Relationships between ultrasonic, immunological changes in the progression of liver steatosis and fibrosis in patients with chronic diffusive liver diseases of various etiologies

Authors

  • Yu. M. Stepanov State Instituton “Institute of Gastroenterology of the National Academy of Medical Sciences of Ukraine”, Dnipro, Ukraine,
  • V. I. Didenko State Instituton “Institute of Gastroenterology of the National Academy of Medical Sciences of Ukraine”, Dnipro, Ukraine,
  • I. S. Konenko State Instituton “Institute of Gastroenterology of the National Academy of Medical Sciences of Ukraine”, Dnipro, Ukraine,
  • O. M. Tatarchuk State Institution “Institute of Gastroenterology of the National Academy of Medical Sciences of Ukraine”, Dnipro, Ukraine,

DOI:

https://doi.org/10.14739/2310-1237.2019.2.177167

Keywords:

fatty liver, steatometry, elasticity imaging techniques, immunity, cytokines

Abstract

 

Objective. To determine the relationships between ultrasound and immunological changes in the progression of steatosis and liver fibrosis in patients with chronic diffuse liver diseases (CLD) of various etiologies.

Materials and methods. We examined 120 patients with CLD. Patients were distributed according to the etiological factor of the development of steatosis and liver fibrosis: Group I – 24 patients with non-alcoholic fatty liver disease (NAFLD), ІІ – 37 patients with non-alcoholic steatohepatitis (NASH); Group III – 21 people with chronic viral hepatitis associated with the C virus (HCV). Group IV consisted of 18 patients with alcoholic liver disease (ALD), group V – 20 patients with toxic hepatitis (TG). Sonographic abdominal examination, ultrasound attenuation coefficient (UAC) and shear wave elastography (SWE) of the liver / spleen were performed. The content of cellular immunity parameters, the level of interleukin (IL)-6, IL-10, tumor necrosis factor alpha (TNF-α), insulin and HOMA-IR were determined. A correlation analysis was made between ultrasound and immunological parameters in the examined patients.

Results. In patients with CLD, changes in liver structure in the form of heterogenety were detected in 97 (80.8 %) (P < 0.001). The maximum values of SWE of the liver were observed in patients with ALD (18.10 ± 2.68) kPa, minimal – with NAFLD. The stiffness of the spleen was highest in patients with ALD 24.09 ± 3.68 kPa. TNF-α was significantly higher than the control values with NASH by 11.6 times (P < 0.05), HCV by 13.9 times (P < 0.05), ALD by 9.4 times (P < 0.05) and TG by 9.5 times (P < 0.05). The concentration of IL-6 was 2.1 times higher (P < 0.05) in patients with NASH and CHC, 2.5 times higher (P < 0.05) in patients with TG. The TNF-α / IL-10 ratio was increased by 7.1 times (P < 0.05) in patients with NAFLD, by 19.3 times (P < 0.05) in patients with NASH, by 14.4 times (P < 0.05) in patients with chronic hepatitis C, by 14.0 times (P < 0.05) in patients with ALD and by 8.4 times (P < 0.05) in patients with TG.

When conducting a correlation analysis, it was revealed that in patients with NAFLD, the level of TNF-α had a positive relationship with the spleen stiffness (r = +0.601, P < 0.01). In patients with HCV, the level of IL-6 was associated with spleen stiffness (r = +0.680, P < 0.05), liver stiffness (r = +0.618, P < 0.05) and the degree of fibrosis (according to METAVIR) (r = +0.573, P < 0.01). In patients with ALD, an increase in liver stiffness is accompanied by a significant increase in the NOMA index (r= +0.843). In patients with TG, a negative relationship was found between the level of T-helper cells and stiffness of spleen (r = - 0.577, P < 0.05) and liver (r = -0.522, P < 0.05).

Conclusion. The progression of liver steatosis is accompanied by a lack of cellular immunity and an increase in the level of pro-inflammatory cytokines. An increase in structural changes of the liver and spleen, as well as the increase in the degree of steatosis, is accompanied by activation of pro-inflammatory cytokines, depletion of the anti-inflammatory response and increased insulin resistance.

