Portopulmonary hypertension

PPH presents roughly equally in male and female cirrhotics; 71% female in an American series and 57% male in a larger French series.Le Pavec et al. Portopulmonary Hypertension: Survival and Prognostic Factors. Am J Respir Crit Care Med Vol 178. pp 637–643, 2008{{cite journal |last1=Kawut |first1=SM |last2=Krowka |first2=MJ |last3=Trotter |first3=JF |last4=Roberts |first4=KE |last5=Benza |first5=RL |last6=Badesch |first6=DB |last7=Taichman |first7=DB |last8=Horn |first8=EM |last9=Zacks |first9=S |last10=Kaplowitz |first10=N |last11=Brown RS |first11=Jr |last12=Fallon |first12=MB |last13=Pulmonary Vascular Complications of Liver Disease Study |first13=Group. |title=Clinical risk factors for portopulmonary hypertension. |journal=Hepatology |date=July 2008 |volume=48 |issue=1 |pages=196–203 |doi=10.1002/hep.22275 |pmid=18537192|pmc=2824885 }} Typically, patients present in their fifth decade, aged 49 +/- 11 years on average.{{cite journal |last1=Benjaminov |first1=FS |last2=Prentice |first2=M |last3=Sniderman |first3=KW |last4=Siu |first4=S |last5=Liu |first5=P |last6=Wong |first6=F |title=Portopulmonary hypertension in decompensated cirrhosis with refractory ascites. |journal=Gut |date=September 2003 |volume=52 |issue=9 |pages=1355–62 |doi=10.1136/gut.52.9.1355 |pmid=12912870|pmc=1773797 }}

In general, PPH is diagnosed 4–7 years after the patient is diagnosed with portal hypertension{{cite journal |last1=Hadengue |first1=A |last2=Benhayoun |first2=MK |last3=Lebrec |first3=D |last4=Benhamou |first4=JP |title=Pulmonary hypertension complicating portal hypertension: prevalence and relation to splanchnic hemodynamics. |journal=Gastroenterology |date=February 1991 |volume=100 |issue=2 |pages=520–8 |doi=10.1016/0016-5085(91)90225-a |pmid=1985048}} and in roughly 65% of cases, the diagnosis is actually made at the time of invasive hemodynamic monitoring following anesthesia induction prior to liver transplantation.

Once patients are symptomatic, they present with right heart dysfunction secondary to pulmonary hypertension and its consequent dyspnea, fatigue, chest pain and syncope.{{cite journal |last1=Martínez-Palli |first1=G |last2=Taurà |first2=P |last3=Balust |first3=J |last4=Beltrán |first4=J |last5=Zavala |first5=E |last6=Garcia-Valdecasas |first6=JC |title=Liver transplantation in high-risk patients: hepatopulmonary syndrome and portopulmonary hypertension. |journal=Transplantation Proceedings |date=November 2005 |volume=37 |issue=9 |pages=3861–4 |doi=10.1016/j.transproceed.2005.09.119 |pmid=16386564}} Patients tend to have a poor cardiac status, with 60% having stage III-IV NYHA heart failure.

PPH is actually independent of the severity of cirrhosis but may be more common in specific types of cirrhosis, in one series more so in autoimmune hepatitis and less in hepatitis C cirrhosis, while in another it was equally distributed throughout the diagnoses.

