Current and future pharmacological therapies for managing cirrhosis and its complications

World J Gastroenterol. 2019 Feb 28;25(8):888-908. doi: 10.3748/wjg.v25.i8.888.

Abstract

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: Beta-blockers; Cirrhosis; Diuretics; Pharmacology; Proton pump inhibitors; Rifaximin; Statins.

Publication types

  • Review

MeSH terms

  • Adrenergic beta-Antagonists / therapeutic use
  • Animals
  • Anti-Bacterial Agents / therapeutic use
  • Antibiotic Prophylaxis / methods
  • Anticoagulants / therapeutic use
  • Antidiuretic Hormone Receptor Antagonists / therapeutic use
  • Ascites / drug therapy*
  • Ascites / etiology
  • Ascites / prevention & control
  • Chronic Disease / drug therapy
  • Disease Models, Animal
  • Diuretics / therapeutic use
  • Esophageal and Gastric Varices / drug therapy*
  • Esophageal and Gastric Varices / etiology
  • Esophageal and Gastric Varices / prevention & control
  • Gastrointestinal Hemorrhage / drug therapy*
  • Gastrointestinal Hemorrhage / etiology
  • Gastrointestinal Hemorrhage / prevention & control
  • Hepatic Encephalopathy / drug therapy*
  • Hepatic Encephalopathy / etiology
  • Hepatic Encephalopathy / prevention & control
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use
  • Hypertension, Portal / drug therapy*
  • Hypertension, Portal / etiology
  • Hypertension, Portal / prevention & control
  • Liver Cirrhosis / complications
  • Liver Cirrhosis / drug therapy*
  • Proton Pump Inhibitors / therapeutic use
  • Secondary Prevention / methods
  • Treatment Outcome

Substances

  • Adrenergic beta-Antagonists
  • Anti-Bacterial Agents
  • Anticoagulants
  • Antidiuretic Hormone Receptor Antagonists
  • Diuretics
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Proton Pump Inhibitors