 

References

Stepanov, Yu. М., Melanich, S. L., Yahmur, V. B., Klenina, I. A., & Konenko, I. S. (2016). Otsinka efektyvnosti zastosuvannia esentsialnykh fosfolipidiv u khvorykh na khronichnyi virusnyi hepatyt C [Evaluating the effectiveness of essential phospholipids in patients with chronic viral hepatitis C]. Hastroenterolohiaa, 1(59), 71–76. doi: 10.22141/2308- 2097.1.59.2016.74531 [in Ukrainian].

Mauss, S., Berg, T., & Rockstroh, J. (2015). Hepatology. Sydney: Flying Publisher.

Enaleeva, D. Sh., Fazylov, V. Kh., & Sozinov, A. S. (2015). Khronicheskie virusnye gepatity В, С i D [Chronic viral hepatitis B, C and D]. Moscow: GE'OTAR-Media. [in Russian].

Zykin, B. I., Postnova, N. A., & Medvedev, M. E. (2012). E'lastographia: anatomia metoda [Elastography: method anatomy]. Promeneva diahnostyka, promeneva terapiia, 2–3, 107–113. [in Russian].

De Ledinghen, V., Vergniol, J., Foucher, J., Merrouche, W. le Bail, B. (2012). Non-invasive diagnosis of liver steatosis using controlled attenuation parameter (CAP) and transient elastography. Liver Int, 32(6), 911–918. doi: 10.1111/j.1478-3231.2012.02820.x

Kharchenko, N. B., Dynnyk, O. B., & Anokhina, G. A. (2016). 51-I mezhdunarodnyi congress EASL: novye gorizonty gepatologii [51st International Liver Congress EASL]. Zdorovia Ukrainy, 2, 16–18. [in Russian].

Lee, S. S., & Park, S. H. (2014). Radiologic evaluation of nonalcoholic fatty liver disease. World J. Gastroenterol, 20(23), 7392–7402. doi: 10.3748/wjg.v20.i23.7392

Caviglia, G. P., Touscoz, G. A., Smedile, A., & Pellicano, R. (2014). Noninvasive assessment of liver fibrosis: key messages for clinicians. Pol. Arch. Med. Wewn, 124(6), 329–335. doi: 10.20452/pamw.2301

O’Neill, E. K., Cogley, J. R., & Miller, F. H. (2015). The ins and outs of liver imaging. Clin. Liver Dis, 19(1), 99–121. doi: 10.1016/j.cld.2014.09.006

Cox, J. A., Lukande, R. L., Kalungi, S., Van de Vijver, K., Van Marck, E., Nelson, A. M., et al. (2014). Practice of percutaneous needle autopsy; a descriptive study reporting experiences from Uganda. BMC Clin. Pathol, 14(1), 44. doi: 10.1186/1472-6890-14-44

Mazur, R., Celmer, M., Silicki, J., Hołownia, D., Pozowski, P., & Międzybrodzki, K. (2018). Clinical applications of spleen ultrasound elastography – a review. J Ultrason, 18, 37–41. doi: 10.15557/JoU.2018.0006

Ostanin, A. A., Starostina, N. M., Meledina, I. V., Shipunov, M. V., Leplina, O. Yu., Shevela, E. Ya., & Chernykh, E. R. (2015). Multipleksnyj analiz 26 citokinov, sekretiruemykh kletkami krovi bol'nykh cerrozom pecheni [A multiplex assay of 26 cytokines secreted by blood cells of patients with liver cirrhosis]. Medicinskaya immunologiya, 17(6), 539–552. https://doi.org/10.15789/1563-0625-2015-6-539-552 [in Russian].

Pompili, M., Biolato, M., Miele, L., & Grieco, A. (2013). Tumor necrosis factor-α inhibitors and chronic hepatitis C: A comprehensive literature review. World J Gastroenterol, 19(44), 7867–7873. doi: 10.3748/wjg.v19.i44.7867

Slyadnev, S. A. (2015). Mediatory mezhkletochnykh vzaimodejstvij pri nealkogol'nooj zhirovoj bolezni pecheni [Mediators of intercellular interactions in nonalcoholic fatty liver disease]. Vestnik molodogo uchenogo, 10(3), 3-8. [in Russian].

