Previous Next

ARCHIVE

№2' 2020

INFECTIOUS DISEASES

International Medical Journal, Vol. 26., Iss. 2, 2020, P. 70−76.

DOI (https://doi.org/10.37436/2308-5274-2020-2-14)

METABOLISM FEATURES OF HAPTOGLOBIN AS INFLAMMATION ACUTE PHASE PROTEIN IN PATIENTS WITH CHRONIC HCV INFECTION

Kharkiv National Medical University, Ukraine

Modern advances in hepatology are characterized by the introduction into practice of interferon−free therapy of chronic hepatitis C, as well as the expansion of the arsenal of methods for non−invasive or minimally invasive diagnosis of morphological changes in the liver. The ineffectiveness of therapy is stipulated by, in particular, the amino acid polymorphism of viral proteins, which determines the resistance of certain variants of HCV to directly acting antiviral drugs. In order to assess the content of haptoglobin in the serum of patients with chronic hepatitis C depending on the activity of cytolytic enzymes in the serum, the degree of inflammatory−necrotic activity of the process, stage of liver fibrosis, virus genotype, viral load, age and sex of patients, prior to, on the background and after antiviral therapy, 215 patients were examined. The results showed that in most patients the content of haptoglobin in the serum was within normal limits. It correlated with the degree of inflammatory−necrotic activity of hepatitis, the stage of liver fibrosis and did not depend on the biochemical activity of the process, virus genotype, viral load, age and sex of the patient. Determining the content of this protein in the serum before the start of combination antiviral therapy, provided that other factors, leading to hypogaptoglobinemia, with a high probability allowed to diagnose severe fibrosis (cirrhosis) of the liver or its absence, and to predict the absence of its effect. On the background of a combined antiviral therapy with ribavirin, there was a decrease in serum haptoglobin, enabling the use of this index to monitor the activity of drug hemolysis and was a reason not to recommend assessment of liver fibrosis by FibroTest during and after treatment, if its protocol included "antiviral Ribavirin".

Key words: HCV infection, morphological changes in liver, liver biopsy, non−invasive diagnosis of fibrosis, antiviral therapy, predictors for treatment outcome, haptoglobin.

REFERENCES

1. Fedorchenko S. V. Koinfektsiya HCV/HBV: monogr. K.: Meditsina, 2018. 120 s.

2. Sarrazin C. Klinicheskoe znachenie ustoichivosti virusa gepatita S k protivovirusnym preparatam pryamogo protivovirusnogo deistviya // J. of Hepatology. 2016. Vol. 64. P. 486−504.

3. Sheptulina A. F., Shirokova E. N., Ivashkin V. T. Neinvazivnaya diagnostika fibroza pecheni: rol' syvorotochnykh markerov // Ros. zhurn. gastroenterologii, gepatologii, koloproktologii. 2015. № 2. S. 28−40.

4. Maloinvazivnaya diagnostika tyazhesti fibroticheskikh izmenenii pecheni u bol'nykh khronicheskim gepatitom S / V. N. Koz'ko i dr. // Mіzhnar. medichnii zhurn. 2019. T. 25, № 1 (97). S. 82−85.

5. Tsimmerman Ya. S. Fibroz pecheni: patogenez, metody diagnostiki, perspektivy lecheniya // Klinicheskaya farmakologiya i terapiya. 2017. № 1. S. 54−58.

6. Fedorchenko S. V. Khronicheskaya HCV−infektsiya. K.: Meditsina, 2010. 271 s.

7. Rekomendatsii EALS po lecheniyu gepatita S // Zhurn. gepatologii. 2017. T. 66. S. 153−194.

8. Evaluation of liver disease progression in the German hepatitis C virus (1b)−contaminated anti−D cohort at 35 years after infection / M. Wiese et al. // Hepatology. 2014. Vol. 59. P. 49−57. doi: https://doi.org/10.1002/hep.26644

9. The present and future disease burden of hepatitis C virus (HCV) infection with today's treatment paradigm / H. Razavi et al. // Viral. Hepat. 2014. Vol. 21. P. 34−59.

10. Topol'nits'kii V. S. Suchasnі danі pro іnterferoni ta taktika їkh zastosuvannya v klіnіchnіi praktitsі // Gepatologіya. 2013. № 2 (20). S. 67−80.

