A presentation on hepatopulmonary syndrome .

1. By-Dr. Chaitanya Bhujbal
Moderator-Dr. R Khyalappa sir

2. • Hepatopulmonary syndrome (HPS) is characterized by
the triad of abnormal arterial oxygenation caused by
intrapulmonary vascular dilatations (IPVDs) in the
setting of liver disease, portal hypertension, or
congenital portosystemic shunts.
• It’s Prevalence varies depending on the diagnostic
criteria, methods used, and population studied ,so the
estimate prevalence among patients with chronic liver
disease range from 4 to 47 percent

3. E
t
i
o
l
o
g
y
Chronic liver diseases particularly with Portal hypertension
Cryptogenic cirrhosis, Alcoholic cirrhosis, Postnecrotic cirrhosis
Primary biliary cholangitis, Primary sclerosing cholangitis
Chronic active hepatitis, Non-cirrhotic portal hypertension
Alpha-1 antitrypsin deficiency
Wilson's disease, Sarcoidosis,
Hemochromatosis, Biliary atresia
Tyrosinemia, Gaucher disease
Schistosomiasis, Short telomere syndrome
Chronic granulomatous hepatitis
Rarely associated with acute liver disease e.g Ischemic or Hypoxic Hepatitis,
Acute hepatitis A.

4. Pathogenesis
Pulmonary
vasodilation
• Increased bacterial translocation and toxin release (intestinal endotoxemia) from portal
hypertension may result in release of vasoactive mediators including nitric oxide (NO),
Heme-oxygenase-derived carbon monoxide and Tumor necrosis factor alpha.
Role of
Damaged
liver
• To clear circulating pulmonary vasodilators
• production of circulating vasodilators
• inhibition of circulating vasoconstrictive substances
Clinical and
pre clinical
studies
• Increased NO and endothelin-1 (ET-1) levels with Vascular endothelial growth factor A
(VEGF),Platelet Derived Growth Factor (PDGF),Placental Growth Factor(PIGF)
• Increased levels of eNOS(Endothelial Nitric Oxide Synthatase)

5. Factors causing IPVD

6. 1.Ventilation Perfusion
Mistmatch
2.Oxyegn Diffusion
Limitation
3.Rarely Shunt

7. Clinical Manifestations
• The clinical features are due to underlying liver Disease and oxygen impairment
i. Weakness
ii. Fatigue
iii. Anorexia
iv. Ascites
v. Spider Angiomata
vi. Palmar erythema
vii. Jaundice
viii. Asterixis
ix. Anasarca
x. Nail changes
xi. Digital clubbing
xii. Hypertrophic osteoarthropathy

8. • Platypnea – Platypnea is an increase in dyspnea that is induced by
moving into an upright position and relieved by recumbency. In one
series, the presence of platypnea was associated with HPS and a
higher rate of platypnea was reported in patients with HPS compared
with patients with liver disease who did not have HPS (66 versus 6
percent)
• Orthodeoxia – Orthodeoxia refers to a decrease in the arterial oxygen
tension (by more than 4 mmHg or arterial oxyhemoglobin desaturation
(by more than 5 percent) when the patient moves from a supine to an
upright position, which is improved by returning to the recumbent
position. Orthodeoxia may be more commonly found than platypnea,
affecting up to 88 percent of patients with HPS Platypnea and
Orthodeoxia by preferential perfusion of intrapulmonary vascular
dilatations (IPVDs; which disproportionately occur in the lung bases)
when the patient is upright.
• Hypoxemia -HPS-related hypoxemia is due to ventilation-perfusion

9. Diagnosis
• HRCT Chest-May reveal two characteristic findings of IPVDs, dilated
peripheral pulmonary vessels and increased pulmonary artery to
bronchus ratios
• Contrast pulmonary angiography-It is an invasive test that is not
routinely performed
i. The type 1 minimal pattern was characterized by normal to finely
diffuse, spidery abnormalities. It was associated with severe
hypoxemia, orthodeoxia, and a good response to 100 percent
inspired oxygen.
ii. The type 1 advanced pattern which evolves from the type 1
minimal pattern. It was characterized by a diffuse spongy or
blotchy angiographic appearance. It was also associated with
severe hypoxemia and orthodeoxia but may be less responsive to
100 percent oxygen.
iii. The type 2 discrete pattern was characterized by localized,
visible arteriovenous communications and was associated with a

10. • Pulmonary function tests-HPS generally have normal
spirometry, The diffusing capacity for carbon monoxide (DLCO)
is typically mildly to severely impaired in HPS patients ,but still
it’s a non specific test.
• ABG-
i. ABGs should be drawn with the patient sitting upright at rest
on room air.
ii. An elevated A-a oxygen gradient ≥15 mmHg. In patients who
are ≥65 years, an A-a gradient ≥20 mmHg or ≥age-adjusted
value is also acceptable.
iii. A PaO2 of <80 mmHg, a PaO2 <70 mmHg is an alternative in

