Reply
Authors: Andrea Lisotti, Francesco Azzaroli, Giuseppe Mazzella
Journal: Hepatology (2014)

Potential conflict of interest: Nothing to report. We read with interest the Pind et al. correspondence and thank the authors for their prompt and precise reply to our results. In our study,1 as stated in the Materials and Methods section, we performed the Indocyanine Green (ICG) retention test using multiple serum samples (before the injection and every 5′ after dye injection for 20′) and evaluated both the ICG retention rate at 15′ (ICG‐r15), half‐life (ICG‐t1/2), and disappearance rate (ICG‐k); moreover, our laboratory gave us the estimation of ICG clearance, calculated as the injected dose/AUC (area under the curve). In our preliminary evaluation, we performed the ICG retention test and compared those results to the estimated ICG‐clearance (data on file) in patients with all stages advanced liver disease.2 As confirmed by Pind et al., we observed a close correlation between these two techniques and we strongly agree with the conclusion that the two methods could be used equally. Based on these findings, we focused our evaluation on the usefulness of the noninvasive test (namely, ICG‐r15) in patients with well‐compensated liver cirrhosis; in this setting, upper endoscopy and hepatic venous pressure gradient (HVPG) measurement are recommended in all patients with newly diagnosed liver cirrhosis in order to obtain a detailed assessment of clinical signs of portal hypertension (PH) and prognostic information. ICG clearance (both the calculated true clearance, the ICG retention test, and the constant infusion technique) reflects the derangement of liver function and the hemodynamic alterations occurring in liver cirrhosis. As discussed in the text, we hypothesized that among patients with well‐preserved liver function, ICG clearance could directly reflect the alteration of liver blood flow and, indirectly, the presence and grade of PH; in order to avoid the interference of impaired liver function we included only a homogeneous group of compensated patients. Thus, the slightly better performance of ICG‐r15 for the identification of severe PH (HVPG ≥12 mmHg) than clinically significant PH (HVPG ≥10 mmHg) (AUROC 0.821 versus 0.808 in our experience; 0.836 versus 0.790 in Pind et al.) could be explained. In fact, liver disease progression is characterized by hemodynamic alterations together with functional impairment; therefore, in patients with severe PH, and also in Child‐Pugh class B‐C ones, the performance of ICG retention test, which is influenced by both of these conditions, the results are more accurate. Concerning the last suggestion, the diagnostic accuracy observed among patients with all Child‐Pugh classes is even higher than in patients with compensated diseases, with preserved function. The prevalence of PH (both clinically significant and severe) and EV in Child‐Pugh class B and C patients is higher than Child‐Pugh class A, and the higher pretest probabilities lead to higher diagnostic accuracy of the ICG retention test.3 However, in our opinion, all Child B‐C patients should undergo upper GI endoscopy in order to achieve reliable assessment and even perform prophylactic treatment (i.e., band ligation) in the case of high‐risk varices. On the other hand, to our knowledge, there are only retrospective or limited data on the prognostic value of HVPG measurement in Child‐Pugh class B and C patients. In this setting, the risk of decompensation and mortality is significantly higher and influenced mainly by liver dysfunction and concurrent phenomena (i.e., infection, renal impairment, or removal of the underlying cause of liver cirrhosis). A relevant study confirmed that the incorporation of ICG clearance (disappearance rate) into Model for Endstage Liver Disease (MELD) (MELD‐ICG score) could integrate information on blood flow to liver function and increase its accuracy as a predictor of mortality in patients with intermediate to advanced cirrhosis.4 Our future direction is the longitudinal validation of ICG‐r15 as a predictor of decompensation in patients with compensated disease. Finally, an intriguing and possible field of multicentric cooperation could be the evaluation of ICG retention test (even combined to MELD or HVPG) as a predictor of rebleeding and survival in patients with variceal bleeding, in order to evaluate the best treatment option (endoscopic band ligation ± early TIPS placement).