Non-selective β-blockers in advanced cirrhosis: a critical review of the effects on overall survival and renal function

Abstract

IntroductionNon-selective β-blockers (NSBBs) are widely prescribed in patients with cirrhosis for primary and secondary prophylaxis of bleeding oesophageal varices. Furthermore, it has been suggested that the clinical benefits of NSBBs may extend beyond their haemodynamic effects. Recently, a potentially harmful effect has been described in patients with refractory ascites or spontaneous bacterial peritonitis.MethodologyA comprehensive literature search on β-blockers and cirrhosis survival using the electronic databases PubMed/MEDLINE, AMED, CINAHL and the Cochrane Central Register of Controlled Trials. Full-text manuscripts published over more than 35 years, from 1980 to April 2016 were reviewed for relevance and reference lists were cross-checked for additional pertinent studies regarding potential NSBB effects, especially focused on those concerned with survival and/or acute kidney injury (AKI).DiscussionThe proposed review will be able to provide valuable evidence to help decision making in the use of NSBB for the treatment of advanced cirrhosis and highlights some limitations in existing evidence to direct future research.

Management of refractory cirrhotic ascites: challenges and solutions

“…In evaluating patients, we should be able to discriminate between diuretic-intractable ascites and diuretic-resistant ascites because the former is presumably more prone to developing dilutional hyponatremia and renal dysfunction during the treatment, and may be associated with poor prognosis. 21 , 29 …”

“… 27 Propranolol (120 mg/day) has been proven to ameliorate gastroduodenal/intestinal permeability and to reduce bacterial translocation (BT) which are partially unrelated to their hemodynamic effects on portal pressure. 28 A comprehensive review by Blasco-Algora et al 29 summarizes these studies and proposes the clinical situations in which NSBBs should be withheld as follows: Child–Pugh–Turcotte class C or Model for End-stage Liver Disease (MELD) score ≥25, and 1) diuretic-intractable refractory ascites, 2) cardiac index ≤1.5 L/min/m 2 , 3) systolic BP ≤90 mmHg (either spontaneous or NSBB-induced), and 4) within 6 months of first episode of SBP, as long as hemodynamic deterioration is sustained (e.g., BP ≤90 mmHg and/or cardiac index ≤1.5 L/min/m 2 ). The authors further recommended that the maximal dose of propranolol should be set at 40–80 mg/day if patients’ MELD score is 18–24 because a high NSBB dose (160 mg/day) is associated with more harmful effects to the systemic circulation and less tolerance.…”

Antimicrobial resistance in chronic liver disease

“…NSBB target the pathophysiological pathways that propagate portal hypertension, and their use might also extend to having beneficial non-hemodynamic pleiotropic effects [48] within a therapeutic window based on stage of cirrhosis that remains controversial and needs to be defined [49]. Their use has been demonstrated recently to not only reduce variceal hemorrhage for which they are primarily prescribed but in compensated cirrhosis to also increase decompensation-free survival in patients with clinically significant portal hypertension [50].…”

Impact of non-selective beta blockers on portal hypertension and hepatic elasticity in hepatitis C virus-related liver cirrhosis

“…Non-selective beta-blockers (NSBB) have been used since 1981 as a therapeutic option for portal hypertension in patients with liver cirrhosis. Patients with refractory ascites experience a diminished sensitivity to the NSBB due to increased levels of splanchnic pro-inflammatory cytokines; the beneficial effects of NSBBs may decrease, and NSBBs may even be harmful (6).…”