Synbiotic-associated improvement in liver function in cirrhotic patients: Relation to changes in circulating cytokine messenger RNA and protein levels.

Authors: STEPHEN M. RIORDAN , NARELLE A. SKINNER , CHRISTOPHER J. MCIVER , QING LIU , STIG BENGMARK , DAVID BIHARI5 & KUMAR VISVANATHAN.

Published: Microbial Ecology in Health and Disease. 2007; 19.

Method and selection

The study was conducted in vivo, involving human participants.

Design: Randomized. Thirty asymptomatic volunteers of similar age and gender distributions to the cirrhotic group, with no history of liver disease, alcohol intake B/20 g/day, normal liver function tests and no predisposition to altered gut flora, extra-intestinal translocation of gut flora or circulating cytokine levels, as above, served as controls.

Treatment: Synbiotic or placebo preparations for 7 days.

Where and when:

Sample size: 30.

Sample criteria: Patients with biopsy-proven cirrhosis. Exclusion: Patients who had not been abstinent from alcohol for the last 3 months, patients with histological features of alcoholic hepatitis, patients with a history within the previous 6 weeks of factors that may influence the intestinal flora (treatment with lactulose or antibiotics), factors that may influence extra-intestinal translocation of gut flora and, hence, circulating endotoxin levels (primary intestinal disorders and gastrointestinal haemorrhage) and factors that may influence circulating cytokine levels (infection, immunomodulatory drug use and renal impairment. In addition to intercurrent infection and gastrointestinal haemorrhage, patients with other possible causes of reversible hepatic functional decompensation, such as drug-related hepatotoxicity and choledocholithiasis, were excluded. As were those with iodine allergy.

Analysed material: Blood samples.

Results and indicative results

Results

Synbiotic treatment was associated with a significant increase in viable faecal counts of Lactobacillus species. No significant change in faecal counts of Lactobacillus species occurred in placebo-treated patients. (s 10).

Synbiotic treatment was associated with a significant improvement in ICG clearance (s. 11).

(Indocyanine green (ICG) clearance has been validated as a valuable tool for identifying patients with impaired preoperative liver function).

Improvement in Child-Pugh classification occurred in 44.4% of patients who were initially Child-Pugh class B or C and who were treated with the synbiotic preparation. And 0% for patients treated with the placebo. (s. 11). (The Child-Pugh Score for Cirrhosis Mortality estimates cirrhosis severity).

ICG clearance improved in all four synbiotic-treated patients in whom an improvement in Child-Pugh status was documented, as well as for 90.9% of patients in whom the Child-Pugh grade remained stable during the period of the study.

The improvement in Child-Pugh classification in initially decompensated synbiotic-treated patients resulted from significant improvements in serum bilirubin and albumin concentrations and in the prothrombin time, expressed as the international normalized ratio. No significant change in serum bilirubin or albumin levels or in the INR occurred in placebo-treated patients. (s. 11).

Synbiotic treatment was associated with further significant increases in several blood levels, with post-treatment values increased in comparison to baseline levels. No significant change in placebo. (s. 11-12).

Indicative results

The report documents significant improvement in liver function in patients with cirrhosis, mostly due to chronic hepatitis C viral infection or alcohol, who underwent short-term treatment with a synbiotic preparation shown to significantly modulate the gut flora (s. 13).

No deterioration in Child-Pugh class occurred in any synbiotic-treated patients, and no significant change occurred in ICG clearance or improvement in Child-Pugh class in placebo-treated patients in the study, despite comparable baseline clinical and demographic profiles and clinical follow-up schedules.

The duration of synbiotic therapy was short but was shown to promote significant changes in the faecal flora of the patients. (s. 13).

The study concludes that short-term use of a synbiotic regimen is proven to modulate the gut flora significantly improves liver function in patients with cirrhosis. (s. 15).

Further research

The duration of synbiotic therapy was short.

Full research study