What is the role of probiotics in the management of cirrhosis of the liver?

Role of Probiotics in Cirrhosis of the Liver

Probiotics should not be routinely used in critically ill patients with acute-on-chronic liver failure (ACLF) and hepatic encephalopathy, but may be considered as adjunctive therapy in stable cirrhotic outpatients with minimal hepatic encephalopathy (MHE) to improve cognitive function and quality of life. 1

Critical Care Setting: ACLF Patients

The most recent high-quality guideline from the Society of Critical Care Medicine (2023) provides clear direction for critically ill patients:

• Do not routinely use probiotics as adjunctive therapy in critically ill ACLF patients with overt hepatic encephalopathy 1
• This is a conditional recommendation based on very low quality evidence 1
• While meta-analysis data (21 RCTs, n=1,420) showed probiotics may reduce development of overt hepatic encephalopathy (RR 0.29,95% CI 0.16-0.51), they showed no mortality benefit (RR 0.58,95% CI 0.23-1.44) 1
• The lack of impact on the most critical outcome—mortality—makes routine use unjustified in this high-acuity population 1

Stable Outpatient Cirrhosis: Selective Use

For stable cirrhotic patients, particularly those with minimal hepatic encephalopathy, probiotics demonstrate more favorable evidence:

Hepatic Encephalopathy Management

• Probiotics significantly reverse MHE (RR 1.54,95% CI 1.03-2.32) and improve overall hepatic encephalopathy (RR 1.94,95% CI 1.24-3.06) 2
• They reduce the development of overt hepatic encephalopathy (OR 0.42,95% CI 0.26-0.70, P=0.0007) in 6 RCTs involving 496 patients 1, 3
• Probiotics improve cognitive function as measured by number connection test scores (MD -30.25,95% CI -49.85 to -10.66 at 4 weeks) 4
• The Korean Association for the Study of the Liver notes that probiotics alter gut microbiome and inhibit ammonia production, though evidence quality remains low 1

Quality of Life and Safety Profile

• Probiotics demonstrate superior safety with lower incidence of serious adverse events (RR 0.71,95% CI 0.58-0.87) compared to controls 2
• They significantly improve quality of life scores (SMD 0.51,95% CI 0.27-0.75) 2
• Probiotic supplementation is well-tolerated and may maintain or improve liver function in stable cirrhosis 5

Liver Function Parameters

• Probiotics potentially improve liver function by reducing MELD scores (SMD -0.57,95% CI -0.85 to -0.30) 2
• In NAFLD/NASH patients, probiotics significantly decreased ALT (WMD -23.71,95% CI -33.46 to -13.95), AST (WMD -19.77,95% CI -32.55 to -7.00), and improved insulin resistance 1

Comparison with Standard Therapy

When comparing probiotics to lactulose (the standard first-line therapy):

• Lactulose appears more effective in reducing number connection test values at 4 weeks (MD 6.7,95% CI 0.58-12.82) 4
• Probiotics show similar efficacy to lactulose in improving MHE (week 4: OR 0.93,95% CI 0.45-1.91; week 12: OR 0.73,95% CI 0.35-1.51) 4
• Both treatments prevent overt HE development with comparable effectiveness 4

Mechanistic Considerations

• Probiotics work by correcting intestinal dysbiosis, reducing bacterial translocation, and decreasing ammonia production 5, 6
• Specific strains like Clostridium butyricum combined with Bifidobacterium infantis significantly improve intestinal mucosal barriers and reduce venous ammonia 6
• Probiotic supplementation increases neutrophil resting burst (2.6-3.2%, P=0.0134) and neopterin levels (7.7-8.4 nmol/L, P=0.001), potentially explaining beneficial immune effects 5

Clinical Algorithm for Probiotic Use

For critically ill ACLF patients with overt HE:

• Prioritize lactulose and rifaximin as first-line therapy 1
• Do not add probiotics routinely 1

For stable cirrhotic outpatients with MHE:

• Consider probiotics as adjunctive therapy to improve cognitive function and quality of life 2, 4
• Use multi-strain formulations containing Lactobacillus, Bifidobacterium, and Clostridium species 6, 2
• Treatment duration of at least 4-12 weeks appears necessary for benefit 4

For cirrhotic patients without HE:

• Probiotics may help maintain liver function but evidence remains limited 5
• Consider in patients with NAFLD/NASH-related cirrhosis for metabolic benefits 1

Important Caveats

• No mortality benefit has been demonstrated with probiotics in any cirrhotic population 1, 3
• Probiotics do not significantly reduce serum ammonia levels (WMD -3.67,95% CI -15.71 to 8.37, P=0.55) despite clinical improvements 3
• Evidence quality remains very low to low across most outcomes 1
• The optimal probiotic strain, dose, and duration remain undefined 1, 2