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Published in: BMC Infectious Diseases 1/2017

Open Access 01-12-2017 | Research article

Novel serum biomarkers modified by the body mass index z-score for the detection of liver fibrosis and steatosis in children with chronic hepatitis C

Authors: Maria Pokorska-Śpiewak, Barbara Kowalik-Mikołajewska, Małgorzata Aniszewska, Magdalena Pluta, Magdalena Marczyńska

Published in: BMC Infectious Diseases | Issue 1/2017

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Abstract

Background

There is a need for validation of noninvasive alternatives to liver biopsy for the evaluation of fibrosis in children with chronic hepatitis C (CHC). The aim of this study was to evaluate the diagnostic performance of serum biomarkers modified by the body mass index z-score (BMI z-score) for the detection of fibrosis and steatosis in children with CHC.

Methods

Thirty children aged 9.4 ± 3.7 years (14 males, 16 females) with CHC underwent liver biopsy. Fibrosis was scored using a 5-point METAVIR scale (≥2 = significant fibrosis). For all the children, the following noninvasive markers were calculated: The aspartate transaminase (AST)-to-platelets ratio index (APRI), the modified APRI (M-APRI: BMI z-score × APRI), the Fibrosis-4 index (FIB-4), the modified FIB-4 (M-FIB-4: BMI z-score × FIB-4), and a novel marker, B-AST (BMI z-score × AST). The area under the receiver operator characteristic curve (AUROC) was calculated to detect significant fibrosis and steatosis.

Results

In the histopathological evaluation, 22/30 (73%) patients presented with fibrosis, and 8/30 (27%) presented with steatosis. For the detection of significant fibrosis, the AUROCs for M-APRI, M-FIB-4 and B-AST were 0.842, 0.823, and 0.848, respectively. For significant steatosis, the AUROCs were more than 0.9 for all markers that included the BMI z-score. B-AST, with a cut-off of 92.8, showed 71% sensitivity and 95% specificity for detecting significant fibrosis. For predicting severe steatosis, B-AST had 100% sensitivity and 92% specificity. Negative values of all three markers that included BMI z-scores excluded all patients with both significant fibrosis and significant steatosis.

