Rifaximin and Propranolol Combination Therapy Is More Effective than Propranolol Monotherapy for the Reduction of Portal Pressure: An Open Randomized Controlled Pilot Study

Abstract

Background/AimsNon-selective beta blockers (NSBBs) are currently the only accepted regimen for preventing portal hypertension (PHT)-related complications. However, the effect of NSBBs is insufficient in many cases. Bacterial translocation (BT) is one of the aggravating factors of PHT in cirrhosis; therefore, selective intestinal decontamination by rifaximin is a possible therapeutic option for improving PHT. We investigated whether the addition of rifaximin to propranolol therapy can improve hepatic venous pressure gradient (HVPG) response.MethodsSixty-four cirrhosis patients were randomly assigned to propranolol monotherapy (n=48) versus rifaximin and propranolol combination therapy (n=16). Baseline and post-treatment HVPG values, BT-related markers (lipopolysaccharide [LPS], LPS-binding protein [LBP], interleukin-6 [IL-6], and tumor necrosis factor α [TNF-α]), serological data, and adverse event data were collected. HVPG response rate was the primary endpoint.ResultsCombination therapy was associated with better HVPG response rates than monotherapy (56.2% vs 87.5%, p=0.034). In combination therapy, posttreatment BT-related markers were significantly decreased (LPS, p=0.005; LBP, p=0.005; IL-6, p=0.005; TNF-α, p=0.047).ConclusionsRifaximin combination therapy showed an additive effect in improving PHT compared to propranolol monotherapy. These pilot data suggest that the addition of rifaximin to NSBBs could be a good therapeutic option for overcoming the limited effectiveness of NSBBs.

Impact of sarcopenia on prognostic value of cirrhosis: going beyond the hepatic venous pressure gradient and MELD score

“…Therefore, HVPG ≥10 mmHg has been denominated ‘clinically significant PH’. Also, an HVPG ≥20 mmHg identifies patients with greater probabilities of poorer evolution in decompensated cirrhosis . Thus, an HVPG ≥20 mmHg has been defined as extremely severe PH .…”

Potential mechanisms linking gut microbiota and portal hypertension

“…The impact of antibiotics such as norfloxacin on liver hemodynamics in cirrhosis was assessed in small, randomized controlled trials with little or no impact on HVPG when compared to placebo . Similarly, use of rifaximin, a non‐absorbable antibiotic with broad‐spectrum antimicrobial activity, was ineffective when given as monotherapy for treating portal hypertension, but proved to be a useful additive to propranolol with improved effects on HVPG and bacterial translocation . The beneficial effects of rifaximin on intestinal permeability may relate to its ability to activate the intestinal pregnane X receptor (PXR), which is involved in the sensing and detoxification of xenobiotics including many microbial metabolites …”

Treatment of Oesophageal Varices in Liver Cirrhosis

“…However, intrahepatic inflammatory stimuli and portal hypertension can persist [13,14]. Larger trials are required to investigate whether patients successfully treated for hepatitis B and hepatitis C infections and those with non-alcoholic steatohepatitis with persistent metabolic damage can profit from adjuvant medications, such as non-selective beta blockers (NSBB) [15], renin-angiotensin system inhibitors [16], statins [17] or rifaximin [18], alone or in combination [19,20]. All these drugs blunt inflammatory stimuli and reduce portal pressure.…”