PPH pathology arises both from the humoral consequences of cirrhosis and the mechanical obstruction of the portal vein.{{cite journal |last1=Budhiraja |first1=R |last2=Hassoun |first2=PM |title=Portopulmonary hypertension: a tale of two circulations. |journal=Chest |date=February 2003 |volume=123 |issue=2 |pages=562–76 |doi=10.1378/chest.123.2.562 |pmid=12576381}} A central paradigm holds responsible an excess local pulmonary production of vasoconstrictors that occurs while vasodilatation predominates systemically.{{cite journal |last1=Moller |first1=S |last2=Henriksen |first2=JH |title=Cardiopulmonary complications in chronic liver disease. |journal=World Journal of Gastroenterology |date=28 January 2006 |volume=12 |issue=4 |pages=526–38 |doi=10.3748/wjg.v12.i4.526 |pmid=16489664|pmc=4066083 |doi-access=free }} Key here are imbalances between vasodilatory and vasoconstricting molecules; endogenous prostacyclin and thromboxane (from Kupffer cells){{cite journal |last1=Christman |first1=BW |last2=McPherson |first2=CD |last3=Newman |first3=JH |last4=King |first4=GA |last5=Bernard |first5=GR |last6=Groves |first6=BM |last7=Loyd |first7=JE |title=An imbalance between the excretion of thromboxane and prostacyclin metabolites in pulmonary hypertension. |journal=The New England Journal of Medicine |date=9 July 1992 |volume=327 |issue=2 |pages=70–5 |doi=10.1056/NEJM199207093270202 |pmid=1603138|doi-access=free }}{{cite journal |last1=Maruyama |first1=T |last2=Ohsaki |first2=K |last3=Shimoda |first3=S |last4=Kaji |first4=Y |last5=Harada |first5=M |title=Thromboxane-dependent portopulmonary hypertension. |journal=The American Journal of Medicine |date=January 2005 |volume=118 |issue=1 |pages=93–4 |doi=10.1016/j.amjmed.2004.11.007 |pmid=15639216}} or nitric oxide (NO) and endothelin-1 (ET-1). ET-1 is the most potent vasoconstrictor under investigation{{cite journal |last1=Giaid |first1=A |title=Nitric oxide and endothelin-1 in pulmonary hypertension. |journal=Chest |date=September 1998 |volume=114 |issue=3 Suppl |pages=208S–212S |doi=10.1378/chest.114.3_supplement.208s |pmid=9741571}} and it has been found to be increased in both cirrhosis{{cite journal |last1=Gerbes |first1=AL |last2=Møller |first2=S |last3=Gülberg |first3=V |last4=Henriksen |first4=JH |title=Endothelin-1 and -3 plasma concentrations in patients with cirrhosis: role of splanchnic and renal passage and liver function. |journal=Hepatology |date=March 1995 |volume=21 |issue=3 |pages=735–9 |pmid=7875671}} and pulmonary hypertension.{{cite journal |last1=Stewart |first1=DJ |last2=Levy |first2=RD |last3=Cernacek |first3=P |last4=Langleben |first4=D |title=Increased plasma endothelin-1 in pulmonary hypertension: marker or mediator of disease? |journal=Annals of Internal Medicine |date=15 March 1991 |volume=114 |issue=6 |pages=464–9 |doi=10.7326/0003-4819-114-6-464 |pmid=1994793}} Endothelin-1 has two receptors in the pulmonary arterial tree, ET-A which mediates vasoconstriction and ET-B which mediates vasodilation. Rat models have shown decreased ET-B receptor expression in pulmonary arteries of cirrhotic and portal hypertensive animals, leading to a predominant vasoconstricting response to endothelin-1.{{cite journal |last1=Luo |first1=B |last2=Liu |first2=L |last3=Tang |first3=L |last4=Zhang |first4=J |last5=Stockard |first5=CR |last6=Grizzle |first6=WE |last7=Fallon |first7=MB |title=Increased pulmonary vascular endothelin B receptor expression and responsiveness to endothelin-1 in cirrhotic and portal hypertensive rats: a potential mechanism in experimental hepatopulmonary syndrome. |journal=Journal of Hepatology |date=May 2003 |volume=38 |issue=5 |pages=556–63 |doi=10.1016/s0168-8278(03)00012-6 |pmid=12713865}}

