Review
Copyright ©The Author(s) 2016.
World J Pharmacol. Mar 9, 2016; 5(1): 15-31
Published online Mar 9, 2016. doi: 10.5497/wjp.v5.i1.15
Table 1 Changes in measurement of portal haemodynamic pressures with different types of portal hypertension
Type of portal hypertensionExampleFHVPWHVPHVPG
Pre-hepaticPortal/splenic vein thrombosisNormalNormalNormal
Pre-sinusoidalPrimary biliary cirrhosis, schistosomiasis, sarcoidosisNormalNormalNormal
SinusoidalAlcoholic hepatitis, NASH/alcoholic/viral cirrhosisNormalIncreasedIncreased
Post-sinusoidalSinusoidal obstruction syndromeNormalIncreasedIncreased
Post-hepaticBudd Chiari1---
Heart failureIncreasedIncreasedNormal
Table 2 Types of non-selective beta-blocker used in cirrhosis
PropanololCarvedilolNadalol
Proposed mechanism of actionβ-1 activity to reduce cardiac output and reduce portal blood flow through splanchnic vasoconstriction viaβ-2 blockadeβ-1 activity to reduce cardiac output and reduce portal blood flow through splanchnic vasoconstriction viaβ-2 blockade. Additional intrinsic α1-adrenergic activityβ-1 activity to reduce cardiac output and reduce portal blood flow through splanchnic vasoconstriction viaβ-2 blockade
Side efffects/cautions1Hypotension, bradycardia, caution in peripheral vascular disease/asthma.Hypotension (more profound than others), bradycardia, caution in peripheral vascular disease/asthma.Hypotension, bradycardia, caution in peripheral vascular disease/asthma.
To be discontinued at time of SBP, renal impairment and hypotension1To be discontinued at time of SBP, renal impairment and hypotension1To be discontinued at time of SBP, renal impairment and hypotension1
IndicationsPrimary prophylaxis of variceal haemorrhage (Level 1A, grade A). In combination with VBL for secondary prevention (Level 1a, grade A)2Primary prophylaxis of variceal haemorrhage (Level 1a, grade A). In combination with VBL for secondary prevention (Level 1b, grade B)2Primary prophylaxis of variceal haemorrhage (Level 1a, grade A). In combination with VBL for secondary prevention (Level 1a, grade A)2
Dose40 mg BD if tolerated or once HR < 50-55 bpm12.5 mg OD if tolerated or once HR < 50-55 bpm40mg OD (maximum dose 240 mg) or once HR < 50-55 bpm
Mode of administrationOralOralOral
Table 3 Summary of studies/recent guidelines with non-selective beta-blocker in advanced cirrhosis
Ref.Year, countryStudy designFindings/recommendationsStrenghts/weaknesses of study (if applicable)
Bañares et al[57]2002, SpainRandomised controlled trialMore favorable reduction of HVPG comparing carvedilol with propranolol however an increase in diuretic requirement in patients on carvedilol suggesting potential worsening of ascitesIncreased requirement of diuretic not a hard end-point
Sersté et al[20]2010, FranceSingle centre observational prospective case studyPatients on NSBB in refractory ascites having higher 1-year mortality than those not on NSBBNon-randomised Lack of haemodynamic data. No competing risk analysis
Mandorfer et al[90]2014, AustraliaSingle centre retrospective studyNSBB associated with higher transplant free survival but increase in renal dysfunction and mortality following episode of SBPGroups not well matched at baseline with NSBB group having higher bilirubin in subgroup analysis
Leithead et al[22]2015, United KingdomSingle centre, retrospective case studyNSBB associated with reduced wait-list mortality and a higher likelihood of survival to transplantationLack of haemodynamic measurements. Non randomized. Well matched groups
Tripathi et al[67]2015, United KingdomBritish guidelinesNSBB to be continued till episode of SBP, hypotension of renal failure (based on level 2b, Grade B evidence)National guidelines based on all available evidence
Kimer et al[99]2015, Denmark61 patients with cirrhosis and ascites (following a review of 14 trials)No survival difference in patients on/not NSBBs in patient cohorts with ascitesSmall retrospective analysis
de Franchis[25]2015, InternationalMeeting consensus statementsNSBB dose reduction or discontinuation can be considered if hypotension/hyponatraemia or renal function impairment in patients with refractory ascites. If a clear precipitant for these (e.g., SBP), NSBB can be restarted once parameters normalisedInternational consensus statements based on evidence
Robins et al[98]2014, United KingdomLetter - retrospective review of 114 patients undergoing LVPNo significant difference in survival comparing patients on NSBB and those notSmall retrospective series
Bossen et al[101]2015, Denmark and FrancePost-hoc analysis of 3 RCTsNSBBs not associated with increase in mortality in patients with cirrhosis and ascites Cessation of NSBB linked thereafter to increase in mortality due to liver decompensation eventsMulticentre trials, 3 RCTs, large data set and reflective of real world experience. Lack of haemodyamic studies and assessment of severity of portal hypertension. NSBBs stopped during admission so? true reflection of their effects on mortality