Pulmonary arterial hypertension (PAH) is a rare disease that is associated with high mortality and is characterized by pulmonary vascular remodeling. Portopulmonary hypertension (POPH) is a form of PAH that occurs in patients with portal hypertension where no alternative cause of PAH can be identified. POPH is documented in approximately 4.5% to 8.5% of liver transplant candidates, 1,2 but there is no relationship between the existence or severity of POPH and the severity of liver dysfunction. 3 Mantz and Craig described the first case of POPH in a 53-year-old woman with enlarged pulmonary arteries that exhibited forceful pulsations more characteristic of the aorta than a low-pressure pulmonary trunk. 4 Autopsy revealed findings of chronic liver disease including a stenotic portal vein, portocaval shunt, and esophageal varices. In both PAH and POPH, pre-capillary pulmonary arteries have characteristic lesions, such as intimal thickening, endothelial proliferation, and thrombotic changes. This 2-part article reviews the diagnosis and treatment of patients with POPH. Here, we review the epidemiology, prognosis, pathogenesis, and diagnosis of POPH; current treatment options for POPH are reviewed in a separate article.
The term POPH was first used by Yoshida et al in 1993 to describe the first successful liver transplant in a patient with POPH, a 39-year-old man with chronic hepatitis. 5 The World Health Organization (WHO) classifies POPH as a form of Group 1 PAH. 6 The criteria that must be met to make a diagnosis of POPH are shown in the Table 1 .7
Moderate POPH is defined as a mean pulmonary artery pressure (MPAP) between 35 mm Hg and < 45 mm Hg, whereas severe POPH is MPAP ≥ 45 mm Hg. Moderate and severe POPH are considered contraindications to liver transplant because of high perioperative and postoperative mortality rates. 8 In 2000, the Mayo Clinic retrospectively reviewed 43 patients with POPH who underwent attempted liver transplantation. 9 The cardiopulmonary-related mortality rate in patients with a MPAP of 35 to < 50 mm Hg was 50% and 100% for those with MPAP > 50 mm Hg. No mortality was noted in patients with a pre-liver transplant MPAP of < 35 mm Hg and transpulmonary gradient (TPG) < 15 mm Hg.
In 1983, a series of 17,901 autopsied patients showed a primary pulmonary hypertension prevalence of 0.13% and a prevalence of 0.73% in patients with cirrhosis. 10 In 1987, Rich et al published data from the National Institutes of Health’s national registry of primary pulmonary hypertension. 11 The registry included data from 187 patients from 32 centers. Further analyses by Groves et al concluded that 8.3% of the patients likely had POPH. 12 Humbert et al published data on the French pulmonary hypertension registry experience in 2006. 13 The French registry included 674 patients from 17 university hospitals; 10.4% of these patients had POPH. The largest prospective study was published by Hadengue et al in 1991. 14 In this study, 507 patients hospitalized with portal hypertension but without known pulmonary hypertension underwent cardiac catheterization; 10 patients (2%) had pulmonary hypertension and more than half were clinically asymptomatic. Finally, the Registry to Evaluate Early And Long-term pulmonary arterial hypertension disease management (REVEAL registry) documented a 5.3% frequency of POPH (174 of 3525) in the United States. 15