Hyaluronic Acid Levels Predict Risk of Hepatic Encephalopathy and Liver-Related Death in HIV/Viral Hepatitis Coinfected Patients

Lars Peters; Amanda Mocroft; Vincent Soriano; Jürgen Rockstroh; Andri Rauch; Anders Karlsson; Brygida Knysz; Christian Pradier; Kai Zilmer; Jens D. Lundgren; M. Losso; M. Kundro; N. Vetter; R. Zangerle; I. Karpov; A. Vassilenko; V. M. Mitsura; O. Suetnov; N. Clumeck; S. De Wit; M. Delforge; R. Colebunders; L. Vandekerckhove; V. Hadziosmanovic; K. Kostov; J. Begovac; L. Machala; D. Jilich; D. Sedlacek; J. Nielsen; G. Kronborg; T. Benfield; M. Larsen; J. Gerstoft; T. Katzenstein; A. B.E. Hansen; P. Skinhøj; C. Pedersen; L. Ostergaard; Jelena Smidt; M. Ristola; C. Katlama; J. P. Viard; P. M. Girard; J. M. Livrozet; P. Vanhems; F. Dabis; D. Neau; R. Schmidt; J. van Lunzen; O. Degen; H. J. Stellbrink; S. Staszewski; J. Bogner; G. Fätkenheuer; J. Kosmidis; P. Gargalianos; G. Xylomenos; J. Perdios; G. Panos; A. Filandras; E. Karabatsaki; H. Sambatakou; D. Banhegyi; F. Mulcahy; I. Yust; D. Turner; M. Burke; S. Pollack; G. Hassoun; S. Maayan; S. Vella; R. Esposito; I. Mazeu; C. Mussini; C. Arici; R. Pristera; F. Mazzotta; A. Gabbuti; V. Vullo; M. Lichtner; A. Chirianni; E. Montesarchio; M. Gargiulo; G. Antonucci; A. Testa; G. D̀offizi; C. Vlassi; M. Zaccarelli; A. Antorini; A. Lazzarin; A. Castagna; N. Gianotti; M. Galli; A. Ridolfo; A. d'Arminio Monforte; B. Rozentale; I. Zeltina; S. Chaplinskas; T. Staub; R. Hemmer; P. Reiss; V. Ormaasen; A. Maeland; J. Bruun; J. Gasiorowski; A. Horban; E. Bakowska; A. Grzeszczuk; R. Flisiak; A. Boron-Kaczmarska; M. Pynka; M. Parczewski; M. Beniowski; E. Mularska; H. Trocha; E. Jablonowska; E. Malolepsza; K. Wojcik; F. Antunes; M. Doroana; L. Caldeira; K. Mansinho; F. Maltez; D. Duiculescu; A. Rakhmanova; N. Zakharova; S. Buzunova; D. Jevtovic; M. Mokráš; D. Staneková; J. Tomazic; J. González-Lahoz; P. Labarga; J. Medrano; S. Moreno; J. M. Rodriguez; B. Clotet; A. Jou; R. Paredes; C. Tural; J. Puig; I. Bravo; J. M. Gatell; J. M. Miró; P. Domingo; M. Gutierrez; G. Mateo; M. A. Sambeat; A. Blaxhult; L. Flamholc; B. Ledergerber; R. Weber; P. Francioli; M. Cavassini; B. Hirschel; E. Boffi; H. Furrer; M. Battegay; L. Elzi; E. Kravchenko; N. Chentsova; V. Frolov; G. Kutsyna; S. Servitskiy; M. Krasnov; S. Barton; A. M. Johnson; D. Mercey; A. Phillips; M. A. Johnson; M. Murphy; J. Weber; G. Scullard; M. Fisher; C. Leen

doi:10.1371/journal.pone.0064283

Hyaluronic Acid Levels Predict Risk of Hepatic Encephalopathy and Liver-Related Death in HIV/Viral Hepatitis Coinfected Patients

