Hepatopulmonary Syndrome
Portopulmonary Hypertension
M. Verhaegen
Ochtendkrans 17-8-2012
End Stage Liver Disease (ESLD)
and Arterial Hypoxemia
• Cardiopulmonary causes irrespective of ESLD
– E.g. heart failure, COPD
• Causes associated with liver disease
– Hepatopulmonary syndrome (HPS)
– Portopulmonary hypertension (POPH)
– Hepatic hydrothorax
• Multifactorial
End Stage Liver Disease (ESLD)
and Arterial Hypoxemia
• Cardiopulmonary causes irrespective of ESLD
– E.g. heart failure, COPD
• Causes associated with liver disease
– Hepatopulmonary syndrome (HPS)
– Portopulmonary hypertension (POPH)
– Hepatic hydrothorax
• Multifactorial
Outline
Hepatopulmonary syndrome
Portopulmonary hypertension
– Definition
– Epidemiology
– Clinical signs and symptoms
– Pathogenesis
– Diagnosis
– Treatment
– Conclusion
Summary
HEPATOPULMONARY SYNDROME
HPS: Definition
• Definition: triad
– Liver disease
• +/- portal hypertension
• +/- cirrhosis
• Acute liver failure and ischemic hepatitis have been associated with
HPS
– Impaired oxygenation
• Age-corrected alveolar-arterial O2 gradient ≥ 15 mmHg while
breathing room air
• Or: PaO2 < 80 mmHg while breathing room air
– Intrapulmonary vascular dilatation
• Exclusion of intrinsic cardiopulmonary pathology
HPS: Definition
• Definition: triad
– Liver disease
• +/- portal hypertension
• +/- cirrhosis
• Acute liver failure and ischemic hepatitis have been associated with
HPS
– Impaired oxygenation
• Age-corrected alveolar-arterial O2 gradient ≥ 15 mmHg while
breathing room air
• PaO2 < 80 mmHg while breathing room air
– Intrapulmonary vascular dilatation
• Exclusion of intrinsic cardiopulmonary pathology
HPS: Pulmonary Vessels
Arteriovenous malformations in the lungs
• Vasodilation of pulmonary (pre)capillary vessels
– 15 – 160 µm (normal: 7 – 15 µm)
• An absolute increase in the number of dilated vessels
• Pleural and pulmonary arteriovenous shunts and
portopulmonary venous anastomoses
HPS: Hypoxemia
• Gas exchange abnormalities leading to hypoxemia
1. Ventilation-perfusion mismatch
2. Intrapulmonary shunting: large right-left shunt
3. Limitation of O2 diffusion
• O2 therapy may improve oxygenation
• Impaired hypoxic pulmonary vasoconstriction
– 30% of patients
Severity of HPS
• There is no universally consistent classification of HPS
according to severity
• Possible classification according to PaO2 (in patients
breathing room air and with A-a O2 gradient ≥ 15 mmHg)
–
–
–
–
Mild:
Moderate:
Severe:
Very severe:
PaO2 ≥ 80 mmHg
PaO2 ≥ 60 – and < 80 mmHg
PaO2 ≥ 50 – and < 60 mmHg
PaO2 < 50 mmHg
(<300 mmHg while breathing 100% oxygen)
• There is discussion about a relationship between the
severity of liver disease the presence or severity of HPS
HPS: Prevalence
A very wide range of prevalence has been reported in
patients with chronic liver disease: 4 - ~ 30%
– Heterogenous diagnostic criteria: various cutoffs for gas exchange
abnormalities
– Diagnostic methods
HPS: Symptoms
• Patients may be asymptomatic
• Dyspnea
– Insidious onset: initially dyspnea at exertion
• Platypnea
– Increasing dyspnea from supine to upright position
• Orthodeoxia
– PaO2 decreases > 4 mmHg or O2 saturation decreases > 5% when the
patients moves from a supine to an upright position
– Pulmonary arteriovenous malformations occur predominantly at the
base of the lungs
increased perfusion of the lower lobes with more
ventilation/perfusion mismatching and increased shunting in the
upright position
HPS: Clinical Signs
• Spider naevi: cutaneous marker for intrapulmonary
vascular dilatation?
