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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
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Adults with Liver Cirrhosis | This cohort includes adults diagnosed with liver cirrhosis, with subgroups defined by complications such as ascites, hepatic hydrothorax, and hepatocellular carcinoma. A subgroup undergoing paracentesis will be assessed before and after fluid removal to evaluate acute changes in diaphragmatic function. In patients with hepatocellular carcinoma, CT scans will be analyzed to calculate skeletal muscle index for correlation with ultrasound findings. A small number of healthy volunteers will also undergo diaphragmatic ultrasound to establish normative reference values; however, they are not considered a separate cohort for analysis. |
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| Measure | Description | Time Frame |
|---|---|---|
| Diaphragmatic Thickness (Tdi-exp, Tdi-insp) [cm] | Diaphragmatic thickness at end-expiration (Tdi-exp) and end-inspiration (Tdi-insp) measured by B-mode ultrasound. | Baseline (Day 1, at enrollment). |
| Diaphragmatic Thickening Fraction (TF) [%] | Thickening fraction calculated as [(Tdi-insp - Tdi-exp) / Tdi-exp] × 100, measured by B-mode ultrasound. | Baseline (Day 1, at enrollment). |
| Diaphragmatic Excursion (DE) [cm] | Amplitude of diaphragmatic displacement measured by M-mode ultrasound during quiet breathing. | Baseline (Day 1, at enrollment). |
| Group Differences in Diaphragmatic Thickness Across Cirrhosis Stages | Mean differences in diaphragmatic thickness (cm) between patients with Child-Pugh A, B, and C cirrhosis, and across MELD score strata. Unit of Measure: Mean difference (cm). | Baseline (Day 1, at enrollment) |
| Group Differences in Diaphragmatic Thickening Fraction Across Cirrhosis Stages | Mean differences in diaphragmatic thickening fraction (%) between patients with Child-Pugh A, B, and C cirrhosis, and across MELD score strata. Unit of Measure: Mean difference (%). | Baseline (Day 1, at enrollment). |
| Group Differences in Diaphragmatic Excursion Across Cirrhosis Stages | Mean differences in diaphragmatic excursion (cm) between patients with Child-Pugh A, B, and C cirrhosis, and across MELD score strata. Unit of Measure: Mean difference (cm). | Baseline (Day 1, at enrollment). |
| Measure | Description | Time Frame |
|---|---|---|
| Correlation between diaphragmatic ultrasound parameters and skeletal muscle index (CT scans) | In patients with hepatocellular carcinoma, triphasic CT scans will be analyzed to calculate skeletal muscle index. These values will be correlated with diaphragmatic ultrasound parameters to assess the utility of ultrasound as a surrogate marker of sarcopenia. | At baseline (single measurement) |
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Inclusion Criteria:
Exclusion Criteria:
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Adults (≥18 years of age) with confirmed diagnosis of liver cirrhosis attending the hepatology outpatient clinic or admitted to the hepatology inpatient unit of the study institution.
Study Subgroups The total study sample will consist of 120 participants, including 95 patients with liver cirrhosis and 25 healthy controls. The cirrhotic cohort will include patients across different Child-Pugh classes and MELD scores and will encompass clinically relevant subgroups such as patients with ascites undergoing paracentesis, hepatic hydrothorax, and hepatocellular carcinoma (HCC).
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Nada Refaat Mohamed, MD | Contact | +201019860918 | nadarefaat411@gmail.com | |
| Mohamed Abdelghany Abdelhamed | Contact | +201112828724 | Moh7111@aun.edu.eg |
| Name | Affiliation | Role |
|---|---|---|
| Ahmed Helmy Salem, professor | Assiut University | Principal Investigator |
| Maiada Kamal Eldeen Hashem | Assiut University | Principal Investigator |
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 24324449 | Background | 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. | |
| 27330520 | Background | 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. |
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| Correlation of Diaphragmatic Thickness with Disease Severity | Correlation between diaphragmatic thickness (cm) and liver disease severity scores (Child-Pugh class, MELD score). Unit of Measure: Correlation coefficient (r). | Baseline (Day 1, at enrollment). |
| Correlation of Diaphragmatic Thickening Fraction (TF) with Disease Severity | Correlation between diaphragmatic thickening fraction (%) and liver disease severity scores (Child-Pugh class, MELD score). Unit of Measure: Correlation coefficient (r). | Baseline (Day 1, at enrollment). |
| Correlation of Diaphragmatic Excursion (DE) with Disease Severity | Correlation between diaphragmatic excursion (cm) and liver disease severity scores (Child-Pugh class, MELD score). Unit of Measure: Correlation coefficient (r). | Baseline (Day 1, at enrollment). |
| Change in Diaphragmatic Thickness After Paracentesis | Change in diaphragmatic thickness (cm) measured by B-mode ultrasound before and within 60 ± 15 minutes after large-volume paracentesis. Unit of Measure: Mean difference (cm). | Pre-paracentesis (Day 1, immediately before procedure) and within 60 minutes post-paracentesis. |
| Change in Diaphragmatic Thickening Fraction After Paracentesis | Change in diaphragmatic thickening fraction (%) measured by B-mode ultrasound before and within 60 ± 15 minutes after large-volume paracentesis. Unit of Measure: Mean difference (%). | Pre-paracentesis (Day 1, immediately before procedure) and within 60 minutes post-paracentesis. |
| Change in Diaphragmatic Excursion After Paracentesis | Change in diaphragmatic excursion (cm) measured by M-mode ultrasound before and within 60 ± 15 minutes after large-volume paracentesis. Unit of Measure: Mean difference (cm). | Pre-paracentesis (Day 1, immediately before procedure) and within 60 minutes post-paracentesis. |
| Diaphragmatic Thickness in Patients With vs. Without Hepatic Hydrothorax | Comparison of mean diaphragmatic thickness (cm) between cirrhotic patients with hepatic hydrothorax and matched cirrhotic controls without hydrothorax. Unit of Measure: Mean difference (cm). | Baseline (Day 1, at enrollment). |
| Diaphragmatic Thickening Fraction in Patients With vs. Without Hepatic Hydrothorax | Comparison of mean diaphragmatic thickening fraction (%) between cirrhotic patients with hepatic hydrothorax and matched cirrhotic controls without hydrothorax. Unit of Measure: Mean difference (%). | Baseline (Day 1, at enrollment). |
| Diaphragmatic Excursion in Patients With vs. Without Hepatic Hydrothorax | Comparison of mean diaphragmatic excursion (cm) between cirrhotic patients with hepatic hydrothorax and matched cirrhotic controls without hydrothorax. Unit of Measure: Mean difference (cm). | Baseline (Day 1, at enrollment). |
| Correlation of Diaphragmatic Dysfunction with Dyspnea Score | Correlation between diaphragmatic dysfunction (defined by ultrasound parameters) and dyspnea severity measured by the mMRC scale (0-4). Unit of Measure: Correlation coefficient (r). | Baseline (Day 1, at enrollment). |
| Correlation of Diaphragmatic Dysfunction with Respiratory Rate | Correlation between diaphragmatic dysfunction and respiratory rate (breaths/min). Unit of Measure: Correlation coefficient (r). | Baseline (Day 1, at enrollment). |
| Correlation of Diaphragmatic Dysfunction with Oxygen Saturation | Correlation between diaphragmatic dysfunction and peripheral oxygen saturation (SpO₂, %). Unit of Measure: Correlation coefficient (r). | Baseline (Day 1, at enrollment). |
| Correlation of Diaphragmatic Dysfunction with Length of Hospital Stay | Correlation between diaphragmatic dysfunction (defined by ultrasound parameters: thickness, thickening fraction, excursion) and length of hospital stay (days). Unit of Measure: Correlation coefficient (r). | During hospitalization (up to 30 days). |
| Correlation of Diaphragmatic Dysfunction with ICU Admission | Correlation between diaphragmatic dysfunction and need for ICU admission. Unit of Measure: Odds ratio (% of patients requiring ICU admission). | During hospitalization (up to 30 days). |
| Correlation of Diaphragmatic Dysfunction with In-Hospital Complications | Correlation between diaphragmatic dysfunction and occurrence of complications (e.g., respiratory failure, infection). Unit of Measure: Incidence (% of patients with complications). | During hospitalization (up to 30 days). |
| 35395861 | Background | 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. Crit Care. 2022 Apr 8;26(1):99. doi: 10.1186/s13054-022-03975-5. |
| 25693448 | Background | 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. |
| 31981519 | Background | 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. |
| 33187310 | Background | 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. |
| 16298014 | Background | 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. |
| 31220351 | Background | 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. |
| 32358646 | Background | Cappellini I, Picciafuochi F, Bartolucci M, Matteini S, Virgili G, Adembri C. Evaluation of diaphragm thickening by diaphragm ultrasonography: a reproducibility and a repeatability study. J Ultrasound. 2021 Dec;24(4):411-416. doi: 10.1007/s40477-020-00462-x. Epub 2020 May 1. |
| 19017880 | Background | Boussuges A, Gole Y, Blanc P. Diaphragmatic motion studied by m-mode ultrasonography: methods, reproducibility, and normal values. Chest. 2009 Feb;135(2):391-400. doi: 10.1378/chest.08-1541. Epub 2008 Nov 18. |
| 33778044 | Background | Boussuges A, Finance J, Chaumet G, Bregeon F. Diaphragmatic motion recorded by M-mode ultrasonography: limits of normality. ERJ Open Res. 2021 Mar 22;7(1):00714-2020. doi: 10.1183/23120541.00714-2020. eCollection 2021 Jan. |
| ID | Term |
|---|---|
| D005355 | Fibrosis |
| D001201 | Ascites |
| D010996 | Pleural Effusion |
| D006528 | Carcinoma, Hepatocellular |
| D055948 | Sarcopenia |
| ID | Term |
|---|---|
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D010995 | Pleural Diseases |
| D012140 | Respiratory Tract Diseases |
| D000230 | Adenocarcinoma |
| D002277 | Carcinoma |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D008113 | Liver Neoplasms |
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
| D004066 | Digestive System Diseases |
| D008107 | Liver Diseases |
| D009133 | Muscular Atrophy |
| D020879 | Neuromuscular Manifestations |
| D009461 | Neurologic Manifestations |
| D009422 | Nervous System Diseases |
| D001284 | Atrophy |
| D020763 | Pathological Conditions, Anatomical |
| D012816 | Signs and Symptoms |
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