Lars Peters^*, Amanda Mocroft, Vincent Soriano, Jürgen Rockstroh, Andri Rauch, Anders Karlsson, Brygida Knysz, Christian Pradier, Kai Zilmer, Jens D. Lundgren, M. Losso, M. Kundro, N. Vetter, R. Zangerle, I. Karpov, A. Vassilenko, V. M. Mitsura, O. Suetnov, N. Clumeck, S. De WitM. Delforge, R. Colebunders, L. Vandekerckhove, V. Hadziosmanovic, K. Kostov, J. Begovac, L. Machala, D. Jilich, D. Sedlacek, J. Nielsen, G. Kronborg, T. Benfield, M. Larsen, J. Gerstoft, T. Katzenstein, A. B.E. Hansen, P. Skinhøj, C. Pedersen, L. Ostergaard, Jelena Smidt, M. Ristola, C. Katlama, J. P. Viard, P. M. Girard, J. M. Livrozet, P. Vanhems, F. Dabis, D. Neau, R. Schmidt, J. van Lunzen, O. Degen, H. J. Stellbrink, S. Staszewski, J. Bogner, G. Fätkenheuer, J. Kosmidis, P. Gargalianos, G. Xylomenos, J. Perdios, G. Panos, A. Filandras, E. Karabatsaki, H. Sambatakou, D. Banhegyi, F. Mulcahy, I. Yust, D. Turner, M. Burke, S. Pollack, G. Hassoun, S. Maayan, S. Vella, R. Esposito, I. Mazeu, C. Mussini, C. Arici, R. Pristera, F. Mazzotta, A. Gabbuti, V. Vullo, M. Lichtner, A. Chirianni, E. Montesarchio, M. Gargiulo, G. Antonucci, A. Testa, G. D̀offizi, C. Vlassi, M. Zaccarelli, A. Antorini, A. Lazzarin, A. Castagna, N. Gianotti, M. Galli, A. Ridolfo, A. d'Arminio Monforte, B. Rozentale, I. Zeltina, S. Chaplinskas, T. Staub, R. Hemmer, P. Reiss, V. Ormaasen, A. Maeland, J. Bruun, J. Gasiorowski, A. Horban, E. Bakowska, A. Grzeszczuk, R. Flisiak, A. Boron-Kaczmarska, M. Pynka, M. Parczewski, M. Beniowski, E. Mularska, H. Trocha, E. Jablonowska, E. Malolepsza, K. Wojcik, F. Antunes, M. Doroana, L. Caldeira, K. Mansinho, F. Maltez, D. Duiculescu, A. Rakhmanova, N. Zakharova, S. Buzunova, D. Jevtovic, M. Mokráš, D. Staneková, J. Tomazic, J. González-Lahoz, P. Labarga, J. Medrano, S. Moreno, J. M. Rodriguez, B. Clotet, A. Jou, R. Paredes, C. Tural, J. Puig, I. Bravo, J. M. Gatell, J. M. Miró, P. Domingo, M. Gutierrez, G. Mateo, M. A. Sambeat, A. Blaxhult, L. Flamholc, B. Ledergerber, R. Weber, P. Francioli, M. Cavassini, B. Hirschel, E. Boffi, H. Furrer, M. Battegay, L. Elzi, E. Kravchenko, N. Chentsova, V. Frolov, G. Kutsyna, S. Servitskiy, M. Krasnov, S. Barton, A. M. Johnson, D. Mercey, A. Phillips, M. A. Johnson, M. Murphy, J. Weber, G. Scullard, M. Fisher, C. Leen

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

24 Scopus citations

Abstract

Background:Whereas it is well established that various soluble biomarkers can predict level of liver fibrosis, their ability to predict liver-related clinical outcomes is less clearly established, in particular among HIV/viral hepatitis co-infected persons. We investigated plasma hyaluronic acid's (HA) ability to predict risk of liver-related events (LRE; hepatic coma or liver-related death) in the EuroSIDA study.Methods:Patients included were positive for anti-HCV and/or HBsAg with at least one available plasma sample. The earliest collected plasma sample was tested for HA (normal range 0-75 ng/mL) and levels were associated with risk of LRE. Change in HA per year of follow-up was estimated after measuring HA levels in latest sample before the LRE for those experiencing this outcome (cases) and in a random selection of one sixth of the remaining patients (controls).Results:During a median of 8.2 years of follow-up, 84/1252 (6.7%) patients developed a LRE. Baseline median (IQR) HA in those without and with a LRE was 31.8 (17.2-62.6) and 221.6 ng/mL (74.9-611.3), respectively (p<0.0001). After adjustment, HA levels predicted risk of contracting a LRE; incidence rate ratios for HA levels 75-250 or ≥250 vs. <75 ng/mL were 5.22 (95% CI 2.86-9.26, p<0.0007) and 28.22 (95% CI 14.95-46.00, p<0.0001), respectively. Median HA levels increased substantially prior to developing a LRE (107.6 ng/mL, IQR 0.8 to 251.1), but remained stable for controls (1.0 ng/mL, IQR -5.1 to 8.2), (p<0.0001 comparing cases and controls), and greater increases predicted risk of a LRE in adjusted models (p<0.001).Conclusions:An elevated level of plasma HA, particularly if the level further increases over time, substantially increases the risk of contracting LRE over the next five years. HA is an inexpensive, standardized and non-invasive supplement to other methods aimed at identifying HIV/viral hepatitis co-infected patients at risk of hepatic complications.

