Delayed hepatic necrosis in a cystic fibrosis patient taking Elexacaftor/Tezacaftor/Ivacaftor (Kaftrio)

Salehi, Mahan; Iqbal, Mubashar; Dube, A; Al-Joudeh, Amer; Edenborough, Frank

doi:10.1016/j.rmcr.2021.101553

Cited by 13 publications

(15 citation statements)

References 3 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…An increased rate of elevated transaminases was observed in individuals taking ELX/TEZ/IVA in trials 3 and following licensing there have been case reports of hepatic necrosis and acute liver failure following treatment with ELX/TEZ/IVA. 41 Conversely, it is unknown whether CFTR modulator therapy may improve the clinical course in CFLD through improved CFTR activity in biliary epithelial cells, intestinal epithelium, and/or vascular endothelium. Results from small studies have been mixed, with one study finding a reduction in liver enzymes in patients after starting LUM/IVA 42 though another found an increase in liver stiffness measurements 6 months after starting LUM/IVA.…”

Section: Cystic Fibrosis Liver Diseasementioning

confidence: 99%

Beyond the Lungs—Emerging Challenges in Adult Cystic Fibrosis Care

Mulrennan

Sapru

Tewkesbury

et al. 2022

Semin Respir Crit Care Med

View full text Add to dashboard Cite

Cystic fibrosis (CF) is a multisystem disease. This article provides an up-to-date review of many of the nonrespiratory complications of CF, including mental health issues, nutritional and gastrointestinal problems, fertility issues, diabetes mellitus, bone health and musculoskeletal problems, liver disease, renal problems, and risk of malignancy. It highlights the recent impact of new therapies, including CF transmembrane conductance regulator modulators, on the nonrespiratory complications of CF and provides insights into the potential challenges faced by an aging population of adults with CF and their caregivers, including the potential future risk for cardiovascular disease.

show abstract

Section: Cystic Fibrosis Liver Diseasementioning

confidence: 99%

Beyond the Lungs—Emerging Challenges in Adult Cystic Fibrosis Care

Mulrennan

Sapru

Tewkesbury

et al. 2022

Semin Respir Crit Care Med

View full text Add to dashboard Cite

show abstract

“…Evaluation for other causes of liver disease were negative and liver biopsy demonstrated confluent necrosis consistent with DILI. The subject eventually recovered to normal liver enzymes and function [15].…”

Section: Severe Hepatitis and Hepatic Failurementioning

confidence: 89%

Cystic fibrosis liver disease in the post-modulator era

Narkewicz

2023

Current Opinion in Pulmonary Medicine

View full text Add to dashboard Cite

Purpose of review Highly effective modulators of cystic fibrosis transmembrane conductance regulator (CFTR) function have had dramatic impact on pulmonary and nutritional outcomes in persons with cystic fibrosis (pwCF). The impact on liver disease in pwCF was not the focus of the registration trials. The purpose of this review is to assess the current literature on the impact of HEMT on liver disease, progression, regression, and safety. Recent findings Short-term studies of HEMT in pwCF have shown that there is no significant impact on the frequency of liver enzyme abnormalities. There is no evidence for significant improvement in liver enzymes over time on HEMT therapy. There is conflicting data on improvement in liver fibrosis determined by fibrosis indices (APRI and GPR) or elastography. One study showed improvement, and another showed worsening in younger (<20 years old) pwCF. There are reports of resolution or improvement in hepatic steatosis. There are rare reports of severe acute hepatitis and one report of hepatic decompensation leading to liver transplantation due to drug-induced liver disease. Summary HEMT have not been shown to have a significant impact on improving liver disease or preventing fibrosis with short-term therapy. Longer studies are needed to assess the impact of HEMT on liver disease in pwCF.

show abstract

“…Drug-induced liver injury is known as a potential side effect of the highly lipophilic CFTR modulators ( Salehi et al, 2021 ; Lowry et al, 2022 ) and the mobilization of gall stones may cause biliary colic shortly after initiation with ELX/TEZ/IVA ( Safirstein et al, 2021 ). Upon initiation of triple CFTR modulator therapy serum levels of bilirubin and liver transaminases will mildly increase after 3 months which is sustained but does not appear to increase further in the majority of pwCF ( Tewkesbury et al, 2023 ).…”

Section: Intestine Pancreas Liver and Nutritionmentioning

confidence: 99%

Post-approval studies with the CFTR modulators Elexacaftor-Tezacaftor—Ivacaftor

Tümmler

2023

Front. Pharmacol.

View full text Add to dashboard Cite

Triple combination therapy with the CFTR modulators elexacaftor (ELX), tezacaftor (TEZ) and ivacaftor (IVA) has been qualified as a game changer in cystic fibrosis (CF). We provide an overview of the body of literature on ELX/TEZ/IVA published between November 2019 and February 2023 after approval by the regulators. Recombinant ELX/TEZ/IVA-bound Phe508del CFTR exhibits a wild type conformation in vitro, but in patient’s tissue a CFTR glyoisoform is synthesized that is distinct from the wild type and Phe508del isoforms. ELX/TEZ/IVA therapy improved the quality of life of people with CF in the real-life setting irrespective of their anthropometry and lung function at baseline. ELX/TEZ/IVA improved sinonasal and abdominal disease, lung function and morphology, airway microbiology and the basic defect of impaired epithelial chloride and bicarbonate transport. Pregnancy rates were increasing in women with CF. Side effects of mental status changes deserve particular attention in the future.

show abstract

Delayed hepatic necrosis in a cystic fibrosis patient taking Elexacaftor/Tezacaftor/Ivacaftor (Kaftrio)

Cited by 13 publications

References 3 publications

Beyond the Lungs—Emerging Challenges in Adult Cystic Fibrosis Care

Beyond the Lungs—Emerging Challenges in Adult Cystic Fibrosis Care

Cystic fibrosis liver disease in the post-modulator era

Post-approval studies with the CFTR modulators Elexacaftor-Tezacaftor—Ivacaftor

Contact Info

Product

Resources

About