In portal hypertension, blood will shunt from portal to systemic circulation, bypassing the liver. This leaves unmetabolized potentially toxic or vasoconstricting substances to reach and attack the pulmonary circulation. Serotonin, normally metabolized by the liver, is returned to the lung instead where it mediates smooth muscle hyperplasia and hypertrophy.{{cite journal |last1=Egermayer |first1=P |last2=Town |first2=GI |last3=Peacock |first3=AJ |title=Role of serotonin in the pathogenesis of acute and chronic pulmonary hypertension. |journal=Thorax |date=February 1999 |volume=54 |issue=2 |pages=161–8 |doi=10.1136/thx.54.2.161 |pmid=10325923|pmc=1745408 }} Moreover, a key pathogenic factor in the decline in status of PPH patients related to this shunting is the cirrhotic cardiomyopathy with myocardial thickening and diastolic dysfunction.{{citation needed|date=November 2020}}

Finally, the pulmonary pathology of PPH is very similar to that of primary pulmonary hypertension.Schraufnagel DE, Kay JM. Structural and pathologic changes in lung vasculature in chronic liver disease. Clin Chest Med 1996; 17: 1 The muscular pulmonary arteries become fibrotic and hypertrophy while the smaller arteries lose smooth muscle cells and their elastic intima. One study found at autopsy significant thickening of pulmonary arteries in cirrhotic patients.{{cite journal |last1=Matsubara |first1=O |last2=Nakamura |first2=T |last3=Uehara |first3=T |last4=Kasuga |first4=T |title=Histometrical investigation of the pulmonary artery in severe hepatic disease. |journal=The Journal of Pathology |date=May 1984 |volume=143 |issue=1 |pages=31–7 |doi=10.1002/path.1711430106 |pmid=6737114|s2cid=25097088 }} This thickening and remodeling forms a positive feedback loop that serves to increase PAP and induce right heart hypertrophy and dysfunction.{{citation needed|date=March 2021}}

The diagnosis of portopulmonary hypertension is based on hemodynamic criteria:{{citation needed|date=October 2021}}

1. . Portal hypertension and/or liver disease (clinical diagnosis—ascites/varices/splenomegaly)
2. . Mean pulmonary artery pressure—MPAP > 20 mmHg at rest (revised from 25 to 20 according to 6th World Pulmonary Hypertension Symposium)
3. . Pulmonary vascular resistance—PVR > 240 dynes s cm−5
4. . Pulmonary artery occlusion pressure— PAOP < 15mmHg or transpulmonary gradient—TPG > 12 mmHg where TPG = MPAP − PAOP.{{cite journal |last1=Swanson |first1=KL |last2=Wiesner |first2=RH |last3=Nyberg |first3=SL |last4=Rosen |first4=CB |last5=Krowka |first5=MJ |title=Survival in portopulmonary hypertension: Mayo Clinic experience categorized by treatment subgroups. |journal=American Journal of Transplantation |date=November 2008 |volume=8 |issue=11 |pages=2445–53 |doi=10.1111/j.1600-6143.2008.02384.x |pmid=18782292|s2cid=25269798 |doi-access= }}

The diagnosis is usually first suggested by a transthoracic echocardiogram, part of the standard pre-transplantation work-up. Echocardiogram estimated pulmonary artery systolic pressures of 40 to 50 mm Hg are used as a screening cutoff for PPH diagnosis, with a sensitivity of 100% and a specificity as high as 96%.Kim et al. Accuracy of Doppler Echos in the assessment of PTHN in liver transplant candidates. Liver Transplant. 6:453, 2000 The negative predictive value of this method is 100% but the positive predictive value is 60%.{{cite journal |last1=Colle |first1=IO |last2=Moreau |first2=R |last3=Godinho |first3=E |last4=Belghiti |first4=J |last5=Ettori |first5=F |last6=Cohen-Solal |first6=A |last7=Mal |first7=H |last8=Bernuau |first8=J |last9=Marty |first9=J |last10=Lebrec |first10=D |last11=Valla |first11=D |last12=Durand |first12=F |title=Diagnosis of portopulmonary hypertension in candidates for liver transplantation: a prospective study. |journal=Hepatology |date=February 2003 |volume=37 |issue=2 |pages=401–9 |doi=10.1053/jhep.2003.50060 |pmid=12540791|s2cid=38503767 }} Thereafter, these patients are referred for pulmonary artery catheterization.{{citation needed|date=March 2021}}