Original language	English
Article number	e64283
Journal	PLoS ONE
Volume	8
Issue number	5
DOIs	https://doi.org/10.1371/journal.pone.0064283
State	Published - 27 May 2013
Externally published	Yes

Funding

Funders	Funder number
European Commission
Seventh Framework Programme	260694
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung	108787

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1371/journal.pone.0064283

Cite this

Peters, L., Mocroft, A., Soriano, V., Rockstroh, J., Rauch, A., Karlsson, A., Knysz, B., Pradier, C., Zilmer, K., Lundgren, J. D., Losso, M., Kundro, M., Vetter, N., Zangerle, R., Karpov, I., Vassilenko, A., Mitsura, V. M., Suetnov, O., Clumeck, N., ... Leen, C. (2013). Hyaluronic Acid Levels Predict Risk of Hepatic Encephalopathy and Liver-Related Death in HIV/Viral Hepatitis Coinfected Patients. PLoS ONE, 8(5), Article e64283. https://doi.org/10.1371/journal.pone.0064283

@article{54b66de8820240c98f535b5d5f444788,

title = "Hyaluronic Acid Levels Predict Risk of Hepatic Encephalopathy and Liver-Related Death in HIV/Viral Hepatitis Coinfected Patients",

abstract = "Background:Whereas it is well established that various soluble biomarkers can predict level of liver fibrosis, their ability to predict liver-related clinical outcomes is less clearly established, in particular among HIV/viral hepatitis co-infected persons. We investigated plasma hyaluronic acid's (HA) ability to predict risk of liver-related events (LRE; hepatic coma or liver-related death) in the EuroSIDA study.Methods:Patients included were positive for anti-HCV and/or HBsAg with at least one available plasma sample. The earliest collected plasma sample was tested for HA (normal range 0-75 ng/mL) and levels were associated with risk of LRE. Change in HA per year of follow-up was estimated after measuring HA levels in latest sample before the LRE for those experiencing this outcome (cases) and in a random selection of one sixth of the remaining patients (controls).Results:During a median of 8.2 years of follow-up, 84/1252 (6.7%) patients developed a LRE. Baseline median (IQR) HA in those without and with a LRE was 31.8 (17.2-62.6) and 221.6 ng/mL (74.9-611.3), respectively (p<0.0001). After adjustment, HA levels predicted risk of contracting a LRE; incidence rate ratios for HA levels 75-250 or ≥250 vs. <75 ng/mL were 5.22 (95% CI 2.86-9.26, p<0.0007) and 28.22 (95% CI 14.95-46.00, p<0.0001), respectively. Median HA levels increased substantially prior to developing a LRE (107.6 ng/mL, IQR 0.8 to 251.1), but remained stable for controls (1.0 ng/mL, IQR -5.1 to 8.2), (p<0.0001 comparing cases and controls), and greater increases predicted risk of a LRE in adjusted models (p<0.001).Conclusions:An elevated level of plasma HA, particularly if the level further increases over time, substantially increases the risk of contracting LRE over the next five years. HA is an inexpensive, standardized and non-invasive supplement to other methods aimed at identifying HIV/viral hepatitis co-infected patients at risk of hepatic complications.",

