Can orthotopic liver transplantation (OLT) result in complete resolution of portopulmonary hypertension (POPH)? More specifically, under what conditions will the normal posttransplant normal hepatic/portal physiology cause a resolution of pulmonary artery hypertension and improve long-term survival? OLT, orthotopic liver transplantation; POPH, portopulmonary hypertension; MELD, model for end-stage liver disease. This survival issue is put into some perspective by the article in this month's Liver Transplantation, wherein Kawut and colleagues describe a 38% 3-year survival when POPH complicates liver disease.1 Their series is small (n = 13), retrospective, and burdened by the uncontrolled management interventions that must address consequences of 2 disorders: pulmonary artery hypertension and portal hypertension. Liver transplantation did not appear to be one of the endpoints in Kawut's analysis. These limited data in the era of OLT mirror the discouraging experience from referrals to other major liver centers. Robalino and Moodie2 via a literature review and Cleveland Clinic experience described a 21% 30-month survival in 49 patients with coexistent pulmonary and portal hypertension in the pre-OLT era. Herve et al. from France3 reported a 50% 5-year survival (n = 39; no data on OLT effects), and Swanson et al. documented a Mayo Clinic experience showing a 28% 5-year survival without OLT (n = 66) and 56% 5-year survival with OLT (n = 28).4 These studies and the Kawut contribution beg 2 broad questions that larger series must address. First, why do such patients with POPH have such poor survival? Second, is it hopeless to consider OLT (with long-term survival) when moderate to severe POPH exists? These questions must be considered in the current context of an evolving treatment armamentarium of vasomodulating (not just vasodilating) drugs such as prostacyclins, endothelin receptor antagonists, and phosphodiesterase inhibitors designed to reverse events that obstruct the pulmonary arterial flow (proliferation of endothelium, platelet aggregation with in situ thrombosis, and vasoconstriction due a proliferation of smooth muscle. For the most part, these drugs appear to be safe and effective in POPH.5-13 Regarding the reasons for poor survival, details are crucial.14 What are the specific cardiovascular endpoints described within the Kawut paper? Has death occurred because of an initiating acute gastrointestinal event (bleeding, sepsis, encephalopathy leading to aspiration with hypoxemia) in the setting of stable or even improving pulmonary hemodynamics? Was death directly a consequence of progressive right heart failure unresponsive to aggressive pulmonary vasomodulating drugs? Did sudden cardiovascular collapse occur (hemodynamically intolerable tachydysrhythmia)? Is survival related to current hepatic disease severity measures such as model for end-stage liver disease (MELD) and Child-Turcotte-Pugh classification, as well as severity of POPH? The statistical overview provided by the Kawut paper does not answer these specific queries. Regarding outcome expectations of OLT in the setting of POPH, is pre-OLT or post-OLT POPH survival related to the changing MELD score? Would we dare assign more MELD points to those with moderate POPH who respond “significantly” to pulmonary vasomodulating drugs or their combinations? The most recent multicenter data suggest that pre-OLT mean pulmonary artery pressure greater than 35 mm Hg (n = 30 with increased pulmonary vascular resistance carries a worrisome OLT prognosis (12 deaths or 40% mortality within 18 days of transplant surgery.15 Only one patient had received pre-OLT prostacyclin.15 One could hypothesize a better outcome facilitated by using current drug therapies. Indeed, the major message of the Kawut study relates to the worse prognosis for POPH compared to idiopathic pulmonary artery hypertension (the new term for primary pulmonary hypertension). To me this is not surprising, since we are trying to cope with and treat effects of disease in 2 vascular beds (pulmonary and portal). But we do need to reconsider the effects of modifying cardiac output and pulmonary vascular resistance in the context of a hyperdynamic circulatory state that accompanies portal hypertension. There probably exists a pathologic point of “no return” in the damaged pulmonary arterial bed, whereby pulmonary hemodynamics are no longer responsive to vasomodulating therapy, despite our best efforts. And the stressed right heart can tolerate only so much adverse change in afterload, preload, and downstream effect of “bad humors” arriving from the portal circulation. Following an accurate diagnosis of POPH, our efforts should (as a minimum) focus upon reducing mean pulmonary artery pressure to less than 35 mm Hg prior to the accomplishment of OLT. Additionally, improvement in other parameters such as pulmonary vascular resistance and indices of right heart function may prove to be prognostic. Hopefully, treatment with a protocolized, combined approach of pulmonary arterial vasomodulation and OLT (cadaveric or living donor) will clarify and improve the POPH long-term survival issue.