Diagnostic accuracy of biochemical markers of fibrosis in black African patients with chronic hepatitis B

Alassan Kouamé Mahassadi, Alain Koffi Attia, Fulgence M. Yao Bathaix, Narcisse Baudouin Agbé, Stanislas Doffou, Henriette Ya Kissi, Isidore Mouhenou Diomandé, Paul Cales, Thérese Ndri-Yoman
DOI: 10.4236/health.2010.212210                

Abstract

Contradictory results of the accuracy of bio-chemical markers to predict the stage of fibrosis in black African patients with chronic hepatitis B (CHB) were previously published. We con-ducted a prospective cohort study to determine the diagnostic accuracy of aspartate ami-notransferase to platelet ratio (APRI), aspartate aminotransferase to alanine aminotransferase ratio (AAR), platelet count, age-platelet (AP) in-dex, and FIB-4 index for the prediction of sig-nificant fibrosis or cirrhosis in 117 black African patients (median age: 38 years, males: 73 %) with CHB not previously treated. Among them, 45 had significant fibrosis and 18 had cirrhosis using the METAVIR score system. Factors as-sociated either with significant fibrosis or cir-rhosis were determined in logistic multivariate analysis. Areas under receiver operating curve were assessed and compared for APRI, AAR, AP index, FIB-4 index and platelet count. Sensitivity, specificity, positive and negative predictive values were determined for each biochemical markers. Multivariate analysis showed that as-partate aminotransferase (p<0.0001) and plate-lets (p=0.03) were the independent factors as-sociated with significant fibrosis and only platelets (p=0.01) were associated with cirrhosis. APRI (cut-off > 1.1) and FIB-4 index (cut-off > 2.1) ruled out significant fibrosis with high specific-ity of 84.7 % and 86.1 % respectively and nega-tive predictive values of 78.2 % and 72.9 % re-spectively. More accurately, APRI (cut-off > 0.63) or FIB-4 index (cut-off > 1.26) ruled out cirrhosis with high sensitivity of 94.4% and 88.9% and high negative predictive values of 98.1% and 96.3% respectively. In conclusion, APRI and FIB-4 index are simple readily available markers to exclude significant fibrosis or more accu-rately cirrhosis in black African patients with CHB.