author = "Lars Peters and Amanda Mocroft and Vincent Soriano and J{\"u}rgen Rockstroh and Andri Rauch and Anders Karlsson and Brygida Knysz and Christian Pradier and Kai Zilmer and Lundgren, {Jens D.} and M. Losso and M. Kundro and N. Vetter and R. Zangerle and I. Karpov and A. Vassilenko and Mitsura, {V. M.} and O. Suetnov and N. Clumeck and {De Wit}, S. and M. Delforge and R. Colebunders and L. Vandekerckhove and V. Hadziosmanovic and K. Kostov and J. Begovac and L. Machala and D. Jilich and D. Sedlacek and J. Nielsen and G. Kronborg and T. Benfield and M. Larsen and J. Gerstoft and T. Katzenstein and Hansen, {A. B.E.} and P. Skinh{\o}j and C. Pedersen and L. Ostergaard and Jelena Smidt and M. Ristola and C. Katlama and Viard, {J. P.} and Girard, {P. M.} and Livrozet, {J. M.} and P. Vanhems and F. Dabis and D. Neau and R. Schmidt and {van Lunzen}, J. and O. Degen and Stellbrink, {H. J.} and S. Staszewski and J. Bogner and G. F{\"a}tkenheuer and J. Kosmidis and P. Gargalianos and G. Xylomenos and J. Perdios and G. Panos and A. Filandras and E. Karabatsaki and H. Sambatakou and D. Banhegyi and F. Mulcahy and I. Yust and D. Turner and M. Burke and S. Pollack and G. Hassoun and S. Maayan and S. Vella and R. Esposito and I. Mazeu and C. Mussini and C. Arici and R. Pristera and F. Mazzotta and A. Gabbuti and V. Vullo and M. Lichtner and A. Chirianni and E. Montesarchio and M. Gargiulo and G. Antonucci and A. Testa and G. {\`D}offizi and C. Vlassi and M. Zaccarelli and A. Antorini and A. Lazzarin and A. Castagna and N. Gianotti and M. Galli and A. Ridolfo and {d'Arminio Monforte}, A. and B. Rozentale and I. Zeltina and S. Chaplinskas and T. Staub and R. Hemmer and P. Reiss and V. Ormaasen and A. Maeland and J. Bruun and J. Gasiorowski and A. Horban and E. Bakowska and A. Grzeszczuk and R. Flisiak and A. Boron-Kaczmarska and M. Pynka and M. Parczewski and M. Beniowski and E. Mularska and H. Trocha and E. Jablonowska and E. Malolepsza and K. Wojcik and F. Antunes and M. Doroana and L. Caldeira and K. Mansinho and F. Maltez and D. Duiculescu and A. Rakhmanova and N. Zakharova and S. Buzunova and D. Jevtovic and M. Mokr{\'a}{\v s} and D. Stanekov{\'a} and J. Tomazic and J. Gonz{\'a}lez-Lahoz and P. Labarga and J. Medrano and S. Moreno and Rodriguez, {J. M.} and B. Clotet and A. Jou and R. Paredes and C. Tural and J. Puig and I. Bravo and Gatell, {J. M.} and Mir{\'o}, {J. M.} and P. Domingo and M. Gutierrez and G. Mateo and Sambeat, {M. A.} and A. Blaxhult and L. Flamholc and B. Ledergerber and R. Weber and P. Francioli and M. Cavassini and B. Hirschel and E. Boffi and H. Furrer and M. Battegay and L. Elzi and E. Kravchenko and N. Chentsova and V. Frolov and G. Kutsyna and S. Servitskiy and M. Krasnov and S. Barton and Johnson, {A. M.} and D. Mercey and A. Phillips and Johnson, {M. A.} and M. Murphy and J. Weber and G. Scullard and M. Fisher and C. Leen",

note = "Funding Information: The authors have declared that no competing interests exist. The EuroSIDA study has received unrestricted grants from Bristol-Myers-Squibb, GlaxoSmithKline, Roche, Gilead, Pfizer, Merck, Tibotec and Boehringer-Ingelheim. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials. ",

