Portopulmonary Hypertension: Treatment
To understand the effect of liver transplantation on POPH, one must understand the hemodynamic changes that occur with POPH and during liver transplant. The right ventricle is able to manage the same volume as the left ventricle under normal circumstances, but is unable to pump against a significant pressure gradient.37 In the setting of POPH, right ventricular hypertrophy occurs and RV output remains stable for some time. With time, pulmonary artery pressure increases secondary to pulmonary arteriolar vasoconstriction, intimal thickening, and progressive occlusion of the pulmonary vascular bed. Right ventricular failure may occur as a result. Cardiac output increases significantly at the time of reperfusion during liver transplant (up to 3-fold in 15 minutes),38 and in the setting of a noncompliant vascular bed, the patient is at risk for right heart failure. This is the likely explanation to such high perioperative mortality rates in patients with uncontrolled POPH. Failure to decrease MPAP to less than 50 mm Hg is considered a complete contraindication to liver transplant at most institutions. Many transplant centers will list patients for liver transplant if MPAP can be decreased to less than 35 mm Hg and PVR < 400 dynes/s/cm–5. These parameters are thought to represent an adequate right ventricular reserve and a compliant pulmonary vascular bed.37 However, even with good pressure control, the anesthesiology and critical care teams must be prepared to deal with acute right heart failure peri-operatively. Intraoperative transesophageal echocardiography has been recommended to closely follow right ventricular function.38 Inhaled or intravenous dilators are the most effective agents in the event of a pulmonary hypertensive crisis.
Review of Outcomes
A retrospective review evaluated 43 patients with untreated POPH who underwent attempted liver transplantation.39 Data were collected from 18 peer-reviewed studies and 7 patients at the authors’ institution. Overall mortality was 35% (15 patients), with almost all of the deaths secondary to cardiac dysfunction. Two deaths occurred intraoperatively and 8 deaths occurred during the transplant hospitalization. The transplant could not be successfully completed in 4 of the patients. MPAP > 50 mm Hg was associated with 100% mortality, whereas patients with MPAP between 35 mm Hg and 50 mm Hg had a 50% mortality. No mortality was noted in patients with MPAP < 35 mm Hg.
Liver transplantation has been shown to be successful in patients with controlled POPH. Sussman et al published their data on 8 patients with severe POPH in 2006. In this prospective study, all patients were treated with sequential epoprostenol infusions and 7 of the 8 patients experienced a significant reduction in MPAP and PVR. Six patients were listed for liver transplant, 4 of who were transplanted successfully and alive up to 5 years later.
The Baylor University Medical Center published their data on POPH patients who received liver transplants in 2007.11 POPH was confirmed by right heart catheterization in 30 patients evaluated for liver transplant. Sixteen patients were considered to be suitable candidates for transplant and MPAP was decreased to less than 35 mmHg in 12 patients with vasodilator therapy. Eleven patients eventually underwent liver transplant and 1- and 5-year survival rates were 91% and 67%.
Compared to medical therapy or liver transplant alone, patients who receive medical therapy followed by liver transplantation have the best survival. The Mayo Clinic retrospectively reviewed 74 POPH patients identified between 1994 and 2007.40 Patients were categorized in 1 of 3 categories: no medical therapy, medical therapy alone for POPH, or medical therapy for POPH followed by liver transplantation. Patients who received no medical therapy for POPH and no liver transplant had the worst outcomes, with a dismal 5-year survival of only 14% with over 50% deceased at 1 year of diagnosis. Five-year survival was 45% in patients who received medical therapy only. Patients who received medical therapy with prostacyclin followed by liver transplantation had the best outcomes, with a 5-year survival of 67% versus 25% in those who were transplanted without prior prostacyclin therapy.