11. Zaitsev I. A. Prognozirovanie rezul'tatov protivovirusnoi terapii bol'nykh khronicheskim virusnym gepatitom S // Gepatologіya. 2013. № 2 (20). S. 4−13.

12. Delayed versus immediate treatment for patients with acute hepatitis C: a randomized controlled noninferiority trial / K. Deterding et al. // Lancet. Infect. Dis. 2013. Vol. 13. P. 497−506.

13. Sustained virological response in a patient with chronic hepatitis C treated by monotherapy with the NS3−4A protease inhibitor telaprevir / F. Suzuki et al. // J. Clin. Virol. 2010. Vol. 47. P. 76−78. doi: https://doi.org/10.1016/j.jcv.2009.09.029

14. 100 % Svr in Il28b Cc patients treated with 12 weeks of telaprevir, peginterferon and ribavirin in the Prove2 trial / J. P. Bronowicki et al. // J. Hepatol. 2012. Vol. 56. P. 430−431. doi: https://doi.org/10.1016/s0168−8278(12)61106−4

15. Bueverov A. O. Profilaktika i korrektsiya gematologicheskikh pobochnykh effektov protivovirusnoi terapii khronicheskogo gepatita S // Ros. zhurn. gastroenerologii, gepatologii, koloproktologii. 2009. № 3. S. 76−81.

16. Formulation and application of a numeral scoring system for assessing histological activity in asymptomatic chronic active hepatitis / R. G. Knodell et al. // Hepatology. 1981. Vol. 1. P. 431−435. doi: https://doi.org/10.1002/hep.1840010511

17. Bedossa P., Poynard T. An algorithm for grading of activity in chronic hepatitis C. The French METAVIR Cooperative Study Group // Hepatology. 1996. Vol. 24. P. 289−293. doi: https://doi.org/10.1002/hep.510240201

18. Syutkin V. E. Sovremennye predstavleniya o fibroze pecheni // Gepatologicheskii forum. 2007. № 2. S. 3−7.

19. Melanіch S. L. Dіagnostichna znachimіst' sirovatkovikh markerіv fіbrozu pechіnki u khvorikh na HCV−іnfektsіyu // Gastroenterologіya. 2013. № 4 (50). S. 43−49.

20. Vel'kov V. V. Syvorotochnye biomarkery fibroza pecheni: do svidaniya, biopsiya? M.: Diakon, 2009. 40 s.

21. Tannapfel A., Dienes H. P., Lohse A. W. The indications for liver biopsy // Dtsch. Arztebl. Int. 2012. № 109 (27−28). P. 477−483.

22. Sanvisens A. Hyaluronic acid, transforming growth factor−beta1 and hepatic fibrosis in patients with chronic hepatitis C virus and human immunodeficiency virus coinfection // Viral. Hepat. 2009. № 16 (7). P. 513−518. doi: https://doi.org/10.1111/j.1365−2893.2009.01103.x

23. Serum concentration of transforming grown factor−beta 1 does not predict advanced liver fibrosis in children with chronic hepatitis B / D. M. Lebensztejn et al. // Hepatogastroenterology. 2004. № 51 (55). R. 229−233.

24. The role of serum biomarkers in predicting fibrosis progression in pediatric and adult hepatitis C virus chronic infection // P. Valva et al. // PloS one. 2011. № 6 (8). R. 17. doi: https://doi.org/10.1371/journal.pone.0023218

25. Khristenko N. E. Vzaimosvyaz' soderzhaniya polovykh gormonov i lipidov u patsientov s khronicheskim gepatitom S // Klinicheskaya infektologiya i parazitologiya. 2018. T. 7, № 3. S. 361−369.

26. Elevated serum levels of caspase−cleaved cytokeratin 18 (CK 18−Asp396) in patiens with non−alcoholic steatohepatitis and chronic hepatitis C / Y. Yilmaz et al. // Med. Sci. Monit. 2009. № 15 (4). R. 189−193.