year = "2013",

month = may,

day = "27",

doi = "10.1371/journal.pone.0064283",

language = "אנגלית",

volume = "8",

journal = "PLoS ONE",

issn = "1932-6203",

publisher = "Public Library of Science",

number = "5",

}

Peters, L, Mocroft, A, Soriano, V, Rockstroh, J, Rauch, A, Karlsson, A, Knysz, B, Pradier, C, Zilmer, K, Lundgren, JD, Losso, M, Kundro, M, Vetter, N, Zangerle, R, Karpov, I, Vassilenko, A, Mitsura, VM, Suetnov, O, Clumeck, N, De Wit, S, Delforge, M, Colebunders, R, Vandekerckhove, L, Hadziosmanovic, V, Kostov, K, Begovac, J, Machala, L, Jilich, D, Sedlacek, D, Nielsen, J, Kronborg, G, Benfield, T, Larsen, M, Gerstoft, J, Katzenstein, T, Hansen, ABE, Skinhøj, P, Pedersen, C, Ostergaard, L, Smidt, J, Ristola, M, Katlama, C, Viard, JP, Girard, PM, Livrozet, JM, Vanhems, P, Dabis, F, Neau, D, Schmidt, R, van Lunzen, J, Degen, O, Stellbrink, HJ, Staszewski, S, Bogner, J, Fätkenheuer, G, Kosmidis, J, Gargalianos, P, Xylomenos, G, Perdios, J, Panos, G, Filandras, A, Karabatsaki, E, Sambatakou, H, Banhegyi, D, Mulcahy, F, Yust, I, Turner, D, Burke, M, Pollack, S, Hassoun, G, Maayan, S, Vella, S, Esposito, R, Mazeu, I, Mussini, C, Arici, C, Pristera, R, Mazzotta, F, Gabbuti, A, Vullo, V, Lichtner, M, Chirianni, A, Montesarchio, E, Gargiulo, M, Antonucci, G, Testa, A, D̀offizi, G, Vlassi, C, Zaccarelli, M, Antorini, A, Lazzarin, A, Castagna, A, Gianotti, N, Galli, M, Ridolfo, A, d'Arminio Monforte, A, Rozentale, B, Zeltina, I, Chaplinskas, S, Staub, T, Hemmer, R, Reiss, P, Ormaasen, V, Maeland, A, Bruun, J, Gasiorowski, J, Horban, A, Bakowska, E, Grzeszczuk, A, Flisiak, R, Boron-Kaczmarska, A, Pynka, M, Parczewski, M, Beniowski, M, Mularska, E, Trocha, H, Jablonowska, E, Malolepsza, E, Wojcik, K, Antunes, F, Doroana, M, Caldeira, L, Mansinho, K, Maltez, F, Duiculescu, D, Rakhmanova, A, Zakharova, N, Buzunova, S, Jevtovic, D, Mokráš, M, Staneková, D, Tomazic, J, González-Lahoz, J, Labarga, P, Medrano, J, Moreno, S, Rodriguez, JM, Clotet, B, Jou, A, Paredes, R, Tural, C, Puig, J, Bravo, I, Gatell, JM, Miró, JM, Domingo, P, Gutierrez, M, Mateo, G, Sambeat, MA, Blaxhult, A, Flamholc, L, Ledergerber, B, Weber, R, Francioli, P, Cavassini, M, Hirschel, B, Boffi, E, Furrer, H, Battegay, M, Elzi, L, Kravchenko, E, Chentsova, N, Frolov, V, Kutsyna, G, Servitskiy, S, Krasnov, M, Barton, S, Johnson, AM, Mercey, D, Phillips, A, Johnson, MA, Murphy, M, Weber, J, Scullard, G, Fisher, M & Leen, C 2013, 'Hyaluronic Acid Levels Predict Risk of Hepatic Encephalopathy and Liver-Related Death in HIV/Viral Hepatitis Coinfected Patients', PLoS ONE, vol. 8, no. 5, e64283. https://doi.org/10.1371/journal.pone.0064283

TY - JOUR

T1 - Hyaluronic Acid Levels Predict Risk of Hepatic Encephalopathy and Liver-Related Death in HIV/Viral Hepatitis Coinfected Patients

AU - Peters, Lars

AU - Mocroft, Amanda

AU - Soriano, Vincent

AU - Rockstroh, Jürgen

AU - Rauch, Andri

AU - Karlsson, Anders

AU - Knysz, Brygida

AU - Pradier, Christian

AU - Zilmer, Kai

AU - Lundgren, Jens D.

AU - Losso, M.

AU - Kundro, M.

AU - Vetter, N.

AU - Zangerle, R.

AU - Karpov, I.

AU - Vassilenko, A.

AU - Mitsura, V. M.

AU - Suetnov, O.

AU - Clumeck, N.

AU - De Wit, S.

AU - Delforge, M.

AU - Colebunders, R.

AU - Vandekerckhove, L.

AU - Hadziosmanovic, V.

AU - Kostov, K.

AU - Begovac, J.

AU - Machala, L.

AU - Jilich, D.

AU - Sedlacek, D.

AU - Nielsen, J.

AU - Kronborg, G.

AU - Benfield, T.

AU - Larsen, M.

AU - Gerstoft, J.

AU - Katzenstein, T.

AU - Hansen, A. B.E.

AU - Skinhøj, P.

