Ultrasound Assessment of Diaphragmatic Structure and Function in Patients With Liver Cirrhosis: A Point-of-Care Tool for Predicting Complications and Sarcopenia in Limited Resource Settings

Обзор

The goal of this observational study is to learn how liver cirrhosis affects the diaphragm, the main muscle used for breathing, in adults. The study will measure diaphragmatic thickness, thickening fraction, and excursion using bedside ultrasound and compare these values between patients with cirrhosis and healthy volunteers. The main questions it aims to answer are: Do patients with cirrhosis show reduced diaphragmatic function compared to healthy adults? Does removal of ascitic fluid by paracentesis improve diaphragmatic mechanics? Can ultrasound measurements of the diaphragm serve as a reliable non-invasive marker of sarcopenia when compared to CT scans? Participants will: Undergo diaphragmatic ultrasound during quiet and deep breathing Provide clinical and laboratory data related to liver disease severity In some cases, have ultrasound repeated before and after paracentesis For patients with hepatocellular carcinoma, CT scans will be analyzed to measure muscle mass

Подробное описание

This study is a prospective observational cohort designed to evaluate diaphragmatic structure and function in adults with liver cirrhosis. Using bedside ultrasound, the study will measure diaphragmatic thickness, thickening fraction, and excursion, and compare these values across different stages of liver disease severity and complications such as ascites, hepatic hydrothorax, and hepatocellular carcinoma. A subgroup of patients undergoing large-volume paracentesis will have ultrasound assessments before and after fluid removal to determine the acute impact of ascites drainage on diaphragmatic mechanics. In patients with hepatocellular carcinoma, existing CT scans will be analyzed to calculate skeletal muscle index, allowing correlation between ultrasound parameters and sarcopenia. Healthy volunteers will serve as a reference group for establishing normative values. Clinical and laboratory data, respiratory outcomes, and hospitalization details will also be collected to explore associations between diaphragmatic dysfunction and patient prognosis. The study aims to validate diaphragmatic ultrasound as a simple, non-invasive tool for respiratory monitoring and sarcopenia assessment in cirrhosis, particularly in resource-limited settings.

Первичные конечные точки

• Diaphragmatic Thickness (Tdi-exp, Tdi-insp) [cm] [Срок оценки: Baseline (Day 1, at enrollment).]
• Diaphragmatic Thickening Fraction (TF) [%] [Срок оценки: Baseline (Day 1, at enrollment).]
• Diaphragmatic Excursion (DE) [cm] [Срок оценки: Baseline (Day 1, at enrollment).]
• Group Differences in Diaphragmatic Thickness Across Cirrhosis Stages [Срок оценки: Baseline (Day 1, at enrollment)]
• Group Differences in Diaphragmatic Thickening Fraction Across Cirrhosis Stages [Срок оценки: Baseline (Day 1, at enrollment).]
• Group Differences in Diaphragmatic Excursion Across Cirrhosis Stages [Срок оценки: Baseline (Day 1, at enrollment).]
• Correlation of Diaphragmatic Thickness with Disease Severity [Срок оценки: Baseline (Day 1, at enrollment).]
• Correlation of Diaphragmatic Thickening Fraction (TF) with Disease Severity [Срок оценки: Baseline (Day 1, at enrollment).]
• Correlation of Diaphragmatic Excursion (DE) with Disease Severity [Срок оценки: Baseline (Day 1, at enrollment).]

Вторичные конечные точки (12)

• Correlation between diaphragmatic ultrasound parameters and skeletal muscle index (CT scans) [Срок оценки: At baseline (single measurement)]
• Change in Diaphragmatic Thickness After Paracentesis [Срок оценки: Pre-paracentesis (Day 1, immediately before procedure) and within 60 minutes post-paracentesis.]
• Change in Diaphragmatic Thickening Fraction After Paracentesis [Срок оценки: Pre-paracentesis (Day 1, immediately before procedure) and within 60 minutes post-paracentesis.]
• Change in Diaphragmatic Excursion After Paracentesis [Срок оценки: Pre-paracentesis (Day 1, immediately before procedure) and within 60 minutes post-paracentesis.]
• Diaphragmatic Thickness in Patients With vs. Without Hepatic Hydrothorax [Срок оценки: Baseline (Day 1, at enrollment).]
• Diaphragmatic Thickening Fraction in Patients With vs. Without Hepatic Hydrothorax [Срок оценки: Baseline (Day 1, at enrollment).]
• Diaphragmatic Excursion in Patients With vs. Without Hepatic Hydrothorax [Срок оценки: Baseline (Day 1, at enrollment).]
• Correlation of Diaphragmatic Dysfunction with Dyspnea Score [Срок оценки: Baseline (Day 1, at enrollment).]
• Correlation of Diaphragmatic Dysfunction with Respiratory Rate [Срок оценки: Baseline (Day 1, at enrollment).]
• Correlation of Diaphragmatic Dysfunction with Oxygen Saturation [Срок оценки: Baseline (Day 1, at enrollment).]
• Correlation of Diaphragmatic Dysfunction with Length of Hospital Stay [Срок оценки: During hospitalization (up to 30 days).]
• Correlation of Diaphragmatic Dysfunction with ICU Admission [Срок оценки: During hospitalization (up to 30 days).]