– More systemic and pulmonary vasodilatation
– More impaired hypoxic pulmonary vasoconstriction
– Higher grades of hypoxemia
• Cyanosis
• Digital clubbing
HPS:
Pathogenesis of Pulmonary Vasodilatation
• Nitric oxide appears to play a key role in the of pulmonary
vascular changes of HPS, but several other mediators and
mechanisms have been proposed
– Increased NO production in the lungs?
– NO theory: incomplete explanation
• Possible mechanisms
– Failure of the damaged liver to clear circulating pulmonary vasodilators
– Production of pulmonary vasodilators by the damaged liver
– Inhibition of circulating vasoconstrictive substances by the damaged liver
HPS: Natural History (1)
• Spontaneous resolution is unlikely
• Hypoxemia is generally progressive
– Mean PaO2 decline: 5.2 (0.4 – 8.3) mmHg/year
• HPS worsens the prognosis of patients with ESLD
Median survival
5-year survival rate
HPS patients
and
no liver TX *
(n = 37)
Matched controls**
(no HPS,
no liver TX)
(n = 47)
24 months
87 months
23 %
63 %
* No liverTX because of age or co-existing conditions
** Matched for cause and severity of liver disease
p
0.0003
Swanson et al., Hepatology 2005; 41: 1122-9
HPS: Natural History (2)
• Cause of death: multifactorial
– Progressive hypoxemic failure: seldom the primary cause of death
– Related to complications of liver disease
• Hepatic failure, multisystem organ failure due to sepsis,
hepatocellular carcinoma, gastrointestinal bleeding
• Development of concomitant portopulmonary
hypertension is unlikely
HPS: Screening
Patients with ESLD planned for liver transplantation should
be screened for HPS: screening for hypoxemia
•
Pulse oximetry
– Useful indicator, but insensitive
– Normal value is possible with mild HPS and increased A-a O2 gradient
•
Arterial PO2
– The combination of spider naevi, digital clubbing, cyanosis, and
severe hypoxemia (PaO2 < 60 mmHg) in the absence of cardiopulmonary disease strongly suggests HPS
In patients with liver disease and hypoxemia further investigations
for intrapulmonary vascular dilatation are indicated
HPS: Diagnosis (1)
Presence of triad
1. Liver disease
2. Impaired oxygenation
3. Intrapulmonary vascular dilatations
2. Impaired oxygenation: arterial PO2
– PaO2 < 80 mmHg indicates impaired oxygenation
• Patients > 65 y: PaO2 < 70 mmHg
– Patient in upright position if possible
– More accurate: calculation of alveolar-arterial O2 gradient
(compensates for hyperventilation)
• A-a O2 gradient ≥ 15 mmHg (> 65 y of age: ≥ 20 mmHg)
• Problem: calculation assumes normal cardiac output
HPS: Diagnosis (2)
3. Detection of intrapulmonary vascular dilatations
–
–
–
–
Pulmonary angiography
Technetium-99m-labeled macroaggregated albumin scanning
Chest computed tomography
Contrast-enhanced echocardiography
• Agitated saline
– Bubbles in left atrium within 3-6 heart cycles after iv injection when shunts
typical of HPS are present
• Sensitive
• Less invasive
• Detection of other problems (e.g. pulmonary hypertension)
HPS: Treatment (1)
• There is no good medical therapy to improve gas
exchange and hypoxemia
– Supplemental O2 as symptomatic therapy
– Various medications have been tried (mostly anecdotically or in
uncontrolled case series): no (sustained) improvement in oxygenation
– Several medical interventions have been tried
• TIPSS: variable response with a few case reports indicating
improvement, but there may be a risk of worsening HPS due to an
increased hyperkinetic state
• Other interventions (embolization, plasma exchange): unsuccessful
• Liver transplantation
Treatment
Efficacy for improving gas exchange
in the HPS
Physically occlude IPVDs
Spring coil embolization
Modest if technically possible
Oppose circulating vasodilators
Octreotide (somatostatin analog)
Nitric oxide synthase inhibitors
Indomethacin
Variable
Variable
Poor
Improve V/Q matching
Almitrine bismesylate
Slight
Treat underlying liver disease
Chemotherapy and corticosteroids
Liver transplantation
Helpful in one patient
Moderately good but variable response
Treat portal hypertension
TIPSS (transjugular intrahepatic portosystemic shunt)
Variable
Other (miscellaneous)
