How does portal hypertension affect pulmonary hypertension?

Portal Hypertension's Effect on Pulmonary Hypertension

Portal hypertension contributes to pulmonary hypertension primarily through the development of portosystemic shunts rather than portal hypertension itself, allowing vasoactive substances to bypass liver metabolism and reach the pulmonary circulation. 1

Pathophysiology and Mechanism

Portal hypertension can lead to a specific form of pulmonary arterial hypertension (PAH) called portopulmonary hypertension (POPH). The key mechanisms include:

• Portosystemic shunts: The development of PAH in patients with portal hypertension is strongly related to portosystemic shunts rather than portal hypertension per se 1

  • Approximately 65% of patients with PAH had surgical shunts while 35% did not 1
  • These shunts allow vasoactive substances to bypass liver metabolism

• Vasoactive mediators: Substances normally cleared by the liver reach the pulmonary circulation 1, 2

  • Serotonin produced by intestinal enterochromaffin cells is a potential mediator 1
  • These substances can cause vasoconstriction and vascular remodeling

• Duration of portal hypertension: The risk of developing PAH increases with longer duration of portal hypertension 1

Epidemiology and Risk Factors

• Prevalence:

  • 2-4% of patients with cirrhosis and portal hypertension develop significant PAH 1
  • 8% of patients in the NIH registry of PAH had portopulmonary hypertension 1

• Risk factors:

  • Duration of portal hypertension (not severity) 1
  • Presence of portosystemic shunts (surgical or spontaneous) 1
  • Not associated with severity of liver disease or degree of portal hypertension 1

Clinical Presentation and Diagnosis

• Clinical features: May be indistinguishable from idiopathic PAH or include symptoms of underlying liver disease 1

• Hemodynamic profile:

  • Higher cardiac output compared to IPAH 1
  • Lower systemic vascular resistance and pulmonary vascular resistance 1
  • Mean pulmonary artery pressure often severely elevated (59 ± 19 mmHg) 3

• Diagnostic approach:

  • Echocardiographic screening is appropriate in symptomatic patients and liver transplant candidates 1
  • Right heart catheterization is essential to confirm diagnosis when increased systolic pulmonary artery pressure is detected 1
  • Hepatic venous pressure gradient >10 mmHg confirms portal hypertension 1

Treatment Considerations

• General measures:

  • Supplemental oxygen to maintain saturations >90% 1
  • Diuretic therapy for volume overload, edema, and ascites 1
  • Anticoagulation should generally be avoided due to bleeding risk 1

• Specific therapies:

  • Vasodilator testing should be performed in mild to moderate PH cases 1
  • Calcium channel blockers may be considered in vasoreactive patients 1
  • Intravenous epoprostenol can significantly improve pulmonary hemodynamics 4
    • Reduces pulmonary vascular resistance by 34% acutely and 47% long-term 4
    • May increase ascites and splenomegaly 1
  • Beta-blockers (used for portal hypertension) may be poorly tolerated in POPH 1, 2

Impact on Liver Transplantation

• Contraindication: Significant PAH (mean PAP >35 mmHg and/or PVR >250 dynes·s·cm⁻⁵) is usually a contraindication for liver transplantation 1

• Pre-transplant management: Aggressive treatment of PAH may reduce pulmonary pressures enough to make transplantation feasible 1

• Post-transplant course: Some patients may experience worsening of PAH after transplantation, while others may improve enough to be weaned off pulmonary vasodilators 1

Prognosis

• Some studies suggest better survival in portopulmonary hypertension compared to idiopathic PAH, though this remains debated 1

• Without treatment, the prognosis is poor with mean survival of approximately 15 months 3

Clinical Pitfalls to Avoid

• Do not assume that the severity of portal hypertension correlates with risk of PAH development 1

• Avoid beta-blockers in patients with moderate to severe portopulmonary hypertension as they may worsen outcomes 2

• Do not miss screening liver transplant candidates for pulmonary hypertension, as undiagnosed severe POPH significantly increases transplant mortality 1

• Remember that the histopathological findings of portopulmonary hypertension are indistinguishable from idiopathic PAH 1