Markers of progression of liver fibrotic changes in patients with chronic toxic drug-induced hepatitis

Main Article Content

V.I. Didenko
O.M. Tatarchuk
O.P. Petishko
I.S. Konenko
S.L. Melanich


Background. In recent years, as a result of the growing expansion of the pharmaceutical market, there has been a clear trend towards an increase in the incidence of chronic toxic drug-induced hepatitis of drug genesis (TDIH). The appearance of fibrosis is considered the most important histological change that determines the further course of the disease. Therefore, the search for non-invasive or minimally invasive markers for assessing fibrotic changes in the liver remains an urgent issue in clinical practice. The purpose was to determine the diagnostic value of immunological parameters for stratification of the severity of liver fibrosis in patients with TDIH. Materials and methods. The study included 41 patients with TDIH, who were divided into three groups: group I consisted of 12 people without liver fibrosis (F0), group II — 22 patients with moderate fibrosis (F1-F2), group III — 7 individuals with severe liver fibrosis (F3-F4). Shear wave elastography was performed using a Soneus P7 system (Ukraine-Switzerland). All patients underwent a biochemical blood test with the determination of alanine aminotransferase (ALT), aspartate aminotransferase (AST). The subpopulation composition of lymphocytes, circulating immune complexes (CIC), the level of interleukins (IL-6, IL-10) and tumor necrosis factor α were assessed. Results. The progression of liver fibrosis is accompanied by an increase in cytolytic syndrome: patients with severe fibrosis have a 3.3-fold increase in the ALT (p < 0.05) compared to the controls and a 2.1-fold (p < 0.05) compared to that in patients with moderate fibrosis. The AST level is significantly higher — by 4.6 times (p = 0.023) in patients with severe fibrosis than in those with moderate fibrosis. With the progression of liver fibrosis, there is a significant decrease in cellular immunity, an increase in the level of CIC and pro-inflammatory cytokines with a simultaneous decrease in the content of anti-inflammatory cytokines, which is confirmed by correlations between the liver stiffness index according to shear wave elastography data and the level of T-helpers (r = –0.466; p = 0.03), IL-6 (r = 0.364; p = 0.01), IL-10 (r = –0.331; p = 0.039) and CIC (r = 0.381; p = 0.017). Conclusions. Markers of the diagnosis of severe liver fibrosis in patients with TDIH are indicators such as the ratio of IL-6/IL-10 higher than 0.83 (sensitivity 81.8 %, specificity 78.9 %), CIC level more than 4.3 optical density units (sensitivity 77.3 %, specificity 72.2 %), the ratio of T-helpers/T-suppressors is less than or equal to 1.6 (sensitivity 72.7 %, specificity 57.9 %).

Article Details

How to Cite
Didenko, V., Tatarchuk, O., Petishko, O., Konenko, I., & Melanich, S. (2021). Markers of progression of liver fibrotic changes in patients with chronic toxic drug-induced hepatitis. GASTROENTEROLOGY, 55(2), 91–97.
Original Researches


Sandhu N, Navarro V. Drug-Induced Liver Injury in GI Practice. Hepatol Commun. 2020 Mar 13;4(5):631-645. doi:10.1002/hep4.1503.

Danan G, Teschke R. RUCAM in Drug and Herb Induced Liver Injury: The Update. Int J Mol Sci. 2015 Dec 24;17(1):14. doi:10.3390/ijms17010014.

Hastings KL, Green MD, Gao B, Ganey PE, Roth RA, Burleson GR. Beyond Metabolism: Role of the Immune System in Hepatic Toxicity. Int J Toxicol. 2020 Mar/Apr;39(2):151-164. doi:10.1177/1091581819898399.

Ibrahim EA, Moawed FSM, Moustafa EM. Suppression of inflammatory cascades via novel cinnamic acid nanoparticles in acute hepatitis rat model. Arch Biochem Biophys. 2020 Dec 15;696:108658. doi:10.1016/

Maiuri AR, Wassink B, Turkus JD, et al. Synergistic Cytotoxicity from Drugs and Cytokines In Vitro as an Approach to Classify Drugs According to Their Potential to Cause Idiosyncratic Hepatotoxicity: A Proof-of-Concept Study. J Pharmacol Exp Ther. 2017 Sep;362(3):459-473. doi:10.1124/jpet.117.242354.

Mannaa FA, Abdel-Wahhab KG. Physiological potential of cytokines and liver damages. Hepatoma Res. 2016;2:131-143. doi:10.20517/2394-5079.2015.58.

Caballería L, Pera G, Arteaga I, et al. High Prevalence of Liver Fibrosis Among European Adults With Unknown Liver Disease: A Population-Based Study. Clin Gastroenterol Hepatol. 2018 Jul;16(7):1138-1145.e5. doi:10.1016/j.cgh.2017.12.048.

Didenko VI, Klenina IA, Tatarchuk OM, Petishko OP. Correlation of immunological and biochemical indicators in patients with chronic diffuse liver diseases depending on the etiological factors of steatosis and liver fibrosis. Gastroenterologìa. 2019;53(2):115-122. doi:10.22141/2308-2097.53.2.2019.168985. (in Ukrainian).

Niederreiter L, Tilg H. Cytokines and fatty liver diseases. Liver Research. 2018;2(1):14-20. doi:10.1016/j.livres.2018.03.003.

Srivastava A, Gailer R, Tanwar S, et al. Prospective evaluation of a primary care referral pathway for patients with non-alcoholic fatty liver disease. J Hepatol. 2019 Aug;71(2):371-378. doi:10.1016/j.jhep.2019.03.033.

Didenko VI, Tatarchuk OM, Melanich SL, Petishko OP. Features of indicators of the functional state of the liver, immune link, cytokine regulation and carbohydrate metabolism in patients with toxic chronic diffuse liver diseases. Gastroenterologìa. 2020;54(2):88-95 doi:10.22141/2308-2097.54.2.2020.206226. (in Ukrainian).

Andrade RJ, Aithal GP, Björnsson ES, et al. EASL Clinical Practice Guidelines: Drug-induced liver injury. J Hepatol. 2019 Jun;70(6):1222-1261. doi:10.1016/j.jhep.2019.02.014.

Petishko OP, Didenko VI, Klenina IA, Tatarchuk OM, Konenko IS. Diagnostic markers of progression of fibrous changes of the liver in patients with chronic diffuse diseases of alcoholic origin. Bulletin of medical and biological research. 2020;(3):47-52. doi:10.11603/bmbr.2706-6290.2020.3.11295. (in Ukrainian).

Ivashkin VT, Baranovsky AYu, Raikhelson KL, et al. Drug-induced liver injuries (clinical guidelines for physicians). Rossijskij žurnal gastroènterologii, gepatologii, koloproktologii. 2019;29(1):101-131. doi:10.22416/1382-4376-2019-29-1-101-131. (in Russian).

Thiele M, Detlefsen S, Sevelsted Møller L, et al. Transient and 2-Dimensional Shear-Wave Elastography Provide Comparable Assessment of Alcoholic Liver Fibrosis and Cirrhosis. Gastroenterology. 2016 Jan;150(1):123-33. doi:10.1053/j.gastro.2015.09.040.

Boutari C, Perakakis N, Mantzoros CS. Association of Adipokines with Development and Progression of Nonalcoholic Fatty Liver Disease. Endocrinol Metab (Seoul). 2018 Mar;33(1):33-43. doi:10.3803/EnM.2018.33.1.33.

Most read articles by the same author(s)

<< < 1 2 3 4 5 6 > >>