Noninvasive Biomarkers in Assessment of Liver Fibrosis in Patients with HBeAg Negative Chronic Hepatitis B

Authors

  • Marija Dimzova University Clinic for Infectious Diseases and Febrile Conditions, Faculty of Medicine, Ss Cyril and Methodius University of Skopje, Skopje
  • Irena Kondova-Topuzovska University Clinic for Infectious Diseases and Febrile Conditions, Faculty of Medicine, Ss Cyril and Methodius University of Skopje, Skopje
  • Mile Bosilkovski University Clinic for Infectious Diseases and Febrile Conditions, Faculty of Medicine, Ss Cyril and Methodius University of Skopje, Skopje
  • Ljubomir Ivanovski University Clinic for Infectious Diseases and Febrile Conditions, Faculty of Medicine, Ss Cyril and Methodius University of Skopje, Skopje
  • Zvonko Milenkovic University Clinic for Infectious Diseases and Febrile Conditions, Faculty of Medicine, Ss Cyril and Methodius University of Skopje, Skopje
  • Vesna Semenakova-Cvetkovska University Clinic for Infectious Diseases and Febrile Conditions, Faculty of Medicine, Ss Cyril and Methodius University of Skopje, Skopje
  • Nikola Orovcanec Institute of Epidemiology and Biostatistics, Faculty of Medicine, Ss Cyril and Methodius University of Skopje, Skopje

DOI:

https://doi.org/10.3889/oamjms.2018.122

Keywords:

Chronic hepatitis B, HBe antigen, Liver fibrosis, Noninvasive biomarkers, Transient elastography, APRI, FIB-4

Abstract

BACKGROUND: Liver biopsy for evaluation of liver fibrosis has several adverse effects, for which reason noninvasive tests have been developed.

AIM: To evaluate the usefulness of noninvasive biomarkers, qHBsAg and HBV DNA levels in predicting liver fibrosis in patients with hepatitis Be antigen (HBeAg) negative chronic hepatitis B (CHB).

MATERIAL AND METHODS: This prospective study included 50 patients with HBeAg negative CHB. All patients underwent laboratory and serology testing, quantification of HBV DNA and HBs antigen. The liver stiffness was measured with elastography. The patients were analysed for APRI and FIB-4, quantitative hepatitis Bs antigen and HBV DNA.

RESULTS: Logistic regression analysis showed that greatest significance in predicting liver fibrosis has FIB-4 (Wald = 3.24, P = 0.07), followed by HBV DNA ≥ 2 000 IU/ml ≤ 20 000 IU/ml (Wald = 2.86, P = 0.09), qHBsAg (Wald = 2.17, P = 0.14), HBV DNA > 20 000 IU/ml (Wald = 0.58, P = 0.45), APRI (Wald = 0.04, P = 0.84).

CONCLUSION: the FIB-4 index has the greatest value in predicting liver fibrosis while APRI has the lowest; the more advanced liver disease is associated with lower serum level of quantitative HBs antigen. Combination of noninvasive blood biomarkers and imaging tests can provide better diagnostic accuracy and exclude the need for liver biopsy.

Downloads

Download data is not yet available.

Metrics

Metrics Loading ...

Plum Analytics Artifact Widget Block

References

Kao JH, Chen DS. Global control of hepatitis B virus infection. Lancet Infect Dis. 2002; 2:395. https://doi.org/10.1016/S1473-3099(02)00315-8

Lok AS, McMahon AJ. Chronic hepatitis B. Hepatology. 2007; 45: 507 539. https://doi.org/10.1002/hep.21513 PMid:17256718

Lozano R et all. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012; 380:2095-2128. https://doi.org/10.1016/S0140-6736(12)61728-0

European Association for the Study of the Liver. EASL clinical practice guidelines: Management of chronic hepatitis B virus infection. J Hepatol. 2017; 67:370–398. https://doi.org/10.1016/j.jhep.2017.03.021 PMid:28427875

Chang ML, Liaw YF. Hepatitis B flares in chronic hepatitis B: pathogenesis, natural course, and management. J Hepatol. 2014; 61:1407â€1417. https://doi.org/10.1016/j.jhep.2014.08.033 PMid:25178562

Zeng DW et al. Noninvasive models for assessment of liver fibrosis in patients with chronic hepatitis B virus infection. World J Gastroenterol. 2016; 22(29): 6663-6672. https://doi.org/10.3748/wjg.v22.i29.6663 PMid:27547009 PMCid:PMC4970475

Terrault NA, Bzowej NH, Chang KM, Hwang JP, Jonas MM, Murad MH. AASLD guidelines for treatment of chronic hepatitis B. Hepatology. 2016; 63:261-283. https://doi.org/10.1002/hep.28156 PMid:26566064

Lee S, Kim DY. Non-invasive diagnosis of hepatitis B virus related cirrhosis. World J. Gastroenterol. 2014; 20(2): 445–459. https://doi.org/10.3748/wjg.v20.i2.445 PMid:24574713 PMCid:PMC3923019