27. Hepatitis C infection in Alaska Natives with persistently normal, persistently elevated or fluctuating alanine aminotransferase levels / M. G. Bruce et. al. // Liver International. 2006. № 26 (6). P. 643−649. doi: https://doi.org/10.1111/j.1478−3231.2006.01281.x

28. Camps J., Marsillach J., Joven J. Measurement of serum paraoxonase−1 activity in the evaluation of liver function // World J. Gastroenterol. 2009. № 15 (16). R. 1929−1933. doi: https://doi.org/10.3748/wjg.15.1929

29. Diagnostic value of serum type IV collagen test in comparison with platelet count for predicting the fibrotic stage in patients with chronic hepatitis / Y. Murawaki et al. // J. Gastroenterol. Hepatol. 2001. Vol. 16. P. 777−781. doi: https://doi.org/10.1046/j.1440−1746.2001.02515.x

30. Significance of serum matrix metalloproteinase−9 and tissue inhibitor of metalloproteinase−1 in chronic hepatitis C patients / G. Badra et al. // Acta Microbiol. Immunol. Hung. 2010. Vol. 57. P. 29−42. doi: https://doi.org/10.1556/amicr.57.2010.1.3

31. Nepryamaya elastografiya s pomoshch'yu ul'trazvuka v diagnostike fibroza: sistematicheskii obzor i meta−analiz / J. A. Talwalkar et al. // Klinicheskaya gastroenterologiya, gepatologiya. Russkoe izdanie. 2008. № 1 (2). C. 76−83.

32. Mul'tiparametricheskaya magnitno−rezonansnaya tomografiya v prognozirovanii klinicheskikh iskhodov u patsientov s khronicheskimi zabolevaniyami pecheni / M. Pavlides et al. // J. Hepatol. Russkoe izdanie. 2016. T. 2, № 2. S. 24−33.

33. Bueverov A. O., Volikovskii L. Ya., Tesaeva E. V. Elastografiya − novii metod neinvazivnoi diagnostiki fibroza pecheni // Gepatologicheskii forum. 2007. № 2. S. 14−18.

34. Fontana R. J. Serum fibrosis marker levels decrease after successful antiviral treatment in chronic hepatitis C patients with advanced fibrosis // Slin. Gastroenterol. Hepatol. 2009. № 7 (2). P. 219−226. doi: https://doi.org/10.1016/j.cgh.2008.10.034

35. Non−invasive evaluation of liver fibrosis in chronic hepatitis C / A. Trifan et al. // Rev. Med. Chir. Soc. Med. Nat. Iasi. 2012. № 116 (1). P. 135−138.

36. Evaluation of FibroTest−ActiTest in children with chronic hepatitis C virus infection. Gastroenterol. Clin. Bio. / B. Hermeziu, D. Messous, M. Fabre, M. Munteanu // Med. Pr. 2010. № 34 (1). P. 16−22. doi: https://doi.org/10.1016/j.gcb.2009.06.007

37. Two or more synchronous combination of noninvasive tests to increase accuracy of liver fibrosis assessement in chronic hepatitis C; results from a cohort of 446 patients / D. Crisan et al. // Hepat. Mon. 2012. № 12 (3). P. 177−184. doi: https://doi.org/10.5812/hepatmon.853

38. Longitudinal evaluation of a fibrosis index combining MMP−1 and PIIINP compared with MMP−9, TIMP−1 and hyaluronic acid in patients with chronic hepatitis C treated by interferon−alpha and ribavirin / C. Trocme et al. // Viral. Hepat. 2006. № 13 (10). R. 643−651. doi: https://doi.org/10.1111/j.1365−2893.2006.00730.x

39. Performance of ELF serum markers in predicting fibrosis stage in pediatric non−alcoholic fatty liver disease / V. Nobili et al. // Gastroenterology. 2009. № 136 (1). R. 160−167. doi: https://doi.org/10.1053/j.gastro.2008.09.013

40. Madsen M., Graversen H. G., Moestrup S. K. A signal receptor scavenging haptoglobin−hemoglobin complexes from plasma // Inf. J. Biochem. and Cell Biol. 2002. № 4. S. 309−314. doi: https://doi.org/10.1016/s1357−2725(01)00144−3

41. Kamyshnikov V. S. Klinicheskie laboratornye testy ot A do Ya i ikh diagnosticheskie profili. M.: MEDpress−inform, 2007. 313 s.

42. Bіokhіmіchnі pokazniki v normі і pri patologії: navch. dovіd. / D. P. Boikіv ta іn.; za red. O. Ya. Sklyarova. K.: Meditsina, 2007. 320 s.

43. Volchkova E. V., Pak S. G., Umbetova K. T. Gumoral'nye i kletochnye adaptatsionnye mekhanizmy pri razvitii intoksikatsionnogo sindroma u bol'nykh ostrymi i khronicheskimi virusnymi gepatitami // Terapevt. arkhiv. 2004. № 11. S. 61−65.