Tatarchuk, O. M., Didenko, V. I., Melanich, S. L., & Kudryavtseva, V. Ye. (2018). Immunolohichna reaktyvnist u khvorykh na khronichni dyfuzni zakhvoriuvannia pechinky [Immunological reactivity in patients with chronic diffuse liver diseases]. Hastroenterolohiia, 52(4), 222–226. doi: https://doi.org/10.22141/2308-2097.52.4.2018.154142 [in Ukrainian].

Zampino, R., Marrone, A., Restivo, L. Guerrera, B., Sellitto, A., Rinaldi, L., et al. (2013). Chronic HCV infection and inflammation: clinical impact on hepatic and extra-hepatic manifestations. World J. Hepatol, 5(10), 528–540. doi: 10.4254/wjh.v5.i10.528/

Sysoev, K. A., Chukhlovin, A. B., Shakhmanov, D. M., Zhdanov, K. V., & Totolian Areg, A. (2013). Profil citokinov i khemokinov v plazme krovi pacientov s khronicheskim gepatitom C [Cytokines and chemokines in the blood plasma of patients with chronic hepatitis C]. Infekciya i immunitet, 3(1), 49–58. https://doi.org/10.15789/2220-7619-2013-1-49-58 [in Russian].

Solomennyk, A. O. (2013). Prognosticheskoe znachenie nekotorykh immunologicheskikh pokazatelej u bol'nykh ostrym gepatitom C [Prognostic value of some immunological indices in patients with acute hepatitis C]. Aktualni problemy suchasnoi medytsyny, 3(13), 273–276. [in Russian].

Oh, H., Jun, D. W., Saeed, W. K., & Nguyen, M. H. (2016). Non-alcoholic fatty liver diseases: update on the challenge of diagnosis and treatment. Clin Mol Hepatol, 22(3), 327–335. doi: 10.3350/cmh.2016.0049

Wieckowska, A., Papouchado, B. G., Li, Z., Lopez, R., Zein, N. N., & Feldstein, A. E. (2008). Increased hepatic and circulating interleukin-6 levels in human nonalcoholic steatohepatitis. Am J Gastroenterol, 103(6), 1372–9. doi: 10.1111/j.1572-0241.2007.01774.x

Kawaratani, H., Tsujimoto, T., Douhara, A., Takaya, H., Moriya, K., Namisaki, T., et al. (2013). The effect of inflammatory cytokines in alcoholic liver disease. Mediators Inflamm, 2013, 49514956. doi: 10.1155/2013/495156

Sasso, M., Tengher-Barna, I., Ziol, M., Miette, V., Fournier, C., Sandrin, L., et al. (2011). Novel controlled attenuation parameter (CAP™) for non-invasive assessment of steatosis using FibroScan®: validation in chronic hepatitis C. J. Viral Hepatitis, 19(4), 224–253. doi: 10.1111/j.1365-2893.2011.01534.x

Paltsev, M. A., Kakturskij, L. M., & Zajratyants, O. V. (Eds.) (2011). Patologicheskaya anatomia [Pathological anatomy]. Мoscow: GEOTAP-Media. [in Russian]

Shadrin, O. G., Chernega, N. F., Marushko, R. V., & Bruzgina, T. S. (2015). Stan zhyrno-kyslotnoho spektru krovi u ditei iz zakhvoriuvanniakh pechinky ta yoho zviazok z pokaznykamy tsytokinovoho statusu [The Condition of Fatty Acid Spectrum in the Serum of the Children with Liver Diseases and its Correlation with Cytokine Status Indices]. Visnyk problem biolohii ta medytsyny, 1(117), 193–198. [in Ukrainian].

Carter-Kent, C., Zein, N. N., & Feldstein, A. E. (2008). Cytokines in the pathogenesis of fatty liver and disease progression to steatohepatitis: implications for treatment. Am. J. Gastroenterol, 103(4), 1036–1042. doi: 10.1111/j.1572-0241.2007.01709.x

How to Cite

1.
Stepanov YM, Didenko VI, Konenko IS, Tatarchuk OM. Relationships between ultrasonic, immunological changes in the progression of liver steatosis and fibrosis in patients with chronic diffusive liver diseases of various etiologies. Pathologia [Internet]. 2019Sep.2 [cited 2024Apr.25];(2). Available from: http://pat.zsmu.edu.ua/article/view/177167

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Original research