MATHEMATICAL MODELS PREDICTING LEUKOPENIA AND NEUTROPENIA IN PATIENTS WITH CHRONIC HEPATITIS C IN THE BACKGROUND INTERFERONCONTAINING SCHEMES
https://doi.org/10.20514/2226-6704-2016-6-5-53-62
Abstract
Currently in the Russian Federation or chronic hepatitis C (CHC) are still relevant Interferon-based regimens. The purpose of this study is to investigate the influence of baseline characteristics and prognosis of the patient HCV genotype 1 for the development of leukopenia (LP) and neutropenia (NP). We investigated factors such as sex, age, body mass index (BMI), viral load, genotype of Interleukin-28 B (IL-28B), the initial level of leukocytes and neutrophils, alanine aminotransferase (ALT), fibrosis, duration of infection, presence of previous therapy. Absolute values of leukocytes and neutrophils were analyzed on 4, 12, 24, 48 weeks of therapy, and at 4, 12, 24 weeks after antiviral treatment with protease inhibitors (PI) 1 and 2 generation. Prognostic criteria were identified, indicating the possible development of the LP and NP expressed during treatment with interferon: female gender, low initial load, TT-genotype of IL-28B, the initial level of white blood cells and neutrophils below 5,7×109/L and 3,4×109/L, respectively. Mathematical models predicting the onset of LP and NP, formalized in the form of decision trees were also constructed. These models have shown the greatest potential for practical use in view of highest accuracy and reliability.
About the Authors
I. G. BakulinRussian Federation
N. Kh. Dianova
Russian Federation
Yu. G. Sandler
Russian Federation
M. Yu. Prostov
Russian Federation
References
1. Abdurakhmanov D.T. , Morozov V.G., Nikitin I.G. et al. Safety and efficacy of Telaprevir in the treatment of chronic hepatitis C in patients with a Russian population included in the study on the early access program. Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2014; 1: 39–46 [In Russian].
2. Bakulin I.G., Sandler Y.G., Sharabanov A.S. Hematological adverse events during antiviral therapy in patients with chronic hepatitis C. Hepatology forum. 2011; 4: 2-14 [In Russian].
3. Bakulin I.G., Sharabanov A.S. The clinical significance of leuko- and neutropenia in patients with chronic hepatitis C during various modes of antiviral therapy. Clinical Gastroenterology 2010; 5: 27-32 [In Russian].
4. Bakulin I.G., Dianova N.Kh. Yunusova Yu.M., Reyzen Y.V. Drug-induced Organizing Pneumonia - rare adverse event of antiviral therapy in patients with Liver Cirrhosis of HCV-etiology. Effective pharmacotherapy. 2014; 43: 30-35 [In Russian].
5. Bakulin I.G., Dianova N.Kh. Prognosis of leukopenia, and neutropenia in patients with chronic hepatitis C against the background of antiviral therapy using 1st and 2nd generation protease inhibitors. Farmateka. 2016; 2: 36-42 [In Russian].
6. Bakulin I.G., Vinnitskaya E.V., Varlamitcheva A.A., Kiseleva A.V., Dianova N. Kh. Null Response in Chronic Hepatitis C: What to Do? Doktor.ru. 2014; 3(91): 95-102 [In Russian].
7. Bueverov SA Prevention and correction of hematological side effects of antiviral therapy for chronic hepatitis C. The Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2009; 19(3): 76-81 [In Russian].
8. Vasilieva I.I., Dontsov D.V., Ambalov Y.M., Proydakov M.A. The process for forecasting the interferon-ribavirin-induced neutropenia in patients with chronic hepatitis C receiving combined antiviral therapy. Patent RU 2444998 [In Russian].
9. Vasilieva I.I., Dontsov D.V., Ambalov Y.M., Proydakov M.A. A method of predicting the development of neutropenia caused by a combination of antiviral therapy in patients with chronic hepatitis C. Patent RU 2449278 [In Russian].