Conclusions

Including the BMI z-score in serum biomarker formulas enhances their diagnostic ability to detect significant fibrosis and steatosis. B-AST may thus act as an effective alternative to liver biopsy.
Literature
1.
go back to reference Dezsofi A, Baumann U, Dhawan A, Durmaz O, Fischler B, Hadzic N, Hierro L, Lacaille F, McLin VA, Nobili V, et al. Liver biopsy in children: position paper of the ESPGHAN Hepatology committee. J Pediatr Gastroenterol Nutr. 2015;60(3):408–20.CrossRefPubMed Dezsofi A, Baumann U, Dhawan A, Durmaz O, Fischler B, Hadzic N, Hierro L, Lacaille F, McLin VA, Nobili V, et al. Liver biopsy in children: position paper of the ESPGHAN Hepatology committee. J Pediatr Gastroenterol Nutr. 2015;60(3):408–20.CrossRefPubMed
2.
go back to reference European Association for the Study of the Liver. EASL recommendations on treatment of hepatitis C 2016. J Hepatol. 2017;66(1):153–94.CrossRef European Association for the Study of the Liver. EASL recommendations on treatment of hepatitis C 2016. J Hepatol. 2017;66(1):153–94.CrossRef
3.
go back to reference Pokorska-Śpiewak M, Kowalik-Mikołajewska B, Aniszewska M, Pluta M, Marczyńska M. Is liver biopsy still needed in children with chronic viral hepatitis? World J Gastroenterol. 2015;21(42):12141–9.CrossRefPubMedPubMedCentral Pokorska-Śpiewak M, Kowalik-Mikołajewska B, Aniszewska M, Pluta M, Marczyńska M. Is liver biopsy still needed in children with chronic viral hepatitis? World J Gastroenterol. 2015;21(42):12141–9.CrossRefPubMedPubMedCentral
4.
go back to reference de Ledinghen V, Le Bail B, Rebouissoux L, Fournier C, Foucher J, Miette V, Castera L, Sandrin L, Merrouche W, Lavrand F, et al. Liver stiffness measurement in children using FibroScan: feasibility study and comparison with Fibrotest, aspartate transaminase to platelets ratio index, and liver biopsy. J Pediatr Gastroenterol Nutr. 2007;45(4):443–50.CrossRefPubMed de Ledinghen V, Le Bail B, Rebouissoux L, Fournier C, Foucher J, Miette V, Castera L, Sandrin L, Merrouche W, Lavrand F, et al. Liver stiffness measurement in children using FibroScan: feasibility study and comparison with Fibrotest, aspartate transaminase to platelets ratio index, and liver biopsy. J Pediatr Gastroenterol Nutr. 2007;45(4):443–50.CrossRefPubMed
5.
go back to reference Castera L. Noninvasive methods to assess liver disease in patients with hepatitis B or C. Gastroenterology. 2012;142(6):1293–1302.e1294.CrossRefPubMed Castera L. Noninvasive methods to assess liver disease in patients with hepatitis B or C. Gastroenterology. 2012;142(6):1293–1302.e1294.CrossRefPubMed
6.
go back to reference Sterling RK, Lissen E, Clumeck N, Sola R, Correa MC, Montaner J, S Sulkowski M, Torriani FJ, Dieterich DT, Thomas DL et al: Development of a simple noninvasive index to predict significant fibrosis in patients with HIV/HCV coinfection. Hepatology 2006, 43(6):1317–1325. Sterling RK, Lissen E, Clumeck N, Sola R, Correa MC, Montaner J, S Sulkowski M, Torriani FJ, Dieterich DT, Thomas DL et al: Development of a simple noninvasive index to predict significant fibrosis in patients with HIV/HCV coinfection. Hepatology 2006, 43(6):1317–1325.
7.
go back to reference Wai CT, Greenson JK, Fontana RJ, Kalbfleisch JD, Marrero JA, Conjeevaram HS, Lok AS. A simple noninvasive index can predict both significant fibrosis and cirrhosis in patients with chronic hepatitis C. Hepatology. 2003;38(2):518–26.CrossRefPubMed Wai CT, Greenson JK, Fontana RJ, Kalbfleisch JD, Marrero JA, Conjeevaram HS, Lok AS. A simple noninvasive index can predict both significant fibrosis and cirrhosis in patients with chronic hepatitis C. Hepatology. 2003;38(2):518–26.CrossRefPubMed
8.
go back to reference Zeng DW, Dong J, Liu YR, Jiang JJ, Zhu YY. Noninvasive models for assessment of liver fibrosis in patients with chronic hepatitis B virus infection. World J Gastroenterol. 2016;22(29):6663–72.CrossRefPubMedPubMedCentral Zeng DW, Dong J, Liu YR, Jiang JJ, Zhu YY. Noninvasive models for assessment of liver fibrosis in patients with chronic hepatitis B virus infection. World J Gastroenterol. 2016;22(29):6663–72.CrossRefPubMedPubMedCentral
9.
go back to reference Pokorska-Śpiewak M, Kowalik-Mikołajewska B, Aniszewska M, Pluta M, Walewska-Zielecka B, Marczyńska M. Determinants of liver disease progression in children with chronic hepatitis C virus infection. Pol J Pathol. 2015;66(4):368–75.CrossRefPubMed Pokorska-Śpiewak M, Kowalik-Mikołajewska B, Aniszewska M, Pluta M, Walewska-Zielecka B, Marczyńska M. Determinants of liver disease progression in children with chronic hepatitis C virus infection. Pol J Pathol. 2015;66(4):368–75.CrossRefPubMed