The limitations of echocardiography are related to the derivative nature of non-invasive PAP estimation. The measurement of PAP by echocardiogram is made using a simplified Bernoulli equation. High cardiac index and pulmonary capillary wedge pressures, however, may lead to false positives by this standard. By one institution's evaluation, the correlation between estimated systolic PAP and directly measured PAP was poor, 0.49.Tapper EB, unpublished data For these reasons, right heart catheterization is needed to confirm the diagnosis.{{citation needed|date=November 2020}}

In general, the treatment of PPH is derived from the treatment of pulmonary hypertension. The best treatment available is the combination of medical therapy and liver transplantation.{{cite journal |vauthors=Swanson KL, Krowka MJ |date= 2006|title=Chapter 9 - Portopulmonary Hypertension

|url= https://www.sciencedirect.com/science/article/pii/B9781416022466500158|journal= Pulmonary Vascular Disease|volume= |issue= |pages= 132–142|doi= 10.1016/B978-1-4160-2246-6.50015-8|isbn= 9781416022466|access-date= 11 August 2021|url-access= subscription}}{{citation needed|date=November 2020}}

The ideal treatment for PPH management is that which can achieve pulmonary vasodilatation and smooth muscle relaxation without exacerbating systemic hypotension. Most of the therapies for PPH have been adapted from the primary pulmonary hypertension literature. Calcium channel blockers, beta blockers and nitrates have all been used – but the most potent and widely used aids are prostaglandin (and prostacyclin) analogs, phosphodiesterase inhibitors, nitric oxide and, most recently, endothelin receptor antagonists and agents capable of reversing the remodeling of pulmonary vasculature.{{citation needed|date=October 2021}}

Inhaled nitric oxide vasodilates, decreasing pulmonary arterial pressure (PAP) and pulmonary vascular resistance (PVR) without affecting systemic artery pressure because it is rapidly inactivated by hemoglobin,{{cite journal |last1=Steudel |first1=W |last2=Hurford |first2=WE |last3=Zapol |first3=WM |title=Inhaled nitric oxide: basic biology and clinical applications. |journal=Anesthesiology |date=October 1999 |volume=91 |issue=4 |pages=1090–121 |doi=10.1097/00000542-199910000-00030 |pmid=10519513}} and improves oxygenation by redistributing pulmonary blood flow to ventilated areas of lung.Lowson. Inhaled alternative to nitric oxide. Anesthesiology 2002;96:1504-13 Inhaled nitric oxide has been used successfully to bridge patients through liver transplantation and the immediate perioperative period, but there are two significant drawbacks: it requires intubation and cannot be used for long periods of time due to methemoglobinemia.{{cite web |url= https://www.lecturio.com/concepts/methemoglobinemia/| title= Methemoglobinemia