Methylene blue
Allium sativum (garlic)
Propranolol
Plasma exchange
Sympathomimetics
Variable in the few patients described
Variable
None
None
None
Lange and Stoller, UpToDate 2012; adapted from Lange PA, Stoller JK, Ann Int Med 1995; 122: 521
HPS: Treatment (2)
• Liver transplantation
– Liver transplantation appears to improve survival in patients with HPS
HPS patients and HPS patients and
no liver TX *
liver TX
(n = 37)
(n = 24)
5-year survival rate
23 %
76 %
p
0.0001
Swanson et al., Hepatology 2005; 41: 1122-9
HPS: Treatment (2)
• Liver transplantation
– Liver transplantation appears to improve survival in patients with HPS
Figure 1. (A) Survival curves from the time of HPS diagnosis for HPS patients and controls (from time of PaO2
determination) undergoing OLT (P = .69); and HPS patients and controls not undergoing OLT (P = .0003); (B)
Survival from the time of OLT for HPS patients with severe hypoxemia and controls (P = .67).
Swanson et al., Hepatology 2005; 41: 1122-1129
HPS: Treatment (2)
• Liver transplantation
– Liver transplantation appears to improve survival in patients with HPS
– Usually there is resolution of dyspnea and hypoxemia (80% of patients)
• Highly variable time course (2 – 14 months)
– Delayed recovery is common
• DLCO may not improve after transplantation, suggesting persistent
subclinical pulmonary vascular changes
– Most problems occur in the early postoperative period
• Early postoperative mortality is higher in patients with HPS
– Risk factors: preoperative PaO2 (room air) ≤ 50 mmHg and
preoperative shunt fraction ≥ 20%
• Case reports: prolonged postoperative mechanical ventilation
– HPS is not considered in MELD score
Schiffer et al., Am J Transplant 2006;6: 1430-7
HPS: Conclusion (1)
•
•
•
•
HPS = liver disease + hypoxemia + pulmonary vascular dilatation
Screening for HPS (PaO2) is indicated in patients with chronic liver
disease and dyspnea, platypnea or orthodeoxia, or in patients
considered for liver transplantation
In patients with liver disease and severe hypoxemia the diagnosis of
HPS is confirmed by the documentation of intrapulmonary vascular
dilatation (contrast enchanced echocardiography)
Hypoxemia due to HPS is usually progressive with a high risk of
morbidity and mortality
– There is no effective medical therapy or intervention for HPS
– O2 therapy generally improves oxygenation in HPS
– HPS without liver transplantation: higher mortality than in patients
with liver dysfunction without HPS
HPS: Conclusion (2)
•
Liver transplantation is the only therapeutic option
– Morbidity and mortality following liver transplantation is (initially) probably
higher in patients with HPS than in patients without HPS
• PaO2 ≤ 50 mmHg and significant intrapulmonary shunting
– Resolution of symptoms due to HPS in 80% of patients
PORTOPULMONARY HYPERTENSION
Portopulmonary Hypertension (POHP):
Definition
Combination of
• Portal hypertension +/- ESLD
– ≈ 10% of patients with POPH do not have liver cirrhosis
– Causes of portal hypertension associated with POPH: cirrhosis, portal
vein thrombosis, hepatic vein sclerosis, congenital portal circulation
abnormalities, periportal fibrosis without cirrhosis
• Pulmonary arterial hypertension (PAH)
–
–
–
–
Mean PAP > 25 mmHg at rest (> 30 mmHg during exercise)
Increased PVR > 240 dynes.s.cm-5
PCWP < 15 mmHg
Exclusion of alternative causes of PAH
POPH: Epidemiology (1)
• POPH represents ~ 10% of the PAH population
• Portal hypertension is a risk factor for developing PAH
– Autopsy studies: the prevalence of PAH is higher in patients with portal
hypertension than in the general population McDonnell et al, Am Rev Respir Dis 1983;127: 437-41
• PAH in unselected patients = 0.13%
• PAH in patients with cirrhosis and portal hypertension = 0.73%
– The risk of developing PAH is independent of the cause of portal
hypertension
– A relationship between the severity of portal hypertension and the
severity of PAH has not been demonstrated
POPH: Epidemiology (2)
• Prevalence: data vary greatly
– Diagnostic methods
– Prospective hemodynamic studies: 2 - 6% of patients with portal
hypertension develop PAH
