Liver International ISSN 1478-3223
Letters to the Editor DOI:10.1111/liv.12810 Liver Int. 2015; 35: 1918–1919
The role of macroaggregated albumin lung perfusion scan in hepatopulmonary syndrome: are we ready to draw conclusions? To the Editor: We read with interest the review by Raevens et al. (1) on hepatopulmonary syndrome (HPS) and portopulmonary hypertension. The diagnosis of HPS requires the presence of liver disease, intrapulmonary vascular dilatation (IPVD) and arterial oxygenation defect. Contrast-enhanced echocardiography (CEE) and technetium-99m-labelled macroaggregated albumin (MAA) lung perfusion scan were both wellaccepted methods for detecting IPVD. Nonetheless, in recent reviews MAA scan was only considered as a complementary tool (1, 2). The diminishing role of MAA scan was in large part due to inferior diagnostic accuracy revealed in previous studies (3–5). However, we believe the exact role of MAA scan could not be defined based on the current literature. Two main techniques have been used to determine the shunt fraction from MAA scans, including wholebody uptake and brain uptake. In the former, shunt fraction is calculated based on the technetium uptake in the entire body outside the lungs, whereas the latter is based on uptake in the brain, which is assumed to receive 13% of the cardiac output (4). Although whole-body uptake is more widely recognized in nuclear medicine, brain uptake was recommended for HPS (2), because whole-body scans take considerable time and may be associated with increased risk of overestimating the shunt fraction as a result of MAA particles breaking down. However, the diagnostic accuracy of these two techniques has not been compared directly. In addition, the technical aspects which could potentially influence the diagnostic accuracy (i.e., MAA particle size, body position during MAA injection and scanning protocol) have also not been standardized on basis of trials. Previous studies have shown that MAA scan has very high specificity but the sensitivity varied widely from 20 to 96% (3–5). These results have been attributed to operator-dependent aspects and the shunt fraction cut-off value of 6%, which was derived from only ten healthy subjects (4). However, we noted that the severity of HPS based on partial pressure of oxygenation (PaO2) appears to have an influence on the brain uptake. After combining the data from the most influential studies (3–5), we found that the sensitivity of MAA scan was virtually 100% (42/44) in patients with
1918
Fig. 1. Relationship between shunt fraction and PaO2.
severe and very severe HPS, whereas it was only 23.8% (5/21) in those with mild and moderate HPS (Fig. 1). In summary, further studies are warranted to standardize MAA scan and comprehend the influence of the severity of HPS on diagnostic accuracy. Acknowledgements
Financial support: This article was made possible by the National Natural Science Fund of China (Grant No. 81371656 to X.L.) and Science and Technology Support Program of Sichuan Province (Grant No. 2014SZ0002-7 to X.L.). Conflict of interest: The authors do not have any disclosures to report. He Zhao1,2, Jiaywei Tsauo1,3, Huai Y. Ma1,2, Xiao Li1 1 Institute of Interventional Radiology, West China Hospital, Sichuan University, Chengdu, Sichuan, China 2 Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, Sichuan, China 3 Department of Radiology, West China Hospital, Sichuan University, Chengdu, Sichuan, China
References 1. Raevens S, Geerts A, Van Steenkiste C, et al. Hepatopulmonary syndrome and portopulmonary hypertension:
Liver International (2015) © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Zhao et al.
recent knowledge in pathogenesis and overview of clinical assessment. Liver Int 2015; 35: 1646–60. 2. Machicao VI, Balakrishnan M, Fallon MB. Pulmonary complications in chronic liver disease. Hepatology (Baltimore, MD) 2014; 59: 1627–37. 3. Abrams GA, Jaffe CC, Hoffer PB, Binder HJ, Fallon MB. Diagnostic utility of contrast echocardiography and lung perfusion scan in patients with hepatopulmonary syndrome. Gastroenterology 1995; 109: 1283–8.