|website=The Lecturio Medical Concept Library |access-date= 11 August 2021}}

Prostaglandin PGE1 (Alprostadil) binds G-protein linked cell surface receptors that activate adenylate cyclase to relax vascular smooth muscle.Kerins et al. Prostacyclin and Prostaglandin E1: Molecular mechanisms and therapeutic utility. Prog Hemostasis Thrombosis 1991;10:307-37 Prostacyclin – PGI2, an arachidonic acid derived lipid mediator (Epoprostenol, Flolan, Treprostenil) – is a vasodilator and, at the same time, the most potent inhibitor of platelet aggregation.Vane et al. Pharmacodynamic profile of prostacyclin. Am J Cardiol 1995;75:3A-10A More importantly, PGI2 (and not nitrous oxide) is also associated with an improvement in splanchnic perfusion and oxygenation.{{cite journal |last1=Eichelbrönner |first1=O |last2=Reinelt |first2=H |last3=Wiedeck |first3=H |last4=Mezödy |first4=M |last5=Rossaint |first5=R |last6=Georgieff |first6=M |last7=Radermacher |first7=P |title=Aerosolized prostacyclin and inhaled nitric oxide in septic shock--different effects on splanchnic oxygenation? |journal=Intensive Care Medicine |date=September 1996 |volume=22 |issue=9 |pages=880–7 |doi=10.1007/BF02044111 |pmid=8905421|s2cid=8567462 }} Epoprostenol and ilioprost (a more stable, longer acting variation{{cite journal |last1=Minder |first1=S |last2=Fischler |first2=M |last3=Muellhaupt |first3=B |last4=Zalunardo |first4=MP |last5=Jenni |first5=R |last6=Clavien |first6=PA |last7=Speich |first7=R |title=Intravenous iloprost bridging to orthotopic liver transplantation in portopulmonary hypertension. |journal=The European Respiratory Journal |date=October 2004 |volume=24 |issue=4 |pages=703–7 |doi=10.1183/09031936.04.00133203 |pmid=15459152|s2cid=8665441 |doi-access=free }}) can and does successfully bridge for patients to transplant.et al. Successful use of chronic epoprostenol as a bridge to liver transplant in severe PPHTN. Transplant 1998 4:457 Epoprostenol therapy can lower PAP by 29-46% and PVR by 21-71%.,Kuo PC, Johnson LB, Plotkin JS, Howell CD, Bartlett ST, Rubin LJ. Continuous intravenous infusion of epoprostenol for the treatment of portopulmonary hypertension. Transplantation 1997; 63: 604 Ilioprost shows no evidence of generating tolerance, increases cardiac output and improves gas exchange while lowering PAP and PVR.{{cite journal |last1=Lowson |first1=SM |title=Inhaled alternatives to nitric oxide. |journal=Critical Care Medicine |date=March 2005 |volume=33 |issue=3 Suppl |pages=S188-95 |doi=10.1097/01.ccm.0000156792.40298.5a |pmid=15753727|s2cid=3103356 }} A subset of patients does not respond to any therapy, likely having fixed vascular anatomic changes.{{citation needed|date=November 2020}}

Phosphodiesterase inhibitors (PDE-i) have been employed with excellent results. It has been shown to reduce mean PAP by as much as 50%,{{cite journal |last1=Makisalo |first1=H |last2=Koivusalo |first2=A |last3=Vakkuri |first3=A |last4=Hockerstedt |first4=K |title=Sildenafil for portopulmonary hypertension in a patient undergoing liver transplantation. |journal=Liver Transplantation |date=July 2004 |volume=10 |issue=7 |pages=945–50 |doi=10.1002/lt.20153 |pmid=15237383|s2cid=43228732 |doi-access=free }} though it prolongs bleeding time by inhibiting collagen-induced platelet aggregation.{{cite journal |last1=Berkels |first1=R |last2=Klotz |first2=T |last3=Sticht |first3=G |last4=Englemann |first4=U |last5=Klaus |first5=W |title=Modulation of human platelet aggregation by the phosphodiesterase type 5 inhibitor sildenafil. |journal=Journal of Cardiovascular Pharmacology |date=April 2001 |volume=37 |issue=4 |pages=413–21 |doi=10.1097/00005344-200104000-00008 |pmid=11300654|s2cid=38632760 |doi-access=free }} Another drug, milrinone, a type 3 PDE-i increases vascular smooth muscle adenosine-3,5-cyclic monophosphate concentrations to cause selective pulmonary vasodilation.Haraldsson et al. The additive pulmonary vasodilatory effect of inhaled prostacyclin and inhaled milrinone in postcardiac surgical patients with pulmonary hypertension. Aesth Analg 2001;93:1439-45 Also, by causing the buildup of cAMP in the myocardium, milrinone increases contractile force, heart rate and the extent of relaxation.

