Bacterial translocation and subsequent monocyte accumulation may also stimulate pulmonary angiogenesis in HPS, which may be partly controlled by genetic factors. However, there remains a need for more human experimental data to support the development of new therapies targeting these proposed mechanisms. The presence of HPS should be considered in all patients with liver disease
who complain of dyspnea, which is common in cirrhosis, but which is present in 50% of patients with HPS.[13] A more specific symptom is platypnea (dyspnea that increases from the supine to the erect position), which may be associated check details with orthodoxia (hypoxia that is worse when erect). Finger clubbing is very common in HPS. In one study, it was found in almost 50% of HPS patients compared with 2% in those without the disorder.[54] This striking difference implies that one should always suspect HPS in patients with chronic liver disease and clubbing. Patients with severe HPS may be sufficiently hypoxic to appear cyanosed at rest, and the rare finding of cyanosis and clubbing in a cirrhotic patient is highly suggestive of the presence of severe HPS.[54] Although some studies show that spider nevi are often seen in HPS, there is no major difference in their prevalence in cirrhotics with HPS compared with control cirrhotic patients with
similar liver disease.[13] BAY 73-4506 cell line The diagnosis of HPS depends on establishing that impaired gas exchange in a patient
with liver disease is due to pulmonary vascular dilatation. In most cases, the results of arterial blood gases and a study to detect intrapulmonary shunting (see later) are sufficiently specific to do this once other intrinsic cardiorespiratory diseases are excluded. Pulse oximetry can be a useful monitoring tool in the outpatient setting, and has been proposed as a screening mafosfamide tool for HPS in the cirrhotic population, with a cut-off value of ≤ 97% providing a high sensitivity and moderate specificity for an arterial oxygen tension (PaO2) ≤ 70 mmHg, but is less sensitive in mild HPS.[55, 56] However, in order to confirm the diagnosis, arterial blood gas estimation should be undertaken with the patient in a sitting position, breathing room air. The degree of gas exchange abnormality that is required for the diagnosis of HPS remains controversial. The most sensitive marker is an increase in the alveolar–arterial oxygen gradient (PA-aO2). Recommended cut-off values for the diagnosis of HPS are PaO2 ≤ 80 mmHg or PA-aO2 ≥ 15 mmHg. To avoid a complex calculation to correct for the increase in PA-aO2 that occurs with age, cut-off values of PaO2 ≤ 70 mmHg or PA-aO2 ≥ 20 mmHg are suggested in patients older than 64 years[2] (Table 1). Two methods of defining intrapulmonary dilatation are available: contrast echocardiography, most often using microbubbles as the contrast, and radioactive lung perfusion scan using macroaggregated albumin (MAA).