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

NCT07667608 | Not Yet Recruiting DMC

• 1 other identifier: DiaphragmCirrhosis_AU26
• Study Type: observational
• Target: 120
• Locations: 0 countries
• Sites: N/A

Brief Summary

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

Conditions

Cirrhosis of the Liver; Ascites; Pleural Effusion Disorder; Hepatocellular Carcinoma (HCC); Sarcopenia; Diaphragm Movement

Outcome Measures

Primary Outcomes (9)

• 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).

• 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).

Secondary Outcomes (13)

• Correlation between diaphragmatic ultrasound parameters and skeletal muscle index (CT scans)

  At baseline (single measurement)

• Change in Diaphragmatic Thickness After Paracentesis

  Pre-paracentesis (Day 1, immediately before procedure) and within 60 minutes post-paracentesis.

• Change in Diaphragmatic Thickening Fraction After Paracentesis

  Pre-paracentesis (Day 1, immediately before procedure) and within 60 minutes post-paracentesis.

• Change in Diaphragmatic Excursion After Paracentesis

  Pre-paracentesis (Day 1, immediately before procedure) and within 60 minutes post-paracentesis.

• Diaphragmatic Thickness in Patients With vs. Without Hepatic Hydrothorax

  Baseline (Day 1, at enrollment).

Study Arms (1)

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.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Assiut University: lead

Related Publications (11)

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• 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.

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• 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.

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• 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.

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• 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.

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• 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.

  PMID: 19017880 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.

  PMID: 33778044 BACKGROUND

MeSH Terms

Conditions

Fibrosis; Ascites; Pleural Effusion; Carcinoma, Hepatocellular; Sarcopenia

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; Pleural Diseases; Respiratory Tract Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases; Muscular Atrophy; Neuromuscular Manifestations; Neurologic Manifestations; Nervous System Diseases; Atrophy; Pathological Conditions, Anatomical; Signs and Symptoms

Study Officials

• Ahmed Helmy Salem, professor

  Assiut University

  PRINCIPAL INVESTIGATOR

• Maiada Kamal Eldeen Hashem

  Assiut University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Nada Refaat Mohamed, MD

CONTACT

+201019860918; nadarefaat411@gmail.com

Mohamed Abdelghany Abdelhamed

CONTACT

+201112828724; Moh7111@aun.edu.eg

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Resident Physician, Department of Gastroenterology and Tropical Medicine, Faculty of Medicine, Assiut University

Study Record Dates

• First Submitted: June 16, 2026
• First Posted: June 25, 2026
• Study Start (Estimated): August 10, 2026
• Primary Completion (Estimated): August 10, 2027
• Study Completion (Estimated): December 10, 2027
• Last Updated: June 25, 2026

Record last verified: 2026-06