Transplant Trial Watch

Effect of probiotics on nutritional status, biochemical parameters, and disease severity in cirrhotic patients referred for liver transplantation-A randomised double blind, placebo-controlled trial.

Ramachandran, G., et al.

Clinical Nutrition ESPEN 2023; 57: 703-710.

This study aimed to investigate how nutritional status, biochemical parameters, and the severity of liver disease are influenced by the administration of probiotics in patients with cirrhosis referred for liver transplantation.

Participants were randomised to receive probiotics or placebo.

215 cirrhotic patients referred for liver transplantation

The main outcomes were assessment of nutritional status using subjective global assessment (SGA) and anthropometric measurements like weight, height, body mass index (BMI), mid upper arm circumference (MUAC), triceps skin fold thickness (TSF), mid-arm muscle circumference (MAMC) and hand grip strength (HGS); liver function parameters including bilirubin, alanine transferase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), and international normalized ratio (INR); and severity of liver disease using the Child Turcotte Pugh classification (CTP) and Model for end-stage liver disea

6 weeks

CET Conclusions
This is a very interesting and well conducted RCT in patients on the liver transplant waiting list. The study was double-blinded, so patients and clinicians were not aware whether each patient was receiving the probiotic treatment or placebo, available in identical capsules. Treatment was given for 6 weeks. Malnutrition is an important complication of cirrhosis and is related to patient outcome with or without transplantation. A sample size was calculated in advance assuming a relatively large dropout proportion, 215 patients were recruited. The assumption on dropout rate was actually quite accurate, and importantly intention to treat analysis was done. Overall patient compliance was very good. The proportion of patients who were well-nourished significantly increased after probiotic therapy, and no change was seen in the placebo group (subjective global assessment). The proportion of overweight and obese patients increased in the treatment group, but not in the placebo group. The proportion of underweight patients did not change in either group. Probiotic use was associated with significant improvement in CTP (Child Turcotte Pugh) score, and reduction in ascites. There was no change in MELD scores. There was no significant difference in survival over the observation period. When compared to baseline biochemical parameters, probiotic treatment was associated with decreased direct bilirubin levels, whilst other parameters remained unchanged. In the placebo group, there was a significant increase in the levels of urea from baseline, and other parameters did not show any significant changes. Overall, the study has shown significant beneficial impacts of probiotic therapy in this patient population without any negative impact of a simple therapy. It is possible that more convincing clinical outcomes would be seen with a longer duration of probiotic therapy, and in a population with more severe liver disease.

Jadad score

Data analysis
Strict intention-to-treat analysis

Allocation concealment

Trial registration

Funding source
Non-industry funded