11. • Transthoracic contrast echocardiography (TTCE) -
i. Evidence of impaired oxygenation (eg, alveolar-arterial [A-a] gradient
≥15 mmHg, arterial oxygen tension [PaO2] <80 mmHg, orthodeoxia on
lying, and standing oximetry or ABG analysis), TTCE should be
performed.
ii. TTCE is usually demonstrates the presence of an intrapulmonary shunt
supportive of underlying IPVDs.
iii. TTCE is performed by injecting contrast material (usually
agitated saline) intravenously during echocardiography. Under normal
resting circumstances, the contrast opacifies only the right heart
chambers because it is filtered by the pulmonary capillary bed.
However, the contrast may opacify the left heart chambers if a right-to-
left intracardiac or intrapulmonary shunt is present. The appearance of
bubbles in the left heart varies with cardiac output, heart rate, and shunt
size.
iv. Left ventricle enlargement and higher systolic velocity, representative of
increased flow through the shunt, may also be seen in patients with

12. Indeterminate location
contrast appears in the left
atrium within one to three
cardiac cycles

13. • Macroaggregated albumin scanning-
i. Macroaggregated albumin (MAA) scanning is an alternative
method of confirming and quantifying shunt from IPVDs in
patients with liver disease. It has been reported to be positive
in up to one third of patients with HPS
ii. It involves intravenously injecting 99m Tc-labeled albumin
macroaggregates that under normal circumstances should be
trapped in the pulmonary capillary bed. Scans that identify
uptake of the radionuclide by the kidneys and/or brain
suggest that the macroaggregates passed through either an
intrapulmonary or intracardiac shunt, although unlike TTCE,
distinguishing intracardiac versus intrapulmonary shunts is
not possible with MAA scanning

15. Severity of hepatopulmonary
syndrome
A-a gradient(Alveolar-
arterial oxygen gradient)
PaO2 (on room air) Graded severity
≥15 mmHg ≥80 mmHg Mild
≥15 mmHg ≥60 mmHg and <80 mmHg Moderate
≥15 mmHg ≥50 mmHg and <60 mmHg Severe
≥15 mmHg <50 mmHg Very severe

16. Treatment
• The approach of treatment has been mainly aimed to improve gas
exchange and decrease hypoxemia
• The treatment modalities according to disease severity are
discussed in next slides

17. I. Mild to moderate hepatopulmonary syndrome -
1) Most patients with mild to moderate HPS require monitoring every 6 to 12
months with pulse oximetry and, when indicated, arterial blood gas analysis
to determine worsening HPS which may prompt a more aggressive
treatment strategy with liver transplantation and/or oxygen supplementation,
early in the course of disease progression.
1) Oxygen supplementation-

18. General indications In the presence of cor
pulmonale
Specific situations
PaO2 ≤55 mmHg or SaO2 ≤88
percent
PaO2 ≤59 mmHg or SaO2 ≤89
percent
PaO2 ≥60 mmHg or SaO2 ≥90
percent with lung disease
and other clinical needs such
as sleep apnea with
nocturnal desaturation not
corrected by CPAP
EKG evidence of P pulmonale If the patient meets criteria
at rest, O2 should also be
prescribed during sleep and
exercise, and appropriately
titrated
Hematocrit >55 percent If the patient is normoxemic
at rest but desaturates during
exercise (PaO2 ≤55 mmHg)
Clinical evidence of right
heart failure

19. • Severe or very severe hepatopulmonary syndrome-
a) Long-term supplemental oxygen therapy (LTOT) is the most frequently
recommended therapy for patients with severe or very severe HPS
b) LTOT only improves features related to intrapulmonary vascular shunts
(eg, dyspnea, fatigue, desaturation) in patients who are hypoxemic due
to HPS
c) Liver transplantation -Patients with HPS and a partial arterial pressure
of oxygen (PaO2) <60 mmHg (8 kPa; ie, severe and very severe HPS,
assigns a standard MELD exception score of 22 for patients with
evidence of intrapulmonary shunting and a room air PaO2 <60 mmHg (8
kPa), with a 10 percent mortality equivalent increase in points every
three months if the PaO2 remains <60 mmHg

20. Physically occlude IPVDs Spring coil embolization
Oppose circulating vasodilators Octreotide, Nitric oxide synthase inhibitors,
Indomethacin
Improve V/Q matching Almitrine bismesylate
Treat underlying liver disease Chemotherapy and corticosteroids, Liver
transplantation
Treat portal hypertension TIPS (Transjugular intrahepatic portosystemic shunt)
Vasoactive Medication Pentoxifylline, Garlic, Quercetin
Antibiotics, Mycophenolate mofetil, Aspirin
Terlipressin,Octreotide,Nitric oxide synthetase
inhibitors,Cyclooxygenase Inhibitors

21. Refractory hepatopulmonary
syndrome
• Refractory HPS applies to patients who fail to improve after LT
or patients who develop recurrent hypoxemia post LT
• Severe post-transplant hypoxemia (defined as 100 percent
oxygen required to maintain saturation ≥85 percent) is seen in 6
to 21 percent of patients and is a common cause of mortality
following LT, placing the patient in the Trendelenburg
position, inhaled epoprostenol , inhaled nitric oxide ,
extracorporeal life support, embolization of pulmonary
arteriovenous malformations
• Treatment Options in this population are limited to maximizing
oxygen supplementation (eg, high-flow oxygen, transtracheal
oxygen)

22. THANK YOU!