10.
go back to reference Pokorska-Śpiewak M, Kowalik-Mikołajewska B, Aniszewska M, Pluta M, Walewska-Zielecka B, Marczyńska M. Liver steatosis in children with chronic hepatitis B and C: prevalence, predictors, and impact on disease progression. Medicine (Baltimore). 2017;96(3):e5832.CrossRef Pokorska-Śpiewak M, Kowalik-Mikołajewska B, Aniszewska M, Pluta M, Walewska-Zielecka B, Marczyńska M. Liver steatosis in children with chronic hepatitis B and C: prevalence, predictors, and impact on disease progression. Medicine (Baltimore). 2017;96(3):e5832.CrossRef
11.
go back to reference Bedossa P, Poynard T. An algorithm for the grading of activity in chronic hepatitis C. The METAVIR Cooperative Study Group. Hepatology. 1996;24(2):289–93.CrossRefPubMed Bedossa P, Poynard T. An algorithm for the grading of activity in chronic hepatitis C. The METAVIR Cooperative Study Group. Hepatology. 1996;24(2):289–93.CrossRefPubMed
12.
go back to reference Panel AIHG. Hepatitis C guidance: AASLD-IDSA recommendations for testing, managing, and treating adults infected with hepatitis C virus. Hepatology. 2015;62(3):932–54.CrossRef Panel AIHG. Hepatitis C guidance: AASLD-IDSA recommendations for testing, managing, and treating adults infected with hepatitis C virus. Hepatology. 2015;62(3):932–54.CrossRef
13.
go back to reference Lin ZH, Xin YN, Dong QJ, Wang Q, Jiang XJ, Zhan SH, Sun Y, Xuan SY. Performance of the aspartate aminotransferase-to-platelet ratio index for the staging of hepatitis C-related fibrosis: an updated meta-analysis. Hepatology. 2011;53(3):726–36.CrossRefPubMed Lin ZH, Xin YN, Dong QJ, Wang Q, Jiang XJ, Zhan SH, Sun Y, Xuan SY. Performance of the aspartate aminotransferase-to-platelet ratio index for the staging of hepatitis C-related fibrosis: an updated meta-analysis. Hepatology. 2011;53(3):726–36.CrossRefPubMed
14.
go back to reference McGoogan KE, Smith PB, Choi SS, Berman W, Jhaveri R. Performance of the AST-to-platelet ratio index as a noninvasive marker of fibrosis in pediatric patients with chronic viral hepatitis. J Pediatr Gastroenterol Nutr. 2010;50(3):344–6.CrossRefPubMedPubMedCentral McGoogan KE, Smith PB, Choi SS, Berman W, Jhaveri R. Performance of the AST-to-platelet ratio index as a noninvasive marker of fibrosis in pediatric patients with chronic viral hepatitis. J Pediatr Gastroenterol Nutr. 2010;50(3):344–6.CrossRefPubMedPubMedCentral
15.
go back to reference Adinolfi LE, Gambardella M, Andreana A, Tripodi MF, Utili R, Ruggiero G. Steatosis accelerates the progression of liver damage of chronic hepatitis C patients and correlates with specific HCV genotype and visceral obesity. Hepatology. 2001;33(6):1358–64.CrossRefPubMed Adinolfi LE, Gambardella M, Andreana A, Tripodi MF, Utili R, Ruggiero G. Steatosis accelerates the progression of liver damage of chronic hepatitis C patients and correlates with specific HCV genotype and visceral obesity. Hepatology. 2001;33(6):1358–64.CrossRefPubMed
17.
go back to reference Guido M, Bortolotti F, Jara P, Giacomelli L, Fassan M, Hierro L, Nebbia G, Zancan L, Rugge M. Liver steatosis in children with chronic hepatitis C. Am J Gastroenterol. 2006;101(11):2611–5.CrossRefPubMed Guido M, Bortolotti F, Jara P, Giacomelli L, Fassan M, Hierro L, Nebbia G, Zancan L, Rugge M. Liver steatosis in children with chronic hepatitis C. Am J Gastroenterol. 2006;101(11):2611–5.CrossRefPubMed
18.
go back to reference Papagianni M, Sofogianni A, Tziomalos K. Non-invasive methods for the diagnosis of nonalcoholic fatty liver disease. World J Hepatol. 2015;7(4):638–48.CrossRefPubMedPubMedCentral Papagianni M, Sofogianni A, Tziomalos K. Non-invasive methods for the diagnosis of nonalcoholic fatty liver disease. World J Hepatol. 2015;7(4):638–48.CrossRefPubMedPubMedCentral
Metadata
Title
Novel serum biomarkers modified by the body mass index z-score for the detection of liver fibrosis and steatosis in children with chronic hepatitis C
Authors
Maria Pokorska-Śpiewak
Barbara Kowalik-Mikołajewska
Małgorzata Aniszewska
Magdalena Pluta
Magdalena Marczyńska
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Infectious Diseases / Issue 1/2017
Electronic ISSN: 1471-2334
DOI
https://doi.org/10.1186/s12879-017-2462-1

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