Efficacy and Safety of Pentoxifylline in Improving Oxygenation in Hepatopulmonary Syndrome

• Status: Not yet recruiting
• Trial end date: 2023-04-30
• Target enrollment: 0
• Participant gender: All

Summary

The triad of liver disease, arterial hypoxia, and extensive pulmonary vascular dilatation is known as the hepatopulmonary syndrome (HPS). The prevalence of this syndrome ranges from 10% to 30% in people with chronic liver disease.

The exact cause of HPS is unknown. Previous research has shown that eicosanoids function as vasoconstrictors and cause an increase in the number of intravascular macrophage-like cells. Cirrhosis has been linked to increased NO generation in the lungs, which has been linked to intrapulmonary venous dilation. Increased pulmonary NO production is attributed to increased expression of pulmonary vascular endothelial NO synthase (eNOS) and inducible NO synthase.

Increased hepatic synthesis and release of low levels of endothelin 1 (ET-1) has been established in recent investigations to function as a trigger for increasing eNO levels. TNF (tumor necrosis factor) and ET-1 have both been linked to the onset of experimental HPS. Increased CO generation and heme oxygenase expression have been linked to the progression of HPS in recent investigations. HPS increases mortality in cirrhotic patients and may affect the frequency and severity of portal hypertension consequences.

To the best of our knowledge there have been only three pilot studies in humans which checked the effect of pentoxifylline in hepatopulmonary syndrome and they showed highly contrasting results. The outcome was also measured in a short interval. Investigator hypothesize that pentoxifylline would improve the oxygenation in patients with hepatopulmonary syndrome

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

Details

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

Criteria

Inclusion Criteria:

• Age 18 - 70 years

• Evidence of portal hypertension

• Intrapulmonary vascular dilatation in the form of shunting diagnosed on contrast echocardiogram

• AaPO2 > 15mmHg on seated room air (ABG) if age <65years and >20mmHg if Age≥ 70 years

Exclusion Criteria:

• Child C cirrhosis with CTP > 10 or with refractory ascites

• Intrinsic significant cardiopulmonary disease

1. PFT indicating severe obstructive ventilatory defect (FEV1/FVC < 70)

2. Hepatic hydrothorax, Portopulmonary hypertension

3. Moderate and severe left ventricular systolic dysfunction

4. Inability to perform Pulmonary function test

5. Intracardiac shunting

• Current use of exogenous nitrates

• Patients already on pentoxifylline

• Prior intolerance to pentoxifylline

• Very severe cases of HPS (A-aO2 gradient ≥ 15mm Hg, PO2 <50 mmHg)

• Active bacterial infections, active hepatic encephalopathy

• Known malignancy including HCC

• SBP on secondary prophylaxis

• CKD with creatinine clearance < 30

• Enrolled in other trials

• Has a liver transplant option