The newest generation in PPH pharmacy shows great promise. Bosentan is a nonspecific endothelin-receptor antagonist capable of neutralizing the most identifiable cirrhosis associated vasoconstrictor,{{cite journal |last1=Rubin |first1=LJ |last2=Badesch |first2=DB |last3=Barst |first3=RJ |last4=Galie |first4=N |last5=Black |first5=CM |last6=Keogh |first6=A |last7=Pulido |first7=T |last8=Frost |first8=A |last9=Roux |first9=S |last10=Leconte |first10=I |last11=Landzberg |first11=M |last12=Simonneau |first12=G |title=Bosentan therapy for pulmonary arterial hypertension. |journal=The New England Journal of Medicine |date=21 March 2002 |volume=346 |issue=12 |pages=896–903 |doi=10.1056/NEJMoa012212 |pmid=11907289|doi-access=free }} safely and efficaciously improving oxygenation and PVR,{{cite journal |last1=Hoeper |first1=MM |last2=Halank |first2=M |last3=Marx |first3=C |last4=Hoeffken |first4=G |last5=Seyfarth |first5=HJ |last6=Schauer |first6=J |last7=Niedermeyer |first7=J |last8=Winkler |first8=J |title=Bosentan therapy for portopulmonary hypertension. |journal=The European Respiratory Journal |date=March 2005 |volume=25 |issue=3 |pages=502–8 |doi=10.1183/09031936.05.00080804 |pmid=15738295|s2cid=14416325 |doi-access=free }}{{cite journal |last1=Kuntzen |first1=C |last2=Gülberg |first2=V |last3=Gerbes |first3=AL |title=Use of a mixed endothelin receptor antagonist in portopulmonary hypertension: a safe and effective therapy? |journal=Gastroenterology |date=January 2005 |volume=128 |issue=1 |pages=164–8 |doi=10.1053/j.gastro.2004.09.005 |pmid=15633133|doi-access=free }} especially in conjunction with sildenafil.{{cite journal |last1=Wilkins |first1=MR |last2=Paul |first2=GA |last3=Strange |first3=JW |last4=Tunariu |first4=N |last5=Gin-Sing |first5=W |last6=Banya |first6=WA |last7=Westwood |first7=MA |last8=Stefanidis |first8=A |last9=Ng |first9=LL |last10=Pennell |first10=DJ |last11=Mohiaddin |first11=RH |last12=Nihoyannopoulos |first12=P |last13=Gibbs |first13=JS |title=Sildenafil versus Endothelin Receptor Antagonist for Pulmonary Hypertension (SERAPH) study. |journal=American Journal of Respiratory and Critical Care Medicine |date=1 June 2005 |volume=171 |issue=11 |pages=1292–7 |doi=10.1164/rccm.200410-1411OC |pmid=15750042}} Finally, where the high pressures and pulmonary tree irritations of PPH cause a medial thickening of the vessels (smooth muscle migration and hyperplasia), one can remove the cause –control the pressure, transplant the liver – yet those morphological changes persist, sometimes necessitating lung transplantation. Imatinib, designed to treat chronic myeloid leukemia, has been shown to reverse the pulmonary remodeling associated with PPH.{{cite journal |last1=Schermuly |first1=RT |last2=Dony |first2=E |last3=Ghofrani |first3=HA |last4=Pullamsetti |first4=S |last5=Savai |first5=R |last6=Roth |first6=M |last7=Sydykov |first7=A |last8=Lai |first8=YJ |last9=Weissmann |first9=N |last10=Seeger |first10=W |last11=Grimminger |first11=F |title=Reversal of experimental pulmonary hypertension by PDGF inhibition. |journal=The Journal of Clinical Investigation |date=October 2005 |volume=115 |issue=10 |pages=2811–21 |doi=10.1172/JCI24838 |pmid=16200212|pmc=1236676 }}{{cite journal |last1=Ghofrani |first1=HA |last2=Seeger |first2=W |last3=Grimminger |first3=F |title=Imatinib for the treatment of pulmonary arterial hypertension. |journal=The New England Journal of Medicine |date=29 September 2005 |volume=353 |issue=13 |pages=1412–3 |doi=10.1056/NEJMc051946 |pmid=16192491|doi-access=free }}

