Probiotics for patients with hepatic encephalopathy

McGee RG, Bakens A, Wiley K, Riordan SM, Webster AC

Published Online:

November 9, 2011

Hepatic encephalopathy is a disorder of the brain function as a result of liver failure and/or portosystemic shunt. It results in confusion, drowsiness, coma, and in some patients, in death. While the cause of hepatic encephalopathy is not fully understood, it is thought to develop as a result of the failure to clear various toxic substances, such as ammonia, from the blood, either because of poor function of the liver cells or because the blood from the intestine is shunted around the liver and is not seen by the liver cells. Protein metabolising bacterial species in the intestine of hepatic encephalopathy patients contribute to ammonia production. Probiotics are live microorganisms who may reduce the prevalence of these harmful ammonia-producing bacteria. This review identified seven trials of which 550 participants were randomised. Each trial used different types of probiotics. Duration of administration of the experimental intervention varied from 10 days to 180 days. The authors of the review assessed a range of outcomes including death, recovery, adverse events, and quality of life. There was no benefit of probiotics shown for any of the primary outcomes including mortality. The authors of the review found a significant difference in plasma ammonia concentration after one month, and a significant change in plasma ammonia concentration at three months treatment compared with no treatment. However, this finding is of questionable importance. Therefore, the use of probiotics for patients with hepatic encephalopathy cannot be currently recommended. Furtehr randomised clinical trials are required.

Abstract (click to read)

Background:

Hepatic encephalopathy is a disorder of brain function as a result of liver failure and/or portosystemic shunt. Both hepatic encephalopathy (clinically overt) and minimal hepatic encephalopathy (not clinically overt) significantly impair patient’s quality of life and daily functioning and represent a significant burden on health care resources. Probiotics are live microorganisms, which when administered in adequate amounts may confer a health benefit on the host.

Objectives:

To quantify the beneficial and harmful effects of any probiotic in any dosage, compared with placebo or no intervention, or with any other treatment for patients with any grade of acute or chronic hepatic encephalopathy as assessed from randomised trials.

Search strategy:

We searched the The Cochrane Hepato-Biliary Group Controlled Trials Register, The Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, Science Citation Index Expanded, conference proceedings, reference lists of included trials and the WHO international clinical trials registry until April 2011 registry platform to identify new and ongoing trials.

Selection criteria:

We included randomised trials that compared probiotics in any dosage with placebo or no intervention, or with any other treatment in patients with hepatic encephalopathy.

Data collection and analysis:

Three authors independently assessed the risk of bias of the included trials and extracted data on relevant outcomes, with differences resolved by consensus. We conducted random-effects model meta-analysis due to obvious heterogeneity of patients and interventions. A P value of 0.05 or less was defined as significant. Dichotomous outcomes are expressed as risk ratio (RR) and continuous outcomes as mean difference (MD) with 95% confidence intervals (CI).

Main results:

We included seven trials of which 550 participants were randomised. Four of the seven trials compared a probiotic with placebo or no treatment in 245 participants, another trial compared a probiotic with lactulose in 40 participants , and the remaining two trials compared a probiotic with both placebo and lactulose in 265 participants. Each trial used different types of probiotics. Duration of administration of the experimental intervention varied from 10 days to 180 days. Two trials were industry funded, and five were unclear about origin of funding. All trials had high risk of bias.

When probiotics were compared with no treatment, there was no significant difference in all-cause mortality (2 trials, 105 participants; 1/57 (2%) versus 1/48 (2%): RR 0.72; 95% CI 0.08 to 6.60), lack of recovery (4 trials, 206 participants; 54/107 (50%) versus 68/99 (69%): RR 0.72; 95% CI 0.49 to 1.05), adverse events (3 trials, 145 participants; 2/77 (3%) versus 6/68 (9%): RR 0.34; 95% CI 0.08 to 1.42), quality of life (1 trial, 20 participants contributed to the physical quality of life measurement, 20 participants contributed to the mental quality of life: MD Physical 0.00; 95% CI -5.47 to 5.47; MD Mental 4.00; 95% CI -1.82 to 9.82), or change of/or withdrawal from treatment (3 trials, 175 participants; 11/92 (12%) versus 7/83 (8%): RR 1.28; 95% CI 0.52 to 3.19). No trial reported sepsis or duration of hospital stay as an outcome. Plasma ammonia concentration was significantly lower for participants treated with probiotic at one month (3 trials, 226 participants: MD -2.99 μmol/L; 95% CI -5.70 to -0.29) but not at two months (3 trials, 181 participants: MD -1.82 μmol/L; 95% CI -14.04 to 10.41). Plasma ammonia decreased the most in the participants treated with probiotic at three months (1 trial, 73 participants: MD -6.79 μmol/L; 95% CI -10.39 to -3.19).

When probiotics were compared with lactulose no trial reported all-cause mortality, quality of life, duration of hospital stay, or septicaemia. There were no significant differences in lack of recovery (3 trials, 173 participants; 47/87 (54%) versus 44/86 (51%): RR 1.05; 95% CI 0.75 to 1.47), adverse events (2 trials, 111 participants; 3/56 (5%) versus 6/55 (11%): RR 0.57; 95% CI 0.06 to 5.74), change of/or withdrawal from treatment at one month (3 trials, 190 participants; 8/95 (8%) versus 7/95 (7%): RR 1.10; 95% CI 0.40 to 3.03), plasma ammonia concentration (2 trials, 93 participants: MD -6.61 μmol/L; 95% CI -30.05 to 16.84), or change in plasma ammonia concentration (1 trial, 77 participants: MD 1.16 μmol/L; 95% CI -1.96 to 4.28).

Authors' conclusions:

The trials we located suffered from a high risk of systematic errors ('bias') and high risk of random errors ('play of chance'). While probiotics appear to reduce plasma ammonia concentration when compared with placebo or no intervention, we are unable to conclude that probiotics are efficacious in altering clinically relevant outcomes. Demonstration of unequivocal efficacy is needed before probiotics can be endorsed as effective therapy for hepatic encephalopathy. Further randomised clinical trials are needed.

This record should be cited as:

McGee RG, Bakens A, Wiley K, Riordan SM, Webster AC. Probiotics for patients with hepatic encephalopathy. Cochrane Database of Systematic Reviews 2011, Issue 11. Art. No.: CD008716. DOI: 10.1002/14651858.CD008716.pub2

Assessed as up to date:

September 19, 2011

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Primary Review Group:

Hepato-Biliary Group

Health topics:

Complementary & alternative medicine > Gastroenterology > Liver diseases

Gastroenterology > Liver diseases > General liver disease

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Probiotics for patients with hepatic encephalopathy

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