Ascites, Cirrhosis of the Liver, Diaphragm Movement, Hepatocellular Carcinoma (HCC), Pleural Effusion Disorder, Sarcopenia
Conditions
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
Detailed description
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.
Interventions
None listed
Sponsors
Assiut University
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
1. Age ≥18 years. 2. Confirmed diagnosis of liver cirrhosis based on clinical, biochemical, histological, or imaging criteria. 3. Ability to provide written informed consent in Arabic or English. 4. For Subgroup A: clinical indication for large-volume paracentesis with an ascitic volume of ≥5 liters. 5. For Subgroup B: confirmed hepatic hydrothorax or confirmed absence of pleural effusion on ultrasound or chest X-ray. 6. 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
1. 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. 2. Recent thoracic surgery, thoracocentesis within the preceding 72 hours, or thoracic trauma. 3. Neuromuscular disease (e.g., myasthenia gravis, amyotrophic lateral sclerosis, Guillain-Barré syndrome) independently affecting diaphragmatic function. 4. Active mechanical ventilation at time of enrollment. 5. Pregnancy. 6. Inability to achieve adequate ultrasound acoustic windows (e.g., due to extreme obesity or surgical dressings). 7. Contraindications to paracentesis in Subgroup A (e.g., disseminated intravascular coagulation, bowel obstruction). 8. Prior or planned liver transplantation within the study period, which would confound longitudinal follow-up. 9. Refusal or inability to provide informed consent.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Diaphragmatic Thickness (Tdi-exp, Tdi-insp) [cm] | Baseline (Day 1, at enrollment). | Diaphragmatic thickness at end-expiration (Tdi-exp) and end-inspiration (Tdi-insp) measured by B-mode ultrasound. |
| Diaphragmatic Thickening Fraction (TF) [%] | Baseline (Day 1, at enrollment). | Thickening fraction calculated as \[(Tdi-insp - Tdi-exp) / Tdi-exp\] × 100, measured by B-mode ultrasound. |
| Diaphragmatic Excursion (DE) [cm] | Baseline (Day 1, at enrollment). | Amplitude of diaphragmatic displacement measured by M-mode ultrasound during quiet breathing. |
| Group Differences in Diaphragmatic Thickness Across Cirrhosis Stages | Baseline (Day 1, at enrollment) | 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). |
| Group Differences in Diaphragmatic Thickening Fraction Across Cirrhosis Stages | Baseline (Day 1, at enrollment). | 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 (%). |
| Group Differences in Diaphragmatic Excursion Across Cirrhosis Stages | Baseline (Day 1, at enrollment). | 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). |
| Correlation of Diaphragmatic Thickness with Disease Severity | Baseline (Day 1, at enrollment). | Correlation between diaphragmatic thickness (cm) and liver disease severity scores (Child-Pugh class, MELD score). Unit of Measure: Correlation coefficient (r). |
| Correlation of Diaphragmatic Thickening Fraction (TF) with Disease Severity | Baseline (Day 1, at enrollment). | Correlation between diaphragmatic thickening fraction (%) and liver disease severity scores (Child-Pugh class, MELD score). Unit of Measure: Correlation coefficient (r). |
| Correlation of Diaphragmatic Excursion (DE) with Disease Severity | Baseline (Day 1, at enrollment). | Correlation between diaphragmatic excursion (cm) and liver disease severity scores (Child-Pugh class, MELD score). Unit of Measure: Correlation coefficient (r). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Correlation between diaphragmatic ultrasound parameters and skeletal muscle index (CT scans) | At baseline (single measurement) | 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. |
| Change in Diaphragmatic Thickness After Paracentesis | Pre-paracentesis (Day 1, immediately before procedure) and within 60 minutes post-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). |
| Change in Diaphragmatic Thickening Fraction After Paracentesis | Pre-paracentesis (Day 1, immediately before procedure) and within 60 minutes post-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 (%). |
| Change in Diaphragmatic Excursion After Paracentesis | Pre-paracentesis (Day 1, immediately before procedure) and within 60 minutes post-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). |
| Diaphragmatic Thickness in Patients With vs. Without Hepatic Hydrothorax | Baseline (Day 1, at enrollment). | Comparison of mean diaphragmatic thickness (cm) between cirrhotic patients with hepatic hydrothorax and matched cirrhotic controls without hydrothorax. Unit of Measure: Mean difference (cm). |
| Diaphragmatic Thickening Fraction in Patients With vs. Without Hepatic Hydrothorax | Baseline (Day 1, at enrollment). | Comparison of mean diaphragmatic thickening fraction (%) between cirrhotic patients with hepatic hydrothorax and matched cirrhotic controls without hydrothorax. Unit of Measure: Mean difference (%). |
| Diaphragmatic Excursion in Patients With vs. Without Hepatic Hydrothorax | Baseline (Day 1, at enrollment). | Comparison of mean diaphragmatic excursion (cm) between cirrhotic patients with hepatic hydrothorax and matched cirrhotic controls without hydrothorax. Unit of Measure: Mean difference (cm). |
| Correlation of Diaphragmatic Dysfunction with Dyspnea Score | Baseline (Day 1, at enrollment). | Correlation between diaphragmatic dysfunction (defined by ultrasound parameters) and dyspnea severity measured by the mMRC scale (0-4). Unit of Measure: Correlation coefficient (r). |
| Correlation of Diaphragmatic Dysfunction with Respiratory Rate | Baseline (Day 1, at enrollment). | Correlation between diaphragmatic dysfunction and respiratory rate (breaths/min). Unit of Measure: Correlation coefficient (r). |
| Correlation of Diaphragmatic Dysfunction with Oxygen Saturation | Baseline (Day 1, at enrollment). | Correlation between diaphragmatic dysfunction and peripheral oxygen saturation (SpO₂, %). Unit of Measure: Correlation coefficient (r). |
| Correlation of Diaphragmatic Dysfunction with Length of Hospital Stay | During hospitalization (up to 30 days). | Correlation between diaphragmatic dysfunction (defined by ultrasound parameters: thickness, thickening fraction, excursion) and length of hospital stay (days). Unit of Measure: Correlation coefficient (r). |
| Correlation of Diaphragmatic Dysfunction with ICU Admission | During hospitalization (up to 30 days). | Correlation between diaphragmatic dysfunction and need for ICU admission. Unit of Measure: Odds ratio (% of patients requiring ICU admission). |
| Correlation of Diaphragmatic Dysfunction with In-Hospital Complications | During hospitalization (up to 30 days). | Correlation between diaphragmatic dysfunction and occurrence of complications (e.g., respiratory failure, infection). Unit of Measure: Incidence (% of patients with complications). |
Contacts
CONTACTNada Refaat Mohamed, MD
CONTACTMohamed Abdelghany Abdelhamed
PRINCIPAL_INVESTIGATORAhmed Helmy Salem, professor
Assiut University
PRINCIPAL_INVESTIGATORMaiada Kamal Eldeen Hashem
Assiut University
Outcome results
None listed