LIVER TRANSPLANTATION MAY BENEFIT A FEW PATIENTS
Liver transplantation may be beneficial in highly selected patients with portopulmonary hypertension. However, this condition increases the risk of intraoperative and immediate postoperative complications of liver transplantation, so patients should be carefully evaluated5,45 at a liver transplantation center experienced in its management, including medical treatment with well-defined protocols regarding timing of liver transplantation.
Patients with mean pulmonary artery pressures greater than 50 mm Hg should not undergo liver transplantation. Those with mean pulmonary artery pressure between 35 and 50 mm Hg also have an increased mortality rate and may benefit from prolonged treatment for pulmonary hypertension.5,46
One successful case of living-related liver transplantation in a patient with portopulmonary hypertension has been published.47 (Most other successful transplants were from unrelated cadaver donors.)
Some patients who initially cannot undergo liver transplantation owing to severe pulmonary hypertension may eventually be able to do so if they receive medical therapy that improves their pulmonary hemodynamic profile, decreasing their mean pulmonary artery pressure and pulmonary vascular resistance. This would apply to a small subset of patients with portopulmonary hypertension.
When patients without pulmonary hypertension undergo liver transplantation, right ventricular function is preserved throughout all phases of the surgery.48 Patients with portopulmonary hypertension, however, may develop hemodynamic instability during liver transplantation. The most critical times are the induction of anesthesia, during and after graft reperfusion, and the immediate postoperative period.49,50
During the surgery, patients may require vasodilators if they have worsening pulmonary hypertension, or inotropic medications if they have right ventricular dysfunction and heart failure. In one study,51 eight patients with portopulmonary hypertension diagnosed at anesthesia induction for liver transplantation all required intraoperative vasodilator therapy after graft reperfusion because of marked increases in pulmonary artery pressures and pulmonary vascular resistance.
The increase in blood flow following reperfusion or necessary fluid challenges may exacerbate pulmonary hypertension, resulting in worsening right heart function and backup into the transplanted liver. Infusion of 1 liter of crystalloid over 10 minutes has been shown to increase mean pulmonary artery pressure and pulmonary artery occlusion pressure in liver transplantation candidates without pulmonary hypertension52; this response may be exaggerated in portopulmonary hypertension.
PROGNOSIS VARIES WITH SEVERITY OF DISEASE
The natural history of untreated portopulmonary hypertension varies with the degree of liver disease and the severity of pulmonary hypertension. Transplant-free survival was 85% at 1 year and 38% at 3 years in one study.45 The cardiac index appears to be the most significant prognostic variable.20
In a retrospective study of 78 patients with portopulmonary hypertension treated conservatively (before prostanoids were available) the median survival was 6 months (range 0–84 months) from the time of diagnosis.53 Causes of death included right heart failure, sudden death, gastrointestinal bleeding, and small bowel perforation.
Most of the data on outcomes of drug treatment and liver transplantation in patients with portopulmonary hypertension come from case series and retrospective reviews; prospective trials have been lacking.
If right ventricular function is normal and pulmonary hypertension is mild (mean pulmonary artery pressure < 35 mm Hg), patients tend to do well with liver transplantation.9
Outcomes are worse if pulmonary hypertension is more severe. In a database54 from 10 liver transplant centers from 1996 to 2001, 13 (36%) of 36 patients undergoing liver transplantation died in the hospital, emphasizing the importance of accurately assessing the severity of pulmonary hypertension before attempting liver transplantation.46 The rate was even higher—92%—in those with a mean pulmonary artery pressure greater than 35 mm Hg. The cause of death in severe pulmonary hypertension was failure of the right ventricle.
However, some patients with moderate to severe portopulmonary hypertension have been bridged with medications to lower pulmonary artery pressures and pulmonary vascular resistance so that liver transplantation can be safely done, and some have even been able to discontinue medications because their pulmonary hypertension resolved.29,31,41,42,47
Unlike in hepatopulmonary syndrome, liver transplantation is not the treatment of choice for portopulmonary hypertension, and pulmonary hypertension does not always resolve after liver transplantation. Many patients continue therapy for pulmonary hypertension after liver transplantation. Pulmonary hypertension may resolve, persist, or even develop de novo after liver transplantation.1 If pulmonary hypertension resolves, it does so over a prolonged time—months to years—favoring a vascular remodeling hypothesis as opposed to simply reversing vasoconstriction.