Keywords

Non Invasive Models; Fibrosis; Cirrhsis; Hepatitis B; Sub-Saharan Africa

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	Lavanchy, D. (2004) Hepatitis B virus epidemiology, disease burden, treatment and current and emerging prevention and control measures. Journal of viral hepatitis, 11(2), 97-107.
[2]	Lok, S.F. and Mc Mahon, B.J. (2007) Chronic hepatitis B. Hepatology, 45(2), 507-539.
[3]	E.A.S.L. (2009) Clinical practice guidelines: management. Journal of Hepatology, 50(2), 227-242.
[4]	Keffe, E.B., Dieterich, D.T., Han, S.H., Jacobson, I.M., Martin, P., Schiff, E.R., and Tobias, H.A. (2008) A treatment algorithm for the management of chronic hepatitis B virus in the United States: 2008 update. Clinical Gastroenterology and Hepatology, 6(12), 1315-1341.
[5]	Bravo, A., Sheth, S.G., and Chopra, S.(2001) Liver biopsy. New England Journal of Medicine, 344(7), 495-500.
[6]	Skripenova, S., Trainer, D.T., Krawitt L.E., and Blaszyk H. (2007) Variability of grade and stage in simultaneous paired liver biopsies in patients with hepatitis C. Journal of Clinical Pathology, 60 (3), 321-324.
[7]	Lauer, M.G. and Walker, B.D. (2001) Hepatitis C virus infection. New England Journal of Medicine, 345(1), 41-50.
[8]	Poynard T., Bedossa, P. and METAVIR, CLINIVIR, cooperative study. (1997) Age and platelet count: a simple index for predicting the presence of histological lesions in patients with antibodies to hepatitis C virus. Journal of Viral Hepatitis, 4(3), 199-208.
[9]	Imbert-Bismuth, F., Ratzui, V., Pieroni, L., Charlotte, F., Benhamou, Y., Poynard T., for the MULTIVRIC group (2001). Biochemical markers of liver fibrosis in patients with hepatitis C virus infection: a prospective study. Lancet, 357, 1069-1075.
[10]	Pohl, A., Behling C., Oliver D., Kilani, M., Monson P. and Hassanein, T. (2001). Serum aminotransferase levels and platelets counts as predictors of degree of fibrosis in chronic hepatitis C infection. American Journal of Gastroenterology, 96(11), 3142-3146.
[11]	Myers R.P., De Torres, M., Imbert-Bismut, F., Ratziu, V., Charlotte, F., and Poynard T. for the MULTIVRIC group. (2003). Biochemical markers of fibrosis in patients with chronic hepatitis C. A comparison with prothrombin time, platelet count and age-platelet index. Digestive Diseases and Sciences, 48(1), 146-153.
[12]	Forns, X., Ampurdanes, S., Llovet, J.M., Aponte, J., Quinto, L., Bauer-Martinez, E., Bruguera, M., Sanchez-Tapias, J..M. and Rodes R. (2002). Identification of chronic hepatitis C patients without hepatic fibrosis by a simple predictive model. Hepatology, 36(4), 987-992.
[13]	Wai, C-T., Greenson, J.K., Fontana, R.J., Kalbfleisch, J.D., Marrero, J.A., Conjeevaram, H.S. and Lok, A.S.F.(2003). A simple non-invasive index can predict both significant fibrosis and cirrhosis in patients with chronic hepatitis C. Hepatology, 38(2),518-526.
[14]	Vallet-Pichard, A., Mallet, V., Nalpas, B.,Verkarre,V., Nalpas, A., Dhalluim-Venier V., Fontaine, H. and Pol S. (2007). FIB-4 index an inexpensive and accurate markers of liver fibrosis in HCV infection. Comparison with liver biopsy and fibrotest. Hepatology,46(1), 32-35.
[15]	Myers, R.P., Tainturier, M-H., Ratziu, V., Piton, A., Thibault, V., Imbert-Bismut, F., Messous, D., Charlotte, F., Di-Martino,V., Benhamou Y. and Poynard T. (2003). Prediction of liver histological lesions with biochemical markers in patients with chronic hepatitis B. Journal of Hepatology, 39(2), 222-230.
[16]	Wai, C-T., Cheng, C.L., Wee, A., Dan , Y.Y., Chua, W., Mak, B., AM, Oo. and Lim, S.G.(2006). Non-invasive models for predicting histology in patients with chronic hepatitis B. Liver international, 26(26), 666-672.
[17]	Kim, B. K., Kim, S.A., Park, Y.N., Cheong, J.Y., Kim, H.S., Park, J.Y., Cho, S.W., Han, K-H., Chon, C.Y., Moon, Y.M. and Ahan, S.H.(2007) Non invasive models to predict liver cirrhosis in patients with chronic hepatitis B. Liver international, 27(7), 969-976.
[18]	Mallet, V., Dhalluin-Venier, V., Roussin, C., Bourlière M., Pettinelli, M.E., Giry, C., Vallet-Pichard, A., Fontaine, H., and Pol, S. ( 2009) The accuracy of FIB-4 for the diagnostic of mild fibrosis in chronic hepatitis B. Alimentary Pharmacology and Therapeutics, 29(4), 409-415.
[19]	Bonnard, P., Sombié, R., Lescure, F.X., Bougouma, A., Guiard-Schmid, J.B., Poynard, T., Cales, P., Housset, C., Callard, P., Le Pendeven, C., Drabo, J., Carrat, F., and Pialoux, G. (2010) Comparison of elastography, serum marker scores, and histology for the assessment of liver fibrosis in hepatitis B virus (HBV)-infected patients in Burkina Faso. American Journal of Tropical Medicine and Hygiene, 82(3), 454-458.
[20]	Plorde, J.J., Jong, C.E. (1983) Schistomiasis. In Petersdrof, R. Adams, R.D., Braunwald, E., Isselbacher, K.J., Martin, J.D., Wilson ed., Harrison’s Principles of Internal Medecine, MacGrw-Hill, Inc., New York, 1217-1222.
[21]	The French METAVIR Cooperative Study Group. (1994) Intraobserver and interobserver variations in liver biopsy interpretation in patients with chronic hepatitis C. Hepatology, 20(1), 15-20.
