Potential conflict of interest: Nothing to report.
Rifaximin reduces endotoxemia and improves liver function and disease severity in patients with decompensated cirrhosis†
Article first published online: 27 JAN 2012
Copyright © 2011 American Association for the Study of Liver Diseases
Volume 55, Issue 2, pages 655–656, February 2012
How to Cite
Kalambokis, G. N. and Tsianos, E. V. (2012), Rifaximin reduces endotoxemia and improves liver function and disease severity in patients with decompensated cirrhosis. Hepatology, 55: 655–656. doi: 10.1002/hep.24751
- Issue published online: 27 JAN 2012
- Article first published online: 27 JAN 2012
- Accepted manuscript online: 26 OCT 2011 12:12PM EST
- Manuscript Accepted: 21 SEP 2011
- Manuscript Revised: 17 SEP 2011
- Manuscript Received: 10 SEP 2011
To the Editor:
We read with great interest the article by Nolan regarding the pathogenetic role of intestinal endotoxin in the development of liver injury.1 Increased circulating levels of gut-derived endotoxin2 and specific sensitivity to endotoxin have been shown in cirrhosis,3 which could worsen further hepatic impairment. However, the effects of changing gut flora on liver function in patients with cirrhosis remain unclear. Treatment with synbiotics improved the Child-Pugh class as a result of significant improvements in serum bilirubin and albumin levels and in prothrombin activity.4 Additionally, probiotics reduced endotoxemia and improved the Child-Pugh score, although not significantly, in patients with compensated cirrhosis.5 Finally, treatment with paromomycin and neomycin for 3-6 months significantly improved serum albumin levels6 and the Child-Pugh score, mainly because of a decreased incidence of ascites and encephalopathy,7 respectively.
Herein, we present preliminary data on the effects of rifaximin, a virtually unabsorbable antibiotic with broad-spectrum antimicrobial activity and an excellent safety profile8 on endotoxemia and liver function and disease severity in 9 liver transplant candidates with alcoholic cirrhosis (male, n = 7; mean age = 56 ± 6 years; Child-Pugh class B/C: 5/4). All patients abstained from alcohol for at least 1 year before inclusion. Plasma endotoxin levels were detected by the Limulus amebocyte lysate chromogenic endpoint assay (Hycult Biotech, Uden, The Netherlands). Clinical infection, upper gastrointestinal bleeding, and use of antibiotics or prebiotics 6 weeks before or during the study were exclusion criteria. Patients were evaluated after an 8-week observational period and after an 8-week course of rifaximin (1,200 mg/day).
All measures remained unchanged during the observational period. Rifaximin significantly reduced plasma endotoxin levels, together with a significant increase in serum albumin levels and significant decreases in serum total bilirubin levels and international normalized ratio. Child-Pugh and model for end-stage liver disease scores decreased significantly after treatment (Table 1).
|Baseline||End of Observational Period (Week 8)||End of Rifaximin Treatment (Week 16)|
|Plasma endotoxin levels (EU/mL)||3.14 ± 1.23||3.32 ± 1.05||1.62 ± 0.85ab|
|Ascites (suppressed by medication/refractory)||8/1||8/1||8/1|
|Encephalopathy (none/suppressed by medication)||4/5||4/5||4/5|
|Serum albumin (g/dL)||3.21 ± 0.08||3.14 ± 0.06||3.45 ± 0.06ab|
|Serum albumin improved (yes/no)||1/8||7/2ab|
|INR||1.66 ± 0.09||1.7 ± 0.07||1.51 ± 0.07ab|
|INR improved (yes/no)||1/8||7/2ab|
|Serum total bilirubin (mg/dL)||2.17 ± 0.16||2.24 ± 0.1||1.72 ± 0.13c§|
|Serum total bilirubin improved (yes/no)||2/7||8/1ab|
|Serum alanine aminotransferase (U/L)||56 ± 4||57 ± 4||52 ± 6|
|Serum aspartate aminotransferase (U/L)||48 ± 5||48 ± 6||46 ± 4|
|Serum creatinine (mg/dL)||1.18 ± 0.09||1.17 ± 0.05||1.13 ± 0.07|
|Child-Pugh score||8.7 ± 0.4||9 ± 0.5||8.1 ± 0.5ab|
|Child-Pugh score improved (yes/no)||0/9||7/2c§|
|MELD score||16 ± 1.2||16.2 ± 1.1||13.7 ± 1c§|
|MELD score improved (yes/no)||0/9||9/0c§|
In conclusion, intestinal decontamination by rifaximin could be a feasible, safe approach to prevent endotoxin-induced liver injury and improve liver function and disease severity in patients with decompenstaed cirrhosis. The present findings should be confirmed in a placebo-controlled trial.
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- 2Endotoxin levels measured by a chromogenic assay in portal, hepatic, and peripheral blood in patients with cirrhosis. HEPATOLOGY 1988; 8: 232-236., , .
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- 5The effect of probiotics on gut flora, level of endotoxin, and Child-Pugh score in cirrhotic patients: results of a double-blind randomized study. Eur J Gastroenterol Hepatol 2007; 19: 1111-1113., , , , , , et al.
- 6Effect of long-term administration of paromomycin sulfate on the level of serum albumin and gamma-globulin in human cirrhosis. Tokai J Exp Clin Med 1983; 8: 349-357., .
- 7Long-term treatment with cisapride and antibiotics in liver cirrhosis: effect on small intestinal motility, bacterial overgrowth, and liver function. Am J Gastroenterol 2001; 96: 1251-1255., , , , .
- 8Rifaximin: a unique gastrointestinal-selective antibiotic for enteric diseases. Curr Opin Gastroenterol 2010; 26: 17-25., .
Georgios N. Kalambokis M.D.*, Epameinondas V. Tsianos M.D., Ph.D., F.E.B.G., A.G.A.F.*, * 1st Division of Internal Medicine and Hepato-Gastroenterology Unit University Hospital, Ioannina, Greece.