European Association for Study of Liver; Asociacion Latinoamericana para el Estudio del Higado. EASL-ALEH Clinical Practice Guidelines: Non-invasive tests for evaluation of liver disease severity and prognosis. J Hepatol. 2015; 63:237-264. https://doi.org/10.1016/j.jhep.2015.04.006 PMid:25911335

Kim BK, Kim DY, Park JY, Ahn SH, Chon CY, Kim JK, Paik YH, Lee KS, Park YN, Han KH. Validation of FIB-4 and comparison with other simple noninvasive indices for predicting liver fibrosis and cirrhosis in hepatitis B virus-infected patients. Liver Int. 2010; 30: 546-553. https://doi.org/10.1111/j.1478-3231.2009.02192.x PMid:20074094

Mallet V, Dhalluin-Venier V, Roussin C, Bourliere M, Pettinelli ME, Giry C, Vallet-Pichard A, Fontaine H, Pol S. The accuracy of the FIB-4 index for the diagnosis of mild fibrosis in chronic hepatitis B. Aliment Pharmacol Ther. 2009; 29: 409-415. https://doi.org/10.1111/j.1365-2036.2008.03895.x PMid:19035983

Sterling RK, Lissen E, Clumeck N, et. al. Development of a simple noninvasive index to predict significant fibrosis patients with HIV/HCV co-infection. Hepatology. 2006; 43:1317-1325. https://doi.org/10.1002/hep.21178 PMid:16729309

Ma J, Jiang Y, Gong G. Evaluation of seven noninvasive models in staging liver fibrosis in patients with chronic hepatitis B virus infection. Eur J Gastroenterol Hepatol. 2013; 25: 428-434. https://doi.org/10.1097/MEG.0b013e32835cb5dd PMid:23358121

Ray Kim W, et all. Evaluation of APRI and FIB-4 scoring systems for non-invasive assessment of hepatic fibrosis in chronic hepatitis B patients. J Hepatol. 2016; 64: 773-780. https://doi.org/10.1016/j.jhep.2015.11.012 PMid:26626497

Werle–Lapostolle B, Bowden S, Locarnini S, et al. Persistence of cccDNA during the natural history of chronic hepatitis B and decline during adefovir dipivoxil therapy. Gastroenterology. 2004; 126:1750â€1758. https://doi.org/10.1053/j.gastro.2004.03.018 PMid:15188170

Manesis EK, Papatheodoridis GV, Tiniakos DG, et al. Hepatitis B surface antigen: relation to hepatitis B replication parameters in HBeAg negative chronic hepatitis B. J Hepatol. 2011; 55:61â€68. https://doi.org/10.1016/j.jhep.2010.10.027 PMid:21145875

Liaw YF. Clinical Utility of Hepatitis B surface Antigen Quantitation in Patients with Chronic Hepatitis B: A Review. Hepatology. 2011; 53:2121-2129. https://doi.org/10.1002/hep.24364 PMid:21503943

Chevaliez S. Is HBsAg quantification ready for prime time? Clin Res Hepatolo Gastroenterol. 2013; 37:559-63. https://doi.org/10.1016/j.clinre.2013.07.004 PMid:23932705

Martinot-Peginoux M et all: HBsAg quantification to predict natural history and treatment outcome in chronic hepatitis B patients. Clin Liver Dis. 2013; 17:399-412. https://doi.org/10.1016/j.cld.2013.05.006 PMid:23905812

Samant H, Joshi A et al. Correlation of Quantitative HBsAg with Quantitative HBV DNA in Different Phases of Chronic Hepatitis B (CHB) Patients. J Liver Res Disord Ther. 2016; 1(3). https://doi.org/10.15406/jlrdt.2016.01.00014

Brunetto MR, Oliveri F, Colombatto P, et al. Hepatitis B surface antigen serum levels help to distinguish active from inactive hepatitis B virus genotype D carriers. Gastroenterology. 2010; 139:483â€490. https://doi.org/10.1053/j.gastro.2010.04.052 PMid:20451520

Jaroszewicz J, Calle Serrano B, Wursthorn K, et al. Hepatitis B surface antigen (HBsAg) levels in the natural history of hepatitis B virus (HBV)- infection: A European perspective. J Hepatol. 2010; 52:514â€522. https://doi.org/10.1016/j.jhep.2010.01.014 PMid:20207438

Iloeje UH, Yang HI, Su J, et al. Predicting cirrhosis risk based on the level of circulating hepatitis B viral load. Gastroenterology. 2006; 130: 678–686. https://doi.org/10.1053/j.gastro.2005.11.016 PMid:16530509

Sharma P, Dhawan S, Bansal R, Tyagi P, Bansal N, Singla V, Kumar A, Matin A and Arora A. The usefulness of transient elastography by FibroScan for the evaluation of liver fibrosis. Indian J Gastroenterol. .2014; 33(5): 445 451. https://doi.org/10.1007/s12664-014-0491-x PMid:25138787

