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 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. This comment refers to the article available at doi:10.1007/s00535013-0841-y.