A clinical case of the triple targeted therapy in a patient with cystic fibrosis complicated with liver cirrhosis
- Authors: Stezhkina E.V.1,2, Umerov Y.A.1, Solovyova S.S.1, Terekhina T.A.1, Smirnova V.V.3
-
Affiliations:
- Ryazan State Medical University
- Ryazan pediatrician outpatient clinic No. 7
- Regional Children Clinical Hospital named after N.V. Dmitrieva
- Issue: Vol 15, No 4 (2024)
- Pages: 93-102
- Section: Clinical observation
- URL: https://journal-vniispk.ru/pediatr/article/view/279243
- DOI: https://doi.org/10.17816/PED15493-102
- ID: 279243
Cite item
Abstract
Cystic fibrosis is a systemic autosomal recessive disease manifested by damage to the exocrine glands due to dysfunction of the CFTR gen. The primary defect leads to insufficiency of all exocrine glands with multiple organ manifestations, among which the respiratory system, digestive tract and exocrine parts of the pancreas, as well as the liver, are especially severely affected. Classical basic therapy for cystic fibrosis is symptomatic. Currently, the most modern is pathogenetic targeted therapy using CFTR modulators. The presence of the F508del mutation in a heterozygous or homozygous state is critical for the use of this therapy. CFTR modulators are metabolized in the liver, which makes it necessary to take drugs with caution if it is affected. The article presents a clinical case of the use of fixed targeted therapy with Ivacaftor (75 mg) + Tezacaftor (25 mg) + Elexacaftor (100 mg) and Ivacaftorin (150 mg) a patient with cystic fibrosis complicated by cirrhosis of the liver. The patient’s clinical picture showed progressive multi-organ lesions with a leading clinical problem in the form of liver cirrhosis with signs of portal hypertension and hepatic failure. The presence of the F508del mutation in a heterozygous state made it possible to use fixed targeted combination, but the potential hepatotoxicity of this drug raised concerns. On the other hand, pre-existing liver damage is one of the manifestations of cystic fibrosis, so we can expect at least a slowdown in the progression of liver damage against the background of targeted therapy. By the council decision in June 2022, it was decided to start targeted therapy for vital indications. This case illustrates the success of this triple targeted combination in a child with cystic fibrosis and cirrhosis of the liver, which is a unique observation. Experience in the use of this combination for treatment of cystic fibrosis complicated by cirrhosis of the liver is extremely scarce, therefore, long-term follow-up of the patient is required to assess its efficacy and safety in the long term.
Keywords
Full Text
##article.viewOnOriginalSite##About the authors
Elena V. Stezhkina
Ryazan State Medical University; Ryazan pediatrician outpatient clinic No. 7
Email: polus1972@yandex.ru
ORCID iD: 0000-0002-1806-0787
MD, PhD, Associate Professor, Department of Faculty and Polyclinic Pediatrics
Russian Federation, 9,Vysokovoltnaya st., Ryazan, 390026; RyazanYurij A. Umerov
Ryazan State Medical University
Author for correspondence.
Email: umerov.yura@mail.ru
ORCID iD: 0009-0003-6838-707X
resident doctor, Department of Faculty and Polyclinic Pediatrics
Russian Federation, 9,Vysokovoltnaya st., Ryazan, 390026Sophya S. Solovyova
Ryazan State Medical University
Email: sophya-00@yandex.ru
ORCID iD: 0009-0004-9778-6042
resident doctor, Department of Faculty and Polyclinic Pediatrics
Russian Federation, 9,Vysokovoltnaya st., Ryazan, 390026Tatiana A. Terekhina
Ryazan State Medical University
Email: t080280f@mail.ru
ORCID iD: 0000-0003-2667-0494
SPIN-code: 2304-4425
MD, PhD, Assistant Professor, Department of Faculty and Polyclinic Pediatrics
Russian Federation, 9,Vysokovoltnaya st., Ryazan, 390026Vera V. Smirnova
Regional Children Clinical Hospital named after N.V. Dmitrieva
Email: svera1966@mail.ru
ORCID iD: 0000-0001-8021-0267
MD, PhD, Head of Pulmonology the Department
Russian Federation, RyazanReferences
- Ventslovayte ND, Efremova NA, Goriacheva LG, Gerasimova OA. Liver transplantation in children: the experience of last decades, current problems and solutions. Children infections. 2020;19(2):52–57. EDN: QCBZZH doi: 10.22627/2072-8107-2020-19-2-52-57
- Kashirskaya NY, Kapranov NI, Kusova ZA, et al. Damage to the hepatobiliary system in cystic fibrosis. Pediatrics. Journal named after G.N. Speransky. 2012;91(4):106–115. (In Russ.) EDN: PAMJSZ
- Union of Pediatricians of Russia, Association of Medical Genetics, Russian Respiratory Society, et al. Clinical recommendations of the Russian Federation — Cystic fibrosis (cystic fibrosis) — 2021–2022–2023. Moscow; 2021. 182 p. (In Russ.)
