Portopulmonary hypertension poses difficulties for patients with liver disease. The elevated pulmonary artery pressure in this disorder makes liver transplantation more dangerous and in fact may rule out the procedure, although in a selected few patients, medical treatment may enable transplantation to proceed. In any event, portopulmonary hypertension should be looked for in patients with liver disease, especially if liver transplantation is being considered.
In this article we discuss the definition, pathophysiology, clinical features, diagnosis, and management of portopulmonary hypertension.
DEFINED BY HEMODYNAMIC CRITERIA
Portopulmonary hypertension—elevated pulmonary artery pressure due to increased resistance to blood flow in patients with portal hypertension—is one of several pulmonary complications of liver disease. A few others to be aware of are pleural effusions (hepatic hydrothorax), dilatation of the pulmonary vasculature with shunting and hypoxemia (hepatopulmonary syndrome), and elevation in pulmonary pressures due to the high cardiac output usually seen in liver disease (flow phenomenon).
The definition of portopulmonary hypertension has evolved as the various hemodynamic profiles that occur in liver disease and their consequences have been described. Currently, it is defined by the following criteria (obtained by right heart catheterization) in a patient with portal hypertension1:
- Elevated mean pulmonary artery pressure (> 25 mm Hg at rest, > 30 mm Hg with exercise);
- Increased pulmonary vascular resistance (> 240 dynes.s.cm−5; pulmonary vascular resistance = [(mean pulmonary artery pressure minus pulmonary artery occlusion pressure) /cardiac output] times 80); and
- Normal pulmonary artery occlusion pressure (< 15 mm Hg) or an elevated transpulmonary gradient (the mean pulmonary artery pressure minus the pulmonary artery occlusion pressure; abnormal is > 12 mm Hg).
The transpulmonary gradient sometimes helps in further assessing the resistance to blood flow in cases that do not meet the other criteria.2 For example, how should we classify a patient whose mean pulmonary artery pressure is 45 mm Hg but whose pulmonary vascular resistance is only 432 dynes.s.cm−5 and whose pulmonary artery occlusion pressure is slightly high at 18 mm Hg? Although this patient does not meet the hemodynamic criteria for portopulmonary hypertension listed above, intuitively, we should not exclude the diagnosis, as the transpulmonary gradient is high at 27 mm Hg.
FLOW PHENOMENON VS TRUE PORTOPULMONARY HYPERTENSION
The cardiopulmonary hemodynamic profile is different in patients with liver disease than in those without liver disease. Understanding the “normal” hemodynamics in liver disease is paramount in understanding the abnormal hemodynamics that occur in portopulmonary hypertension. In general, patients with liver disease have a high cardiac output at baseline (high flow). They may also have an increased blood volume due to fluid shifts (elevated pulmonary artery occlusion pressure).
Right heart catheterization is necessary to make the diagnosis of portopulmonary hypertension, as pulmonary artery pressures may be increased simply from increases in cardiac output and blood volume without an increase in pulmonary vascular resistance.
Consider, for example, a patient whose mean pulmonary artery pressure is 38 mm Hg, pulmonary artery occlusion pressure 14 mm Hg, and cardiac output 8.8 L/minute. In this case, the pulmonary vascular resistance is 218 dynes.s.cm−5. About 30% to 50% of patients with cirrhosis have this type of hyperdynamic pattern, with high cardiac output, low systemic vascular resistance, and low pulmonary vascular resistance.1,3,4 These patients typically have a much better prognosis than those with portopulmonary hypertension and do well with liver transplantation.
Right heart catheterization is also helpful in assessing whether elevated pulmonary pressures are due to increased volume (increased pulmonary artery occlusion pressure), in which case the patient might benefit from more aggressive diuresis.
In true portopulmonary hypertension, the pulmonary vascular resistance is increased due to obstruction of arterial blood flow. Cardiac output may be elevated initially and then decline as pulmonary hypertension becomes more severe. These hemodynamic patterns have different treatment implications and are important when liver transplantation is being considered.5
HOW COMMON IS PORTOPULMONARY HYPERTENSION?
The incidence and prevalence of portopulmonary hypertension is difficult to assess, as many of the estimates are in patients with severe liver disease undergoing evaluation for liver transplantation. Its prevalence in patients with cirrhosis and refractory ascites has been documented at 16.1%,6 while its prevalence in patients with cirrhosis without refractory ascites has been in the range of 0.25% to 4%.7–9
Overall, about 8% of candidates for liver transplantation have portopulmonary hypertension and are at risk of its complications.10 In view of this figure, screening for it should be performed before proceeding with liver transplantation.