prospective cohort study. Setting: Italian HIV care centers participating to the ICONA Foundation cohort. Participants: Treatment-naive patients enrolled in ICONA were selected who: initiated cART, had hepatitis C virus (HCV) serology results, were HBsAg negative, had an available FIB-4 index at cART start and during follow up. Methods: Cox regression models were used to determine the association of FIB4 with the risk of major LRE (gastrointestinal bleeding, ascites, hepatic encephalopathy, hepato-renal syndrome or hepatocellular carcinoma) or LRD. Results: Three-thousand four-hundred seventy-five patients were enrolled: 73.3% were males, 27.2% HCV seropositive. At baseline (time of cART initiation) their median age was 39 years, had a median CD4+ T cell count of 260 cells/uL, and median HIV RNA 4.9 log copies/ mL, 65.9% had a FIB-4 <1.45, 26.4% 1.45-3.25 and 7.7% > 3.25. Over a follow up of 18,662 person-years, 41 events were observed: 25 major LRE and 16 LRD (incidence rate, IR, 2.2 per 1,000 PYFU [95% confidence interval, CI 1.6-3.0]). IR was higher in HCV seropositives as compared to negatives (5.9 vs 0.5 per 1,000 PYFU). Higher baseline FIB-4 category as compared to <1.45 (FIB-4 1.45-3.25: HR 3.55, 95% CI 1.09-11.58; FIB-4 > 3.25: HR 4.25, 1.21-14.92) and time-updated FIB-4 (FIB-4 1.45-3.25: HR 3.40, 1.02-11.40; FIB- 4> 3.25: HR 21.24, 6.75-66.84) were independently predictive of major LRE/LRD, after adjusting for HIV- and HCV-related variables, alcohol consumption and type of cART. Conclusions: The FIB-4 index at cART initiation, and its modification over time are risk factors for major LRE or LRD, independently of infection with HCV and could be used to monitor patients on cART.

AB - Objective: To evaluate the Fibrosis (FIB)-4 index as a predictor of major liver-related events (LRE) and liver-related death (LRD) in human immunodeficiency virus (HIV) type-1 patients initiating combination antiretroviral therapy (cART). Design: Retrospective analysis of a prospective cohort study. Setting: Italian HIV care centers participating to the ICONA Foundation cohort. Participants: Treatment-naive patients enrolled in ICONA were selected who: initiated cART, had hepatitis C virus (HCV) serology results, were HBsAg negative, had an available FIB-4 index at cART start and during follow up. Methods: Cox regression models were used to determine the association of FIB4 with the risk of major LRE (gastrointestinal bleeding, ascites, hepatic encephalopathy, hepato-renal syndrome or hepatocellular carcinoma) or LRD. Results: Three-thousand four-hundred seventy-five patients were enrolled: 73.3% were males, 27.2% HCV seropositive. At baseline (time of cART initiation) their median age was 39 years, had a median CD4+ T cell count of 260 cells/uL, and median HIV RNA 4.9 log copies/ mL, 65.9% had a FIB-4 <1.45, 26.4% 1.45-3.25 and 7.7% > 3.25. Over a follow up of 18,662 person-years, 41 events were observed: 25 major LRE and 16 LRD (incidence rate, IR, 2.2 per 1,000 PYFU [95% confidence interval, CI 1.6-3.0]). IR was higher in HCV seropositives as compared to negatives (5.9 vs 0.5 per 1,000 PYFU). Higher baseline FIB-4 category as compared to <1.45 (FIB-4 1.45-3.25: HR 3.55, 95% CI 1.09-11.58; FIB-4 > 3.25: HR 4.25, 1.21-14.92) and time-updated FIB-4 (FIB-4 1.45-3.25: HR 3.40, 1.02-11.40; FIB- 4> 3.25: HR 21.24, 6.75-66.84) were independently predictive of major LRE/LRD, after adjusting for HIV- and HCV-related variables, alcohol consumption and type of cART. Conclusions: The FIB-4 index at cART initiation, and its modification over time are risk factors for major LRE or LRD, independently of infection with HCV and could be used to monitor patients on cART.

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U2 - 10.1371/journal.pone.0140877

DO - 10.1371/journal.pone.0140877

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SN - 1932-6203

IS - 12

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