Критерии участия

Критерии включения

• Age ≥18 years.
• Confirmed diagnosis of liver cirrhosis based on clinical, biochemical, histological, or imaging criteria.
• Ability to provide written informed consent in Arabic or English.
• For Subgroup A: clinical indication for large-volume paracentesis with an ascitic volume of ≥5 liters.
• For Subgroup B: confirmed hepatic hydrothorax or confirmed absence of pleural effusion on ultrasound or chest X-ray.
• For Subgroup C: radiologically confirmed HCC by triphasic CT or MRI according to EASL/AASLD diagnostic criteria, with available CT imaging for L3 SMI analysis.

Критерии исключения

• Significant pre-existing primary pulmonary disease (e.g., moderate-to-severe COPD defined as FEV1/FVC <70% with FEV1 <60% predicted, interstitial lung disease, pulmonary fibrosis) that independently affects diaphragmatic mechanics.
• Recent thoracic surgery, thoracocentesis within the preceding 72 hours, or thoracic trauma.
• Neuromuscular disease (e.g., myasthenia gravis, amyotrophic lateral sclerosis, Guillain-Barré syndrome) independently affecting diaphragmatic function.
• Active mechanical ventilation at time of enrollment.
• Pregnancy.
• Inability to achieve adequate ultrasound acoustic windows (e.g., due to extreme obesity or surgical dressings).
• Contraindications to paracentesis in Subgroup A (e.g., disseminated intravascular coagulation, bowel obstruction).
• Prior or planned liver transplantation within the study period, which would confound longitudinal follow-up.
• Refusal or inability to provide informed consent.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Публикации

• Lakens D. Calculating and reporting effect sizes to facilitate cumulative science: a practical primer for t-tests and ANOVAs. Front Psychol. 2013 Nov 26;4:863. doi: 10.3389/fpsyg.2013.00863. PMID 24324449
• Koo TK, Li MY. A Guideline of Selecting and Reporting Intraclass Correlation Coefficients for Reliability Research. J Chiropr Med. 2016 Jun;15(2):155-63. doi: 10.1016/j.jcm.2016.02.012. Epub 2016 Mar 31. PMID 27330520
• Haaksma ME, Smit JM, Boussuges A, Demoule A, Dres M, Ferrari G, Formenti P, Goligher EC, Heunks L, Lim EHT, Mokkink LB, Soilemezi E, Shi Z, Umbrello M, Vetrugno L, Vivier E, Xu L, Zambon M, Tuinman PR. EXpert consensus On Diaphragm UltraSonography in the critically ill (EXODUS): a Delphi consensus statement on the measurement of diaphragm ultrasound-derived parameters in a critical care setting. C PMID 35395861
• Goligher EC, Laghi F, Detsky ME, Farias P, Murray A, Brace D, Brochard LJ, Bolz SS, Rubenfeld GD, Kavanagh BP, Ferguson ND. Measuring diaphragm thickness with ultrasound in mechanically ventilated patients: feasibility, reproducibility and validity. Intensive Care Med. 2015 Apr;41(4):642-9. doi: 10.1007/s00134-015-3687-3. Epub 2015 Feb 19. PMID 25693448
• GBD 2017 Cirrhosis Collaborators. The global, regional, and national burden of cirrhosis by cause in 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet Gastroenterol Hepatol. 2020 Mar;5(3):245-266. doi: 10.1016/S2468-1253(19)30349-8. Epub 2020 Jan 22. PMID 31981519
• Ebadi M, Bhanji RA, Dunichand-Hoedl AR, Mazurak VC, Baracos VE, Montano-Loza AJ. Sarcopenia Severity Based on Computed Tomography Image Analysis in Patients with Cirrhosis. Nutrients. 2020 Nov 11;12(11):3463. doi: 10.3390/nu12113463. PMID 33187310
• D'Amico G, Garcia-Tsao G, Pagliaro L. Natural history and prognostic indicators of survival in cirrhosis: a systematic review of 118 studies. J Hepatol. 2006 Jan;44(1):217-31. doi: 10.1016/j.jhep.2005.10.013. Epub 2005 Nov 9. No abstract available. PMID 16298014
• Carey EJ, Lai JC, Sonnenday C, Tapper EB, Tandon P, Duarte-Rojo A, Dunn MA, Tsien C, Kallwitz ER, Ng V, Dasarathy S, Kappus M, Bashir MR, Montano-Loza AJ. A North American Expert Opinion Statement on Sarcopenia in Liver Transplantation. Hepatology. 2019 Nov;70(5):1816-1829. doi: 10.1002/hep.30828. Epub 2019 Aug 19. PMID 31220351

Идентификаторы

NCT: NCT07667608 · DiaphragmCirrhosis_AU26

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