Observational Study
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Mar 27, 2018; 10(3): 379-387
Published online Mar 27, 2018. doi: 10.4254/wjh.v10.i3.379
Management of restless legs syndrome in chronic liver disease: A challenge for the correct diagnosis and therapy
Rita Moretti, Paola Caruso, Marzia Tecchiolli, Silvia Gazzin, Claudio Tiribelli
Rita Moretti, Paola Caruso, Marzia Tecchiolli, Neurology Clinic, Department of Medical, Surgical and Health Sciences, University of Trieste, Trieste 34149, Italy
Silvia Gazzin, Claudio Tiribelli, Italian Liver Foundation, Centro Studi Fegato, Trieste 34149, Italy
Author contributions: Moretti R, Caruso P and Gazzin S contributed to study conception and design; Moretti R, Caruso P, Tecchiolli M and Gazzin S contributed to data acquisition, data analysis and interpretation, and writing of the article; Moretti R, Caruso P, Tecchiolli M and Tiribelli C contributed to editing, reviewing and final approval of the article.
Institutional review board statement: This observational study has been reviewed by the Committee of Research of Cattinara Hospital.
Informed consent statement: Participants gave informed consent for data sharing.
Conflict-of-interest statement: No conflicting interests (commercial, personal, political, intellectual or religious interests) are related to this work. The authors do not have any conflict of interest to declare.
Data sharing statement: Technical appendix, statistical code, and dataset available from the corresponding author at moretti@units.it.
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/
Correspondence to: Rita Moretti, MD, PhD, Senior Scientist, Department of Medical, Surgical and Health Sciences, University of Trieste, Strada di Fiume 447, Trieste 34149, Italy. moretti@units.it
Telephone: +39-40-3994572 Fax: +39-40-3994284
Received: October 30, 2017
Peer-review started: October 31, 2017
First decision: December 26, 2017
Revised: December 27, 2017
Accepted: January 23, 2018
Article in press: January 23, 2018
Published online: March 27, 2018

To investigate the association between restless legs syndrome (RLS) and well-defined chronic liver disease, and the possible therapeutic options.


Two hundred and eleven patients with chronic liver disease, complaining of sleep disturbances, painful leg sensation and daily sleepiness, were included. Patients with persistent alcohol intake, recent worsening of clinical conditions, or hepatitis C virus were excluded. Diagnosis of RLS was suggested by the Johns Hopkins questionnaire and verified by fulfilling the diagnostic criteria by Allen. All patients were tested, both at baseline and during follow-up, with the Hamilton rating scale for depression, sleep quality assessment (PSQI), Epworth sleepiness scale (ESS), International Restless Legs Syndrome Study Group evaluation, and international RLS severity (IRLS) scoring system. Iron-free level, ferritin, folate, vitamin B12 and D-OH25 were detected. Neurological examinations and blood test occurred at the beginning of the therapy, after 2 wk, and at the 28th, 75th, 105th, 135th, 165th and 205th day. Regarding therapy, pramipexole or gabapentin were used.


Patients were moderately depressed, with evident nocturnal sleep problems and concomitant daily sleepiness. Sleep problems and involuntary leg movements had been underestimated, and RLS syndrome had not been considered before the neurological visit. All (211/211) patients fulfilled the RLS diagnostic criteria. Twenty-two patients considered their symptoms as mild, according to IRSL, but 189 found them moderate to very severe. No correlation was found between ammonium level and ESS or PSQI. Augmentation was rather precocious in our patients (135th day), and more frequent (35%) than previous data (8.3%-9.1%). The dosage of dopamine agonists was found to be associated with augmentation and appears in range with the literature. Previous intake of alcohol and lower levels of vitamins have been related to the phenomenon in our study.


RLS is a common disorder, requiring rapid diagnosis and treatment. Further research is therefore fundamental.

Keywords: Restless legs syndrome, Chronic liver disease, Dopamine agonist treatment, Augmentation

Core tip: The diagnosis of restless legs syndrome (RLS) relies on the presence of unpleasant sensation in the legs associated with the urge to move. Symptoms mostly begin during periods of rest or inactivity and worsen in the evening or night. Partial or total relief is related to movement. Chronic hepatic failure was recently described in association with RLS, but there are very limited studies, with no mention to treatment. We describe RLS syndrome associated with well-defined chronic liver disease along with therapeutic options, discussing risks, benefits and potential side effects, with a particular look at the augmentation phenomenon in hepatic failure.