The gamma-glutamyl transpeptidase to platelet ratio (GPR) predicts significant liver fibrosis and cirrhosis in patients with chronic HBV infection in West Africa

Maud Lemoine, Yusuke Shimakawa, Shevanthi Nayagam, Mustapha Khalil, Penda Suso, Jo Lloyd, Robert Goldin, Harr-Freeya Njai, Gibril Ndow, Makie Taal, Graham Cooke, Umberto D'Alessandro, Muriel Vray, Papa Saliou Mbaye, Ramou Njie, Vincent Mallet, Mark Thursz, Maud Lemoine, Yusuke Shimakawa, Shevanthi Nayagam, Mustapha Khalil, Penda Suso, Jo Lloyd, Robert Goldin, Harr-Freeya Njai, Gibril Ndow, Makie Taal, Graham Cooke, Umberto D'Alessandro, Muriel Vray, Papa Saliou Mbaye, Ramou Njie, Vincent Mallet, Mark Thursz

Abstract

Background: Simple and inexpensive non-invasive fibrosis tests are highly needed but have been poorly studied in sub-Saharan Africa.

Methods: Using liver histology as a gold standard, we developed a novel index using routine laboratory tests to predict significant fibrosis in patients with chronic HBV infection in The Gambia, West Africa. We prospectively assessed the diagnostic accuracy of the novel index, Fibroscan, aspartate transaminase-to-platelet ratio index (APRI), and Fib-4 in Gambian patients with CHB (training set) and also in French and Senegalese CHB cohorts (validation sets).

Results: Of 135 consecutive treatment-naïve patients with CHB who had liver biopsy, 39% had significant fibrosis (Metavir fibrosis stage ≥F2) and 15% had cirrhosis (F4). In multivariable analysis, gamma-glutamyl transpeptidase (GGT) and platelet count were independent predictors of significant fibrosis. Consequently, GGT-to-platelet ratio (GPR) was developed. In The Gambia, the area under the receiver operating characteristic curve (AUROC) of the GPR was significantly higher than that of APRI and Fib-4 to predict ≥F2, ≥F3 and F4. In Senegal, the AUROC of GPR was significantly better than Fib-4 and APRI for ≥F2 (0.73, 95% CI 0.59 to 0.86) and better than Fib-4 and Fibroscan for ≥F3 (0.93, 0.87 to 0.99). In France, the AUROC of GPR to diagnose ≥F2 (0.72, 95% CI 0.59 to 0.85) and F4 (0.87, 0.76 to 0.98) was equivalent to that of APRI and Fib-4.

Conclusions: The GPR is a more accurate routine laboratory marker than APRI and Fib-4 to stage liver fibrosis in patients with CHB in West Africa. The GPR represents a simple and inexpensive alternative to liver biopsy and Fibroscan in sub-Saharan Africa.

Keywords: FIBROSIS; HEPATITIS B.

Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Figures

Figure 1
Figure 1
Flow diagram of the study population and reasons for exclusion, from November 2011 to November 2013, The Gambia. CHB, chronic HBV; HCC, hepatocellular carcinoma; HDV, hepatitis D virus; LB, liver biopsy; TB, tuberculosis.
Figure 2
Figure 2
Box plots of gamma-glutamyl transpeptidase (GGT) (A), platelet count (B), GGT to platelet ratio (GPR) (C), liver stiffness measurement (LSM) (D), aspartate transaminase-to-platelet ratio index (APRI) (E), and Fib-4 (F) according to the Metavir fibrosis stage in the Gambian cohort.

