DOI: 10.1148/radiol.2291012171
(Radiology 2003;229:64-67.)
© RSNA, 2003
Case 63: Hepatopulmonary Syndrome1
Ann N. Leung, MD
1 From the Department of Radiology, Stanford University Medical Center, 300 Pasteur Dr, S072A, Stanford, CA 94305-5105. Received January 17, 2002; revision requested March 6; revision received April 23; accepted June 19. Address correspondence to the author (e-mail: aleung@stanford.edu).
Index terms: Diagnosis Please • Hepatic arteries, abnormalities, 952.766 • Liver, cirrhosis, 761.79 • Lung, vascular disease, 564.1559 • Pulmonary arteries, abnormalities, 944.75, 944.766
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HISTORY
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A 38-year-old man presented to the emergency room with a 3-week history of dyspnea. His shortness of breath occurred on exertion or standing and was improved by lying flat. Past medical history included alcohol and drug abuse. The results of a physical examination were unremarkable, except for decreased breath sounds at the base of the right lung. An arterial blood gas analysis was performed while the patient breathed room air, and the results of this test indicated a pH of 7.46, partial pressure of carbon dioxide of 28 mm Hg, and partial pressure of oxygen of 46 mm Hg. Additional laboratory tests were performed and revealed elevated levels of liver enzymes and bilirubin and a prolonged prothrombin time. Bedside radiography of the chest (Fig 1) and a lung perfusion study (Fig 2) were performed.
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Figure 2. Pulmonary perfusion images obtained with technetium 99m (99mTc) macroaggregated albumin shows bilateral pleural effusions (short arrows) and extrapulmonary uptake in the kidneys (long arrows).
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IMAGING FINDINGS
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The bedside chest radiograph (Fig 1) showed low lung volumes, a mildly enlarged main pulmonary artery, and a small pleural effusion on the right side. Although parenchymal opacities were present in bilateral lower lung zones, which may have represented atelectasis, the extent of parenchymal involvement was discordant with the degree of hypoxemia and suggested a nonparenchymal site of disease.
Pulmonary perfusion imaging with 99mTc macroaggregated albumin showed small bilateral pleural effusions (eg, the fissure sign) and extrapulmonary uptake in both kidneys (Fig 2). The presence of extrapulmonary radionuclide activity indicates that the tagged macroaggregates have crossed the filter of the pulmonary capillaries as a result of an intracardiac or intrapulmonary right-to-left shunt.
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DISCUSSION
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The differential considerations of a right-to-left shunt in a patient with symptoms of hypoxemia and liver dysfunction include Eisenmenger syndrome, portopulmonary hypertension with portopulmonary vein anastomoses or a patent foramen ovale, and hepatopulmonary syndrome (HPS). Given the lack of a cardiac murmur at physical examination and the unusual symptom of platypnea (an increase in shortness of breath when in the upright position that is relieved by recumbency), the most likely, and the correct, diagnosis is HPS. This diagnosis was confirmed with conventional angiography of the right side of the heart, which did not show an intracardiac shunt, and pulmonary angiography, which revealed the characteristic intrapulmonary vascular dilatations (Fig 3).
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Figure 3. Left lower lobe pulmonary angiogram shows innumerable small vascular dilatations (arrows) that have a spongy appearance (type 1 angiographic pattern) that is associated with early venous filling.
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HPS is characterized by a clinical triad of hepatic dysfunction or portal hypertension, increased alveolar-arterial gradient when breathing room air, and intrapulmonary vascular dilatations (1,2). It is an uncommon condition that has been reported in approximately 10%–20% of candidates for liver transplantation (3). Signs and symptoms of liver disease, such as ascites, gastrointestinal tract bleeding, jaundice, and abnormal results of liver function tests, constitute the most common clinical signs of HPS. In approximately 20% of affected patients, dyspnea is the initial symptom, as occurred in this patient (4). Although HPS may be associated with either acute or chronic liver disease, the majority of affected patients have cirrhosis of any cause and portal hypertension (1).
The most striking findings at physical examination are cyanosis and clubbing of the digits in patients with severe hypoxemia. Findings at physical examination of the chest are usually unremarkable. Platypnea and orthodeoxia (reduction in partial pressure of oxygen when changing from a supine to an upright position) may be elicited in the majority of patients with HPS (4).