Letters to the Editor
4. Abrams GA, Nanda NC, Dubovsky EV, Krowka MJ, Fallon MB. Use of macroaggregated albumin lung perfusion scan to diagnose hepatopulmonary syndrome: a new approach. Gastroenterology 1998; 114: 305–10. 5. Krowka MJ, Wiseman GA, Burnett OL, et al. Hepatopulmonary syndrome: a prospective study of relationships between severity of liver disease, PaO(2) response to 100% oxygen, and brain uptake after (99 m)Tc MAA lung scanning. Chest 2000; 118: 615–24.
DOI:10.1111/liv.12821 Liver Int. 2015; 35: 1919–1920
Response to ‘The role of macroaggregated albumin lung perfusion scan in hepatopulmonary syndrome: are we ready to draw conclusions?’ To the Editor: We appreciate the comments of Zhao et al. (1) on the topic of the current use of technetium 99 mlabelled macroaggregated albumin (MAA) lung scan for detecting intrapulmonary vascular dilations (IPVDs) as a criterion for detecting hepatopulmonary syndrome (HPS). As mentioned in our review (2), the presence of IPVDs is documented either on microbubble transthoracic echocardiography (MTTE) or MAA scan. Clinical recommendations on screening for HPS were mainly based on the European Respiratory Society Task Force guideline (3). MTTE has always been considered the gold standard for detecting HPS based on clinical studies. Important advantages include (i) its high sensitivity to detect IPVDs; (ii) its possibility to distinguish intrapulmonary from intracardiac shunting and (iii) the additional possibility of screening for portopulmonary hypertension (2–4). On the other hand, HPS can be diagnosed and the degree of shunting can even be quantified on MAA scan (2–4). However, this technique cannot distinguish between intrapulmonary and intracardiac shunting, and has been proven to be associated with lower sensitivity (3). Accordingly, the severity of HPS based on PaO2 is negatively correlated with the degree of brain uptake during MAA scan, as was nicely illustrated in figure 1 by Zhao et al. (1), by summarizing the patient data of earlier performed studies by Abrams et al. and Krowka et al. Indeed, patients with mild-tomoderate hypoxia are those patients with rather small or few IPVDs and shunts, resulting in lower brain uptake. We agree with the comment that the technical aspects of MAA scan lack standardization, which indeed affects its diagnostic accuracy (1). To address this issue, further prospective studies are certainly warranted. However, MAA scan yields important clinical information in specific situations. First, it has to be performed in severe hypoxic patients with underlying intrinsic lung
Liver International (2015) © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
disease and suspected HPS (4). Significant brain uptake on MAA scan provides indirect evidence of HPS contributing to the hypoxic status. Second, MAA scan may offer complementary information to stratify HPS patients at greater risk of post-transplantation mortality (shunt fraction ≥20%) (4). Third, in case of extensive shunting, suggesting large arteriovenous connections, HPS patients should be referred for pulmonary angiography in order to plan coil embolization (4). In summary, current hepatology guidelines recommend microbubble transthoracic echocardiography as best screening tool to detect HPS. However, in specific clinical situations MAA scan may offer essential complementary information. Further prospective studies are needed to standardize the MAA scan technique. Acknowledgements
Financial support: Sarah Raevens received a scholarship (FWO14/ASP/200) from the Research Foundation – Flanders (Aspirant mandaat FWO Vlaanderen). Conflict of interest: The authors do not have any disclosures to report.