References

    1. Ott JJ, Stevens GA, Groeger J, et al. . Global epidemiology of hepatitis B virus infection: new estimates of age-specific HBsAg seroprevalence and endemicity. Vaccine 2012;30:2212–19. 10.1016/j.vaccine.2011.12.116
    1. Parkin DM, Sitas F, Chirenje M, et al. . Part I: Cancer in Indigenous Africans—burden, distribution, and trends. Lancet Oncol 2008;9:683–92. 10.1016/S1470-2045(08)70175-X
    1. Jemal A, Bray F, Forman D, et al. . Cancer burden in Africa and opportunities for prevention. Cancer 2012;118:4372–84. 10.1002/cncr.27410
    1. Thursz M, Njie R, Lemoine M. Hepatitis: global eradication of hepatitis B-feasible or fallacy? Nat Rev Gastroenterol Hepatol 2012;9:492–4. 10.1038/nrgastro.2012.155
    1. Castera L. Noninvasive methods to assess liver disease in patients with hepatitis B or C. Gastroenterology 2012;142:1293–302 e4. 10.1053/j.gastro.2012.02.017
    1. Marcellin P, Ziol M, Bedossa P, et al. . Non-invasive assessment of liver fibrosis by stiffness measurement in patients with chronic hepatitis B. Liver Int 2009;29:242–7. 10.1111/j.1478-3231.2008.01802.x
    1. Degos F, Perez P, Roche B, et al. . Diagnostic accuracy of FibroScan and comparison to liver fibrosis biomarkers in chronic viral hepatitis: a multicenter prospective study (the FIBROSTIC study). J Hepatol 2010;53:1013–21. 10.1016/j.jhep.2010.05.035
    1. Chan HL, Wong GL, Choi PC, et al. . Alanine aminotransferase-based algorithms of liver stiffness measurement by transient elastography (Fibroscan) for liver fibrosis in chronic hepatitis B. J Viral Hepat 2009;16:36–44. 10.1111/j.1365-2893.2008.01037.x
    1. Kim do Y, Kim SU, Ahn SH, et al. . Usefulness of FibroScan for detection of early compensated liver cirrhosis in chronic hepatitis B. Dig Dis Sci 2009;54:1758–63. 10.1007/s10620-008-0541-2
    1. Cardoso AC, Carvalho-Filho RJ, Stern C, et al. . Direct comparison of diagnostic performance of transient elastography in patients with chronic hepatitis B and chronic hepatitis C. Liver Int 2012;32:612–21. 10.1111/j.1478-3231.2011.02660.x
    1. Wai CT, Greenson JK, Fontana RJ, et al. . A simple noninvasive index can predict both significant fibrosis and cirrhosis in patients with chronic hepatitis C. Hepatology 2003;38:518–26.
    1. Sterling RK, Lissen E, Clumeck N, et al. . Development of a simple noninvasive index to predict significant fibrosis in patients with HIV/HCV coinfection. Hepatology 2006;43:1317–25. 10.1002/hep.21178
    1. WHO. World Health Organization. Guidelines for the Prevention, Care and Treatment of Persons with chronic Hepatitis B infection 2015. (accessed 17 Mar 2015).
    1. Bonnard P, Sombie R, Lescure FX, et al. . Comparison of elastography, serum marker scores, and histology for the assessment of liver fibrosis in hepatitis B virus (HBV)-infected patients in Burkina Faso. Am J Trop Med Hyg 2010;82:454–8. 10.4269/ajtmh.2010.09-0088
    1. Mbaye PS, Sarr A, Sire JM, et al. . Liver stiffness measurement and biochemical markers in Senegalese chronic hepatitis B patients with normal ALT and high viral load. PLoS ONE 2011;6:e22291 10.1371/journal.pone.0022291
    1. NCT02129829 clinicaltrialsorg. (15 Mar 2015).
    1. Mallet V, Dhalluin-Venier V, Roussin C, et al. . The accuracy of the FIB-4 index for the diagnosis of mild fibrosis in chronic hepatitis B. Aliment Pharmacol Ther 2009;29:409–15. 10.1111/j.1365-2036.2008.03895.x
    1. Njai HF, Shimakawa Y, Sanneh B, et al. . Validation of rapid point-of-care (POC) tests for the detection of hepatitis B surface antigen (HBsAg) in field and laboratory settings in The Gambia, West Africa. J Clin Microbiol 2015;53:1156–63. 10.1128/JCM.02980-14
    1. Coco B, Oliveri F, Maina AM, et al. . Transient elastography: a new surrogate marker of liver fibrosis influenced by major changes of transaminases. J Viral Hepat 2007;14:360–9. 10.1111/j.1365-2893.2006.00811.x