– Patients undergoing liver transplantation: prevalence of up to 10%
– There appears to be no association between the severity of liver
dysfunction and the risk of PAH
POPH: Pathogenesis (1)
Numerous theories have been proposed, but no definitive
mechanism has been detected
• Histology: analogous to PAH at the level of the distal
pulmonary arteries
–
–
–
–
–
–
Vasoconstriction
Intimal proliferation
Medial hypertrophy
Fibrotic changes
Plexiform lesions
In situ thrombosis
POPH: Pathogenesis (2)
• Possible mechanisms
– Humoral: imbalance of vasoconstrictor and vasodilatator factors at the
pulmonary vasculature
• Portosystemic shunts allows vascular mediators to bypass the liver metabolism
• Decreased synthesis of vasoactive factors
• Serotonin, endothelin-1, thromboxane A2, vasoactive intestinal peptide,
interleukin-6, nitric oxide, prostacyclin, …..
– Endothelial damage with vascular remodeling due to excessive
pulmonary blood flow
– Smooth muscle proliferation
– Microvascular thrombosis
– Genetic predisposition
• Likely multifactorial
POPH: Symptoms
1. Clinical manifestations of portal hypertension
– Time interval between first manifestations of portal hypertension and
documentation of PAH: 2 – 15 years (average 4 – 7 y)
2. Clinical manifestations of pulmonary arterial hypertension
– Early stages of POPH: asymptomatic
– Initially dyspnea on exertion
– Possibly fatigue, chest pain, syncope, peripheral edema, orthopnea,
hemoptysis
POPH: Clinical Signs
• Severe POPH: physical findings of right heart dysfunction
and eventually right heart failure
–
–
–
–
–
Elevated jugular pressure
Tricuspid systolic murmur (tricuspid regurgitation)
Pulmonary diastolic murmur (pulmonary insufficiency)
Dependent pitting edema
Ascites
POPH: Screening and Diagnosis (1)
There is no good screening method for POPH
• Arterial blood gasses
– Possibly hypoxemia (mild to moderate) and an increased A-a gradient
• Pulmonary function tests
– Normal or decreased diffusion
• General cardiology screening tests: low sensitivity
– ECG: right ventricular hypertrophy, right atrial hypertrophy, right axis
deviation, right bundle branch block
– Chest X-ray: enlargement of right heart chambers, dilatation of the pulmonary
arteries
Suggestive of right heart strain
Further investigations for POPH are indicated
POPH: Screening and Diagnosis (2)
Transthoracic echocardiography
•
Echocardiographic screening: in symptomatic patients with portal
hypertension and in candidates for liver transplantation
– There are at present no data demonstrating that screening with TTE in
asymptomatic patients with portal hypertension and liver cirrhosis not
severe enough to require tranplantation is beneficial
•
PAPs > 40 mmHg
right heart catheterization
– TTE has a low positive predictive value for POPH
• TTE and estimated RVSP > 50 mmHg
only 65% of patients
have an increased PVR (Krowka, Liver Transplant 2003; 9: 1336-7)
POPH: Screening and Diagnosis (3)
Right heart catheterization: gold standard for definitive
diagnosis of POPH
•
Confirmation of diagnosis of POPH
– Pulmonary artery pressure: increased
– Pulmonary capillary wedge pressure: normal
– Pulmonary vascular resistance: increased
• Differentiation from ESLD with increased PAP due to high cardiac output,
but with a normal PVR (30-50 % of ESLD patients)
– Hepatic venous wedge pressure: increased
•
•
Exclusion of other causes of PAH
Severity of POPH: prognostic and therapeutic implications
Porres-Aguilar et al, Annals of Hepatology, 2008; 7: 321-30
Distinguishing cardiopulmonary features of portopulmonary hypertension, chronic liver
disease, and pulmonary arterial hypertension
Kuo et al., Chest 1997; 112: 980-986
Distinguishing cardiopulmonary features of portopulmonary hypertension, chronic liver
disease, and pulmonary arterial hypertension
Kuo et al., Chest 1997; 112: 980-986
POPH: Prognosis
•
•
Untreated POPH: outcome depends on the severity of PAH and
on the severity of liver disease
Data indicate that survival is worse in patients with POPH
(without liver transplantation) than in patients with PAH of
other causes
– Delayed treatment of POPH?
