Podcast: Medical interventions to prevent graft rejection after liver transplantation

Liver transplantation is the main treatment option for people with severe, advanced liver disease, but it’s a challenging procedure that can lead to serious complications. The Cochrane Hepato-Biliary Group has produced several reviews to look at the evidence to help overcome these, and a new review from March 2017 examines immunosuppressive therapy to prevent the body from rejecting the transplanted liver. We asked the lead author, Kurinchi Gurusamy from the UCL Medical School in London in the UK to tell us what they found.

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John: Hello, I'm John Hilton, editor of the Cochrane Editorial unit. Liver transplantation is the main treatment option for people with severe, advanced liver disease, but it’s a challenging procedure that can lead to serious complications. The Cochrane Hepato-Biliary Group has produced several reviews to look at the evidence to help overcome these, and a new review from March 2017 examines immunosuppressive therapy to prevent the body from rejecting the transplanted liver. We asked the lead author, Kurinchi Gurusamy from the UCL Medical School in London in the UK to tell us what they found.

Kurinchi: When a liver is transplanted, the body of the person receiving it will mount an immune response, which can be serious enough to lead to rejection and loss of the liver, and the death of the patient. Various drugs are used to try to suppress this response, alone or in combination, but it’s not clear which regimen is the best and we wanted to try to find out by doing this Cochrane Review. We focused on the regimens that are used in maintenance therapy, which usually begins a few months after the transplantation and lasts the rest of the patient’s life.
We included randomised trials reported up to October 2016 in which patients had undergone liver transplantation, and we used an advanced form of statistical analysis, called network meta-analysis to simultaneously combine the evidence for different interventions from many separate trials. However, because some important information was missing from the studies that we identified, we need to be cautious about the results of the network meta-analysis.
In total, we found 26 randomised trials with nearly 4000 participants. We were able to use data on 3700 of these patients, from 23 trials, but rated all the trials as being at high risk of bias and judged the overall quality of the evidence to be low or very low.
Several immunosuppressive regimens were compared in the trials but we found no evidence of difference in the risk of death or loss of the transplanted liver between the different immunosuppressive regimens based on the network meta-analysis. In a direct comparison in a single trial of 222 participants, the risk of death and loss of the liver was higher with the combination of tacrolimus plus sirolimus than with tacrolimus alone.
There was no clear evidence for any differences between the various immunosuppressive regimens in the proportion of people who had adverse events, kidney problems, or rejection of the liver, whether or not it required treatment. But the number of adverse events was lower with cyclosporine A than with many other immunosuppressive regimens, although re-transplantations were more common with this drug than with tacrolimus.
In summary, despite more than 20 trials to date, we still can’t be sure which maintenance immunosuppressive regimen is best after liver transplantation. There is an ongoing need for well-designed randomised trials, and we suggest that these should include tacrolimus as one of the comparison groups.

John: If you would like to read more about the trials that have been done and the efforts of these Cochrane Reviews to make maximum use of the existing data, you can find the full review at Cochrane Library dot com with a simple search for ‘maintenance immunosuppression and liver transplantation’. That’s also the way to find future updates should the additional trials become available.

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