Clinical features of hepatopulmonary syndrome in cirrhotic patients.

Abstract

To evaluate the frequency, clinical and paraclinical features of hepatopulmonary syndrome (HPS) and to determine their predictive values in diagnosis of this syndrome in patients in Iran.
Fifty four cirrhotic patients underwent contrast enhanced echocardiography to detect intrapulmonary and intracardiac shunts by two cardiologists. Arterial blood oxygen, O(2) gradient (A-a) and orthodoxy were measured by arterial blood gas (ABG) test. The patients positive for diagnostic criteria of HPS were defined as clinical HPS cases and those manifesting the intrapulmonary arterial dilation but no other criteria (arterial blood hypoxemia) were defined as lHPS cases. HPS frequency, sensitivity, positive and negative predictive values of clinical and paraclinical features were studied.
Ten (18.5%) and seven (13%) cases had clinical and subclinical HPS, respectively. The most common etiology was hepatitis B. Dyspnea (100%) and cyanosis (90%) were the most prevalent clinical features. Dyspnea and clubbing were the most sensitive and specific clinical features respectively. No significant relationship was found between HPS and splenomegaly, ascites, edema, jaundice, oliguria, and collateral veins. HPS was more prevalent in hepatitis B. PaO(2)< 70 and arterial-alveolar gradient had the highest sensitivity in HPS patients. Orthodoxy specificity was 100%.
Clubbing with positive predictive value (PPV) of 75% and dyspnea with negative predictive value (NPV) of 75% are the best clinical factors in diagnosis of HPS syndrome. PaO(2)< 70 and P (A-a) O(2)> 30 and their sum, are the most valuable negative and positive predictive values in HPS patients.

