Predictors of eligibility for reimbursement of antiviral treatment in HBe-Ag negative chronic hepatitis B patients with high ALT levels

Predictors of eligibility for reimbursement of antiviral treatment



Chronic hepatitis B, HBeAg-negative, High ALT, Reimbursement


Background/Aim: A liver biopsy is required for the reimbursement of antiviral therapy in Hepatitis B e-antigen (HBe-Ag) negative chronic hepatitis B patients. Liver biopsy is an invasive procedure with potential complications, such as bleeding, pain, pneumothorax, and even death. The study aimed to evaluate simple and non-invasive parameters that may help predict histological criteria that would be eligible for antiviral treatment reimbursement.

Methods: HBeAg-negative chronic hepatitis B patients with alanine transaminase (ALT) levels > upper normal limit (40 IU/L) and HBV DNA viral load > 2000 IU/ml who underwent liver biopsy were enrolled in this retrospective cohort study. ALT, aspartate aminotransferase (AST), alpha-fetoprotein (AFP) values, hepatitis B virus (HBV) DNA levels, platelet count, and hepato-steatosis grade based on ultrasonography were used to predict the eligibility for antiviral therapy reimbursement. Eligibility for reimbursement of antiviral treatment regarding histological criteria defined by National Social Security Institution is based on the hepatitis activity index (HAI) score ≥ 6 and/or fibrosis score ≥ 2 according to Ishak’s scoring system.

Results: One hundred and fifteen patients were included in the study; 79 patients (68.7%) were male. The mean age of patients was 46.51 (11.39). Sixty-two patients (53.9%) had a fibrosis score ≥ 2, and 80 (69.6%) patients had an HAI score ≥ 6. Ninety-two (80%) of the patients fulfilled histological criteria for antiviral treatment reimbursement. Multivariate analysis revealed that age and platelet count were independent predictors of eligibility for antiviral treatment reimbursement. The platelet count cut-off point was 198 x 109 /L for predicting eligibility for antiviral treatment reimbursement.

Conclusion: Most patients (92/115, 80%) with high ALT and DNA viral load were eligible for antiviral treatment reimbursement. Platelet count and age may be used as simple non-invasive parameters for predicting the eligibility for antiviral treatment reimbursement in terms of histological findings.


Download data is not yet available.


World Health Organization. Global health sector strategy on viral hepatitis 2016–2021. WHO (2016).

Tozun N, Ozdogan O, Cakaloglu Y, Idilman R, Karasu Z, Akarca U, et al. Seroprevalence of hepatitis B and C virus infections and risk factors in Turkey: a fieldwork TURHEP study. Clin Microbiol Infect. 2015;21(11):1020-6. doi: 10.1016/j.cmi.2015.06.028. DOI:

Fattovich G, Bortolotti F, Donato F. Natural history of chronic hepatitis B: special emphasis on disease progression and prognostic factors. J Hepatol. 2008;48(2):335-52. doi: 10.1016/j.jhep.2007.11.011. DOI:

European Association for the Study of the Liver. EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection. J Hepatol. 2017;67(2):370-98. doi: 10.1016/j.jhep.2017.03.021. DOI:

Tian G, Kong D, Jiang T, Li L. Complications After Percutaneous Ultrasound-Guided Liver Biopsy: A Systematic Review and Meta-analysis of a Population of More Than 12,000 Patients From 51 Cohort Studies. J Ultrasound Med. 2020;39(7):1355-65. doi: 10.1002/jum.15229. DOI:

Sezgin O, Yaras S, Ates F, Altintas E, Saritas B. Effectiveness of Sedoanalgesia in Percutaneous Liver Biopsy Premedication. Euroasian J Hepatogastroenterol. 2017;7(2):146-9. doi: 10.5005/jp-journals-10018-1236. DOI:

Wai CT, Greenson JK, Fontana RJ, Kalbfleisch JD, Marrero JA, Conjeevaram HS, et al. A simple noninvasive index can predict both significant fibrosis and cirrhosis in patients with chronic hepatitis C. Hepatology. 2003;38(2):518-26. doi: 10.1053/jhep.2003.50346. DOI:

Sterling RK, Lissen E, Clumeck N, Sola R, Correa MS, Montaner J, et al. Development of a simple noninvasive index to predict significant fibrosis in patients with HIV/HCV coinfection. Hepatology. 2006;43(6):1317-25. doi: 10.1002/hep.21178. DOI:

Ishak K, Baptista A, Bianchi L, Callea F, De Groote J, Gudat F, et al. Histological grading and staging of chronic hepatitis. J Hepatol. 1995;22(6):696-9. doi: 10.1016/0168-8278(95)80226-6. DOI:

Ormeci A, Aydın Y, Sumnu A, Baran B, Soyer OM, Pınarbasi B, et al. Predictors of treatment requirement in HBeAg-negative chronic hepatitis B patients with persistently normal alanine aminotransferase and high serum HBV DNA levels. Int J Infect Dis. 2016;52:68-73. doi: 10.1016/j.ijid.2016.09.007. DOI:

Papatheodoridis GV, Manesis EK, Manolakopoulos S, Elefsiniotis IS, Goulis J, Giannouis J, et al. Is there a meaningful serum hepatitis B virus DNA cutoff level for therapeutic decisions in hepatitis B e antigen-negative chronic hepatitis B virus infection? Hepatology. 2008;48(5):1451-9. doi: 10.1002/hep.22518. DOI:

Barut S, Gemici Ü, Güneş F, Demir O, Duygu F. Predictors of histological indication for treatment in HBeAg negative chronic HBV infection. J Med Virol. 2017;89(11):1952-7. doi: 10.1002/jmv.24879. DOI:

Afdhal N, McHutchison J, Brown R, Jacobson I, Manss M, Poordad F, et al. Thrombocytopenia associated with chronic liver disease. J Hepatol. 2008;48(6):1000-7. doi: 10.1016/j.jhep.2008.03.009. DOI:

Ishikawa T, Ichida T, Matsuda Y, Sugitani S, Sugiyama M, Kato T, et al. Reduced expression of thrombopoietin is involved in thrombocytopenia in human and rat liver cirrhosis. J Gastroenterol Hepatol. 1998;13(9):907-13. doi: 10.1111/j.1440-1746.1998.tb00760.x. DOI:

Zhong LK, Zhang G, Luo SY, Yin W, Song HY. The value of platelet count in evaluating the degree of liver fibrosis in patients with chronic hepatitis B. J Clin Lab Anal. 2020;34(7):e23270. doi: 10.1002/jcla.23270. DOI:

Karasu Z, Tekin F, Ersoz G, Gunsar F, Batur Y, Ilter T, et al. Liver fibrosis is associated with decreased peripheral platelet count in patients with chronic hepatitis B and C. Dig Dis Sci. 2007;52(6):1535-9. doi: 10.1007/s10620-006-9144-y. DOI:






Research Article

How to Cite

Engin İsmail, Duman AE, Ataoğlu HE, Örmeci A Çifçibaşı, Poturoğlu Şule. Predictors of eligibility for reimbursement of antiviral treatment in HBe-Ag negative chronic hepatitis B patients with high ALT levels: Predictors of eligibility for reimbursement of antiviral treatment. J Surg Med [Internet]. 2022 Jul. 29 [cited 2024 May 18];6(7):705-8. Available from: