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
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
研究概览
详细说明
研究类型
注册 (估计的)
联系人和位置
学习联系方式
- 姓名：Nada Refaat Mohamed, MD
- 电话号码：+201019860918
- 邮箱：nadarefaat411@gmail.com
研究联系人备份
- 姓名：Mohamed Abdelghany Abdelhamed
- 电话号码：+201112828724
- 邮箱：Moh7111@aun.edu.eg
参与标准
资格标准
适合学习的年龄
- 成人
- 年长者
接受健康志愿者
取样方法
研究人群
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).
- Subgroup A: Ascites/Paracentesis (n=30): Patients with tense or refractory ascites for whom large-volume paracentesis is clinically indicated. This subgroup will contribute both cross-sectional and longitudinal (pre/post paracentesis) data.
- Subgroup B: Hepatic Hydrothorax (n=40): Twenty patients with confirmed hepatic hydrothorax (HH; defined as pleural effusion >500 mL in the absence of primary cardiopulm
描述
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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.
学习计划
研究是如何设计的？
设计细节
队列和干预
团体/队列 |
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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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研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
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Diaphragmatic Thickness (Tdi-exp, Tdi-insp) [cm]
大体时间：Baseline (Day 1, at enrollment).
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Diaphragmatic thickness at end-expiration (Tdi-exp) and end-inspiration (Tdi-insp) measured by B-mode ultrasound.
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Baseline (Day 1, at enrollment).
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Diaphragmatic Thickening Fraction (TF) [%]
大体时间：Baseline (Day 1, at enrollment).
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Thickening fraction calculated as [(Tdi-insp - Tdi-exp) / Tdi-exp] × 100, measured by B-mode ultrasound.
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Baseline (Day 1, at enrollment).
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Diaphragmatic Excursion (DE) [cm]
大体时间：Baseline (Day 1, at enrollment).
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Amplitude of diaphragmatic displacement measured by M-mode ultrasound during quiet breathing.
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Baseline (Day 1, at enrollment).
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Group Differences in Diaphragmatic Thickness Across Cirrhosis Stages
大体时间：Baseline (Day 1, at enrollment)
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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)
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Group Differences in Diaphragmatic Thickening Fraction Across Cirrhosis Stages
大体时间：Baseline (Day 1, at enrollment).
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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).
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Group Differences in Diaphragmatic Excursion Across Cirrhosis Stages
大体时间：Baseline (Day 1, at enrollment).
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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).
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Correlation of Diaphragmatic Thickness with Disease Severity
大体时间：Baseline (Day 1, at enrollment).
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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).
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Correlation of Diaphragmatic Thickening Fraction (TF) with Disease Severity
大体时间：Baseline (Day 1, at enrollment).
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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).
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Correlation of Diaphragmatic Excursion (DE) with Disease Severity
大体时间：Baseline (Day 1, at enrollment).
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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).
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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Correlation between diaphragmatic ultrasound parameters and skeletal muscle index (CT scans)
大体时间：At baseline (single measurement)
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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.
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At baseline (single measurement)
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Change in Diaphragmatic Thickness After Paracentesis
大体时间：Pre-paracentesis (Day 1, immediately before procedure) and within 60 minutes post-paracentesis.
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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.
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Change in Diaphragmatic Thickening Fraction After Paracentesis
大体时间：Pre-paracentesis (Day 1, immediately before procedure) and within 60 minutes post-paracentesis.
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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.
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Change in Diaphragmatic Excursion After Paracentesis
大体时间：Pre-paracentesis (Day 1, immediately before procedure) and within 60 minutes post-paracentesis.
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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.
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Diaphragmatic Thickness in Patients With vs. Without Hepatic Hydrothorax
大体时间：Baseline (Day 1, at enrollment).
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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).
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Diaphragmatic Thickening Fraction in Patients With vs. Without Hepatic Hydrothorax
大体时间：Baseline (Day 1, at enrollment).
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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).
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Diaphragmatic Excursion in Patients With vs. Without Hepatic Hydrothorax
大体时间：Baseline (Day 1, at enrollment).
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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).
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Correlation of Diaphragmatic Dysfunction with Dyspnea Score
大体时间：Baseline (Day 1, at enrollment).
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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).
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Correlation of Diaphragmatic Dysfunction with Respiratory Rate
大体时间：Baseline (Day 1, at enrollment).
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Correlation between diaphragmatic dysfunction and respiratory rate (breaths/min). Unit of Measure: Correlation coefficient (r). |
Baseline (Day 1, at enrollment).
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Correlation of Diaphragmatic Dysfunction with Oxygen Saturation
大体时间：Baseline (Day 1, at enrollment).
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Correlation between diaphragmatic dysfunction and peripheral oxygen saturation (SpO₂, %). Unit of Measure: Correlation coefficient (r). |
Baseline (Day 1, at enrollment).
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Correlation of Diaphragmatic Dysfunction with Length of Hospital Stay
大体时间：During hospitalization (up to 30 days).
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Correlation between diaphragmatic dysfunction (defined by ultrasound parameters: thickness, thickening fraction, excursion) and length of hospital stay (days).
Unit of Measure: Correlation coefficient (r).
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During hospitalization (up to 30 days).
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Correlation of Diaphragmatic Dysfunction with ICU Admission
大体时间：During hospitalization (up to 30 days).
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Correlation between diaphragmatic dysfunction and need for ICU admission.
Unit of Measure: Odds ratio (% of patients requiring ICU admission).
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During hospitalization (up to 30 days).
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Correlation of Diaphragmatic Dysfunction with In-Hospital Complications
大体时间：During hospitalization (up to 30 days).
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Correlation between diaphragmatic dysfunction and occurrence of complications (e.g., respiratory failure, infection).
Unit of Measure: Incidence (% of patients with complications).
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During hospitalization (up to 30 days).
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合作者和调查者
调查人员
- 首席研究员：Ahmed Helmy Salem, professor、Assiut University
- 首席研究员：Maiada Kamal Eldeen Hashem、Assiut University
出版物和有用的链接
一般刊物
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
研究记录日期
研究主要日期
学习开始 (估计的)
初级完成 (估计的)
研究完成 (估计的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (实际的)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
更多信息
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