[22]	Hanley J.A., and McNeil, B.J.(1983) A method of comparing the areas under receveir operating characteristic curves derived from the same cases. Radiology, 148(3), 839-843.
[23]	Hongbo, L., Xiaohui, L., Hong, K., Wei, W., and Yon, Z. (2007) Assessing routine and serum markers ol liver fibrosis in chronic hepatitis B patients using parallel and serial interpretation. Clinical biochemistry, 40(8),562-566.
[24]	Ignatus, C.M., Emeka, E.N., and Blessing, N.E.(2008) Effect of malaria parasitemia on liver enzyme tests. International Journal of Tropical Medecine, 3(3), 49-52.
[25]	Wu, S.D., Wang, J.Y. and Li, L.(2010) Staging of liver fibrosis in chronic hepatitis B patients with a composite predictive model: a comparative study. World Journal of Gastroenterology, 16(4),501-517.
[26]	Kim, B.K., Kim do, Y., Park J.Y., Ahn, S.H., Chon, C.Y., Kim, J.K. Paik, Y.H., Lee, K.S., Park, Y.N., and Han, K.H.(2010) Validation of FIB-4 and comparison with other simple noninvasive indices for predictiong liver fibrosis and cirrhosis in hepatitis B virus-infected patients. Liver international, 45(3), 355-360.
[27]	Zarsky, J.P., Marcellin, P., Leroy, V., Trepo, C., Samuel, D., Ganne-Carrie N., Barange, K., Canva, V., Doffoel M., Cales, P., and Fédération Nationale des P?les de Références et des Réseaux Hépatites. (2006) Characteristics of patients with chronic hepatitis Bin France: predominant frequency of HBe antigen negative cases. Journal of hepatology, 45(3), 355-360.
[28]	Suzuki, S., Sugauchi F., Orito, E., Kato, H., Usuda, S., Siransy, L., Arita, I., Sakamoto, Y., Yoshihara, N; El-Gohary, A., Ueda, R., and Mizokami, M. (2003) Distribution of hepatitis B virus (HBV) genotype among HBV carriers in the C?te d’Ivoire: Complete genome sequence and phylogenetic relatedness of HBV genotype E. Journal of Medical Virology, 69(4):946-953.
[29]	Baptista, M., Kramvis, A., and Kew, MC. (1999) High prevalence of 1762 (T) 1764(A) mutations in the basic core promoter of hepatitis B virus isolated from black Africans with hepatocellular carcinoma compared with asymptomatic carriers. Hepatology,29(3), 946-953.
[30]	Kew, M.C. (2002) Epidemiology of hepatocellular carcinoma. Toxicology, 27(181-182), 35-38.
[31]	Karasu, Z., Tekin, F., Ersoz, G., Gunsar, F., Batur, Y., Ilter, T., and Akarca U.S.(2007) Liver fibrosis is associated with decreased peripheral platelet count in patients with chronic hepatitis B and C. Digestive Diseases and Sciences, 52(6), 1535-1539.
[32]	Goulis, J., Chau, T.N., Jordan. S, Metha, A.B., Watkinson, A., Rolles, K., and Burroughs, A.K. (1999) Thrombopoietin concentrations are low in patients with cirrhosis and thrombocytopenia and are restored after orthotopic liver transplantation. Gut, 44 (6), 754-758.
[33]	Zeng, M.D., Lu, L.G., Mao, Y.M., Qui; D.K., Li, M.B., Wan, C.W., Chen, J.Y., Wang, X., Gao, C.F., and Zhou, X.Q.(2005) Prediction of significant fibrosis in HbeAg-positive patients with chronic hepatitis B by a non-invasive model. Hepatology, 42(6),1437-1445.
[34]	Schmilovitz-Weiss, H., Tovar, A., Halpern, M., Sulkes, J., Braun, M., and Rotman, Y., (2006) Predictive value of serum globulin levels for the extent of hepatic fibrosis in patients with chronic hepatitis B infection. Journal of viral hepatitis, 13(10), 671-677.
[35]	Hui, A.Y., Chan, H.L., Wong, V.W., Liew, C.T., Chim, A.M., Chan, F.K., and Sung, J.J. (2005) Identification of chronic hepatitis B patients without significant liver fibrosis by a simple non invasive predictive model. American Journal of Gastroenterology, 100(3), 616-623.
[36]	Mohamadnejad, M., Montazeri, G., Fazlollahi, A., Zamani, F., Nasiri, J., Nobakht, H., Forouzanfar, M.H., Abedian, S., Tavangar, S.M., Mohamadkhani, A., Ghoujeghi, F., Estakhri, A., Nouri, N., Farzadi, Z., Najjari, A., and Malekzadeh, R., (2006) Noninvasive markers of liver fibrosis and inflammation in chronic hepatitis B-virus related liver disease. American Journal of Gastroenterology,101(11), 2537-2545.
[37]	Cales, P., Desmorat, H., Vinel, J.P., Caucanas, J.P., Ravaud, P., Gerin, P., Brouet, P., and Pascal, J.P. (1990) Incidence of large oesophageal varices in patients with cirrhosis: application to prophylaxis of first bleeding. Gut, 31(11), 1298-1302.
[38]	de Franchis, R., and Baveno V faculty. (2010) Faculty Revising consensus in portal hypertension: report of the Baveno V consensus workshop on methodology of diagnosis and therapy in portal hypertension. Journal of hepatology, 53(4),762-768.
[39]	Marrone, A., Zampino, R., Karayannis, P., Cirillo, G., Cesaro, G., Guerrera, B., Riccioti, R., Del Giudice, E.M., Utili, R., Adinolfi, L.E., and Ruggiero, G.(2005) Clinical reactivation during lamivudine treatment correlates with mutations in the precore/core promoter and polymerase regions of hepatitis B virus in patients with anti-Hepatitis B e-positive chronic hepatitis. Alimentary Pharmacology and Therapeutics, 22 (8),707-714.