Are prostaglandins (a drug given to protect the liver) a useful treatment in adults who have had liver transplantation surgery?
Key messages
In adults who have had liver transplantation surgery, prostaglandins may reduce death from any cause, up to one month after surgery, compared with placebo (sham treatment) or standard care. Prostaglandins may result in a large reduction in the development of acute kidney failure requiring dialysis.
Prostaglandins may result in little to no difference in serious adverse events (side effects), and we do not know the effect of prostaglandins on adverse events considered non-serious.
Further updates of this review, based on future studies, may help in reaching more certain conclusions about prostaglandins.
What is liver transplantation?
The treatment for advanced liver disease and liver failure is liver transplantation. It involves replacing a diseased liver with a new, healthy one.
What are prostaglandins?
Prostaglandins are medicines that could help in prompt functioning of the new liver. Prostaglandins are also produced by the body and increase blood supply to the liver and kidneys.
What did we want to find out?
We wanted to know if prostaglandins are a useful treatment after liver transplantation and if they caused any side effects when compared to placebo or usual care.
We looked at the following outcomes: deaths from any cause up to one month after treatment; any side effects; effects on quality of life; whether the need for retransplantation was decreased; whether initial poor or non-function of the liver was decreased; whether early kidney injury needing dialysis was decreased; and whether length of hospital stay was decreased.
What did we do?
We searched for studies on prostaglandins used to treat adults who had received a liver transplant compared with placebo or standard care. Participants could be of any sex or ethnicity.
We compared the results of the studies and rated them, based on factors such as study methods and sizes.
What did we find?
We found 11 studies with 771 participants. Of these, 378 participants were given prostaglandins. Apart from one study, all other studies took place in high- and upper-middle-income countries.
Main results
Death from any cause
Prostaglandins may reduce death from any cause (11 studies, 771 people). In 1000 people, we may expect that 21 fewer people would die with prostaglandins compared with standard care or placebo.
Did people get better with prostaglandins?
– Prostaglandins may result in little to no difference in need for retransplantation (6 studies, 468 participants).
– Prostaglandins may result in little to no difference in initial poor function of the liver (1 study, 99 participants).
– Prostaglandins may result in little to no difference in initial non-function of the liver (7 studies, 624 participants).
– Prostaglandins may result in a large reduction in the development of acute kidney injury needing dialysis (5 studies, 477 participants).
Did people get worse with prostaglandins?
We did not find any information to suggest that prostaglandins cause harm.
Quality of life
None of the studies reported quality of life.
Unwanted effects
We found no information to suggest that prostaglandins cause harm.
What are the limitations of the evidence?
Our evidence is limited because studies used different methods to measure and record their results, and we did not find studies for some of our outcomes of interest. In addition, our confidence in the evidence was low for all outcomes except for serious adverse events considered non-serious, for which our confidence in the evidence was very low. Low and very low confidence in the evidence means that the obtained results are uncertain, and when further studies are performed and data are added, results will change further.
How up-to-date is this evidence?
This evidence is current to 27 December 2022.
Eleven trials evaluated prostaglandins in adult liver transplanted recipients. Based on low-certainty evidence, prostaglandins may reduce all-cause mortality up to one month; may cause little to no difference in serious adverse events, liver retransplantation, early allograft dysfunction, primary non-function of the allograft, and length of hospital stay; and may have a large reduction in the development of acute kidney injury requiring dialysis. We do not know the effect of prostaglandins on adverse events considered non-serious. We lack adequately powered, high-quality trials evaluating the effects of prostaglandins for people undergoing liver transplantation.
Prostaglandins are naturally occurring lipids that are synthesised from arachidonic acid. Multiple studies have evaluated the benefits of prostaglandins in reducing ischaemia reperfusion injury after liver transplantation. New studies have been published since the previous review, and hence it was important to update the evidence for this intervention.
To evaluate the benefits and harms of prostaglandins in adults undergoing liver transplantation compared with placebo or standard care.
We used standard, extensive Cochrane search methods. The latest search date was 27 December 2022.
We included randomised clinical trials evaluating prostaglandins initiated in the perioperative period compared with placebo or standard care for adults undergoing liver transplantation. We included trials irrespective of reported outcomes.
We used standard Cochrane methods. Our primary outcomes were 1. all-cause mortality, 2. serious adverse events, and 3. health-related quality of life. Our secondary outcomes were 4. liver retransplantation, 5. early allograft dysfunction, 6. primary non-function of the allograft, 7. acute kidney failure, 8. length of hospital stay, and 9. adverse events considered non-serious. We used GRADE to assess certainty of evidence.
We included 11 randomised clinical trials with 771 adult liver transplant recipients (mean age 47.31 years, male 61.48%), of whom 378 people were randomised to receive prostaglandins and 393 people were randomised to either placebo (272 participants) or standard care (121 participants). All trials were published between 1993 and 2016. Ten trials were conducted in high- and upper-middle-income countries.
Prostaglandins may reduce all-cause mortality up to one month (risk ratio (RR) 0.86, 95% confidence interval (CI) 0.61 to 1.23; risk difference (RD) 21 fewer per 1000, 95% CI 63 fewer to 36 more; 11 trials, 771 participants; low-certainty evidence). Prostaglandins may result in little to no difference in serious adverse events (RR 0.92, 95% CI 0.60 to 1.40; RD 81 fewer per 1000, 95% CI 148 fewer to 18 more; 6 trials, 568 participants; low-certainty evidence). None of the included trials reported health-related quality of life. Prostaglandins may result in little to no difference in liver retransplantation (RR 0.98, 95% CI 0.49 to 1.96; RD 1 fewer per 1000, 95% CI 33 fewer to 62 more; 6 trials, 468 participants; low-certainty evidence); early allograft dysfunction (RR 0.62, 95% CI 0.33 to 1.18; RD 137 fewer per 1000, 95% CI 241 fewer to 47 more; 1 trial, 99 participants; low-certainty evidence); primary non-function of the allograft (RR 0.58, 95% CI 0.26 to 1.32; RD 23 fewer per 1000, 95% CI 40 fewer to 16 more; 7 trials, 624 participants; low-certainty evidence); and length of hospital stay (mean difference (MD) −1.15 days, 95% CI −5.44 to 3.14; 4 trials, 369 participants; low-certainty evidence). Prostaglandins may result in a large reduction in the development of acute kidney failure requiring dialysis (RR 0.42, 95% CI 0.24 to 0.73; RD 100 fewer per 1000, 95% CI 132 fewer to 49 fewer; 5 trials, 477 participants; low-certainty evidence). The evidence is very uncertain about the effect of prostaglandins on adverse events considered non-serious (RR 1.19, 95% CI 0.42 to 3.36; RD 225 fewer per 1000, 95% CI 294 fewer to 65 fewer; 4 trials, 329 participants; very low-certainty evidence).
Two trials reported receiving funding; one of these was with vested interests.
We found one registered ongoing trial.