What is the best and latest treatment for hepatopulmonary syndrome?

Treatment of Hepatopulmonary Syndrome

Liver transplantation is the only definitive and successful treatment for hepatopulmonary syndrome, resulting in complete reversal or significant improvement in more than 85% of patients with severe hypoxemia. 1

Definitive Treatment: Liver Transplantation

Patients with HPS and PaO2 <60 mmHg should be evaluated for liver transplantation immediately, as it is the only treatment proven effective for improving mortality and quality of life. 1

Transplant Outcomes and Timing

• Five-year survival after liver transplantation improved dramatically from 67% in the pre-MELD era to 88% in the MELD era, reflecting both MELD exception policies and improved perioperative management. 1

• Patients with HPS receive MELD exception scores (initial score of 22 with increases every three months) to prioritize transplantation before severe hypoxemia develops. 1

• Severe hypoxemia with PaO2 ≤44-50 mmHg remains associated with increased post-transplant mortality, making early transplant evaluation critical before this threshold is reached. 1

Monitoring While Awaiting Transplant

• Arterial blood gas analysis should be performed every six months in patients awaiting transplantation, as hypoxemia worsens progressively with a median PaO2 decrease of 5.2 mmHg per year. 1

• Regular monitoring facilitates transplantation before very severe hypoxemia develops, which significantly impacts post-transplant survival. 1

Supportive Medical Management

Long-Term Oxygen Therapy

Long-term oxygen therapy is recommended for patients with HPS and severe hypoxemia (PaO2 <60 mmHg) as symptomatic treatment while awaiting transplantation. 1

• This remains the most frequently recommended therapy for symptoms, though data on effectiveness, tolerance, cost-effectiveness, compliance, and survival benefit are lacking. 1

• Oxygen therapy serves as a bridge to transplantation rather than definitive treatment. 1

Pharmacological Therapies: Not Recommended

No medical therapy is currently established or recommended for HPS treatment. 1

The following medications have been uniformly unsuccessful in treating HPS: 1

• Beta-blockers
• Cyclooxygenase inhibitors
• Systemic glucocorticoids and cyclophosphamide
• Almitrine bismesylate
• Inhaled nitric oxide
• Nitric oxide inhibitors
• Antimicrobial agents

Additional therapies with insufficient or contradictory evidence: 1

• Pentoxifylline showed contradictory results with frequent gastrointestinal side effects
• Garlic administration showed improvement in one small randomized study but has been associated with hepatotoxicity
• Endothelin-1 receptor antagonists and angiogenesis inhibitors have not been tested in HPS patients

Interventional Procedures: Limited Role

TIPS (Transjugular Intrahepatic Portosystemic Shunt)

No recommendation can be made for TIPS placement to treat HPS. 1

• Data are insufficient even when systematic reviews are considered. 1

• Concern exists that TIPS may enhance pulmonary vasodilation by exacerbating hyperkinetic circulation. 1

• One case report suggests TIPS may serve as a bridge to transplantation in severe hypoxemia, but this cannot be recommended as routine practice due to lack of data. 2

Coil Embolization

• Embolotherapy has shown temporary improvement in arterial oxygenation only in patients with angiographic arteriovenous communications. 1

• Pulmonary angiography should be performed only in patients with severe hypoxemia (PaO2 <60 mmHg) poorly responsive to 100% oxygen, when discrete arteriovenous communications amenable to embolization are strongly suspected. 1

Perioperative Management

For patients undergoing transplantation with severe HPS, the following may improve oxygenation immediately post-transplant: 1

• Inhaled nitric oxide
• Methylene blue
• Extracorporeal membrane oxygenation
• Non-invasive ventilation

Critical Pitfalls to Avoid

• Do not delay transplant evaluation in patients with HPS, as mortality is nearly double compared to cirrhotic patients without HPS, independent of MELD score and other predictors. 1

• Do not attempt medical management as definitive therapy, as spontaneous resolution is uncommon and five-year survival without transplantation is only 23% compared to 63% in matched cirrhotic patients without HPS. 1

• Do not wait until PaO2 falls below 44-50 mmHg to pursue transplantation, as this threshold is associated with significantly increased post-transplant mortality. 1

• Do not use TIPS routinely for HPS treatment given insufficient evidence and potential to worsen pulmonary vasodilation. 1