10. Dontsov D.V., Ambalov Y.M. A method of forecasting the interferon-ribavirin-induced neutropenia in patients with chronic hepatitis C. Kuban Research Medical Gazette. 2011; 3(126): 67-70 [In Russian].
11. Moiseev S.V., Abdurakhmanov D.T. How to improve the standard of antiviral therapy in patients with chronic hepatitis C: the role of hematopoietic growth factors. Clinical Pharmacology and Therapeutics. 2011; 20(2): 35-40 [In Russian].
12. Pimenov N.N., Chulanov V.P., etc. Hepatitis C in Russia. Epidemiological characteristics and ways to improve the diagnosis and surveillance. Epidemiology and Infectious Diseases. 2012; 3: 4-10 [In Russian].
13. Recommendations for the diagnosis and treatment of adult patients with hepatitis C / Expert Group. Guidelines for doctors. M., 2014; 32-33 [In Russian].
14. Yushchuk N.D., Znoyko O.O. et al. The social and economic burden of hepatitis C: a methodology for assessing and calculating difficulties in the Russian Federation. Medical technology. Evaluation and selection. 2012; 4: 46-50 [In Russian].
15. Andreone P., Colombo M., Enejosa J., et al. ABT-450, Ritonavir, Ombitasvir and Dasabuvir achieves 97% and 100% sustained virological response with or without Ribavirin in treatment-experienced patients with HCV genotype 1b infection. Gastroenterology. 2014; 147(2): 359-365.
16. Bacon B. R., Gordon S. C., Lawitz E., Marcellin P., Poordad F., et al. Boceprevir for previously treated chronic HCV genotype 1 infection. New England Journal of Medicine. 2011; 364: 1207-1217.
17. Bakulin I., Pasechnikov V., Varlamicheva A., Sannikova I. NS3 protease inhibitors for treatment of chronic hepatitis C: Efficacy and safety. World J. Hepatol. 2014; 6(5): 326–339
18. Cooper C.L., Al-Bedwawi S., Lee C., Garber G. Rate of infectious complications during interferon-based therapy for Hepatitis C is not related to neutropenia. Clinical Infectious Diseases. 2006; 42: 1674-1678.
19. EASL Recommendation on Treatment of Hepatitis C. Hepatology. 2015; 63: 199-236.
20. Hezode C., Dorival C., Zoulium F., et al. Safety of Telaprevir or Boceprevir in Combination with Peginterferon alfa/Ribavirin, in Cirrhotic Non Responders. First Results of the French Early Access Program (ANRS CO-20-CUPIC). 47 Annual Meeting of the European Association for the Study of the Liver (EASL 2012). Barcelona, April 18-22, 2012.
21. Kowdley K. V. Hematologic side effects of interferon and ribavirin therapy. Clinical Gastroenterology. 2005; 39: Suppl. 3-8.
22. Leach H. J., O’Connor D. P., Simpson R. J., Rifai H. S., Mama Sch. K., Lee R. E. An exploratory decision tree analysis to predict cardiovascular disease risk in African American women. Health Psychology. 2016; 35(4): 397-402.
23. Poordad F., McCone J., Bacon B.R. et al. Boceprevir for untreated chronic HCV genotype 1 infection. New England Journal of Medicine. 2011; 364(13): 1195-1206
24. Sulkowski M.S. Management of the hematologic complications of hepatitis C therapy. Clinical Liver Diseases. 2005; 9: 601-616.
25. Soza A., Everhart J.E., Ghany M.G.et al. Neutropenia during combination therapy of interferon alfa and ribavirin for chronic hepatitis C. Hepatology. 2002; 36: 1273-1279.
Review
For citations:
Bakulin I.G., Dianova N.Kh., Sandler Yu.G., Prostov M.Yu. MATHEMATICAL MODELS PREDICTING LEUKOPENIA AND NEUTROPENIA IN PATIENTS WITH CHRONIC HEPATITIS C IN THE BACKGROUND INTERFERONCONTAINING SCHEMES. The Russian Archives of Internal Medicine. 2016;6(5):53-62. (In Russ.) https://doi.org/10.20514/2226-6704-2016-6-5-53-62