    1. Bedossa P, Poynard T. An algorithm for the grading of activity in chronic hepatitis C. The METAVIR Cooperative Study Group. Hepatology 1996;24:289–93. 10.1002/hep.510240201
    1. Lemoine M, Shimakawa Y, Njie R, et al. . Food intake increases liver stiffness measurements and hampers reliable values in patients with chronic hepatitis B and healthy controls: the PROLIFICA experience in The Gambia. Aliment Pharmacol Ther 2014;39:188–96. 10.1111/apt.12561
    1. Sandrin L, Fourquet B, Hasquenoph JM, et al. . Transient elastography: a new noninvasive method for assessment of hepatic fibrosis. Ultrasound Med Biol 2003;29:1705–13. 10.1016/j.ultrasmedbio.2003.07.001
    1. Boursier J, Zarski JP, de Ledinghen V, et al. . Determination of reliability criteria for liver stiffness evaluation by transient elastography. Hepatology 2013;57:1182–91. 10.1002/hep.25993
    1. Bossuyt PM, Reitsma JB, Bruns DE, et al. . Towards complete and accurate reporting of studies of diagnostic accuracy: the STARD initiative. Ann Intern Med 2003;138:40–4. 10.7326/0003-4819-138-1-200301070-00010
    1. Castera L, Foucher J, Bertet J, et al. . FibroScan and FibroTest to assess liver fibrosis in HCV with normal aminotransferases. Hepatology 2006;43:373–4; author reply 5–6 10.1002/hep.21019
    1. Ziol M, Handra-Luca A, Kettaneh A, et al. . Noninvasive assessment of liver fibrosis by measurement of stiffness in patients with chronic hepatitis C. Hepatology 2005;41:48–54. 10.1002/hep.20506
    1. Castera L, Vergniol J, Foucher J, et al. . Prospective comparison of transient elastography, Fibrotest, APRI, and liver biopsy for the assessment of fibrosis in chronic hepatitis C. Gastroenterology 2005;128:343–50. 10.1053/j.gastro.2004.11.018
    1. Castera L, Bernard PH, Le Bail B, et al. . Transient elastography and biomarkers for liver fibrosis assessment and follow-up of inactive hepatitis B carriers. Aliment Pharmacol Ther 2011;33:455–65. 10.1111/j.1365-2036.2010.04547.x
    1. Suthar AB, Rutherford GW, Horvath T, et al. . Improving antiretroviral therapy scale-up and effectiveness through service integration and decentralization. Aids 2014;28(Suppl 2):S175–85. 10.1097/QAD.0000000000000259
    1. Shin WG, Park SH, Jang MK, et al. . Aspartate aminotransferase to platelet ratio index (APRI) can predict liver fibrosis in chronic hepatitis B. Dig Liver Dis 2008;40:267–74. 10.1016/j.dld.2007.10.011
    1. Lemoine M, Njai HF, Shimakawa Y, et al. . Rural and urban community-based screening for HBs antigen in the Gambia: assessment of chronic hepatitis B and proportion of eligible patients for antiviral therapy. J Hepatol 2013;58.
    1. Myers RP, Tainturier MH, Ratziu V, et al. . Prediction of liver histological lesions with biochemical markers in patients with chronic hepatitis B. J Hepatol 2003;39:222–30. 10.1016/S0168-8278(03)00171-5
    1. Vardar R, Vardar E, Demiri S, et al. . Is there any non-invasive marker replace the needle liver biopsy predictive for liver fibrosis, in patients with chronic hepatitis? Hepatogastroenterology 2009;56:1459–65.
    1. Eminler AT, Irak K, Ayyildiz T, et al. . The relation between liver histopathology and GGT levels in viral hepatitis: more important in hepatitis B. Turk J Gastroenterol 2014;25:411–15.
    1. Choi BC. Sensitivity and specificity of a single diagnostic test in the presence of work-up bias. J Clin Epidemiol 1992;45:581–6. 10.1016/0895-4356(92)90129-B
    1. Bedossa P, Dargere D, Paradis V. Sampling variability of liver fibrosis in chronic hepatitis C. Hepatology 2003;38:1449–57. 10.1016/j.hep.2003.09.022

Source: PubMed

Sponsorit ja yhteistyökumppanit

Sairaudet

Huumeiden interventiot

3
Tilaa