Sarah Raevens1, Christophe Van Steenkiste1,2 and Isabelle Colle1,3 1 Department of Gastroenterology and Hepatology, Ghent University Hospital, Ghent, Belgium 2 Department of Gastroenterology and Hepatology, Maria Middelares Hospital, Ghent, Belgium 3 Department of Gastroenterology and Hepatology, Algemeen Stedelijk Ziekenhuis ASZ, Aalst, Belgium
References 1. Zhao H, Tsauo J, Ma HY, Li X. The role of macroaggregated albumin lung perfusion scan in hepatopulmonary
1919
Letters to the Editor DOI:10.1111/liv.12810 Liver Int. 2015; 35: 1918–1919
The role of macroaggregated albumin lung perfusion scan in hepatopulmonary syndrome: are we ready to draw conclusions? To the Editor: We read with interest the review by Raevens et al. (1) on hepatopulmonary syndrome (HPS) and portopulmonary hypertension. The diagnosis of HPS requires the presence of liver disease, intrapulmonary vascular dilatation (IPVD) and arterial oxygenation defect. Contrast-enhanced echocardiography (CEE) and technetium-99m-labelled macroaggregated albumin (MAA) lung perfusion scan were both wellaccepted methods for detecting IPVD. Nonetheless, in recent reviews MAA scan was only considered as a complementary tool (1, 2). The diminishing role of MAA scan was in large part due to inferior diagnostic accuracy revealed in previous studies (3–5). However, we believe the exact role of MAA scan could not be defined based on the current literature. Two main techniques have been used to determine the shunt fraction from MAA scans, including wholebody uptake and brain uptake. In the former, shunt fraction is calculated based on the technetium uptake in the entire body outside the lungs, whereas the latter is based on uptake in the brain, which is assumed to receive 13% of the cardiac output (4). Although whole-body uptake is more widely recognized in nuclear medicine, brain uptake was recommended for HPS (2), because whole-body scans take considerable time and may be associated with increased risk of overestimating the shunt fraction as a result of MAA particles breaking down. However, the diagnostic accuracy of these two techniques has not been compared directly. In addition, the technical aspects which could potentially influence the diagnostic accuracy (i.e., MAA particle size, body position during MAA injection and scanning protocol) have also not been standardized on basis of trials. Previous studies have shown that MAA scan has very high specificity but the sensitivity varied widely from 20 to 96% (3–5). These results have been attributed to operator-dependent aspects and the shunt fraction cut-off value of 6%, which was derived from only ten healthy subjects (4). However, we noted that the severity of HPS based on partial pressure of oxygenation (PaO2) appears to have an influence on the brain uptake. After combining the data from the most influential studies (3–5), we found that the sensitivity of MAA scan was virtually 100% (42/44) in patients with
1918
Fig. 1. Relationship between shunt fraction and PaO2.
severe and very severe HPS, whereas it was only 23.8% (5/21) in those with mild and moderate HPS (Fig. 1). In summary, further studies are warranted to standardize MAA scan and comprehend the influence of the severity of HPS on diagnostic accuracy. Acknowledgements
Financial support: This article was made possible by the National Natural Science Fund of China (Grant No. 81371656 to X.L.) and Science and Technology Support Program of Sichuan Province (Grant No. 2014SZ0002-7 to X.L.). Conflict of interest: The authors do not have any disclosures to report. He Zhao1,2, Jiaywei Tsauo1,3, Huai Y. Ma1,2, Xiao Li1 1 Institute of Interventional Radiology, West China Hospital, Sichuan University, Chengdu, Sichuan, China 2 Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, Sichuan, China 3 Department of Radiology, West China Hospital, Sichuan University, Chengdu, Sichuan, China
References 1. Raevens S, Geerts A, Van Steenkiste C, et al. Hepatopulmonary syndrome and portopulmonary hypertension:
Liver International (2015) © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Zhao et al.
recent knowledge in pathogenesis and overview of clinical assessment. Liver Int 2015; 35: 1646–60. 2. Machicao VI, Balakrishnan M, Fallon MB. Pulmonary complications in chronic liver disease. Hepatology (Baltimore, MD) 2014; 59: 1627–37. 3. Abrams GA, Jaffe CC, Hoffer PB, Binder HJ, Fallon MB. Diagnostic utility of contrast echocardiography and lung perfusion scan in patients with hepatopulmonary syndrome. Gastroenterology 1995; 109: 1283–8.
