Effects of the adjunctive probiotic VSL#3 on portal haemodynamics in patients with cirrhosis and large varices: a randomized trial

Background Probiotics, by altering gut flora, may favourably alter portal haemodynamics in patients with cirrhosis.Aim To investigate the effect of probiotics on portal pressure in patients with cirrhosis. Methods Randomized double-blind placebo-controlled trial conducted in G.B. Pant Hospital, New Delhi. A total of 94 cirrhotic patients having large oesophageal varices without history of variceal bleeding were randomized to three treatment groups and given 2months' treatment with propranolol plus placebo, propranolol plus antibiotics (norfloxacin 400mg BD) or propranolol plus probiotic (VSL#3, 900 billion/day) randomly assigned in 1:1:1 ratio. Outcome measures were change in Hepatic venous pressure gradient (HVPG): Response rate (Percentage of patients having a decrease from baseline of 20% or to 12mmHg) and changes from baseline; biochemical markers of inflammation: changes from baseline. Results Adjunctive probiotics increased the response rate compared with propranolol alone (58% vs. 31%, P=0.046), similar to adjunctive antibiotics (54%). The mean fall in HVPG was greater with either adjunctive probiotics (3.7mmHg vs. 2.1mmHg, P=0.061) or adjunctive antibiotics (3.4mmHg) than with propranolol alone. Both adjunctive therapies were associated with greater decreases in TNF- levels (in both peripheral and hepatic venous blood) that resulted from propranolol-only treatment. No clinically relevant between-group differences were observed in the type or frequency of adverse events. Conclusions Adjunctive probiotic (VSL#3) improved the response rate to propranolol therapy and was safe and well tolerated in patients with cirrhosis. Adjunctive probiotic therapy merits further study for reduction in portal pressure.