Case report

A 57-year-old man, not known to have liver disease, felt dizzy while waiting for transportation home after a routine orthopaedic clinic visit. In the emergency room, pulse oximetry recording at room air was alarmingly low at 78% and a simultaneous PaO₂ of 6.26 kPa (normal 11–13 kPa) confirmed the hypoxaemia. With 100% oxygen delivered by a face mask, his oxygen saturation improved to 88%. On inquiry, he reported mildly progressive exertional dyspnoea for 24 months, dizziness for 18 months, weakness and fatigue for 12 months, and minimal lower extremity swelling for the past 2 weeks. He denied any other cardiorespiratory symptoms. He reported a 30-year history of alcohol abuse that had ended 18 months earlier. He was an active smoker with a 60-pack-year history. Examination revealed a middle-aged Caucasian male in no apparent distress. His other vital signs were stable. Positive findings were mild jaundice, digital clubbing, numerous spider naevi on the chest, and trace ankle oedema. Pulmonary and cardiac examinations were unremarkable. There was no obvious ascites on abdominal examination and the hepatic span was 8 cm. Spleen was not palpable. Laboratory studies showed a haematocrit of 46% (normal 42–52%), haemoglobin of 161 g/l (140–180 g/l) and a mean corpuscular volume of 107.9 fl (86–98 fl). Whole blood count was 10.9 × 10⁹/l (4.3–10.3 × 10⁹/l) and the platelet count was 97 × 10⁹/l (130–400 × 10⁹/l). Total bilirubin was 53.01 μmol/l (5.1–17 μmol/l) with a direct fraction of 20.52 μmol/l (1.7–5.1 μmol/l). Alkaline phosphatase was 148 IU/l (30–120 IU/l), alanine aminotransferase 58 IU/l (0–35 IU/l), and aspartate aminotransferase 135 IU/l (0–35 IU/l). Serum albumin level was 29 g/l (35–55 g/l), total protein 66 g/l (55–80 g/l), and INR was 3.0. Serum glucose, electrolytes, creatinine and blood urea nitrogen levels were normal. Serological testing for viral hepatitis was negative. Antinuclear antibody was not detected. Electrocardiogram and chest radiograph were normal. A technetium-99m labelled macroaggregated albumin (^99mTc-MAA) perfusion scan of the lung (figure) showed no perfusion defects suggestive of a pulmonary embolus. However, a significant amount of the radioisotope was taken up by the kidneys and brain indicating an arteriovenous shunt, and the shunt fraction was quantified at 38% (normal < 5%). A contrast echocardiogram using microbubbles generated by agitation of normal saline showed crossover of bubbles from the right ventricle to the left atrium after five ventricular beats, excluding an intracardiac shunt and confirming its intrapulmonary location. Pulmonary function tests showed normal spirometry and lung volumes. The diffusing capacity for carbon monoxide was reduced at 58% of the predicted value. Computed tomography (CT) of the lungs was normal except for minimal pleural thickening at the posterior aspect of the right lung base. A CT scan of the abdomen revealed a small nodular liver, with a preserved caudate lobe. The liver was surrounded by a mild to moderate amount of ascites. Mild enlargement of the spleen with varices in the splenic hilum were noted. These radiological findings were consistent with liver cirrhosis and portal hypertension. Endoscopy showed 2+ oesophageal varices and moderate portal hypertensive gastropathy. A diagnosis of alcohol-related liver disease (probably cirrhosis) and hepatopulmonary syndrome was made.

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Figure Perfusion scan with ^99mTc-MAA. Uptake over kidneys, liver, spleen and brain suggests abnormal passage through pulmonary vascular bed

Discussion

HPS is characterised by the triad of arterial hypoxaemia, liver disease, and intrapulmonary vascular dilatation. The presence of other concomitant pulmonary disorders such as obstructive airway disease does not exclude the diagnosis of HPS.1

There are several compelling reasons why internists need to be aware of the HPS:

• the relatively high prevalence of the syndrome: 47% of patients investigated with endstage liver disease,4 and 38% with less severe liver disease, were shown to have intrapulmonary shunting5

• as in this case, commonly encountered liver diseases can present with HPS. In a review of the aetiologies in 57 patients with HPS, 12 were due to alcoholic cirrhosis and 10 due to chronic active hepatitis6

• clinical features of HPS (dyspnoea and clubbing) are non-specific. Although the majority present with hepatic manifestations, up to 18% of patients with HPS have presented with predominantly pulmonary symptoms,7 as did this patient

• failure to recognise HPS can be serious. Progressive decline in oxygenation can occur despite stable hepatic function8; 41% mortality a mean of 2.5 years after the onset of dyspnoea has been reported7

• another reason to recognise HPS early, is that treatment with selective embolization of the dilated pulmonary vasculature9 or liver transplantation,10offers hope for a cure.

• diagnosis of HPS is easy and requires no fancy equipment.

^99mTc-MAA perfusion scanning is one of the modalities used to demonstrate intrapulmonary vascular dilatation. Injected peripherally, the majority of the labelled albumin (20–60 μm in diameter) is normally trapped in the pulmonary vasculature and the lungs take up most of the radioisotope. In the presence of intrapulmonary or intracardiac shunting, the albumin is not trapped totally in the pulmonary capillary bed and is taken up in the brain, kidneys, liver and spleen.11 The amount of shunted radioisotope can be quantified. To demonstrate the presence of intrapulmonary vascular dilatation causing an arteriovenous shunt and to localise it anatomically to the lungs, the current gold standard is contrast-enhanced echocardiography.8 Agitated saline-generated microbubbles injected intravenously are normally trapped by the pulmonary capillary bed. Should the bubbles appear in the left side of the heart a shunt is implied. Timing of the arrival of the microbubbles in the left atrium helps distinguish intracardiac from intrapulmonary shunting. A 4–6 beat delay after opacification of the right ventricle indicates intrapulmonary shunting.12 Apart from a reduced diffusing capacity for carbon monoxide, pulmonary function tests are normal, but chest radiographs often show bibasilar nodular or reticulonodular opacities.13 Laboratory investigations show evidence of hepatic dysfunction, but there is no correlation between the degree of biochemical abnormalities and the development of HPS.6

The dilated pulmonary capillary has an expanded diameter, oxygen molecules from the adjacent alveoli cannot diffuse to the centre of the dilated vessel to oxygenate haemoglobin in erythrocytes at the centre of the venous stream, thus resulting in hypoxaemia.11 The factors causing the dilatation itself have not been established.