– Outcome in patients with POPH depends not only on PAH but also on
underlying liver disease
•
Survival is significantly higher in patients with POPH receiving
specific therapy for PAH compared to POPH patients not
receiving specific therapy for PAH
5 y survival = 45 %
5 y survival = 14 %
Swanson et al, Am J Transplant 2008; 8: 2445-53
5 y survival = 67 %
5 y survival = 45 %
5 y survival = 14 %
Swanson et al, Am J Transplant 2008; 8: 2445-53
POPH: Treatment
Insufficient data from studies in patients with POPH: most
treatments are copied from studies in patients with PAH of
other causes
• General management
• Specific therapy for PAH
• Liver transplantation
POPH: General Management (1)
• Oxygen supplementation
• Diuretics
– Treatment of pulmonary hypertension
– Treatment of ascites and/or peripheral edema
• Concerns: too rapid fluid removal (hypovolemia) and electrolyte disturbances
(hypokalemia
intracellular acidosis
hyperammonemia
hepatic coma)
• Anticoagulation
– No good data on efficacy and safety in patients with POPH
– Contraindications related to liver disease
Not recommended in POPH patients
Decision on individual basis
POPH: General Management (2)
• Calcium channel blockers: contraindicated in patients
with POPH?
– Mesenteric dilatation
worsening of portal hypertension
• Stop β-blockade
– In patients with portal hypertension β-blockade is often started to
prevent bleeding from esophageal varices
– Patients with POPH: stopping β-blockade has a beneficial effect on
pulmonary hypertension
• No data on effect on esophageal variceal hemorrhage
• Avoid TIPSS?
– Risk of acute increase in cardiac output and mPAP
POPH: Specific Therapy for PAH
• Prostanoids
• Endothelin receptor antagonists
• Phosphodiesterase type-5 inhibitors
No data from RCTs in patients with POPH
– Case series, small observational studies
– Risk of hepatotoxicity
– Some data indicate improved survival with specific therapy for PAH
(epoprostenol, bosentan, sildenafil), but other data do not support this
• Greater survival benefit for patients with milder liver disease?
– Combined therapy: case reports only
Treatment to enable liver transplantation?
– Target: mPAP < 35 mmHg and PVR < 400 dynes.s.cm-5 ?
Swanson et al, Am J Transplant 2008; 8: 2445-53
POPH: Prostanoids (1)
• Epoprostenol (Flolan®)
– Data (no RCTs) indicate improved hemodynamics (mPAP, PVR, CO)
and exercise capacity
– No documented long-term survival benefit
– Increased incidence of splenomegaly and thrombocytopenia
– Adverse effects on hepatic function or portal hypertension?
• Iloprost (Ventavis®)
Figure 2. Changes in pulmonary hemodynamic
measurements in patients treated with epoprostenol
(epoprostenol group) from baseline to most recent right heart
catheterization. (A) Mean MPAP significantly improved from
48.4 to 36.1 mm Hg (*P < .0001). TPG improved from 38.5
to 23.2 mm Hg (*P < .0001). There was no significant
change in PCWP. (B) Mean CO improved from 5.7 to 7.7
L/min (**P = .0009). There was no significant change in CI.
