Rifaximin improves thrombocytopenia in patients with alcoholic cirrhosis in association with reduction of endotoxaemia

Abstract

Background: Thrombocytopenia is a major haematological disorder of cirrhosis with unclear pathogenesis. Endotoxaemia resulting from intestinal bacterial overgrowth could reduce platelet counts directly or through cytokine release.

Aims: To correlate endotoxaemia with platelet counts and study the effects of intestinal decontamination with rifaximin on thrombocytopenia in relation to changes in endotoxin and cytokine concentrations in patients with alcoholic cirrhosis.

Methods: Platelet counts, plasma endotoxin levels and serum interleukin-1 (IL-1), interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α) levels were measured in 23 thrombocytopenic cirrhotic patients (platelet count<150 000/μl) before and after 4-week treatment with rifaximin 1200 mg/d (n = 13) or no treatment (n = 10) and at baseline in 10 cirrhotic patients without thrombocytopenia; spleen size was measured at baseline in all patients.

Results: Endotoxin and IL-6 levels were significantly higher in patients with thrombocytopenia than in those without thrombocytopenia (2.76 ± 0.69 vs. 0.64 ± 0.09 EU/ml; P < 0.001 and 24.26 ± 3.38 vs. 2.66 ± 0.74 pg/ml; P = 0.001 respectively). Platelet counts were inversely correlated with endotoxin levels (r = -0.589; P = 0.003), Child-Pugh score (r = -0.625; P = 0.001), IL-6 levels (r = -0.464; P = 0.02) and spleen size (r = -0.455; P = 0.02) in patients with thrombocytopenia. Following rifaximin, platelet counts increased significantly (83 100 ± 9700 vs. 99 600 ± 11 200/μl; P = 0.006) in line with significant reductions in endotoxin (1.28 ± 0.41 vs. 2.54 ± 0.86 EU/ml; P = 0.005), IL-1 (3.1 ± 0.5 vs. 4.4 ± 1.2 pg/ml; P = 0.04), IL-6 (12.8 ± 2.5 vs. 21.1 ± 4.2 pg/ml; P = 0.01) and TNF-α (3.6 ± 1.3 vs. 5.8 ± 1.7; P = 0.02) levels. Platelet count changes were correlated with the changes in endotoxin (r = 0.573; P = 0.04), TNF-α (r = 0.554; P = 0.05) and IL-6 (r = 0.495; P = 0.07) levels.

Conclusions: Rifaximin improves cirrhosis-related thrombocytopenia and this could be related with the reduction of endotoxaemia.