Letters to the Editor
4. Abrams GA, Nanda NC, Dubovsky EV, Krowka MJ, Fallon MB. Use of macroaggregated albumin lung perfusion scan to diagnose hepatopulmonary syndrome: a new approach. Gastroenterology 1998; 114: 305–10. 5. Krowka MJ, Wiseman GA, Burnett OL, et al. Hepatopulmonary syndrome: a prospective study of relationships between severity of liver disease, PaO(2) response to 100% oxygen, and brain uptake after (99 m)Tc MAA lung scanning. Chest 2000; 118: 615–24.
DOI:10.1111/liv.12821 Liver Int. 2015; 35: 1919–1920
Response to ‘The role of macroaggregated albumin lung perfusion scan in hepatopulmonary syndrome: are we ready to draw conclusions?’ To the Editor: We appreciate the comments of Zhao et al. (1) on the topic of the current use of technetium 99 mlabelled macroaggregated albumin (MAA) lung scan for detecting intrapulmonary vascular dilations (IPVDs) as a criterion for detecting hepatopulmonary syndrome (HPS). As mentioned in our review (2), the presence of IPVDs is documented either on microbubble transthoracic echocardiography (MTTE) or MAA scan. Clinical recommendations on screening for HPS were mainly based on the European Respiratory Society Task Force guideline (3). MTTE has always been considered the gold standard for detecting HPS based on clinical studies. Important advantages include (i) its high sensitivity to detect IPVDs; (ii) its possibility to distinguish intrapulmonary from intracardiac shunting and (iii) the additional possibility of screening for portopulmonary hypertension (2–4). On the other hand, HPS can be diagnosed and the degree of shunting can even be quantified on MAA scan (2–4). However, this technique cannot distinguish between intrapulmonary and intracardiac shunting, and has been proven to be associated with lower sensitivity (3). Accordingly, the severity of HPS based on PaO2 is negatively correlated with the degree of brain uptake during MAA scan, as was nicely illustrated in figure 1 by Zhao et al. (1), by summarizing the patient data of earlier performed studies by Abrams et al. and Krowka et al. Indeed, patients with mild-tomoderate hypoxia are those patients with rather small or few IPVDs and shunts, resulting in lower brain uptake. We agree with the comment that the technical aspects of MAA scan lack standardization, which indeed affects its diagnostic accuracy (1). To address this issue, further prospective studies are certainly warranted. However, MAA scan yields important clinical information in specific situations. First, it has to be performed in severe hypoxic patients with underlying intrinsic lung
Liver International (2015) © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
disease and suspected HPS (4). Significant brain uptake on MAA scan provides indirect evidence of HPS contributing to the hypoxic status. Second, MAA scan may offer complementary information to stratify HPS patients at greater risk of post-transplantation mortality (shunt fraction ≥20%) (4). Third, in case of extensive shunting, suggesting large arteriovenous connections, HPS patients should be referred for pulmonary angiography in order to plan coil embolization (4). In summary, current hepatology guidelines recommend microbubble transthoracic echocardiography as best screening tool to detect HPS. However, in specific clinical situations MAA scan may offer essential complementary information. Further prospective studies are needed to standardize the MAA scan technique. Acknowledgements
Financial support: Sarah Raevens received a scholarship (FWO14/ASP/200) from the Research Foundation – Flanders (Aspirant mandaat FWO Vlaanderen). Conflict of interest: The authors do not have any disclosures to report.
Sarah Raevens1, Christophe Van Steenkiste1,2 and Isabelle Colle1,3 1 Department of Gastroenterology and Hepatology, Ghent University Hospital, Ghent, Belgium 2 Department of Gastroenterology and Hepatology, Maria Middelares Hospital, Ghent, Belgium 3 Department of Gastroenterology and Hepatology, Algemeen Stedelijk Ziekenhuis ASZ, Aalst, Belgium
References 1. Zhao H, Tsauo J, Ma HY, Li X. The role of macroaggregated albumin lung perfusion scan in hepatopulmonary
1919
