To Study the Safety and Efficacy of Simvastatin in Patients With Hepatopulmonary Syndrome in Cirrhosis.

• Status: Not yet recruiting
• Trial end date: 2023-10-01
• Target enrollment: 0
• Participant gender: All

Summary

Hepatopulmonary syndrome (HPS) is a frequent pulmonary complication of end-stage liver disease that is characterized by decreased arterial oxygenation caused by intrapulmonary vascular dilatation. Due to the different diagnostic criteria used in different studies, its prevalence ranges from 4% to 47% in patients with cirrhosis. Main underlaying pathogensis for HPS being activation of macrophages which are responsible for iNOS, PDGF and VEGF release contributing to development of intrapulmonary vascular dilatation(IPVD) , and neoangiogenesis leading to anatomical shunt resulting decreased oxygenation. Sphingosine 1 phosphate (S1P) is an essential compound produced and secreted by endothelial cells, platelets and RBC's. S1P prevents adhesion, transmigration and release of inflammatory mediators from macrophages. S1P levels are decreased in cirrhotics. Simvastatin, a HMG CoA inhibitor has many pleotropic effects, Of which one is by agonizing the S1P response and improving oxygenation in HPS patients. Simvastatin at a optimal dose of 40mg/day for 6months. Pre and post simvastatin treatment related oxygenation changes and concurrently its effect on liver fibrosis will be evaluated.

• Phase: N/A
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Institute of Liver and Biliary Sciences, India
• Treatments: Simvastatin

Criteria

Inclusion Criteria:

1. Diagnosed case of Hepato-pulmonary syndrome AaPO2 > 15 mm Hg on standing room air arterial blood gas (ABG). PaO2<80 mmHg for clinical HPS between 18-70 years of years

2. Child A/B cirrhosis, Child C with CTP score of =/<10

3. Patient with no liver transplant option

Exclusion Criteria:

1. Child-C cirrhosis CTP >10

2. Very Severe HPS

3. Acute-on-chronic liver failure

4. Thrombosis of splenoportal axis

5. Hepatocellular carcinoma

6. Renal dysfunction

7. Patients intolerant to beta blockers (history of hypotension or bradycardia)

8. Contraindication for beta-blockers (history of chronic obstructive pulmonary disease, atrioventricular block)

9. Pregnant females

10. Refusal to participate in the study

11. Hepatic Hydrothorax