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PO Box 2345, Beijing 100023, China World J Gastroenterol 2006 March 28; 12(12): 1954-1956
www.wjgnet.com World Journal of Gastroenterology ISSN 1007-9327
wjg@wjgnet.com © 2006 The WJG Press. All rights reserved.
RAPID COMMUNICATION
Clinical features of hepatopulmonary syndrome in cirrhotic
patients
Amir Houshang Mohammad Alizadeh, Seyed Reza Fatemi, Vahid Mirzaee, Manoochehr Khoshbaten,
Bahman Talebipour, Afsaneh Sharifi an, Ziba Khoram, Farhad Haj-sheikh-oleslami,
Masoomeh Gholamreza-shirazi, Mohammad Reza Zali
Amir Houshang Mohammad Alizadeh, Seyed Reza Fatemi,
Vahid Mirzaee, Manoochehr Khoshbaten, Bahman Talebipour,
Afsaneh Sharifian, Ziba Khoram, Mohammad Reza Zali,
Research Center for Gastroenterology and Liver Disease, Shaheed
Beheshti University of Medical Sciences, Tehran, Iran
Farhad Haj-sheikh-oleslami, Masoomeh Gholamreza-shirazi,
Cardiologist, Shaheed Beheshti University of Medical Sciences,
Tehran, Iran
Correspondence to: Amir Houshang Mohammad Alizadeh,
Research Center for Gastroenterology and Liver Disease, Shaheed
Beheshti University of Medical Sciences, 7th floor, Taleghani
Hospital, Yaman Str., Evin, 19857 Tehran, Iran. article@rcgld.org
Telephone: +98-21-22418871 Fax: +98-21-22402639
Received: 2005-02-06 Accepted: 2005-08-26
Abstract
AIM: To evaluate the frequency, clinical and
paraclinical features of hepatopulmonary syndrome
(HPS) and to determine their predictive values in di-
agnosis of this syndrome in patients in Iran.
METHODS: Fifty four cirrhotic patients underwent
contrast enhanced echocardiography to detect intra-
pulmonary and intracardiac shunts by two cardiolo-
gists. Arterial blood oxygen, O2 gradient (A-a) and
orthodoxy were measured by arterial blood gas (ABG)
test. The patients positive for diagnostic criteria of
HPS were defined as clinical HPS cases and those
manifesting the intrapulmonary arterial dilation but no
other criteria (arterial blood hypoxemia) were defi ned
as lHPS cases. HPS frequency, sensitivity, positive and
negative predictive values of clinical and paraclinical
features were studied.
RESULTS: Ten (18.5%) and seven (13%) cases had
clinical and subclinical HPS, respectively. The most
common etiology was hepatitis B. Dyspnea (100%)
and cyanosis (90%) were the most prevalent clinical
features. Dyspnea and clubbing were the most sen-
sitive and specific clinical features respectively. No
signifi cant relationship was found between HPS and
splenomegaly, ascites, edema, jaundice, oliguria, and
collateral veins. HPS was more prevalent in hepatitis
B. PaO2 < 70 and arterial-alveolar gradient had the
highest sensitivity in HPS patients. Orthodoxy speci-
fi city was 100%.
CONCLUSION: Clubbing with positive predictive val-
ue (PPV) of 75% and dyspnea with negative predic-
tive value (NPV) of 75% are the best clinical factors
in diagnosis of HPS syndrome. PaO2 < 70 and P (A-a)
O2 > 30 and their sum, are the most valuable negative
and positive predictive values in HPS patients.
© 2006 The WJG Press. All rights reserved.
Key words: Hepatopulmonary syndrome; Cirrhosis;
Contrast enhanced echocardiography
Mohammad Alizadeh AH, Fatemi SR, Mirzaee V, Khoshbaten
M, Talebipour B, Sharifi an A, Khoram Z, Haj-sheikh-oleslami
F, Gholamreza-shirazi M, Zali MR. Clinical features of
hepatopulmonary syndrome in cirrhotic patients. World J
Gastroenterol 2006; 12(12): 1954-1956
http://www.wjgnet.com/1007-9327/12/1954.asp
INTRODUCTION
Ascites by elevating the diaphragm and confounding
the ventilation/perfusion might lead to mild hypoxemia
in most patients due to chronic hepatic involvement,
not regarding the etiology. When cirrhotic patients
have no sign of any cardiovascular diseases, severe
hypoxemia(PO2 < 60mmHg) strongly recommends
hepatopulmonary syndrome[1-3]. Hepatopulmonary
syndrome is one of the pulmonary complications of
cirrhosis which affects the treatment and disease prognosis
and is a factor for arterial blood oxygen reduction. The
diagnosis of this syndrome is confi rmed by presence of
cirrhosis in liver biopsy, absence of cardiovascular diseases,
arterial blood oxygen reduction found in arterial blood
gas (ABG) tests and pulmonary vein dilation in imaging[4].
Many studies have been performed on evaluating the
prevalence, etiology, clinical features, early diagnosis,
treatment and prognosis of this syndrome worldwide.
The aim of this study was to evaluate the clinical and
paraclinical characteristics and their predictive values in
diagnosis of this syndrome.
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Mohammad Alizadeh AH et al. Hepatopulmonary syndrome in cirrhotic patients 1955
MATERIALS AND METHODS
This study was performed in 54 randomly chosen cirrhotic
patients referred to Gasteroenterology Department of
Taleghani Hospital in 2004. In the patients who entered
the study, cirrhosis was confi rmed by biopsy, clinical and
paraclinical evaluations. Echocardiography and pulmonary
function tests were done for all patients and plain chest
x-ray was taken. Those with cardiovascular and known
respiratory diseases were excluded from this study. The
patients with ascites underwent large volume paracentesis.
These 54 patients underwent contrast enhanced
echocardiography performed by two cardiologists from
Cardiovascular Department of Talaghani Hospital. The
procedure was performed by injecting agitated saline into
patient’s right hand cubital vein. Left and right sides of
the heart were evaluated by echo after 5 beats. Presence
of opacity after 5 beats in the left heart was determined as
intrapulmonary shunt. If opacity was present immediately
after injection, it was a sign of intracardiac shunt. ABG
test was performed in patients at supine. After one hour in
vertical position, the oxygenation saturation, arterial blood
oxygen, (A-a) O2 gradient and orthodoxy were evaluated.
Physical examination was performed to detect clinical
features including clubbing in fingers and toes, central
and peripheral cyanosis, presence of spider angioma,
telangiectasia, jaundice, collateral veins in abdomen, ascites,
consciousness, splenomegaly, dyspnea, peripheral edema,
palmar erythema, oliguria or anuria and pleural effusion
for the underlying etiology. All patients were tested for
hepatitis B, hepatitis C, biliary, autoimmune, metabolic,
cardiac, alcoholic and idiopathic etiologies. Complete
blood count (CBC), liver function test (LFT), creatinine,
prothrombin time (PT), partial thromboplastin time (PTT),
albumin and other routine tests were measured in all
patients. Ascitic fl uid was tested for protein, albumin and
white blood cells.
The patients presenting the three diagnostic criteria of
hepatopulmonary syndrome, including hepatic cirrhosis,
arterial blood deoxygenation (PO2 < 80 mmHg) and
intrapulmonary arterial dilation were defined as clinical
hepatopulmonary cases. Those presenting intrapulmonary
arterial dilation but no other two criteria (arterial blood
hypoxemia) were defi ned as subclinical hepatopulmonary
cases. The study was carried out in accordance with
the Helsinki Declaration and approved by the Ethics
Committee of the Research Center for Gastroenterology
and Liver Disease, Shaheed Beheshti University of
Medical Sciences. The data were presented by descriptive
statistics. The variables were compared by χ
Sensitivity, specificity, positive and negative predictive
values of clinical and paraclinical features in diagnosis of
hepatopulmonary syndrome were evaluated. P < 0.05 was
considered statistically signifi cant.
2 test.
RESULTS
Among the 54 patients who participated in the study,
10(18.5%) met the clinical hepatopulmonary syndrome
criteria and 7(13%) with intrapulmonary arterial dilation
(but no other criteria) were defined as subclinical
hepatopulmonary cases. Most frequent age group was
71-80 years. Figure 1 shows the age distribution. The most
common etiology was HBV, but there was no signifi cant
relation. Figure 2 shows the prevalence of HPS etiologies.
By paying attention to the frequency of clinical features
in HPS patients, dyspnea (100%) and cyanosis (90%) were
the most prevalent. Dyspnea and clubbing were the most
sensitive and specific clinical features. Table 1 presents
the characteristics and diagnostic values of signs and
symptoms in HPS patients.
No signifi cant relation was found between splenomegaly,
ascites, edema, jaundice, oliguria, collateral veins and
hepatopulmonary syndrome. Table 2 presents the patients
with or without hepatopulmonary syndrome. HPS was
more common in class C. Table 3 presents the diagnostic
value of arterial blood gas in HPS. PaO2 and arterial–
alveolar oxygen gradients were most sensitive in diagnosis
of HPS. Orthodoxy specifi city was 100%.
DISCUSSION
Hepatopulmonary syndrome includes the triad of liver
Table 1 Characteristics and diagnostic values of signs and
symptoms in hepatopulmonary syndrome
Symptoms
and signs
Frequency
in HPS (%)Sensitivity
PosNeg
9015.9
809.1
10025
8029.5
8029.5
(%)
Specifi city
(%)
PPV
(%)
NPV
(%)
P
Cyanosis
Clubbing
Dyspnea
Palmar erythema
Spider angioma
90
80
100
80
80
80.1
90.9
75
70.5
70.5
60
75
50
38
38
97
95
100
94
94
<0.0001
<0.0001
<0.0001
0.003
0.005
Table 2 Child class in hepatopulmonary syndrome and subclinical
patients
Child classifi cation
Class A
Class B
Class C
Total
HPS positive
0
2
8
10
HPS negative
5
27
12
44
Total
5
29
20
54
12
10
8
6
4
2
0
21-30 31-40 41-50 51-60 61-70 71-80
P = 0.249, Age group (yr)
HPS Pos
HPS Neg
Figure 1 Age distribution in patients with hepatopulmonary syndrome.
www.wjgnet.com
HPS: hepatopulmonary syndrome, PPV: positive predictive value, NPV:
negative predictive value.

