J Gastroenterol DOI 10.1007/s00535-014-0935-1
LETTER TO THE EDITOR
Correlation between Indocyanine green retention test and esophageal varices among patients with hepatocellular carcinoma Andrea Lisotti • Francesco Azzaroli • Marco Montagnani • Alberto Porro • Giuseppe Mazzella
Received: 20 August 2013 / Accepted: 22 August 2013 Ó Springer Japan 2014
Keywords Esophageal varices Upper endoscopy Cirrhosis Bleeding Decompensation
Dear Editor, We recently read with great interest the manuscript entitled ‘‘Prophylactic impact of endoscopic treatment for esophageal varices in liver resection: a prospective study’’ [1] in which Dr. Yamazaki et al. demonstrated the usefulness of endoscopic prophylactic treatment of esophageal varices (EV) and evaluated different risk factors for post-operative progression and bleeding. The authors observed that in patients with hepatocellular carcinoma (HCC), various laboratory variables were significantly different according to the presence or absence of EV; for example, indocyanine green (ICG) retention rate at 15 min (ICG-r15) was 10.9 % (2.1–37.7) in patients
This comment refers to the article available at doi:10.1007/s00535013-0841-y. A. Lisotti (&) F. Azzaroli M. Montagnani A. Porro G. Mazzella Department of Medical and Surgical Science, DIMEC, S.Orsola-Malpighi Hospital, University of Bologna, via Massarenti 9, 40138 Bologna, Italy e-mail: [email protected] F. Azzaroli e-mail: [email protected] M. Montagnani e-mail: [email protected] A. Porro e-mail: [email protected] G. Mazzella e-mail: [email protected]
without EV and 15.4 % (3.7–46.0) in patients with EV (P \ 0.001). Finally, they observed that ICG-r15 [ 30 % is independently correlated with the risk of worsening varices. We recently reported our experience [2] aimed to evaluate ICG 15-min retention test as a non-invasive marker of PH and EV in patients with compensated liver cirrhosis in which we demonstrated that among patients with well-preserved liver function, ICG retention tests indirectly correlate with the presence and degree of portal hypertension and its complications (EV). According to the observations of Dr. Yamazaki et al., ICG-r15 correlated with the presence of esophageal varices; we found two different ICG-r15 cut-off points able to accurately rule out and rule in the presence of EV (\10 % and C22.9 %, respectively). Liver-mediated uptake of organic anions (drugs or xenobiotics) is mainly mediated by organic anion transporting polypeptides (OATPs) and organic anion transporters (OATs); ICG presents a potent inhibitor effect on OATP isoforms and Na-taurocholate transporting polypeptide (NTCP). OATP1B3 and NTCP are the transporters involved in the hepatic uptake of ICG [3]. The organic anion transporter peptides (OATP) 1B1 and 1B3 are variably and progressively lost during liver carcinogenesis; a previous study performed on patients who underwent OLT because of HCC demonstrated a correlation between the loss of OATP 1B1/ 1B3 and tumor morphological features [4]. These molecular findings could, in our opinion, justify the higher ICG-r15 values observed by Dr. Yamazaki et al. in their population. Indeed, the ICG retention test, among patients with liver cirrhosis, represents both liver parenchymal reserve and hepatic blood flow; in patients with HCC, this interplay is altered by the introduction of a third variable (cancer biology) and could not be argued.
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J Gastroenterol Conflict of interest The authors declare that they have no conflict of interest. We received no financial support or grant for the preparation of this manuscript.
References 1. Yamazaki S, Takayama T, Nakamura M, et al. Prophylactic impact of endoscopic treatment for esophageal varices in liver resection: a prospective study. J Gastroenterol. 2013. doi:10.1007/s00535-0130841-y (epub ahead of print).
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2. Lisotti A, Azzaroli F, Buonfiglioli F, et al. Indocyanine green retention test as a non-invasive marker of portal hypertension and esophageal varices in compensated liver cirrhosis. Hepatology 2014;59(2):643–50. doi:10.1002/hep.26700. 3. de Graaf W, Ha¨usler S, Heger M, et al. Transporters involved in the hepatic uptake of (99 m)Tc-mebrofenin and indocyanine green. J Hepatol. 2011;54(4):738–45. doi:10.1016/j.jhep.2010.07.047. 4. Vasuri F, Golfieri R, Fiorentino M, et al. OATP 1B1/1B3 expression in hepatocellular carcinomas treated with orthotopic liver transplantation. Virchows Arch. 2011;459(2):141–6. doi:10. 1007/s00428-011-1099-5.