(C) Mean PVR improved from 632 to 282 dynes · s · cm−5
(*P < .0001). Abbreviations: MPAP, mean pulmonary artery
pressure; PCWP, pulmonary capillary wedge pressure; TPG,
transpulmonary gradient; CO, cardiac output; CI, cardiac
index; PVR, pulmonary vascular resistance.
Fix et al, Liver Transplant 2007; 13: 875-85
p= 0.77
Fix et al, Liver Transplant 2007; 13: 875-85
POPH: Prostanoids (2)
• Epoprostenol (Flolan®)
• Iloprost (Ventavis®)
– Inhaled iloprost: acute hemodynamic and functional improvement over
a period of 12 months, but this effect was not sustained over a period
of 3 years Hoeper et al, Eur Resp J 2007; 30: 1096-1102
POPH: Endothelin Receptor Antagonists (1)
• Bosentan (Tracleer®)
– 10 % of patients: (reversible) liver function abnormalities (TA increase)
– Case reports in POPH
• Improved symptoms, increased exercise capacity, significant drop in
pulmonary vascular resistance
• No elevation in transaminase levels
– Retrospective analysis: hemodynamic and functional improvement
over a period of 3 years Hoeper et al, Eur Resp J 2007; 30: 1096-1102
• Ambrisentan (Volibris®)
Hoeper et al, Eur Resp J 2007; 30: 1096-1102
50
53
53
828
895
925
45
579
Fig. 2— Individual haemodynamic
response to treatment with inhaled
iloprost (○) or bosentan (•), expressed
as change from baseline to first followup measurement of a) mean pulmonary
arterial pressure (―Ppa) and b)
pulmonary vascular resistance (PVR).
a, b) n = 11 in iloprost group and n = 13
in bosentan group.
Hoeper et al, Eur Resp J 2007; 30: 1096-1102
Fig. 1— a) Overall survival and b) event-free
survival of patients with portopulmonary
hypertension treated with bosentan (–––––) or
inhaled iloprost (···········) are shown. Events
were deaths, transplantation or clinical
worsening requiring the introduction of a new
treatment for pulmonary hypertension. The
number of subjects at risk were as follows. a)
Bosentan group: n = 18, 18, 17, 16, 14, 14 and 11
at 0, 6, 12, 18, 24, 30 and 36 months,
respectively. Iloprost group: n = 13, 13, 10, 8, 8, 7
and 6 at 0, 6, 12, 18, 24, 30 and 36 months,
respectively. b) Bosentan group: n = 18, 18, 17,
16, 14, 14 and 9 at 0, 6, 12, 18, 24, 30 and 36
months, respectively. Iloprost group: n = 13, 12,
10, 6, 6, 6 and 2 at 0, 6, 12, 18, 24, 30 and 36
months, respectively. a) p = 0.029; b) p = 0.017.
Hoeper et al, Eur Resp J 2007; 30: 1096-1102
POPH: Endothelin Receptor Antagonists (2)
• Ambrisentan (Volibris®)
– Observational study of 13 patients with POPH Cartin-Ceba et al, Chest 2011; 139:109-14
• Moderate to severe pulmonary hypertension
• Results following 12 months of therapy
– Improved hemodynamic parameters (mPAP, PVR, CO)
– Improved biomarker (B-type natriuretic peptide)
– Improved symptoms (WHO functional class)
• No change in level of liver enzymes
POPH: Phosphodiesterase Type-5 Inhibitors
• Sildenafil (Revatio®)
– Insufficient data in POPH
– Retrospective case series of 14 patients (Reichenberger et al;. Eur Respir J 2006:; 28:563-67)
• Moderate to severe POPH
• +/- prostanoid (6/8)
• Sustained improvement of 6-minute walk test and B-type natriuretic
peptide levels (up to 12 months)
• Hemodynamic benefit (mPAP and PVR decrease) at 3 months was not
sustained at 12 months
POPH and Liver Transplantation (1)
• Severity of PAH and liver transplantation in POPH patients
– Mild to moderate PAH: no major influence on outcome
– Severe PAH: high perioperative risk and poor clinical outcome
• Pulmonary problems
• Liver congestion and primary graft dysfunction
• Contraindication?
