Noninvasive diagnosis of portal hypertension and esophageal varices through the identification of liver blood flow markers


  • Potential conflict of interest: Nothing to report.

To the Editor:

We read with great interest the article entitled “Use of noninvasive markers of portal hypertension and timing of screening endoscopy for gastroesophageal varices in patients with chronic liver disease”[1] in which the authors, Dr. Annalisa Berzigotti and Prof. Jaime Bosch, describe the usefulness of noninvasive tools for the diagnosis of clinically significant portal hypertension (CSPH, hepatic vein pressure gradient [HVPG] ≥10 mmHg) and esophageal varices (EV).

The most recent guidelines[2] on portal hypertension strongly suggest performing upper endoscopy and, where available, HVPG measurement in all patients with liver cirrhosis. Moreover, endoscopy should be repeated every 2-3 years in patients without esophageal varices and more frequently (according to bleeding risk) in patients with EV. As recognized by Berzigotti et al.,[1] this screening and follow-up program leads to significant healthcare costs and patient discomfort since cirrhosis is, nowadays, frequently diagnosed in a very initial stage when varices are still absent. Therefore, in the near future the selection of high-risk patients represents a clinical challenge for the hepatologist in order to reduce futile examinations, the related costs, and the patients' burden.

We strongly agree with the idea of sparing HVPG measurement and endoscopy in patients with less than 20% probability of CSPH based on the combination of noninvasive tests and to perform it in the remaining patients with higher pretest probability. As the authors correctly point out, a number of noninvasive tests based on liver elastography (alone or combined with other parameters) or on spleen stiffness can help to reliably rule out and diagnose CSPH.

Besides the above-mentioned noninvasive tests, we would like to remember the Indocyanine Green Retention Test (ICG-r15), which is a quantitative function test reflecting liver functional reserve and blood flow. Among patients with initial cirrhosis and well-preserved liver function, ICG-r15 correlates with the presence, degree, and complication of portal hypertension, reflecting the modifications of liver blood flow.

We recently evaluated ICG-r15 as a noninvasive marker of CSPH and EV in a population of 96 consecutive patients with compensated liver cirrhosis of different etiologies[3]; in our study an ICG-r15 <10% correctly ruled out the presence of varices in 26 out 27 patients. Therefore, the good diagnostic performance of ICG-r15 (Table 1) makes it a valid tool for the assessment of PH and EV in cirrhosis patients. Although these results have to be validated in a larger or multicentric population and confirmed by longitudinal analysis, this simple and reproducible test allows an initial stratification of cirrhosis patients.

Table 1. Diagnostic Performance of Indocyanine Green 15 Minutes Retention Test for the Rule-Out of Clinically Significant Portal Hypertension and Esophageal Varices
 No.Prediction of CSPH (HVPG ≥ 10 mmHg)Prediction of EV
  1. CSPH: Clinically Significant Portal Hypertension; EV: Esophageal Varices; ICG-r15: Indocyanine Green retention at 15 minutes; AUROC: area under ROC curve; −LR: negative likelihood ratio.


In conclusion, we definitely agree with the authors on the need to spare unnecessary HVPG and upper endoscopies in this clinical setting and suggest that ICG-r15 might be another test to consider besides those based on transient elastography or liver stiffness, particularly in centers where these technologies are not available.

  • Andrea Lisotti, M.D. Francesco Azzaroli, M.D. Marco Montagnani, M.D. Giuseppe Mazzella, M.D., Ph.D.

  • Department of Medical and Surgical Science University of Bologna S. Orsola-Malpighi Hospital Bologna, Italy