Prospective Study
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Jul 8, 2016; 8(19): 815-824
Published online Jul 8, 2016. doi: 10.4254/wjh.v8.i19.815
Is neutrophil gelatinase associated lipocalin useful in hepatitis C virus infection?
Alessio Strazzulla, Giuseppe Coppolino, Concetta Di Fatta, Francesca Giancotti, Giuseppina D’Onofrio, Maria Concetta Postorino, Maria Mazzitelli, Selma Valerie Mammone, Innocenza Gentile, Laura Rivoli, Eleonora Palella, Tiziana Gravina, Chiara Costa, Vincenzo Pisani, Vincenzo De Maria, Giorgio Settimo Barreca, Nadia Marascio, Alfredo Focà, Giorgio Fuiano, Elio Gulletta, Carlo Torti
Alessio Strazzulla, Maria Concetta Postorino, Maria Mazzitelli, Selma Valerie Mammone, Chiara Costa, Vincenzo Pisani, Carlo Torti, Infectious Diseases Unit, Department of Medical and Surgical Sciences, “Magna Graecia” University, 88100 Catanzaro, Italy
Giuseppe Coppolino, Giuseppina D’Onofrio, Nephrology and Dialysis Unit, “Pugliese-Ciaccio” Hospital, 88100 Catanzaro, Italy
Concetta Di Fatta, Innocenza Gentile, Eleonora Palella, Elio Gulletta, Clinical Pathology Unit, Department of Health Sciences, “Magna Graecia” University, 88100 Catanzaro, Italy
Francesca Giancotti, Tiziana Gravina, Vincenzo De Maria, Hepatology Unit, “Mater Domini” Teaching Hospital, 88100 Catanzaro, Italy
Laura Rivoli, Giorgio Fuiano, Nephrology Unit, Department of Medical and Surgical Sciences, “Magna Graecia” University, 88100 Catanzaro, Italy
Giorgio Settimo Barreca, Nadia Marascio, Alfredo Focà, Microbiology Unit, Department of Health Sciences, “Magna Graecia” University, 88100 Catanzaro, Italy
Author contributions: Strazzulla A, Rivoli L and Torti C drafted the article; Coppolino G, Focà A, Fuiano G, Gulletta E and Torti C participated in oversight the study; Di Fatta C made NGAL measurements; Giancotti F, D’Onofrio G, Mazzitelli M, Mammone SV, Gravina T, Costa C, Pisani V, De Maria V and Marascio N were involved in data collection; Postorino MC and Rivoli L performed statistical analysis; Gentile I and Palella E were involved in storing samples; Barreca GS performed microbiological analysis; all authors approved the final version to be published.
Institutional review board statement: The study was approved by the IRB of “Mater Domini” Teaching Hospital in the session of January 2014.
Informed consent statement: All study participants provided written consent prior to study enrollment.
Conflict-of-interest statement: All authors declare that they do not have any conflicts of interest for the content of this paper.
Data sharing statement: There are no additional data available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Dr. Alessio Strazzulla, Infectious Diseases Unit, Department of Medical and Surgical Sciences, “Magna Graecia” University, Unità Operativa Malattie Infettive, Policlinico “Mater Domini”, viale Europa, 88100 Catanzaro, Italy. alessiostrazzulla@yahoo.it
Telephone: +39-961-3647203 Fax: +39-961-3647544
Received: January 26, 2016
Peer-review started: January 27, 2016
First decision: March 23, 2016
Revised: May 22, 2016
Accepted: June 14, 2016
Article in press: June 16, 2016
Published online: July 8, 2016
Processing time: 162 Days and 9.3 Hours
Abstract

AIM: To evaluate neutrophil gelatinase associated lipocalin (NGAL) in patients infected by hepatitis C virus (HCV) before and during treatment with directly acting antivirals (DAAs).

METHODS: NGAL was measured in a group of patients with chronic HCV infection ranked, at baseline, by age, gender, anti-hypertensive therapy, HCV viral load, liver fibrosis stage and, either at baseline or after 1 year, estimated glomerular filtration rate (eGFR). Then, NGAL and eGFR evolutions were monitored in a subgroup of patients who started antiviral therapy with DAAs. Differences of median NGAL levels were evaluated through Wilcoxon-Mann-Whitney test for non-parametric data. Differences in dichotomous variables were evaluated through χ2 test. At baseline, a univariate regression analysis was conducted to verify if NGAL values correlated with other quantitative variables [age, fibrosis four (FIB-4), AST to platelet ratio index (APRI), and eGFR].

RESULTS: Overall, 48 patients were enrolled, 8 of them starting HCV treatment. At baseline, statistically significant differences were found in median NGAL values only between patients with eGFR < 60 mL/min vs patients with eGFR ≥ 90 mL/min. Differences in NGAL were not significant among patients ranked by HCV viral load, FIB-4 score and APRI, when patients with NGAL > 118.11 ng/dL were compared with those of NGAL ≤ 118.11 ng/dL, not statistically significant differences were present for age, gender, chronic kidney disease classification and liver fibrosis (P > 0.05). Linear correlation was found between NGAL and both age (P = 0.0475) and eGFR (P = 0.0282) values. Not statistically significant predictions of NGAL at baseline were demonstrated for eGFR evolution 1 year later. Interestingly, in the 8 patients treated with DAAs, median NGAL significantly increased at week 12 compared to baseline (P = 0.0239).

CONCLUSION: Our results suggest that NGAL should be further evaluated as an adjunct marker of kidney function in these patients.

Keywords: Directly acting antivirals; Hepatitis C virus; Inflammation; Neutrophil gelatinase lipocalin; Tubular impairment

Core tip: For the first time, we evaluated the evolution of neutrophil gelatinase associated lipocalin (NGAL), a novel biomarker of renal impairment, in patients infected by hepatitis C virus before and during treatment with directly acting antivirals (DAAs). In our study, we documented a significant increase of NGAL during the first 12 wk of therapy with DAAs and a correlation of NGAL with both age and estimated glomerular filtration rate before starting treatment. In a context of paucity of information about safety of the new DAAs, we believe that these data are both informative and novel, provoking urgent investigations.