- Kondratyeva EI. Innovative treatments for cystic fibrosis. Vrach. 2016;(2):77–80. EDN: VQZUPR
- Kondratieva EI, Tsirulnikova OM, Voronkova AY, et al. Cirrhosis and liver transplantation experience in children and adolescents with cystic fibrosis. Pediatrics. Journal named after G.N. Speransky. 2017;96(6): 36–47. EDN: ZTPVRH doi: 10.24110/0031-403X-2017-96-6-36-47
- Krasovskiy SA, Adyan TA, Amelina EL, et al. Cystic fibrosis: some issues of epidemiology and genetics. Practical pulmonology. 2019;(4):45–49. EDN: OAECXD
- Kondratieva EI, Kashirskaya NYu, Kapranov NI, editors. National Consensus (2nd ed.) Cystic fibrosis: definition, diagnostic criteria, therapy. Moscow: LLC “BORGES Company”; 2018. 356 p. (In Russ.)
- Kondratieva EI, Krasovsky SA, Starinova MA, et al editors. Register of patients with cystic fibrosis in the Russian Federation. 2020. 2022. 68 p. (In Russ.)
- Chermensky AG, Gembitskaya TE, Orlov AV, Makhmutova VR. The use of targeted therapy lumacaftor/ivacaftor in patients with cystic fibrosis. Medical council. 2022;16(4):98–106. EDN: NEGKBM doi: 10.21518/2079-701X-2022-16-4-98-106
- Gardiner A, Volovets A, Haber P, et al. ELX/TEZ/IVA use in cystic fibrosis liver disease: Is the perspective of improved lung function worth the risk? J Cyst Fibros. 2022;21(5):881–884. doi: 10.1016/j.jcf.2022.06.008
- Leung DH, Narkewicz MR. Cystic Fibrosis-related cirrhosis. J Cyst Fibros. 2017;16(2):50–61. doi: 10.1016/j.jcf.2017.07.002
- Debray D, Kelly D, Houwen R, et al. Best practice guidance for the diagnosis and management of cystic fibrosis-associated liver disease. J Cyst Fibros. 2011;10(2):S29–S36. doi: 10.1016/S1569-1993(11)60006-4
- Bartlett JR, Friedman KJ, Ling SC, et al. Genetic modifiers of liver disease in cystic fibrosis. JAMA. 2009;302(10):1076–1083. doi: 10.1001/jama.2009.1295
- Lee J-A, Cho A, Huang EN, et al. Gene therapy for cystic fibrosis: new tools for precision medicine. J Transl Med. 2021;19:452. doi: 10.1186/s12967-021-03099-4
- Milkiewicz P, Skiba G, Kelly D, et al. Transplantation for cystic fibrosis: outcome following early liver transplantation. J Gastroenterol Hepatol. 2002;17(2):208–213. doi: 10.1046/j.1440-1746.2002.02671.x
- Salvatore F, Scudiero O, Castaldo G. Genotype-phenotype correlation in cystic fibrosis: the role of modifier genes. Am J Med Genet. 2002;111(1):88–95. doi: 10.1002/ajmg.10461
- Sakiani S, Kleiner DE, Heller T, Koh C. Hepatic manifestations of cystic fibrosis. Clin Liver Dis. 2019;32(2):263–277. doi: 10.1016/j.cld.2018.12.008
- Tewkesbury DH, Athwal V, Bright-Thomas RJ, et al. Longitudinal effects of elexacaftor/tezacaftor/ivacaftor on liver tests at a large single adult cystic fibrosis centre. J Cyst Fibros. 2023;22(2):256–262. doi: 10.1016/j.jcf.2023.01.007
- Flass T, Narkewicz MR. Cirrhosis and other liver disease in cystic fibrosis. J Cyst Fibros. 2012;12(2):116–124. doi: 10.1016/j.jcf.2012.11.010
- Zaher A, Elsaygh J, Elsori D, et al. A Review of Trikafta: Triple cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy. Cureus. 2021;13(7):e16144. doi: 10.7759/cureus.16144
Supplementary files
