Observational Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jun 7, 2019; 25(21): 2665-2674
Published online Jun 7, 2019. doi: 10.3748/wjg.v25.i21.2665
Management of betablocked patients after sustained virological response in hepatitis C cirrhosis
Marta Abadía, María Luisa Montes, Dolores Ponce, Consuelo Froilán, Miriam Romero, Joaquín Poza, Teresa Hernández, Rubén Fernández-Martos, Antonio Olveira, on behalf of the “La Paz Portal Hypertension” Study Group Investigators
Marta Abadía, Consuelo Froilán, Miriam Romero, Joaquín Poza, Rubén Fernández-Martos, Antonio Olveira, Servicio de Aparato Digestivo, Hospital Universitario La Paz, Madrid 28046, Spain
María Luisa Montes, Unidad VIH, Servicio de Medicina Interna, Hospital Universitario La Paz, Madrid 28046, Spain
Dolores Ponce, Teresa Hernández, Servicio de Radiología, Hospital Universitario La Paz, Madrid 28046, Spain
Author contributions: Abadía M, Montes ML, and Olveira A designed the research; Abadía M, Montes ML, Ponce D, Froilán C, Romero M, Poza J, Hernández T, Fernández-Martos R, Olveira A and the remaining “La Paz Portal Hypertension” Study Group Investigators (Castillo P, Erdozain JC, García-Samaniego J, González J, Gonzalo N, García A, Marín E, Martín-Carbonero L, Mora P, Novo J, Fernández-Rodríguez L, Valencia E) performed the research; Abadía M, Montes ML, Froilán C, and Olveira A analyzed the data; Abadía M, Montes ML, and Olveira A wrote the paper.
Supported by RIS (Red Temática de Investigación Cooperativa en SIDA) RD16/0025/0018 (translation and statistical analysis);the RIS is funded by the Instituto de Salud Carlos III as part of the Plan Nacional R + D + I and cofinanced by ISCIII-Subdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER).
Institutional review board statement: The study was reviewed and approved by the Human Research and Ethics Committee at Hospital Universitario La Paz (Madrid).
Informed consent statement: Written informed consent was obtained from each patient included in the study.
Conflict-of-interest statement: The authors have no conflict of interest to declare.
STROBE statement: The authors have read the STROBE Statement—checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Marta Abadía, MD, Doctor, Servicio de Aparato Digestivo, Hospital Universitario La Paz, Paseo de La Castellana 261, Madrid 28046, Spain. mabadiab@gmail.com
Telephone: +34-646388528 Fax: +34-912071466
Received: February 17, 2019
Peer-review started: February 18, 2019
First decision: March 5, 2019
Revised: March 13, 2019
Accepted: March 24, 2019
Article in press: March 25, 2019
Published online: June 7, 2019
Research background

Baveno VI Consensus addresses management of patients without baseline oesophageal varices, or with small varices, in whom aetiological factor has been removed. No recommendation is given in those under betablockers. Main Liver Associations Guidelines on this topic simply refer to Baveno.

Research motivation

Future research in this field should confirm our results in a larger number of patients. Alternative aetiologies, not only hepatitis C virus (HCV) cirrhosis, should be explored.

Research objectives

We tried to satisfy a real-life, unmet situation: how to manage betablockers in our patients after sustained virological response (SVR).

Research methods

All our study patients were recruited from our clinic. Baseline data [before direct-acting antivirals (DAA) treatment] were collected and checked against evolutionary data after SVR. As a novelty, endoscopy variceal size was confronted to hepatic venous pressure gradient having in mind endoscopy has been advocated by some authors to be a reliable tool after SVR. Transient elastography was also challenged in this SVR setting.

Research results

After more than one year of SVR, 39% of our patients evolved below the oesophageal bleeding threshold. The only predictable factor of this favourable evolution was a drop of at least 1 point in Model for End-Stage Liver Disease score. Transient elastography and endoscopy did not confidently detect this change. In those patients below 12 mmHg, permanently stopping betablockers was safe as no bleeding episode has appeared after more than one year of follow-up. Main remaining problem is the evolution of those patients still above 12 mmHg. Portal hypertension regression seems to be a dynamic condition after SVR. Therefore, some of them could still evolve satisfactorily in future evaluations but others could have reached a point of no return.

Research conclusions

After more than one year of SVR, 39% of patients with baseline HCV cirrhosis and oesophageal varices under prophylactic betablockers are below the bleeding threshold. Transient elastography and endoscopy are unreliable in this setting. Permanently stopping betablockers seems to be safe in those below 12 mmHg. Evolution of portal hypertension after SVR in the subgroup of patients under betablocker treatment. Unreliability of transient elastography and endoscopy in this setting. Safety of permanently stopping betablockers in those below 12 mmHg. Portal hypertension can regress even in those with the more severe condition, making prophylaxis with betablockers unnecessary. Several studies recently characterize portal hypertension evolution in the new scenario of easy-to-reach SVR after interferon-free DAA treatment. Data on the evolution of portal hypertension and its management in those patients with the more severe condition (i.e., under betablockers) were lacking. Betablockers can be permanently stopped in those below 12 mmHg after SVR. Non-invasive assessment of post-SVR bleeding threshold is not reliable. Portal hypertension in those with the more severe condition is a dynamic regressive process with a clinical benefit for patients. Severe portal hypertension regresses in some patients and betablockers can be safely stopped. Endoscopy and transient elastography are not reliable assessing post-SVR bleeding risk. Betablockers can be safely discontinued in those below 12 mmHg.

Research perspectives

Do not trust non-invasive assessment of bleeding risk after SVR. Reliable tools for non-invasive assessment of bleeding risk after removal of aetiological factor. We presume combinatory algorithm with liver and spleen elastographies. Perhaps ultrasound-based contrast-enhanced arrival time to hepatic vein.