Effects of CFTR modulator therapies on liver stiffness and bile flow: A single-centre experience

Calvo, Pier Luigi; Giugliano, Laura; Evangelista, Andrea; Bignamini, Elisabetta; Pinon, Michele

doi:10.1016/j.jhep.2023.02.006

Cited by 6 publications

(7 citation statements)

References 10 publications

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“…Currently, nearly all studies examining the effects of CFTR modulators on liver health are relatively small, single-center retrospective studies (lumacaftor/ivacaftor: 3 studies, cumulative n=124; elexacaftor/tezacaftor/ivacaftor: 4 studies, cumulative n=57). 103 – 108 Collectively, the data suggest that lumacaftor/ivacaftor may improve liver enzymes, APRI, and GPR. 105 – 107 One large retrospective review of a US private insurance claims database examined 955 patients with CF on CFTR modulators between 2012 and 2017 and found decreased cirrhosis in those on modulators.…”

Section: Methodsmentioning

confidence: 89%

Section: Methodsmentioning

confidence: 99%

“…One large retrospective review of a US private insurance claims database examined 955 patients with CF on CFTR modulators between 2012 and 2017 and found decreased cirrhosis in those on modulators 109 . Potential effects of elexacaftor/tezacaftor/ivacaftor are less clear, with one study showing decreased liver stiffness, but another showing no change, or even increased liver stiffness in PwCF on elexacaftor/tezacaftor/ivacaftor 103,104 . Some evidence suggests improvements in hepatic steatosis 108,110 .…”

Section: Methodsmentioning

confidence: 99%

“… 109 Potential effects of elexacaftor/tezacaftor/ivacaftor are less clear, with one study showing decreased liver stiffness, but another showing no change, or even increased liver stiffness in PwCF on elexacaftor/tezacaftor/ivacaftor. 103 , 104 Some evidence suggests improvements in hepatic steatosis. 108 , 110 Improvements in cholesterol biosynthesis and bile acid homeostasis have also been reported.…”

Section: Methodsmentioning

confidence: 99%

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Cystic fibrosis screening, evaluation, and management of hepatobiliary disease consensus recommendations

Sellers,

Assis,

Paranjape

et al. 2023

Hepatology

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Background and Aims Cystic fibrosis (CF) may cause a spectrum of hepatobiliary complications, including portal hypertension, multilobular cirrhosis, and liver failure. Current guidelines on the detection and monitoring of hepatobiliary complications in CF were published in 1999. The CF Foundation assembled a committee to evaluate research advances and formulate revised guidelines for CF-associated liver disease. Approach A committee of hepatologists, gastroenterologists, pulmonologists, pharmacist, nurse, dietitian, individual with CF, and parent of a child with CF devised “population, intervention, comparison, and outcome” (PICO) questions regarding hepatobiliary disease in CF. PubMed literature searches were performed for each PICO question. Recommendations were voted on with 80% agreement required to approve a recommendation. Public comment on initial recommendations was solicited prior to formulation of final recommendations. Results 31 PICO questions were assembled, 6,401 manuscripts were title screened for relevance, with 1,053 manuscripts undergoing detailed full text review. Seven recommendations were approved for screening, 13 for monitoring of existing disease, and 14 for treatment of CF-associated hepatobiliary involvement or advanced liver disease. One recommendation on liver biopsy did not meet the 80% threshold. One recommendation on screening ultrasound was revised and re-voted on. Conclusions Through a multidisciplinary committee and public engagement, we have assembled updated recommendations and guidance on screening, monitoring and treatment of CF-associated hepatobiliary involvement and advanced liver disease. While research gaps remain, we anticipate that these recommendations will lead to improvements in CF outcomes through earlier detection and increased evidence-based approaches to monitoring and treatment.

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Section: Methodsmentioning

confidence: 89%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Cystic fibrosis screening, evaluation, and management of hepatobiliary disease consensus recommendations

Sellers,

Assis,

Paranjape

et al. 2023

Hepatology

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“…At 6 months, there was a significant reduction in liver stiffness by 0.46 kPa. Most of the reduction occurred early and was primarily seen in the participants with mild or moderate/severe fibrosis [23 ▪ ].…”

Section: Hepatic Fibrosismentioning

confidence: 99%

Cystic fibrosis liver disease in the post-modulator era

Narkewicz

2023

Current Opinion in Pulmonary Medicine

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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.

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Pathophysiology of Cystic Fibrosis Liver Disease

Kasper,

Assis

2024

Pediatric Pulmonology

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Hepatobiliary complications of Cystic Fibrosis (CF) constitute a significant burden for persons with CF of all ages, with advanced CF liver disease in particular representing a leading cause of mortality. The causes of the heterogeneity of clinical manifestations, ranging from steatosis to focal biliary cholestasis and biliary strictures, are poorly understood and likely reflect a variety of environmental and disease‐modifying factors in the setting of underlying CFTR mutations. This review summarizes the current understanding of the pathophysiology of hepatobiliary manifestations of CF, and discusses emerging disease models and therapeutic approaches that hold promise to impact this important yet incompletely addressed aspect of CF care.

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Effects of CFTR modulator therapies on liver stiffness and bile flow: A single-centre experience

Cited by 6 publications

References 10 publications

Cystic fibrosis screening, evaluation, and management of hepatobiliary disease consensus recommendations

Cystic fibrosis screening, evaluation, and management of hepatobiliary disease consensus recommendations

Cystic fibrosis liver disease in the post-modulator era

Pathophysiology of Cystic Fibrosis Liver Disease

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