AU - Pedersen, C.

AU - Ostergaard, L.

AU - Smidt, Jelena

AU - Ristola, M.

AU - Katlama, C.

AU - Viard, J. P.

AU - Girard, P. M.

AU - Livrozet, J. M.

AU - Vanhems, P.

AU - Dabis, F.

AU - Neau, D.

AU - Schmidt, R.

AU - van Lunzen, J.

AU - Degen, O.

AU - Stellbrink, H. J.

AU - Staszewski, S.

AU - Bogner, J.

AU - Fätkenheuer, G.

AU - Kosmidis, J.

AU - Gargalianos, P.

AU - Xylomenos, G.

AU - Perdios, J.

AU - Panos, G.

AU - Filandras, A.

AU - Karabatsaki, E.

AU - Sambatakou, H.

AU - Banhegyi, D.

AU - Mulcahy, F.

AU - Yust, I.

AU - Turner, D.

AU - Burke, M.

AU - Pollack, S.

AU - Hassoun, G.

AU - Maayan, S.

AU - Vella, S.

AU - Esposito, R.

AU - Mazeu, I.

AU - Mussini, C.

AU - Arici, C.

AU - Pristera, R.

AU - Mazzotta, F.

AU - Gabbuti, A.

AU - Vullo, V.

AU - Lichtner, M.

AU - Chirianni, A.

AU - Montesarchio, E.

AU - Gargiulo, M.

AU - Antonucci, G.

AU - Testa, A.

AU - D̀offizi, G.

AU - Vlassi, C.

AU - Zaccarelli, M.

AU - Antorini, A.

AU - Lazzarin, A.

AU - Castagna, A.

AU - Gianotti, N.

AU - Galli, M.

AU - Ridolfo, A.

AU - d'Arminio Monforte, A.

AU - Rozentale, B.

AU - Zeltina, I.

AU - Chaplinskas, S.

AU - Staub, T.

AU - Hemmer, R.

AU - Reiss, P.

AU - Ormaasen, V.

AU - Maeland, A.

AU - Bruun, J.

AU - Gasiorowski, J.

AU - Horban, A.

AU - Bakowska, E.

AU - Grzeszczuk, A.

AU - Flisiak, R.

AU - Boron-Kaczmarska, A.

AU - Pynka, M.

AU - Parczewski, M.

AU - Beniowski, M.

AU - Mularska, E.

AU - Trocha, H.

AU - Jablonowska, E.

AU - Malolepsza, E.

AU - Wojcik, K.

AU - Antunes, F.

AU - Doroana, M.

AU - Caldeira, L.

AU - Mansinho, K.

AU - Maltez, F.

AU - Duiculescu, D.

AU - Rakhmanova, A.

AU - Zakharova, N.

AU - Buzunova, S.

AU - Jevtovic, D.

AU - Mokráš, M.

AU - Staneková, D.

AU - Tomazic, J.

AU - González-Lahoz, J.

AU - Labarga, P.

AU - Medrano, J.

AU - Moreno, S.

AU - Rodriguez, J. M.

AU - Clotet, B.

AU - Jou, A.

AU - Paredes, R.

AU - Tural, C.

AU - Puig, J.

AU - Bravo, I.

AU - Gatell, J. M.

AU - Miró, J. M.

AU - Domingo, P.

AU - Gutierrez, M.

AU - Mateo, G.

AU - Sambeat, M. A.

AU - Blaxhult, A.

AU - Flamholc, L.

AU - Ledergerber, B.

AU - Weber, R.

AU - Francioli, P.

AU - Cavassini, M.

AU - Hirschel, B.

AU - Boffi, E.

AU - Furrer, H.

AU - Battegay, M.

AU - Elzi, L.

AU - Kravchenko, E.

AU - Chentsova, N.

AU - Frolov, V.

AU - Kutsyna, G.

AU - Servitskiy, S.

AU - Krasnov, M.

AU - Barton, S.

AU - Johnson, A. M.

AU - Mercey, D.

AU - Phillips, A.

AU - Johnson, M. A.

AU - Murphy, M.

AU - Weber, J.

AU - Scullard, G.

AU - Fisher, M.

AU - Leen, C.

N1 - Funding Information: The authors have declared that no competing interests exist. The EuroSIDA study has received unrestricted grants from Bristol-Myers-Squibb, GlaxoSmithKline, Roche, Gilead, Pfizer, Merck, Tibotec and Boehringer-Ingelheim. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials.

