Prostaglandins for liver transplanted patients

Liver transplantation is the most effective treatment for patients with advanced liver disease (cirrhosis). However, early postoperative problems such as graft failure or acute renal failure requiring dialysis are common. Patients evolving with such problems are at increased risk of death. Prostaglandins are substances produced by the human body with several actions including vasodilation. They might prevent perioperative hepatic and kidney lesions caused by lack of blood supply. This review summarised and meta-analysed the evidence from randomised clinical trials on the effect of prostaglandins for adult liver transplanted patients. We found ten trials randomising 652 patients. Evidence from these trials is inconclusive on the role of prostaglandins regarding outcomes such as death or liver re-transplantation. The risk of acute kidney failure requiring dialysis may be reduced by two thirds if a liver transplant patient receives prostaglandins, although the level of evidence is only moderate due to risks of systematic errors (bias) and random errors (play of chance). No severe adverse events are reported. Therefore, further randomised trials with low risk of bias and sufficient sample sizes are still needed to establish whether prostaglandins should be administered for liver transplanted patients.

Authors' conclusions: 

We found no evidence that the administration of prostaglandins to liver transplanted patients reduces the risk of death, primary non-function of the allograft, or liver re-transplantation. Prostaglandins might reduce the risk of acute kidney failure requiring dialysis, but the quality of the evidence is considered only moderate due to high risk of bias in most of the included trials. Moreover, there are risks of outcome measure reporting bias and random errors. Therefore, further randomised, placebo-controlled trials are deemed necessary.

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Background: 

Prostaglandins may reduce ischaemic injury after liver transplantation. Several small randomised trials have evaluated the effects of prostaglandins in patients undergoing liver transplantation. Results of these trials are inconsistent, and none has enough power to reliably exclude effects of prostaglandins.

Objectives: 

To assess the benefits and harms of prostaglandin E1 or E2 in adult liver-transplanted patients.

Search strategy: 

We searched 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, and LILACS (search on 20 April 2011). In addition, we perused the reference lists of the identified studies and contacted trials investigators, and national and international experts in order to identify more trials for the review.

Selection criteria: 

We included randomised clinical trials evaluating prostaglandin E1 or E2 initiated in the perioperative period versus placebo or standard treatment for adult patients undergoing liver transplantation. We did not apply any language or publication status restrictions.

Data collection and analysis: 

Two authors independently evaluated methodological quality, ie, risk of bias of the included trials, and extracted data using standardised data extraction forms. We contacted trial investigators in attempt to retrieve information not available in the original manuscripts. We used random-effects model meta-analyses and fixed-effect model meta-analyses to estimate the odds ratio with 95% confidence interval (CI).

Main results: 

We included ten trials in which 652 patients were randomised. The risk of bias was considered high in most trials. There was no significant effect of prostaglandins on all-cause mortality (37/298[12.4%] in prostaglandin group versus 47/312[15.1%] in control group; OR 0.84, 95% CI 0.53 to 1.37; I2 = 0%), on primary non-function of the allograft (8/238 [3.4%] versus. 16/250[6.4%] ;OR 0.55, 95% CI 0.23 to 1.33; I2 = 0%), and on liver re-transplantation (12/161[7.5%] versus 14/171[8.2%]; OR 0.99, 95% CI 0.44 to 2.25; I2 = 0%). Prostaglandins seemed to significantly decrease the risk of acute kidney failure requiring dialysis (13/158[8.2%] versus 34/171[9.9%]; OR 0.37, 95% CI 0.18 to 0.75; I2 = 0%). There was no significant increase in the risk of adverse events with prostaglandins.

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