The hepatopulmonary syndrome: NO way out?

To the Editors:

The hepatopulmonary syndrome (HPS) is defined by the triad of chronic liver disease, abnormal pulmonary gas exchange (low arterial oxygen tension (Pa,O₂) and transfer factor of the lung for carbon monoxide), and intrapulmonary vascular dilatation 1. The recent editorial on HPS 2 suggests that “hunting endogenous vasodilators that reduce pulmonary vascular tone logically became a sound strategy for those whose quest was to unravel the missing ‘molecular’ link between the diseased liver and the affected lung”. But, is this strategy actually so logical? The key feature of the intrapulmonary vascular dilatation in HPS is the intrapulmonary shunt shown physiologically by a low Pa,O₂ after 100% oxygen breathing, and anatomically by the passage of radiolabelled albumin macroaggregates (20–60 µm in diameter), or echobubbles, through the pulmonary capillary bed 3. The striking feature pathologically is gross dilatation of capillaries in the alveolar septum, diameters of 100 µm, as compared with the normal 7–15 µm being described 4. Is it likely that endogenous vasodilators are responsible for “relaxing” alveolar capillaries to such an extent? Of course, endogenous vasodilators may play a part in “remodelling” these capillaries.

With regard to pulmonary gas exchange, two factors seem to operate in severe hepatopulmonary syndrome: 1) a hyperdynamic state with low pulmonary vascular resistance and rapid microvascular transit, and 2) vascular remodelling with dilatation of capillaries and a low transfer factor of the lung for carbon monoxide. After liver transplantation, arterial oxygen tension improves, but transfer factor of the lung for carbon monoxide often remains low 5, implying improvement in process 1 more than process 2. Since pulmonary nitric oxide levels return to normal after orthotopic liver transplantation 6, nitric oxide is an unlikely cause of the pulmonary capillary dilatation. Figure 1 in the European Respiratory Journal editorial 2 focuses on pulmonary vascular smooth muscle, but it cannot be the only factor.