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Review
. 2023 Aug 4;8(8):CD006006.
doi: 10.1002/14651858.CD006006.pub3.

Prostaglandins for adult liver transplanted recipients

Zubair Umer Mohamed  1   2 , Christi Titus Varghese  3 , Abish Sudhakar  4 , Lakshmi Kumar  1 , Unnikrishnan Gopalakrishnan  3 , Dinesh Balakrishnan  3 , Ramachandran Narayanamenon  3 , Surendran Sudhindran  3
Affiliations
Review

Prostaglandins for adult liver transplanted recipients

Zubair Umer Mohamed et al. Cochrane Database Syst Rev. .

Abstract

Background: 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.

Objectives: To evaluate the benefits and harms of prostaglandins in adults undergoing liver transplantation compared with placebo or standard care.

Search methods: We used standard, extensive Cochrane search methods. The latest search date was 27 December 2022.

Selection criteria: 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.

Data collection and analysis: 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.

Main results: 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.

Authors' conclusions: 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.

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Conflict of interest statement

ZUM: none.

CTV: none.

AS: none.

LK: none.

UG: none.

DB: none.

RN: none.

SS: none.

Figures

1
1
Study flow diagram Date of last search 27 December 2022
2
2
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
3
3
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
4
4
All‐cause mortality. The Trial Sequential Analysis results showed that the Trial Sequential Analysis adjusted 95% CI of risk ratio (RR), using the random‐effects model, was 0.87 (95% CI 0.21 to 3.59), and the diversity‐adjusted required information size (DARIS) for detecting an intervention effect was 11,719 participants. The blue line (Z‐curve) shows the cumulative z value (771 participants). The horizontal green dotted lines show the threshold for significance in conventional meta‐analysis, at 1.96 of the Z‐value, corresponding to the P‐value of 0.05. The red lines, at the left top and bottom corners, show the trial sequential boundaries for benefit or harm, representing the threshold for statistical significance in the TSA. The red dotted triangular shape to the right shows the futility boundaries and futility area of the TSA.
1.1
1.1. Analysis
Comparison 1: Prostaglandins versus placebo/standard care, Outcome 1: All‐cause mortality
1.2
1.2. Analysis
Comparison 1: Prostaglandins versus placebo/standard care, Outcome 2: Serious adverse events
1.3
1.3. Analysis
Comparison 1: Prostaglandins versus placebo/standard care, Outcome 3: Liver retransplantation
1.4
1.4. Analysis
Comparison 1: Prostaglandins versus placebo/standard care, Outcome 4: Early allograft dysfunction
1.5
1.5. Analysis
Comparison 1: Prostaglandins versus placebo/standard care, Outcome 5: Primary non‐function of the allograft
1.6
1.6. Analysis
Comparison 1: Prostaglandins versus placebo/standard care, Outcome 6: Acute kidney failure requiring dialysis
1.7
1.7. Analysis
Comparison 1: Prostaglandins versus placebo/standard care, Outcome 7: Length of hospital stay (days)
1.8
1.8. Analysis
Comparison 1: Prostaglandins versus placebo/standard care, Outcome 8: Adverse events considered non‐serious
2.1
2.1. Analysis
Comparison 2: Prostaglandins compared with placebo/standard care: subgroup analyses, Outcome 1: All‐cause mortality
2.2
2.2. Analysis
Comparison 2: Prostaglandins compared with placebo/standard care: subgroup analyses, Outcome 2: Liver retransplantation
2.3
2.3. Analysis
Comparison 2: Prostaglandins compared with placebo/standard care: subgroup analyses, Outcome 3: Primary non‐function
2.4
2.4. Analysis
Comparison 2: Prostaglandins compared with placebo/standard care: subgroup analyses, Outcome 4: Acute kidney failure requiring dialysis
3.1
3.1. Analysis
Comparison 3: Intention‐to‐treat analysis compared with per‐protocol analysis: subgroup analyses, Outcome 1: All‐cause mortality
3.2
3.2. Analysis
Comparison 3: Intention‐to‐treat analysis compared with per‐protocol analysis: subgroup analyses, Outcome 2: Liver retransplantation
3.3
3.3. Analysis
Comparison 3: Intention‐to‐treat analysis compared with per‐protocol analysis: subgroup analyses, Outcome 3: Primary non‐function
3.4
3.4. Analysis
Comparison 3: Intention‐to‐treat analysis compared with per‐protocol analysis: subgroup analyses, Outcome 4: Acute kidney failure requiring dialysis
4.1
4.1. Analysis
Comparison 4: Trials funded for‐profit compared to trials without for‐profit support: subgroup analyses, Outcome 1: All‐cause mortality
5.1
5.1. Analysis
Comparison 5: Sensitivity analysis, Outcome 1: All‐cause mortality
See this image and copyright information in PMC

Update of

References

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Almazroo 2021 {published data only}
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Briegel 1992 {published data only}
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Bucuvalas 2001 {published data only}
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Ghonem 2011 {published data only}
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Onoe 2013 {published data only}
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