Injection of micro-opaque gelatin into pulmonary arteries in autopsy specimens with HPS has documented the presence of precapillary pulmonary vascular dilatations and direct arteriovenous communications (5). These intrapulmonary vascular abnormalities are believed to be caused by an excess production of vasodilators, with nitric oxide as the most likely mediator (1). Hypoxemia results from a combination of ventilation and perfusion mismatching, oxygen diffusing limitation, and intrapulmonary shunting (6). Because the vascular abnormalities predominate in the middle and lower lung zones, patients experience worsening hypoxemia when moving from the supine to the erect position, as blood flow to the more severely involved lung regions increases (7).
The characteristic finding of HPS on chest radiographs is medium-sized nodular or reticulonodular opacities that occur predominantly in the bases of the lungs (8). These opacities likely represent either individual or multiple dilated vessels and have been reported in 46%–100% of affected patients (8). Mild cardiomegaly and enlargement of central pulmonary arteries may be associated findings (8).
On computed tomographic (CT) scans, the vascular dilatations are depicted as enlarged vessels that do not taper normally, extend to the pleural surface, and are most numerous in the bases of the lungs (8). By using measurements obtained with thin-section CT, Lee et al (9) found that the ratio of segmental arterial diameter to bronchial diameter in the right lower lobe of the lung is substantially higher in patients with HPS than in those with normoxemic liver cirrhosis. In addition, peripheral pulmonary vessel diameter was found to have a significant inverse correlation with measured partial pressure of oxygen (r = -0.91, P = .001) (9).
Lung perfusion imaging with 99mTc macroaggregated albumin can be used both in the detection of a right-to-left shunt and in the quantification of the degree of the shunt. In patients with normal pulmonary vasculature, nearly all the radioactive particles—which typically range in size from 20 to 50 µm—lodge in the pulmonary vascular bed, since pulmonary capillaries are only 8–15 µm in diameter (10). The presence of intrapulmonary vascular dilatations in patients with HPS allows passage of the radiolabeled macroaggregated albumin into the systemic circulation and results in the characteristic appearance of extrapulmonary uptake. Several studies that have evaluated prognostic factors in patients with HPS have shown that mortality is associated with higher shunt fractions, as measured with 99mTc macroaggregated albumin perfusion imaging (11–13).
Contrast material–enhanced echocardiography is considered to be the standard in the diagnosis of HPS (1,7). In this examination, 10 mL of agitated saline is injected into the right atrium. In patients with normal pulmonary vasculature, the microbubbles become lodged in the pulmonary circulation and are absorbed. The appearance of microbubbles in the left side of the heart indicates a right-to-left shunt. When bubbles appear in the left atrium or left ventricle immediately after they appeared in the right atrium, this finding is consistent with an intracardiac shunt. When bubbles appear in the left side of the heart three to four beats after they appeared in the right atrium, this finding is consistent with an intrapulmonary shunt. Contrast-enhanced echocardiography was attempted in this patient after the right-to-left shunt was discovered on perfusion images; however, the echocardiogram was suboptimal, and we were not able to differentiate between an intracardiac versus an intrapulmonary shunt.
The angiographic findings of HPS vary in severity (1,2,14). In the type 1 angiographic pattern, the pulmonary angiogram may appear normal; show diffuse, small spiderlike branches; or, if the disease is more advanced, appear spongy or blotchy and be associated with early venous filling (2,14) (Fig 3). The less common type 2 angiographic pattern consists of frank arteriovenous communications or malformations (2,14).
The natural history of HPS is not well described because of a lack of prospective studies. In one retrospective study of 22 patients, nine (41%) died within a mean time of 2.5 years after the onset of dyspnea (4). To our knowledge, no medical therapies have been shown to be effective in the treatment of this syndrome. Embolization of distinct arteriovenous malformations may improve oxygenation; however, this effect is often temporary, as additional lesions develop months or years later (15). Liver transplantation is the only therapeutic option of proved benefit, and it can result in total resolution or substantial improvement in postoperative gas exchange abnormalities (1,16). Progressive hypoxemia is currently considered an indication for transplantation in both children and adults (16).
