14. Management - Supplemental oxygen
• 1 liter of supplemental oxygen per minute at rest and 3
liters per minute (L/min) with exertion
15. Hepatopulmonary syndrome (HPS):
Definition
1. room air pO2 <80mmHg or A-a gradient
>15mmHg
2. evidence of intrapulmonary shunting (typically
on contrast-enhanced echocardiography or a
lung perfusion scan)
3. portal hypertension with or without cirrhosis
16. Hepatopulmonary syndrome: Characteristics
• 10–30% of patients referred for LTx evaluation and only
1% of patients with chronic liver disease in the non-
transplant setting (Deibert 2006)
• Dilatation at both the pre- and capillary level of the
pulmonary circulation, especially in the lower lobes
17. Clinical course
• Improved gradually with oxygen therapy
• Patient was placed on the liver transplant list with a
MELD exception for HPS
18. 1/2013
Current condition
• Dyspnoea in mild exertion since 6months
• NYHA 3
• BMI: 28kg/cm2
• SAT 96%, no clubbing
• HR 65/min,
• BP 120/80mmHg
• Loud P2
• No ascites/ mild peripheral edema
• Palpable liver/spleen
6MWT (without oxygen)
Pre Post
SpO2 96 87
HF 63 111
Borg 0 6
Total walked distance 452 m
25. ERS Task Force Pulmonary-Hepatic Vascular Disorders Scientific
Committee Guidelines for PoPH candidates for OLT
Rodriguez-Roisin R et al. Eur Respir J 2004
26. Therapy
• Patient was taken off the liver transplant list
• Patient was put on ambrisentan 5 mg od with close LFT
monitoring.
• Propranolol (primary prevention) discontinued
27. 6 months later – clinical assessment
• Clinical improvement
• NYHA 2
• 6MWT 536m
• Does not need supplemental oxygen therapy
• Echo: borderline RV size and normal systolic function
• BNP: normal
28. Hb: 11.5 g/dl,
HR: 77/min
BSA: 1.8m2
Baseline
Pressure (mmHg) SAT (%)
RA 9
RV 67/19
PA 67/36/49 78
PAWP 10
Ao 120/70 98
PVR (Wood) 3.98
PVRi (Woodxm2) 7.2
CI (L/min/m2) 5.5
At 6 months
repeat RHC - thermodilution
29. Baseline (Fick) after 6 months (TD)
6MWT (m) 452 536
PA (mmHg)
PVR (W)
CI (L/min/m2)
77/31/m46
6.7
2.9
67/36/m49
3.9
5.5
30. Significant CI increase could be
attributed to
1. targeted therapy with ERA
2. b-blocker cessation
3. 1 and 2
31. β-blocker cessation in PoPH
• All patients (n=10) were free of PAH targeted therapies
• 28% increase in cardiac output with no change in mean pulmonary
artery pressure, resulting in a 19% decrease in pulmonary vascular
resistance
Provencher et al. Gastroenterology 2006
33. Targeted PAH therapy with bosentan
n=34 consecutive patients with PoPH treated with first-line bosentan
Short-term evaluation was performed after 5±2 months after bosentan
initiation
Savale et al. ERJ 2013
34. Targeted PAH therapy with ambrisentan
Cartin-Ceba et al. Chest 2011
n=17 patients with PoPH treated with ambrisenten monotherapy
35. Anemia can also increase cardiac output
baseline after 6 months
6MWT (m) 452 536
PA (mmHg)
PVR (W)
CI (L/min/m2)
77/31/m46
6.7
2.9
67/36/m49
3.9
5.5
Hb (g/dl) 13 11.5
36. How would you proceed with this
patient?
1. Add a PDE-5 inhibitor
2. Do nothing
3. Repeat the RHC using the indirect Fick method
39. Hemodynamic improve is not related to the
severity of the liver disease
The short-term haemodynamic response was significantly
better in patients with C-P class B cirrhosis compared with
those with C-P class A cirrhosis or with noncirrhotic portal
hypertension
Savale et al. ERJ 2013
40. Incidence of PoPH
1-3 per million population
(Humbert 2006)
Cirrhosis <1%
(Mc Donnell 1983)
Portal Hypertension 2-3%
(Hadengue 1991, Yang 2000)
Liver transplant candidates 6-8.5%
(Colle 2003, Ramsay 1997)
Liver transplant recipients 2.5-4%
(Galie 2001, Taura 1996, Castro 1996)
41. Portopulmonary Hypertension
• Identification of POPH is usually made at an average of
4–7 yrs after the diagnosis of portal hypertension
• Risk factors: Autoimmune etiology and female sex
• Independent of the severity of the liver disease
• Prognosis is related to the severity of cirrhosis and to
cardiac function
42. Portopulmonary Hypertension and liver
transplantation
• Untreated or treated, if mean PAP>50mmHg peri-
transplant mortality is well over 50%
• If mean PAP is 35-50mmHg and PVR greater than
250dynes, mortality 50%
• Consensus goals of PAH therapy in PoPH:
– Mean PAP less than 35mmHg
– Mean PAP 35-50mmHg with PVR less than 250 dynes and
normal RV function
43. RCTs on medical therapy
• PoPH patients are usually excluded from RCTs with
PAH-specific therapies
44.
45. Take home messages
• HPS should be suspected in symptomatic patients with portal
hypertension who present with desaturation at rest or during
exercise
• HPS and PoPH are clinically distinct entities with seemingly distinct
pathophysiologies, but they can very rarely occur simultaneously or
sequentially in the same patient
• The effect of PAH targeted therapies in PoPH seem to be similar to
those observed in other forms of PAH
• Β-blockers should be discontinued when possible in patients with
PoPH
49. 44% had >20% difference
between thermodilution and Fick
Using PVR >3 Wood units as a
diagnostic criteria for PAH, 27
patients (13±2%) would have
inconsistency in PAH diagnosis
between TD and Fick
n=213 RHCs, 79 (40%) of whom had PAH
50. PAH determinants of prognosis
ESC guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Heart J 2009
This scenario occurred in 22% of PoPH patients in one echocardiographic study [5].
Current criteria include: 1) the presence of portal hypertension (either inferred from the presence of splenomegaly, thrombocytopenia, porto- systemic shunts, oesophageal varices or portal vein abnormalities, or confirmed by haemodynamic measurements), but not necessarily the presence of cirrhosis;
mild peripheral pulmonary fibrosis and enlargement of the distal pulmonary arterioles and nontapering pulmonary vessels