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disease, arterial blood deoxygenation and pulmonary vein
dilation. Although the mortality of this syndrome is high,
its infl uence on patient survival is unknown. In our study,
the prevalence of hepatopulmonary syndrome was 18.5%
and the prevalence of pulmonary vein dilation was 13%.
Our fi ndings are compatible with those of other studies in
this fi eld[1-5].
In our study, age and Child class C were signifi cantly
associated with HPS, suggesting that this syndrome
is related with development of cirrhosis. Studies have
shown a relation between HPS and cyanosis, clubbing
and orthodoxy, although spider angioma is significantly
related to intrapulmonary vein dilation[1]. The same results
were observed in our study also. Cyanosis, clubbing and
orthodoxy had positive and negative predictive values of
75% and 100% in hepatopulmonary syndrome.
Previous studies showed that the most common
underlying etiologies of HPS were cryptogenic cirrhosis
and cirrhosis due to hepatitis B[3,4]. The reported positive
predictive values were 37% and 53% for (A-a) O2 gradients
and 93% and 94% for PaO2[3,4]. Orthodoxy has been
reported to be 88%, but in our study it was 66% and no
signifi cant statistical relation was found[6-7]. These clinical
results strongly lead to diagnosis of HPS and the above
tests can be used in screening patients.
In conclusion, hepatopulmonary syndrome and
intrapulmonary vein dilation are relatively frequent in
patients with portal hypertension. Clubbing with the
highest positive predictive value (75%) and dyspnea with
the highest negative predictive value (100%) are the best
clinical features in HPS patients. Further studies are
needed to confi rm our results.
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2
3
4
5
6
7
Table 3 Diagnostic value of arterial blood gases in
hepatopulmonary syndrome
Laboratory
results
Frequency
(%)
Pos
100
Sensitivity
(%)
Specifi city
(%)
PPV
(%)
NPV
(%)
P
Neg
4.5
Pa02 < 70 and
(A-a)02>30
Pa02 < 70
a02 < 65
Pa02 < 60
(A-a)02>15
(A-a)02>20
(A-a)02>30
(A-a)02>40
Orthodoxy>10
1009285100< 0.0001
100
70
30
100
100
100
90
60
4.5
4.5
4.5
75
63.6
31.8
11.4
0
100
70
30
100
100
100
90
60
95
98
92
25
36
70
88
100
83
77
66
23
26
88
65
15
100
95
87
10
100
89
75
93
< 0.0001
< 0.0001
0.039
0.1
0.24
0.001
< 0.0001
< 0.001
HPS Pos
HPS Neg
Figure 2 Causes of liver disease in patients
with hepatopulmonary syndrome.
14
12
10
8
6
4
2
0
Hepatitis B Cryptogenic Hepatitis C AIH Biliary Metabolic PBC Alcoholic

Etiology
S- Editor Guo SY L- Editor Wang XL E- Editor Bi L
1956 ISSN 1007-9327 CN 14-1219/ R World J Gastroenterol March 28, 2006 Volume 12 Number 12
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P = 0.980