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FOOTNOTES
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Part 1 of this case appeared 4 months previously and may contain larger images.
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REFERENCES
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- Fallon MB, Abrams GA. Hepatopulmonary syndrome. Curr Gastroenterol Rep 2000; 2:40-45.[Medline]
- Krowka MJ, Cortese DA. Hepatopulmonary syndrome: current concepts in diagnostic and therapeutic considerations. Chest 1994; 105:1528-1537.[Free Full Text]
- Krowka MJ. Caveats concerning hepatopulmonary syndrome. J Hepatol 2001; 34:756-758.[CrossRef][Medline]
- Krowka MJ, Dickson ER, Cortese DA. Hepatopulmonary syndrome: clinical observations and lack of therapeutic response to somatostatin analogue. Chest 1993; 104:515-521.[Abstract/Free Full Text]
- Berthelot P, Walker JG, Sherlock S, Reid L. Arterial changes in the lungs in cirrhosis of the liver: lung spider nevi. N Engl J Med 1966; 274:291-298.
- Krowka MJ, Porayko MK, Plevak DJ, et al. Hepatopulmonary syndrome with progressive hypoxemia as an indication for liver transplantation: case reports and literature review. Mayo Clin Proc 1997; 72:44-53.[Medline]
- Scott VL, Dodson SF, Kang Y. The hepatopulmonary syndrome. Surg Clin North Am 1999; 79:23-41.[CrossRef][Medline]
- McAdams HP, Erasmus J, Crockett R, Mitchell J, Godwin JD, McDermott VG. The hepatopulmonary syndrome: radiologic findings in 10 patients. AJR Am J Roentgenol 1996; 166:1379-1385.[Abstract/Free Full Text]
- Lee KN, Lee HJ, Shin WW, Webb WR. Hypoxemia and liver cirrhosis (hepatopulmonary syndrome) in eight patients: comparison of the central and peripheral pulmonary vasculature. Radiology 1999; 211:549-553.[Abstract/Free Full Text]
- Wolfe JD, Tashkin DP, Holly FE, Brachman MB, Genovesi MG. Hypoxemia of cirrhosis: detection of abnormal small pulmonary vascular channels by a quantitative radionuclide method. Am J Med 1977; 63:746-754.[CrossRef][Medline]
- Egawa H, Kasahara M, Inomata Y, et al. Long-term outcome of living related liver transplantation for patients with intrapulmonary shunting and strategy for complications. Transplantation 1999; 67:712-717.[Medline]
- Krowka MJ, Wiseman GA, Burnett OL, et al. Hepatopulmonary syndrome: a prospective study of relationships between severity of liver disease, PaO2 response to 100% oxygen, and brain uptake after (99m)Tc MAA lung scanning. Chest 2000; 118:615-624.[Abstract/Free Full Text]
- Uemoto S, Inomata Y, Egawa H, et al. Effects of hypoxemia on early postoperative course of liver transplantation in pediatric patients with intrapulmonary shunting. Transplantation 1997; 63:407-414.[CrossRef][Medline]
- Hansoti RC, Shah NJ. Cirrhosis of liver simulating congenital cyanotic heart disease. Circulation 1966; 33:71-77.[Free Full Text]
- Krowka MJ. Hepatopulmonary syndrome and extrahepatic vascular abnormalities. Liver Transpl 2001; 7:656-657.[CrossRef][Medline]
- Krowka MJ. Hepatopulmonary syndrome: recent literature (1997 to 1999) and implications for liver transplantation. Liver Transpl 2000; 6(suppl 1):31-35.
