The Role of Ursodeoxycholic Acid in Prevention of Liver Injury Caused by Chemotherapy of Acute Lymphoblastic Leukemia Associated with Obesity

##plugins.themes.bootstrap3.article.main##

Г. С. Маслова
І. М. Скрипник
О. В. Щербак

Abstract

Chemotherapy (ChT) in patients with acute lymphoblastic leukemias (ALL) is associated with higher risk of hepatotoxic reactions onset, especially in case of additional risk factors.

The objective: to assess the efficiency of ursodeoxycholic acid (UDCA) for hepatotoxic reactions prevention in patients with ALL and concomitant obesity who undergo ChT.

Materials and methods. 26 patients with newly diagnosed ALL and concomitant overweight and obesity were examined, 9 (34.6%) of them were females and 17 (65.4%) – males. Patients’ examination was conducted twice: before ChT and on the 28th day. Biochemical blood tests were made: alanine aminotransferase (ALT), aspartate aminotransferase, total protein, total bilirubin, alkaline phosphatase, gamma-glutamyl transpeptidase (GGT), urea. The patients were divided onto two groups: І (n=12) – patients with ALL and obesity who were prescribed only ChT; II (n=14) – patients with ALL and obesity who were prescribed ChT and UDCA 15 mg/kg/day from the 1st to the 28th days.

Results. 83.3% (10/12) patients of the Іst group and 14.3% (2/14) patients of the ІІnd group had changes in liver function tests after ChT. The patients with ALL an concomitant obesity who underwent ChT were under the risk of hepatotoxic reactions (RR=5.00; 95% СІ=1.37-18.17; р<0.05), that were characterized by ALT elevation 2.05 times more, GGT – 2.4 times more, total bilirubin – 2.08 times and simultaneous decline of total protein 1.4 less (р<0.05). UDCA prescription to the patients with ALL and obesity, who undergo ChT is accompanied by decreased risk of cytostatic-induced liver injury (RR=0.17; 95% СІ=0.046-0.63; р<0.05).

Conclusions. In the settings of ChT, hepatotoxic reactions of mixed type are developed in patients with ALL and obesity, and UDCA prescription is an effective method for their prophylaxis.

##plugins.themes.bootstrap3.article.details##

How to Cite
Маслова, Г. С., Скрипник, І. М., & Щербак, О. В. (2020). The Role of Ursodeoxycholic Acid in Prevention of Liver Injury Caused by Chemotherapy of Acute Lymphoblastic Leukemia Associated with Obesity. Family Medicine, (1-2), 77–80. https://doi.org/10.30841/2307-5112.1-2.2020.204518
Section
For practicing physicians
Author Biographies

Г. С. Маслова, Ukrainian Medical Stomatological Academy

Hanna S. Maslova,

Department of Internal Medicine No 1

І. М. Скрипник, Ukrainian Medical Stomatological Academy

Ihor M. Skrypnyk,

Department of Internal Medicine No 1

О. В. Щербак, Ukrainian Medical Stomatological Academy

Olha V. Shcherbak,

Department of Internal Medicine No 1

References

Домникова НП, Непомнящих ГИ, Тетерина НВ. Клинические особенности поражения печени у больных гемобластозами. Бюллетень СО РАМН. 2008;6(134):41-6.

Непомнящих ГИ, Постникова ОА, Домникова НП, Бакарев МА. Морфологический анализ патологии печени при острых лейкозах и лимфопролиферативных заболеваниях. Сибирский онкологический журнал. 2012;1(49):26-30.

Скрипник ІМ, Маслова ГС. Оцінка частоти розвитку і характеру гепатотоксичних реакцій у хворих на гострі лейкемії в динаміці індукції ремісії. Сучасна гастроентерологія. 2018; 2(100):16-22.

Щербак ОВ, Маслова ГС. Оптимізація лікування хворих на ішемічну хворобу серця у поєднанні з неалкогольним стеатогепатитом. Сучасна гастроентерологія. 2016;5(91):76-83.

Bonkovsky HL, Jones DP, Russo MW et al. Drug-induced liver injury. 6th edn. Ch 25 W.B. Saunders: Philadelphia, PA, 2011, p. 417-61.

Chalasani NP, Hayashi PH, Bonkovsky HL et al. ACG Clinical Guideline: The Diagnosis and management of idiosyncratic drug-induced liver injury. Am J Gastroenterol. 2014 Jul;109(7):950-66; quiz 967. doi: 10.1038/ajg.2014.131.

Chiaretti S, Zini G, Bassan R. Diagnosis and subclassification of acute lymphoblastic leukemia. Mediterr J Hematol Infect Dis. 2014;6:e2014073.

Dhakal P, Lyden E, Lee A, Michalski J, Al-Kadhimi ZS, Maness LJ, et al. Effects of Obesity on Overall Survival of adults with acute Myeloid Leukemia. Clin Lymphoma Myeloma Leuk. 2020;20(3):e131-6. doi: 10.1016/j.clml.2019.11.001.

Fob R, Guarini A, Vitale A. Approach to the patient with a suspect of ALL. In Goekbuget N, Bassan R, Dombret H et al. (eds), Reccommendations of the European Working Group for adult ALL. Bremen-London-Boston: UNI-MED Verlag AG, 2011;24-31.

Hoelzer D, Bassan R, Dombret H et al. Acute lymphoblastic leukaemia in adult patients: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2016 Sep;27 (suppl 5):v69-v82.

Inaba H, Greaves M, Mullighan CG. Acute lymhoblastic leukaemia. Lancet. 2013;381:1943-55.

Orgel E, Sea JL, Mittelman SD. Mechanisms by Which Obesity Impacts Survival from Acute Lymphoblastic Leukemia. J Natl Cancer Inst Monogr. 2019;2019(54):152-6. doi: 10.1093/jncimonographs/lgz020.

Paumgartner G, Beuers U. Ursodeoxycholic acid in cholestatic liver disease: mechanisms of action and therapeutic use revisited. Hepatology. 2002;36(3):525-31.

Sheng X, Mittelman SD. The role of adipose tissue and obesity in causing treatment resistance of acute lymphoblastic leukemia. Front Pediatr. 2014;2:53. doi: 10.3389/fped.2014.00053

Skrypnyk I, Maslova G. Drug-induced liver injury. 10-th International Symposium of gastroenterology: Abstr. (Czech Republic, Prague, June 12–14 2014). Prague, 2014, P.44.

Skrypnyk I, Maslova G. Rational approach to the choice of the treatment of antracycline-induced liver injury. Highlights from Hepatology 2015: from chronic hepatitis to hepatocellular carcinoma: Abstr. Falk Symposium 199 (October 14–15, 2015). Freiburg, 2015, P.75.

Stine JG, Lewis JH. Current and future directions in the treatment and prevention of drug-induced liver injury: a systematic review. Expert Rev Gastroenterol Hepatol. 2016;10(4):517-36. doi: 10.1586/17474124.2016.1127756.

Wree A, Dechлne A, Herzer K, Hilgard P, Syn WK, Gerken G, et al. Steroid and ursodesoxycholic аcid combination therapy in severe drug-induced liver injury. Digestion. 2011;84(1):54-9. doi: 10.1159/000322298.

Yoon S, Lee H, Ji SC, Yoon SH, Cho JY, Chung JY. Pharmacokinetics and Pharmacodynamics of Ursodeoxycholic Acid in an Overweight Population With Abnormal Liver Function. Clin Pharmacol Drug Dev. 2020; Available from: https://accp1.onlinelibrary.wiley.com/doi/abs/10.1002/cpdd.790. doi: 10.1002/cpdd.790.