Following diagnosis, mean survival of patients with PPH is 15 months.{{cite journal |last1=Ramsay |first1=MA |last2=Simpson |first2=BR |last3=Nguyen |first3=AT |last4=Ramsay |first4=KJ |last5=East |first5=C |last6=Klintmalm |first6=GB |title=Severe pulmonary hypertension in liver transplant candidates. |journal=Liver Transplantation and Surgery |date=September 1997 |volume=3 |issue=5 |pages=494–500 |doi=10.1002/lt.500030503 |pmid=9346791|doi-access=free }} The survival of those with cirrhosis is sharply curtailed by PPH but can be significantly extended by both medical therapy and liver transplantation, provided the patient remains eligible.{{citation needed|date=March 2021}}

Eligibility for transplantation is generally related to mean pulmonary artery pressure (PAP). Given the fear that those PPH patients with high PAP will have right heart failure following the stress of post-transplant reperfusion or in the immediate perioperative period, patients are typically risk-stratified based on mean PAP. Indeed, the operation-related mortality rate is greater than 50% when pre-operative mean PAP values lie between 35 and 50 mm Hg; if mean PAP exceeds 40–45, transplantation is associated with a perioperative mortality of 70-80% (in those cases without preoperative medical therapy){{cite journal |last1=Csete |first1=M |title=Intraoperative management of liver transplant patients with pulmonary hypertension. |journal=Liver Transplantation and Surgery |date=July 1997 |volume=3 |issue=4 |pages=454–5 |doi=10.1002/lt.500030422 |pmid=9346782|doi-access= }} Patients, then, are considered to have a high risk of perioperative death once their mean PAP exceeds 35 mmHg.{{cite journal |last1=Krowka |first1=MJ |last2=Plevak |first2=DJ |last3=Findlay |first3=JY |last4=Rosen |first4=CB |last5=Wiesner |first5=RH |last6=Krom |first6=RA |title=Pulmonary hemodynamics and perioperative cardiopulmonary-related mortality in patients with portopulmonary hypertension undergoing liver transplantation. |journal=Liver Transplantation |date=July 2000 |volume=6 |issue=4 |pages=443–50 |doi=10.1053/jlts.2000.6356 |pmid=10915166|s2cid=25182926 |doi-access= }}

Survival is best inferred from published institutional experiences. At one institution, without treatment, 1-year survival was 46% and 5-year survival was 14%. With medical therapy, 1-year survival was 88% and 5-year survival was 55%. Survival at 5 years with medical therapy followed by liver transplantation was 67%. At another institution, of the 67 patients with PPH from 1652 total cirrhotics evaluated for transplant, half (34) were placed on the waiting list. Of these, 16 (48%) were transplanted at a time when 25% of all patients who underwent full evaluation received new livers, meaning the diagnosis of PPH made a patient twice as likely to be transplanted, once on the waiting list. Of those listed for transplant with PPH, 11 (33%) were eventually removed because of PPH, and 5 (15%) died on the waitlist. Of the 16 transplanted patients with PPH, 11 (69%) survived for more than a year after transplant, at a time when overall one-year survival in that center was 86.4%. The three-year post-transplant survival for patients with PPH was 62.5% when it was 81.02% overall at this institution.

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{{DEFAULTSORT:Portopulmonary Hypertension}}

Category:Hepatology

Category:Lower respiratory tract diseases

Category:Hypertension