Natural history of hepatopulmonary syndrome: Impact of liver transplantation

Abstract

H epatopulmonary syndrome (HPS) is a pulmonary vascular disorder characterized by the clinical triad of chronic liver disease, intrapulmonary vascular dilatations, and arterial hypoxemia. 1,2 Portal hypertension (with or without cirrhosis) is often present. 2,3 The intrapulmonary vascular dilatations are identified by transthoracic contrast echocardiography (qualitative) or radionuclide lung perfusion scanning with brain uptake to measure shunt fraction (quantitative). 2 The degree of arterial hypoxemia associated with HPS has an unpredictable correlation with the severity or cause of the underlying liver disease. [1][2][3] The mechanism by which portal hypertension results in pulmonary vascular dilatation is unknown but appears to involve local effects of increased nitric oxide. 4 Although orthotopic liver transplantation (OLT) has become the mainstay of therapy for HPS in many centers, few data exist that describe long-term survival. 1,5 Despite the well-documented resolution of HPS after OLT, 1,5,6 we were interested in the long-term clinical course of all patients with this syndrome since the inception of the liver transplantation program at Mayo Clinic Rochester in 1985. Our aims were to determine longterm survival in HPS versus case controls, assess the impact of OLT on survival, and document partial pressure of arterial oxygen (PaO 2 ) change pre-and post-OLT. TcMAA. From the Patients and Methods Patient

Clinical implications of the hyperdynamic syndrome in cirrhosis

“…HPS is defined as the presence of liver disease and/or PH and intrapulmonary vascular dilatation, resulting in an abnormal age-corrected alveolar-arterial oxygen gradient (partial pressure of oxygen [PaO2] of b80 mmHg, and an AaPO2 of N15 mmHg, or N20 mmHg in patients N64 years of age) [58]. A taxonomy of the severity of the HPS based on alterations in oxygenation is essential because severity influences survival and is useful in determining the timing and the risks of orthotopic liver transplantation (OLT) [59,60]. The pulmonary gas exchange abnormalities of HPS are characterized by hyperventilation and arterial deoxygenation that can be mild (PaO2 b 80 mmHg), moderate (PaO2 b70 mmHg), or severe (PaO2 b 60 mmHg) [58].…”

Intrapulmonary vascular dilatations are common in portopulmonary hypertension and may be associated with decreased survival

“…Pharmacological agents have not proven to be uniformly beneficial in HPS, and liver transplantation (LT) is currently the only effective treatment option available for these patients. [3][4][5] POPH, on the other hand, involves elevated pulmonary artery (PA) pressures (mean, MPAP) and increased PVR, as measured by right heart catheterization (RHC), because of generalized pulmonary arterial vasoconstriction and proliferative vasculopathy, with microthrombi, vascular remodeling, and plexiform changes. Symptoms include dyspnea, along with signs of right heart failure.…”

Proposed Management Algorithm for Severe Hypoxemia After Liver Transplantation in the Hepatopulmonary Syndrome

“…Along these lines, “extended‐criteria” allografts have been associated with increased graft dysfunction 51, and their use must be considered judiciously, on a case‐by‐case basis in HPS patients at high risk of developing severe posttransplant hypoxemia. However, given that the risk of severe posttransplant hypoxemia increases with the severity of baseline hypoxemia 10, and that hypoxemia is rapidly progressive in HPS 7, 9, this risk must be weighed against the benefit of reduced transplant wait times afforded by use of extended‐criteria organs. This is an area that requires further research.…”

“…Although select, highly specialized centers have demonstrated good posttransplant outcomes in very severely hypoxemic patients with HPS 9, 52, in addition to the increased risk of posttransplant hypoxemia 10, studies have demonstrated increased overall posttransplant mortality in patients with a pretransplant PaO 2 ≤50 mmHg 7, 11, 53. These data, along with the expected decline in PaO 2 of 5.2–13.5 mmHg per year in patients with HPS 7, 9 coupled with expected delays to transplantation, form the basis for the UNOS MELD exception threshold of PaO 2 <60 mmHg in HPS. In centers with transplant waiting times that routinely result in a drop in PaO 2 to ≤50 mmHg by the time of transplant in these patients (despite allocation of MELD exception points), even more aggressive prioritization approaches may be required to reduce the incidence of this complication.…”

“…This disease is associated with progressive hypoxemia and a high mortality 3, 5. Although liver transplantation (LT) is curative in HPS, these patients have an elevated postoperative complication rate 6, 7, 8, 9. In particular, “severe posttransplant hypoxemia,” defined as a need for 100% inspired oxygen (FiO 2 ) to maintain a saturation of ≥85% (out of proportion to any other concurrent lung process) 10, has been identified as a major complication leading to prolonged ICU stay and death in this population 6, 9, 10, 11, 12.…”