Clinical risk factors for portopulmonary hypertension

Abstract

Portopulmonary hypertension affects up to 6% of patients with advanced liver disease, but the predictors and biologic mechanism for the development of this complication are unknown. We sought to determine the clinical risk factors for portopulmonary hypertension in patients with advanced liver disease. We performed a multicenter case-control study nested within a prospective cohort of patients with portal hypertension recruited from tertiary care centers. Cases had a mean pulmonary artery pressure > 25 mm Hg, pulmonary vascular resistance > 240 dynes ⅐ second ⅐ cm ؊5 , and pulmonary capillary wedge pressure < 15 mm Hg. Controls had a right ventricular systolic pressure < 40 mm Hg (if estimable) and normal right-sided cardiac morphology by transthoracic echocardiography. The study sample included 34 cases and 141 controls. Female sex was associated with a higher risk of portopulmonary hypertension than male sex (adjusted odds ratio ‫؍‬ 2.90, 95% confidence interval 1.20-7.01, P ‫؍‬ 0.018). Autoimmune hepatitis was associated with an increased risk (adjusted odds ratio ‫؍‬ 4.02, 95% confidence interval 1.14-14.23, P ‫؍‬ 0.031), and hepatitis C infection was associated with a decreased risk (adjusted odds ratio ‫؍‬ 0.24, 95% confidence interval 0.09-0.65, P ‫؍‬ 0.005) of portopulmonary hypertension. The severity of liver disease was not related to the risk of portopulmonary hypertension. Conclusion: Female sex and autoimmune hepatitis were associated with an increased risk of portopulmonary hypertension, whereas hepatitis C infection was associated with a decreased risk in patients with advanced liver disease. Hormonal and immunologic factors may therefore be integral to the development of portopulmonary hypertension. (HEPATOLOGY 2008;48:196-203.) See Editorial on Page 13 P ulmonary arterial hypertension (PAH) is a progressive disease which is characterized by elevated pulmonary vascular resistance, right heart failure, exercise limitation, and an increased risk of death. Histopathologic examination reveals intimal proliferation, medial hypertrophy, and adventitial fibrosis in the small muscular pulmonary arteries. Plexiform lesions and in situ thrombosis are also commonly seen. Most commonly idiopathic, PAH may also be associated with portal hypertension, termed portopulmonary hypertension (PPHTN

Macrophage Migration Inhibitory Factor as a Novel Biomarker of Portopulmonary Hypertension

“…Last, although the number of deaths was small, high pulmonary MIF levels were associated with an increased risk of death. Despite significant advances in our knowledge regarding clinical and genetic risk factors for POPH, 11,22 its pathogenesis remains poorly understood. Studies have identified decreased prostacyclin synthase expression, 23 higher serum estradiol levels, and genetic variations in aromatase in patients with POPH, 22 but the mechanistic link between these findings and the pathogenesis of POPH remains unknown.…”

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“…Recent publications favor the role of cytokines, especially endothelin 1 and interleukin 6. 19 Other studies have demonstrated that sex (females), autoimmune diseases, 20 single-nucleotide polymorphisms of estrogen receptor 1 and phosphodiesterase 5 genes, 21 and other factors 22 were associated with an increased incidence of POPH.…”

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“…9,10 Those results agree with a previous study in which a negative correlation between hepatitis C virus infection and portopulmonary hypertension was shown to exist. 11 Portopulmonary hypertension is usually diagnosed in the fourth or fifth decades of life. 3 Female sex and autoimmune hepatitis are independently associated with portopulmonary hypertension.…”

“…3 Female sex and autoimmune hepatitis are independently associated with portopulmonary hypertension. 11 In addition, the prevalence and severity of portopulmonary hypertension are not correlated with the severity of liver disease. 4,8,11 The severity of portopulmonary hypertension measured by RHC has also not been found to correlate with the severity of portal hypertension.…”