PY - 2013/5/27

Y1 - 2013/5/27

N2 - Background:Whereas it is well established that various soluble biomarkers can predict level of liver fibrosis, their ability to predict liver-related clinical outcomes is less clearly established, in particular among HIV/viral hepatitis co-infected persons. We investigated plasma hyaluronic acid's (HA) ability to predict risk of liver-related events (LRE; hepatic coma or liver-related death) in the EuroSIDA study.Methods:Patients included were positive for anti-HCV and/or HBsAg with at least one available plasma sample. The earliest collected plasma sample was tested for HA (normal range 0-75 ng/mL) and levels were associated with risk of LRE. Change in HA per year of follow-up was estimated after measuring HA levels in latest sample before the LRE for those experiencing this outcome (cases) and in a random selection of one sixth of the remaining patients (controls).Results:During a median of 8.2 years of follow-up, 84/1252 (6.7%) patients developed a LRE. Baseline median (IQR) HA in those without and with a LRE was 31.8 (17.2-62.6) and 221.6 ng/mL (74.9-611.3), respectively (p<0.0001). After adjustment, HA levels predicted risk of contracting a LRE; incidence rate ratios for HA levels 75-250 or ≥250 vs. <75 ng/mL were 5.22 (95% CI 2.86-9.26, p<0.0007) and 28.22 (95% CI 14.95-46.00, p<0.0001), respectively. Median HA levels increased substantially prior to developing a LRE (107.6 ng/mL, IQR 0.8 to 251.1), but remained stable for controls (1.0 ng/mL, IQR -5.1 to 8.2), (p<0.0001 comparing cases and controls), and greater increases predicted risk of a LRE in adjusted models (p<0.001).Conclusions:An elevated level of plasma HA, particularly if the level further increases over time, substantially increases the risk of contracting LRE over the next five years. HA is an inexpensive, standardized and non-invasive supplement to other methods aimed at identifying HIV/viral hepatitis co-infected patients at risk of hepatic complications.

AB - Background:Whereas it is well established that various soluble biomarkers can predict level of liver fibrosis, their ability to predict liver-related clinical outcomes is less clearly established, in particular among HIV/viral hepatitis co-infected persons. We investigated plasma hyaluronic acid's (HA) ability to predict risk of liver-related events (LRE; hepatic coma or liver-related death) in the EuroSIDA study.Methods:Patients included were positive for anti-HCV and/or HBsAg with at least one available plasma sample. The earliest collected plasma sample was tested for HA (normal range 0-75 ng/mL) and levels were associated with risk of LRE. Change in HA per year of follow-up was estimated after measuring HA levels in latest sample before the LRE for those experiencing this outcome (cases) and in a random selection of one sixth of the remaining patients (controls).Results:During a median of 8.2 years of follow-up, 84/1252 (6.7%) patients developed a LRE. Baseline median (IQR) HA in those without and with a LRE was 31.8 (17.2-62.6) and 221.6 ng/mL (74.9-611.3), respectively (p<0.0001). After adjustment, HA levels predicted risk of contracting a LRE; incidence rate ratios for HA levels 75-250 or ≥250 vs. <75 ng/mL were 5.22 (95% CI 2.86-9.26, p<0.0007) and 28.22 (95% CI 14.95-46.00, p<0.0001), respectively. Median HA levels increased substantially prior to developing a LRE (107.6 ng/mL, IQR 0.8 to 251.1), but remained stable for controls (1.0 ng/mL, IQR -5.1 to 8.2), (p<0.0001 comparing cases and controls), and greater increases predicted risk of a LRE in adjusted models (p<0.001).Conclusions:An elevated level of plasma HA, particularly if the level further increases over time, substantially increases the risk of contracting LRE over the next five years. HA is an inexpensive, standardized and non-invasive supplement to other methods aimed at identifying HIV/viral hepatitis co-infected patients at risk of hepatic complications.

UR - http://www.scopus.com/inward/record.url?scp=84878329914&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0064283

DO - 10.1371/journal.pone.0064283

M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???

AN - SCOPUS:84878329914

SN - 1932-6203

VL - 8

JO - PLoS ONE

JF - PLoS ONE

IS - 5

M1 - e64283

ER -

Hyaluronic Acid Levels Predict Risk of Hepatic Encephalopathy and Liver-Related Death in HIV/Viral Hepatitis Coinfected Patients

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