LETTER TO THE EDITOR
Correlation between Indocyanine green retention test and esophageal varices among patients with hepatocellular carcinoma Andrea Lisotti • Francesco Azzaroli • Marco Montagnani • Alberto Porro • Giuseppe Mazzella
Received: 20 August 2013 / Accepted: 22 August 2013 Ó Springer Japan 2014
Keywords Esophageal varices Upper endoscopy Cirrhosis Bleeding Decompensation
Dear Editor, We recently read with great interest the manuscript entitled ‘‘Prophylactic impact of endoscopic treatment for esophageal varices in liver resection: a prospective study’’ [1] in which Dr. Yamazaki et al. demonstrated the usefulness of endoscopic prophylactic treatment of esophageal varices (EV) and evaluated different risk factors for post-operative progression and bleeding. The authors observed that in patients with hepatocellular carcinoma (HCC), various laboratory variables were significantly different according to the presence or absence of EV; for example, indocyanine green (ICG) retention rate at 15 min (ICG-r15) was 10.9 % (2.1–37.7) in patients
This comment refers to the article available at doi:10.1007/s00535013-0841-y. A. Lisotti (&) F. Azzaroli M. Montagnani A. Porro G. Mazzella Department of Medical and Surgical Science, DIMEC, S.Orsola-Malpighi Hospital, University of Bologna, via Massarenti 9, 40138 Bologna, Italy e-mail: [email protected] F. Azzaroli e-mail: [email protected] M. Montagnani e-mail: [email protected] A. Porro e-mail: [email protected] G. Mazzella e-mail: [email protected]
without EV and 15.4 % (3.7–46.0) in patients with EV (P \ 0.001). Finally, they observed that ICG-r15 [ 30 % is independently correlated with the risk of worsening varices. We recently reported our experience [2] aimed to evaluate ICG 15-min retention test as a non-invasive marker of PH and EV in patients with compensated liver cirrhosis in which we demonstrated that among patients with well-preserved liver function, ICG retention tests indirectly correlate with the presence and degree of portal hypertension and its complications (EV). According to the observations of Dr. Yamazaki et al., ICG-r15 correlated with the presence of esophageal varices; we found two different ICG-r15 cut-off points able to accurately rule out and rule in the presence of EV (\10 % and C22.9 %, respectively). Liver-mediated uptake of organic anions (drugs or xenobiotics) is mainly mediated by organic anion transporting polypeptides (OATPs) and organic anion transporters (OATs); ICG presents a potent inhibitor effect on OATP isoforms and Na-taurocholate transporting polypeptide (NTCP). OATP1B3 and NTCP are the transporters involved in the hepatic uptake of ICG [3]. The organic anion transporter peptides (OATP) 1B1 and 1B3 are variably and progressively lost during liver carcinogenesis; a previous study performed on patients who underwent OLT because of HCC demonstrated a correlation between the loss of OATP 1B1/ 1B3 and tumor morphological features [4]. These molecular findings could, in our opinion, justify the higher ICG-r15 values observed by Dr. Yamazaki et al. in their population. Indeed, the ICG retention test, among patients with liver cirrhosis, represents both liver parenchymal reserve and hepatic blood flow; in patients with HCC, this interplay is altered by the introduction of a third variable (cancer biology) and could not be argued.
123
J Gastroenterol Conflict of interest The authors declare that they have no conflict of interest. We received no financial support or grant for the preparation of this manuscript.
References 1. Yamazaki S, Takayama T, Nakamura M, et al. Prophylactic impact of endoscopic treatment for esophageal varices in liver resection: a prospective study. J Gastroenterol. 2013. doi:10.1007/s00535-0130841-y (epub ahead of print).
123
2. Lisotti A, Azzaroli F, Buonfiglioli F, et al. Indocyanine green retention test as a non-invasive marker of portal hypertension and esophageal varices in compensated liver cirrhosis. Hepatology 2014;59(2):643–50. doi:10.1002/hep.26700. 3. de Graaf W, Ha¨usler S, Heger M, et al. Transporters involved in the hepatic uptake of (99 m)Tc-mebrofenin and indocyanine green. J Hepatol. 2011;54(4):738–45. doi:10.1016/j.jhep.2010.07.047. 4. Vasuri F, Golfieri R, Fiorentino M, et al. OATP 1B1/1B3 expression in hepatocellular carcinomas treated with orthotopic liver transplantation. Virchows Arch. 2011;459(2):141–6. doi:10. 1007/s00428-011-1099-5.