– In the past: a mPAP ≥ 35 mmHg was considered a contraindication
• Level of mPAP is a strong predictor of survival
– mPAP ≥ 35 mmHg: very high perioperative mortality rate (35-60%)
• Case series: succesful liver transplantation with mPAP ≥ 35 mmHg
– At present: mPAP ≥ 45 mmHg?
POPH and Liver Transplantation (2)
• Reversibility of POPH after liver transplantation?
– If PAH resolves, it may take months to years
– AASLD guidelines: consider liver transplantation in patients with severe
POPH only if PAH can be effectively controlled with medical therapy
Careful selection of patients
– Well-defined protocols
– Role of medical treatment before liver transplantation?
– MELD score underestimates mortality risk of POPH patients on waiting
list for liver transplantation
– Regular echocardiographic follow-up while on waiting list (biannual?)
• Combined liver-(heart)-lung transplantation: insufficient
outcome data
POPH: Conclusion (1)
•
•
•
POPH = portal hypertension + pulmonary arterial hypertension
Screening for POPH (contrast enhanced echocardiography) is
indicated in symptomatic (dyspnea) patients with portal
hypertension or in patients with portal hypertension considered for
liver transplantation
In patients with a systolic pulmonary artery pressure > 40 mmHg a
right heart catheterization is indicated
– Diagnosis/differential diagnosis
– Severity classification and therapeutic implications
•
Severe POPH has a high risk of mortality
– Prognosis is worse in patients with PAH caused by POPH than in patients
with other causes of PAH
POPH: Conclusion (2)
•
Specific treatment for PAH is not well documented in POPH patients
– Patients with POPH treated with advanced pharmacological therapy for PAH
appear to have a better prognosis than untreated POPH patients
– Treatment as a bridge to liver transplantation?
•
Liver transplantation is a therapeutic option in selected patients
– Mild POPH (mPAP 25-34 mmHg): generally good outcome following
transplantation and reversibility of PAH
– Moderate POPH (mPAP 35-44 mmHg): generally favorable outcome following
transplantation, but reversibility of PAH is questionable
– Severe POPH (mPAP ≥ 45 mmHg): generally poor outcome following
transplantation and no reversibility of PAH
•
After liver transplantation, it may take months to years for PAH to
resolve in POPH patients
HPS
Definition
1. Liver disease
2. Impaired oxygenation
PaO2<80mmHg, A-a O2≥15 mmHg
3. Intrapulmonary vascular dilation
POPH
1. Portal hypertension
2. Pulmonary arterial hypertension
Mean PAP > 25 mmHg
PVR > 240 dynes.s.cm-5
PCWP < 15 mmHg
Exclusion other causes of PAH
Common symptoms
Dyspnea
Platypnea
Orthodeoxia
Dyspnea on exertion
Orthopnea
Clinical signs
Cyanosis and finger clubbing
Spider naevi
Signs of right heart failure
ECG
No specific abnormalitiies
RBTB, right axis, RV strain and
hypertrophy
Chest X-ray
No specific abnormalitiies
Cardiomegaly
Large main pulmonary arteries
HPS
POPH
Arterial blood gasses
Moderate to severe hypoxemia
Normal or mild hypoxemia
Contrast-enhanced
echocardiography
Positive (LA opacification for > 3-6
cardiac cycles after RA opacification)
Negative
Pulmonary hemodynamics
and angiographic findings
Normal
Discrete AV communications
Mean PAP at rest > 25 mmHg
Mean PCWP < 15 mmHg
PVR > 240 dynes.s.cm-5
Dilated main pulmonary arterial
tree
Distal arterial pruning
Liver transplantation
Always indicated, even in severe
cases
Mild to moderate POPH: indicated
Severe POPH: generally not
indicated
Referenties
•
•
•
Hepatopulmonary Syndrome – A Liver-Induced Lung Vascular Disorder.
Giusca et al.: Eur J Int Med 2011; 22: 441-447
Portopulmonary hypertension: From diagnosis to treatment.
Rodriguez-Roisin and Krowka: N Engl J Med 2008; 358: 2378-87
Portopulmonary hypertension and hepatopulmonary syndrome.
Hoeper et al.: Lancet 2004; 363: 1461-68