{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T16:33:55Z","timestamp":1788453235889,"version":"build-2803163510"},"reference-count":42,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T00:00:00Z","timestamp":1769126400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T00:00:00Z","timestamp":1769126400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Br J Clin Pharmacol"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>Elexacaftor\/tezacaftor\/ivacaftor (ETI) has markedly improved cystic fibrosis (CF) outcomes. However, its long\u2010term impact on nutrition, metabolism and liver health remains underexplored. We assessed 30\u2010month changes in pulmonary, nutritional, metabolic and inflammatory markers in people with CF (PwCF) homozygous for F508del.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We retrospectively analysed 112 PwCF (median age\u201031\u2009years) treated with ETI from July 2021 to December 2024. Clinical, spirometric and biochemical data were collected at baseline and at 6, 12, 24 and 30\u2009months.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      ETI produced sustained lung function gains (percent predicted FEV\u2081\u2009+\u200915 points at 24\u2009months, p\u2009&lt;\u20090.001), BMI increase (+1.7\u00a0kg\/m\n                      <jats:sup>2<\/jats:sup>\n                      in year\u2010one, p\u2009&lt;\u20090.001) and marked C\u2010reactive protein reduction (\u221280% at 6\u00a0months), with an 85% decrease in pulmonary exacerbations. Nutritional recovery shifted BMI distribution: underweight prevalence declined from 12.5% to 1.8%, while overweight rose from 15.2% to 27.7%. Adolescents improved in weight\u2010for\u2010age Z\u2010scores (+0.42, p\u2009=\u20090.01). Total and LDL cholesterol increased but remained within reference ranges; HDL, triglycerides and glycaemic control stayed stable, with no new cystic fibrosis\u2013related diabetes (CFRD). Vitamin D improved; vitamin B12 fluctuated with supplementation. Mild, transient transaminase elevations occurred in 4.5% of PwCF, with no fibrosis progression (APRI\/FIB\u20104 below risk thresholds).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>ETI provides durable multisystem benefits, preserving lung function and improving nutritional and metabolic profiles. However, the shift towards overweight\/obesity and biochemical signs of hepatic stress suggests evolving cardiometabolic risks. These findings support early ETI initiation and reinforce the need for ongoing monitoring of nutrition, lipid profile and liver function, together with updated CF care strategies to mitigate long\u2010term cardiometabolic complications.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/bcp.70460","type":"journal-article","created":{"date-parts":[[2026,1,24]],"date-time":"2026-01-24T06:31:37Z","timestamp":1769236297000},"page":"1822-1832","source":"Crossref","is-referenced-by-count":3,"title":["Long\u2010term impact of Elexacaftor\/Tezacaftor\/ivacaftor on pulmonary, nutritional and metabolic outcomes in homozygous F508del cystic fibrosis patients: A real\u2010world cohort study"],"prefix":"10.1002","volume":"92","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0809-5118","authenticated-orcid":false,"given":"Nicola","family":"Perrotta","sequence":"first","affiliation":[{"name":"Department of Physiology and Pharmacology \u201cV. Erspamer\u201d Sapienza University  Rome Italy"},{"name":"Policlinico Umberto I Hospital Sapienza University  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigi Angelo","family":"Fiorito","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology \u201cV. Erspamer\u201d Sapienza University  Rome Italy"},{"name":"Policlinico Umberto I Hospital Sapienza University  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Vescovo","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Technology of Drugs Sapienza University  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Virgilio","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Technology of Drugs Sapienza University  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Amato","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Technology of Drugs Sapienza University  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Cimino","sequence":"additional","affiliation":[{"name":"Regional Cystic Fibrosis Center, Policlinico Umberto I Hospital Sapienza University  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,1,23]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcf.2023.03.011"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213\u20102600(19)30408\u20104"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2021.113195"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/life13071431"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcf.2023.10.002"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1908639"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc10\u20101768"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clnu.2023.12.017"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00080312"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1053\/jhep.2003.50346"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.21178"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1097\/HEP.0000000000000646"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(19)32597\u20108"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcf.2025.04.012"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/cts.70373"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2024.e28508"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/prp2.70083"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/ppul.27272"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcf.2018.01.006"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010024\u201059622\u20102"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcf.2025.10.001"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1177\/17534666251314706"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu14061216"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010024\u201068511\u20107"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/ncp.11332"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcf.2024.09.022"},{"key":"e_1_2_10_28_1","article-title":"One year of treatment with elexacaftor\/tezacaftor\/ivacaftor in patients with cystic fibrosis homozygous for the F508del mutation causes a significant increase in liver biochemical indexes. 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