TOC | Pulm The Hepatopulmonary Syndrome     (Review 1995)

James K. Stoller, MD Annals of Internal Medicine. 1995;122:521-529
ACP Library on Disk 2- (c) 1997 - American College of Physicians

The triad of hepatopulmonary syndrome:

• liver cirrhosis disease
• hypoxemia -an increased alveolar-arterial gradient while breathing room air - impaired arterial oxygenation
• evidence of intrapulmonary vascular dilatations

Other cardiopulmonary abnormalities (such as pleural effusions or decreased lung volumes) are common and may coexist in patients with the hepatopulmonary syndrome.

Several clinical signs and symptoms characterize this syndrome; most persons will present with

• Liver features include gastrointestinal bleeding, esophageal varices, ascites, palmar erythema, spider nevi, and splenomegaly.
• Pulmonary features include digital clubbing, cyanosis, dyspnea, platypnea, and orthodeoxia.
  Platypnea, defined as dyspnea induced by the upright position and relieved by recumbency,
  Orthodeoxia, defined as arterial deoxygenation accentuated in the upright position and relieved by recumbency.
  Other pulm. features include alveolar hyperventilation with hypocapnia and a hyperdynamic circulation characterized by systemic & pulmonary vasodilatation and elevated cardiac output. End-stage liver disease may be characterized by various other derangements of pulmonary function, including a restrictive pattern of lung function characterized by decreased total lung capacity, air flow obstruction, impairment of diffusing capacity, and a widened alveolar-arterial oxygen gradient.

Chest X-ray: decreased lung volumes (57%), pleural effusions (19.3%), increased basilar & pulmonary interstitial markings (13.8%), and increased pulmonary vascular markings (3.7%).

Two radiographic patterns for the hepatopulmonary syndrome on the basis of pulmonary angiographic features in seven patients with this syndrome.

• Type 1, or minimal pattern, is characterized by a pattern of finely diffuse, spidery infiltrates, and may be associated with severe hypoxemia, orthodeoxia, and a good oxygenation response to 100% inspired oxygen.
• Type 2 is characterized by discrete, localized arteriovenous communications, and may respond poorly to supplemental oxygen.

Mechanisms of Hypoxemia in the Hepatopulmonary Syndrome
Putative mechanisms include changes in the affinity of hemoglobin for oxygen, intrapulmonary and portopulmonary shunt, alveolar capillary diffusion limitation , ventilation-perfusion inequality, and combinations of these factors. Changes in hemoglobin dissociation and portopulmonary shunt have largely been dismissed as causes of the severe hypoxemia characteristic of the hepatopulmonary syndrome.

Diagnosis of Intrapulmonary Vascular Dilatations: Imaging Techniques
The presence of intrapulmonary vascular dilatations can be confirmed using one of three imaging modalities: contrast-enhanced echocardiography, perfusion lung scan - technetium 99m-labeled macroaggregated albumin scanning, and pulmonary arteriography.

RX of The Hepatopulmonary Syndrome

Medical Therapy
Medical therapy has been disappointing. To date, small, observational studies have examined several drugs, including garlic (allium sativum) , indomethacin, almitrine bismesylate, and octreotide, and plasma exchange has been attempted to remove a circulating vasodilator. However, all of these treatments have been associated with at best minimal improvement in oxygenation and shunt.

* IV methylene blue  (a potent inhibitor of guanylate cyclase) 3 mg/kg over 15 min improved hypoxemia & hyperdynamic circulation in patients with liver cirrhosis and severe hepatopulmonary syndrome.  (AIM Nov.7, 2000;133:701 Peter Schenk, etc.)

Liver Transplantation
Several early reports and more recent experience have documented striking improvements in oxygenation and reversal of shunt both with resolution of liver disease and after liver transplantation in some patients. Later reports have confirmed resolution of the hepatopulmonary syndrome after liver transplantation.

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