Congratulations to the 73 individuals who submitted the most likely diagnosis (hepatopulmonary syndrome) for Diagnosis Please, Case 63. The names and locations of the individuals, as submitted, are as follows:
- Simeon Abramson, Boston, Mass
- Gholamali Afshang, MD, Tinley Park, Ill
- Albert J. Alter, Madison, Wis
- Roger Antonelli, MD, Dayton, Ohio
- Leon Axel, PhD, MD, New York, NY
- Ken Baliga, Rockford, Ill
- James R. Barrie, Edmonton, Alberta, Canada
- Eric L. Bressler, MD, Minnetonka, Minn
- Keenan Larry Carroll, MD, Nassau, Bahamas
- Daniel M. Chernoff, MD, PhD, Saratoga Springs, NY
- Timothy Clark, MD, Greenville, NC
- Jay Colby, MD, Westerly, RI
- James W. Cole, MD, Cincinnati, Ohio
- Marco Cura, Miami Beach, Fla
- John Curtis, MRCP, FRCR, Liverpool, England, UK
- Hung Q. Dam, MD, Newark, Del
- Wagner Diniz de Paula, MD, Brasilia, Brazil
- Paul Dee, Kristiansand, Norway
- Mustafa Kemal Demir, MD, Ataköy, Istanbul, Turkey
- María Jesús Díaz Candamio, La Coruña, Spain
- Ricardo B. Fonseca, MD, São Paulo, Brazil
- Irwin M. Freundlich, MD, Tucson, Ariz
- Thomas C. Hoffer, MD, El Paso, Tex
- J. Hurst, MD, York, Pa
- Dany Jasinowodolinski, MD, São Paulo, Brazil
- Sanjeeva Prasad Kalva, MD, Boston, Mass
- Patrick Kiely, FRCR, FFR(RCSI), Limerick, Ireland
- Eric Kinder, MD, Seattle, Wash
- Takuji Kiryu, MD, Gifu, Japan
- Mitchell A. Klein, MD, Milwaukee, Wis
- Masashi Koyama, Aichi, Japan
- Stefanos Lachanis, MD, Athens, Greece
- Mario Laguna, West Allis, Wis
- Donald R. Lewis, Jr, MD, Huntington, WV
- N. B. S. Mani, MD, Nassau, Bahamas
- Ingrid A. Mayer, MD, São Paulo, Brazil
- Edward Menges, MD, Aptos, Calif
- Michael P. Meyers, MD, FRCPC, Winnipeg, Manitoba, Canada
- Manabu Minami, MD, Tokyo, Japan
- Eduardo Mondello, MD, Buenos Aires, Argentina
- Tammam Nehme, Milwaukee, Wis
- Mike O’Loughlin, MD, West Hartford, Conn
- Sanford M. Ornstein, MD, Phoenix, Ariz
- Ann Owen, MD, Murfreesboro, Tenn
- David M. Panicek, MD, New York, NY
- Harish Panicker, MD, Washington, DC
- Panagiotis N. Papanagiotou, Larissa, Greece
- Narendrakumar P. Patel, MD, Newburgh, NY
- M. P. Pliego, MD, Bloomington, Minn
- Shawn P. Quillin, MD, Charlotte, NC
- Dr. T. N. Anuradha Rao, Toronto, Ontario, Canada
- Danny Rappaport, Etobicoke, Ontario, Canada
- James Ravenel, MD, Charleston, SC
- Enrique Remartinez Escobar, MD, Melilla, Spain
- Pierre J. Sauvage, MD, Mâcon, France
- Mustafa Secil, MD, Izmir, Turkey
- Sumit Seth, Columbus, Ohio
- Matt Shapiro, MD, Staunton, Va
- Darrin S. Smith, MD, Fresno, Calif
- Mladen Sostaric, Brezice, Slovenia
- Paul Stark, MD, La Jolla, Calif
- Kouichi Sugiyama, Hamamatsu, Japan
- Satoru Takahashi, Osaka, Japan
- Douglas L. Teich, MD, Brookline, Mass
- Meriç Tüzün, Ankara, Turkey
- Christopher Vittore, MD, Rockford, Ill
- Zhen Jane Wang, MD, San Francisco, Calif
- Richard Wasley, MD, Laguna Hills, Calif
- Jeff West, MD, Jacksonville, Fla
- Dr. Hulya Wieshmann, Liverpool, England, UK
- Benjamin M. Yeh, MD, San Francisco, Calif
- Joe Yut, Olathe, Kan
- Jeffrey H. Zapolsky, MD, Oshkosh, Wis
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TOP
HISTORY
IMAGING FINDINGS
