Pulmonary arterial hypertension after liver transplantation

Pulmonary Arterial Hypertension (PAH) could rarely develop in liver recipients as recurrence/worsening of preexisting PAH associated to portal hypertension ( PoH ); however the occurrence of PAH after liver transplantation in the absence of PoH and with good graft function, has not been reported. We describe a 40 years old male patient, who in the 2002 underwent to liver transplantation for hepatitis B ( HBV ) related cirrhosis and before transplantation screening studies for hepatopulmonary syndrome or pulmonary hypertension were negative. In 2008, he was evaluated for progressive and unexplained dyspnea. Lung volumes and perfusion scan were normal with a severe reduction of DLCO (TLCO 31% th; TLCO/VA 39%th) and hypoxemia at rest ( PaO2 52mmHg; PaCO2 27mmHg, pH 7.38); 6MWT was stopped after 3 min for dyspnea and significant oxygen desaturation. Echocardiografy revealed pulmonary hypertension ( PAPs 79 mmHg) ( figure1) and NMR study confirmed severe right heart impairment. Radiological studies were negative for PoH or portosystemic dominant collaterals. Right-heart catheterization demonstrated moderate PAH with significant response to acute epoprostenol infusion; however the patient did not tolerate one month of calcium blocker treatment and clinical picture remained unchanged. Sildenafil was then started at 20mg tid being well tolerated with clinical improvement in functional capacity at 3 and 6 months without interference with gas exchange ( Figure 2). Discussion: From the recent literature review ( Koch et al, Liver transplantation 2009 ), PH after LTx could represent a rare event of recurrent PH mainly in patients transplanted for biliary disease; also as a de novo event, it is usually associated to the persistence of PoH. In our patient both liver biopsy and radiological studies did not reveal graft disease or PoH; we can only speculate on pathogenic mechanism of PAH; remarkably in our case, PAH was responsive to acute vasodilatory testing despite poor subsequent clinical response to calcium blockers; however a long-term favourable response to phosfodiesterase-5 inhibitor was documented suggesting endothelium dysfunctioning in this patient. Conclusion: de novo pulmonary arterial hypertension after liver transplantation should be considered in the differential diagnosis of new onset of cardiopulmonary symptoms in the liver recipient even several years after liver transplantation; it may occur in the absence of known causes as persistence of PoH or graft host reaction; accordingly the role of endothelium dysfunction and the possible treatment choices of PAH in this setting should deserve further studies.