Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Feb 28, 2019; 25(8): 888-908
Published online Feb 28, 2019. doi: 10.3748/wjg.v25.i8.888
Current and future pharmacological therapies for managing cirrhosis and its complications
David Kockerling, Rooshi Nathwani, Roberta Forlano, Pinelopi Manousou, Benjamin H Mullish, Ameet Dhar
David Kockerling, Rooshi Nathwani, Roberta Forlano, Pinelopi Manousou, Benjamin H Mullish, Ameet Dhar, Liver Unit/Division of Integrative Systems Medicine and Digestive Disease, Imperial College London, London W2 1NY, United Kingdom
Author contributions: Kockerling D and Nathwani R performed the literature search and wrote the first draft of the manuscript; Mullish BH, Manousou P, Forlano R and Dhar A provided critical review of the first draft and contributed to amendment of the text; all authors contributed to and approved the final submission.
Supported by The Division of Integrative Systems Medicine and Digestive Disease at Imperial College London receives financial support from the National Institute for Health Research (NIHR) Imperial Biomedical Research Centre (BRC) based at Imperial College Healthcare NHS Trust and Imperial College London. This article is independently funded by the NIHR BRC, and the views expressed in this publication are those of the authors and not necessarily those of the NHS, NIHR, or the Department of Health. Mullish BH is the recipient of a Medical Research Council Clinical Research Training Fellowship (grant number: MR/R00875/1). Forlano R is the recipient of the EASL Juan Rodes PhD fellowship.
Conflict-of-interest statement: None declared for all authors.
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:
Corresponding author: Ameet Dhar, BSc, MBBS, MRCP, PhD, Consultant Hepatologist, Liver Unit/Division of Integrative Systems Medicine and Digestive Disease, Imperial College London, 10th Floor, QEQM Wing, St Mary’s Hospital Campus, South Wharf Road, Paddington, London W2 1NY, United Kingdom.
Telephone: +44-20-33126454 Fax: +44-20-77249369
Received: December 7, 2018
Peer-review started: December 9, 2018
First decision: January 11, 2019
Revised: January 17, 2019
Accepted: January 26, 2019
Article in press: January 26, 2019
Published online: February 28, 2019

Due to the restrictions of liver transplantation, complication-guided pharmacological therapy has become the mainstay of long-term management of cirrhosis. This article aims to provide a complete overview of pharmacotherapy options that may be commenced in the outpatient setting which are available for managing cirrhosis and its complications, together with discussion of current controversies and potential future directions. PubMed/Medline/Cochrane Library were electronically searched up to December 2018 to identify studies evaluating safety, efficacy and therapeutic mechanisms of pharmacological agents in cirrhotic adults and animal models of cirrhosis. Non-selective beta-blockers effectively reduce variceal re-bleeding risk in cirrhotic patients with moderate/large varices, but appear ineffective for primary prevention of variceal development and may compromise renal function and haemodynamic stability in advanced decompensation. Recent observational studies suggest protective, haemodynamically-independent effects of beta-blockers relating to reduced bacterial translocation. The gut-selective antibiotic rifaximin is effective for secondary prophylaxis of hepatic encephalopathy; recent small trials also indicate its potential superiority to norfloxacin for secondary prevention of spontaneous bacterial peritonitis. Diuretics remain the mainstay of uncomplicated ascites treatment, and early trials suggest alpha-adrenergic receptor agonists may improve diuretic response in refractory ascites. Vaptans have not demonstrated clinical effectiveness in treating refractory ascites and may cause detrimental complications. Despite initial hepatotoxicity concerns, safety of statin administration has been demonstrated in compensated cirrhosis. Furthermore, statins are suggested to have protective effects upon fibrosis progression, decompensation and mortality. Evidence as to whether proton pump inhibitors cause gut-liver-brain axis dysfunction is conflicting. Emerging evidence indicates that anticoagulation therapy reduces incidence and increases recanalisation rates of non-malignant portal vein thrombosis, and may impede hepatic fibrogenesis and decompensation. Pharmacotherapy for cirrhosis should be implemented in accordance with up-to-date guidelines and in conjunction with aetiology management, nutritional optimisation and patient education.

Keywords: Cirrhosis, Beta-blockers, Rifaximin, Diuretics, Statins, Proton pump inhibitors, Pharmacology

Core tip: Pharmacological therapy is central to the management of cirrhosis and its complications. Whilst there has been recent debate about the safety of beta-blockade in patients with ascites, conversely there is growing interest in potential benefits relating to a reduction in gut bacterial translocation and hepatocellular carcinoma risk. In addition to its well-established role in treating hepatic encephalopathy, rifaximin may also have a key role in preventing secondary infections. In this review, we summarise these and other uncertainties, controversies and novel developments related to pharmacotherapy in the clinical management of chronic liver disease.