Stebbing J, Farouk L, Panos G, Anderson M, Jiao LR, Mandalia S, Bower M, Gazzard B, Nelson M. A meta analysis of transient elastography for the detection of hepatic fibrosis. J Clin Gastroenterol. 2010; 44: 214 219. https://doi.org/10.1097/MCG.0b013e3181b4af1f PMid:19745758

Lin ZH, Xin YN, Dong QJ, et al. Performance of the aspartate aminotransferase-to-platelet ratio index for the staging of hepatitis C-related fibrosis: an updated meta-analysis. Hepatology. 2011; 53:726-36. https://doi.org/10.1002/hep.24105 PMid:21319189

Croagh CM, Bell SJ, Slavin J, Kong YX, Chen RY, Locarnini S, Desmond PV. Increasing hepatitis B viral load is associated with risk of significant liver fibrosis in HBeAg-negative but not in HBeAg-positive chronic hepatitis B. Liver Int. 2010; 30 (8):1115–1122. https://doi.org/10.1111/j.1478-3231.2010.02267.x PMid:20492511

Xiao L, Xian J, Li Y, Geng A, Yang X, Han L, Xu H. Parameters Associated with Significant Liver Histological Changes in Patients with Chronic Hepatitis B. ISRN Gastroenterol. 2014; 2014:913890. https://doi.org/10.1155/2014/913890

Shao J, Wei L, Wang H, Sun Y, Zhang LF, Li J, Dong JQ. Relationship between hepatitis B virus DNA levels and liver histology in patients with chronic hepatitis B. World J Gastroenterol. 2007; 13(14):2104-7. https://doi.org/10.3748/wjg.v13.i14.2104 PMid:17465456 PMCid:PMC4319133

Yim HJ, Lok AS. Natural history of chronic hepatitis B virus infection: what we knew in 1981 and what we know in 2005. Hepatology. 2006; 43(1): S173-S181. https://doi.org/10.1002/hep.20956 PMid:16447285

Yuen MF, Ng IO, Fan ST, Yuan HJ, Wong DK, Yuen JC, Sum SS, Chan AO, Lai CL. Significance of HBV DNA levels in liver histology of HBeAg and Anti-HBe positive patients with chronic hepatitis B. Am J Gastroenterol. 2004; 99: 2032-2037. https://doi.org/10.1111/j.1572-0241.2004.40440.x PMid:15447768

Zacharakis G, Koskinas J, Kotsiou S, Tzara F, Vafeiadis N, Papoutselis M, Maltezos E, Sivridis E, Papoutselis K. The role of serial measurement of serum HBV DNA levels in patients with chronic HBeAg(-) hepatitis B infection: association with liver disease progression. A prospective cohort study. J Hepatol. 2008; 49 (6):884-91. https://doi.org/10.1016/j.jhep.2008.06.009 PMid:18674840

Gheorghița V. et al. Quantitative serum HBsAg in chronic hepatitis B. Therapeutics, Pharmacology and Clinical Toxicology. 2012; 16 (3): 155-162.

Cornberg M, Wong VW, Locarnini S, Brunetto M, Janssen HL, Chan HL. The role of quantitative hepatitis B surface antigen revisited. J Hepatol. 2017; 66:398â€411. https://doi.org/10.1016/j.jhep.2016.08.009 PMid:27575311

Martinot-Peignoux M, Lapalus M, Laouenan C, et al. Prediction of disease reactivation in asymptomatic hepatitis B e antigen-negative chronic hepatitis B patients using baseline serum measurements of HBsAg and HBV-DNA.J Clin Virol. 2013; 58:401â€407. https://doi.org/10.1016/j.jcv.2013.08.010 PMid:24004660

Xiang KH, Michailidis E, Ding H, et al. Effects of amino acid substitutions in hepatitis B virus surface protein on virion secretion, antigenicity,HBsAg and viral DNA. J Hepatol. 2017; 66:288â€296. https://doi.org/10.1016/j.jhep.2016.09.005 PMid:27650283 PMCid:PMC5523976

Martinot-Peignoux M, Carvalho RJ, Cardoso AC, Lapalus M, Lada O, Asselah T, Krause F, Marcellin P. Hepatitis B surface antigen serum level is associated with fibrosis severity in treatment-naïve, e antigen positive patients. Hepatol. 2013; 58(6):1089-95. https://doi.org/10.1016/j.jhep.2013.01.028 PMid:23369792

Scott R, Guha IN, Non-invasive monitoring of liver fibrosis. British Medical Bulletin. 2014; 112: 97–106. https://doi.org/10.1093/bmb/ldu031 PMid:25342721

Published

2018-06-08

How to Cite

1.
Dimzova M, Kondova-Topuzovska I, Bosilkovski M, Ivanovski L, Milenkovic Z, Semenakova-Cvetkovska V, Orovcanec N. Noninvasive Biomarkers in Assessment of Liver Fibrosis in Patients with HBeAg Negative Chronic Hepatitis B. Open Access Maced J Med Sci [Internet]. 2018 Jun. 8 [cited 2024 Apr. 26];6(6):1052-8. Available from: https://oamjms.eu/index.php/mjms/article/view/oamjms.2018.122

Issue

Section

B - Clinical Sciences