To document the safety and efficacy of laparoscopic living donor hepatectomy in comparison with open liver resection for living donor liver transplantation.
Medline database, EMASE and Cochrane library were searched for original studies comparing laparoscopic living donor hepatectomy (LLDH) and open living donor hepatectomy (OLDH) by January 2015. Meta-analysis was performed to evaluate donors’ perioperative outcomes.
Nine studies met selection criteria, involving 1346 donors of whom 318 underwent LLDH and 1028 underwent OLDH. The Meta analysis demonstrated that LLDH group had less operative blood loss [patients 1346; WMD: -56.09 mL; 95%CI: -100.28-(-11.90) mL; P = 0.01], shorter hospital stay [patients 737; WMD: -1.75 d; 95%CI: -3.01-(-0.48) d; P = 0.007] but longer operative time (patients 1346; WMD: 41.05 min; 95%CI: 1.91–80.19 min; P = 0.04), compared with OLDH group. There were no significant difference in other outcomes between LLDH and OLDH groups, including overall complication, bile leakage, postoperative bleeding, pulmonary complication, wound complication, time to dietary intake and period of analgesic use.
Citation: Xu J, Hu C, Cao H-L, Zhang M-L, Ye S, Zheng S-S, et al. (2016) Meta-Analysis of Laparoscopic versus Open Hepatectomy for Live Liver Donors. PLoS ONE 11(10): e0165319. https://doi.org/10.1371/journal.pone.0165319
Editor: Salvatore Gruttadauria, Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione, ITALY
Received: July 27, 2016; Accepted: October 9, 2016; Published: October 27, 2016
Copyright: © 2016 Xu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Data Availability: All relevant data are within the paper and its Supporting Information files.
Funding: The author(s) received no specific funding for this work.
Competing interests: The authors have declared that no competing interests exist.
Living donor liver transplantation(LDLT) has developed rapidly over the couple decades since the first treatment in 1989 in children. The indication for LDLT has been extended to adult recipients[2–4]. LDLT serves as an established treatment for patients with end-stage liver disease (ESLD) when a deceased donor liver is not available. Partial hepatic allografts from live donors, compared with deceased donors, have been found to reduce the risk of the recipient dying on the waiting list. And the recipient survival is comparable to that in cadaveric liver transplantation[5–9].
The major concerns of potential donor are mainly the pain, morbidity associated with surgery and postoperative recovery. The method of open living donor hepatectomy (OLDH) has been nowadays challenged by less invasive techniques, although the most majority of procedures are still conventional open donor partial hepatectomy. Laparoscopic living donor hepatectomy (LLDH) are being increasingly performed in experienced centers.
The first LLDH was performed for a pediatric recipient by Cherqui in 2002 . Since then, many transplant centers worldwide have adopted LLDH. Smaller incision sizes have stimulated reports of many investigations of lower blood loss, shorter hospital stay and faster physical recovery[12, 13]. However, the LLDH still remains the most controversial application of laparoscopic liver surgery. The overriding concern for the transplant community is donor safety. Advocates of OLDH have concerned that laparoscopic surgery has been too rapidly extended to living liver donor candidates.
Several studies have compared donors’ perioperative complications between LLDH and the widely used standard OLDH. However, no definite consensus has been reached. We therefore performed a systematic review and meta-analysis to better clarify this issue.
Materials and Methods
We attempted to report this meta-analysis follow the proposed MOOSE (meta-analysis of observational studies in epidemiology) guidelines. The MEDLINE, EMBASE and Cochrane database were searched to retrieve relevant studies published from January 2002 to January 2015. The following medical search headings and keywords were used: “laparoscopy” or “laparoscopic” or “minimally invasive surgery” or “minimal access surgery” and “hepatectomy” or “liver resection” or “hepatic resection” or “liver segmentectomy” or “hepatic segmentectomy” and “living donor” or “liver donor”. The “related articles” function was used to broaden our search. Reference lists of all retrieved articles were manually searched for additional studies. No language restriction was applied.
Data extraction was carried out by two independent reviewers (J.X. and C.H.). The following parameters were extracted: study name, first authors, publication year, study population characteristics, study design, number of subjects operated on with each procedure, and outcomes of interest. Disagreement between the reviewers were resolved by discussion and consensus between all authors.
Outcomes of Interest
Operative outcomes: Operative time and intraoperative blood loss.
Postoperative outcomes: overall complication, bile leakage, postoperative bleeding, pulmonary complication, wound complication, period of analgesic use, time to dietary intake and hospital stay.
Criteria for Inclusion and Exclusion
To be selected, a study had to meet the following criteria: (1) looked at laparoscopic and open donor hepatectomy surgical techniques for live liver donors. (2) compared the perioperative complications for LLDH and OLDH. (3) reported on at least one of the outcomes mentioned and had detailed the demographics to enable comparison and stratification of outcomes.
Abstracts, letters, editorials, expert opinions, case reports, reviews without original data and studies lacking control groups were excluded. Studies with less complete date from the same author or institution that contained significant overlap of patient data were also excluded.
The quality of studies was assessed according to the Newcastle-Ottawa Scale (NOS), by examining three factors: patient selection, comparability of the study groups and assessment of outcome. Studies achieving more than 6 points (maximum 11) were defined as higher quality.
The meta-analysis was performed using the Review Manager version 5.3 software (The Cochrane Collaboration, Oxford, United Kingdom). Analyses were performed using odds ratios (OR) for dichotomous variables and weighted mean differences (WMD) for continuous variables. The corresponding 95% confidence intervals (CIs) were reported. Heterogeneity was assessed by using the inconsistency statistic (I2). The fixed-effects model was used for calculations of all outcomes. However, when the heterogeneity was more than 25%, a random-effects model was used. Statistical significance was considered at P < 0.05. Sensitivity analysis was performed by removing extreme data (the maximum or the minimum) and analyzing the effect on the overall results. Graphical funnel plots were generated to make visual inspections for publication bias. Egger test (Stata version 12.0) was used to detect the funnel plot asymmetry statistically. Publication bias was considered at P < 0.05.
Flow of Included Studies
As shown in the flow chart (Fig 1), the search strategy initially generated 467 potentially relevant studies. After the titles and abstracts were retrieved, 442 articles were excluded. Twenty-five articles were reviewed in detail. Finally, 9 non-randomized comparative studies were included for the current meta-analysis[12, 13, 21–27].
The characteristics of included studies are shown in Table 1. The nine studies included a total of 1346 patients: 318 in LLDH group and 1028 in OLDH group. Four studies were conducted in Korea[22, 23, 25, 27], one in the United States, one in France, one in China., one in Japan, and one in India. The sample size of the included studies ranged from 22 to 493 patients. Seven of the nine studies reported on the conversion rate in LLDH group, which varied from 0 to 10%[12, 13, 21–24, 26]. The reasons for conversion including a left portal branch injury (n = 1), a right hepatic vein injury (n = 1) and an inferior vena cava injury (n = 1). And the reasons for the other two conversions were not detailed described.
Nine studies[12, 13, 21–27] provided mean operation time, analysis of which showed that LLDH had significantly longer operative time compared to OLDH (patients 1346; WMD: 41.05 min; 95%CI: 1.91–80.19 min; P = 0.04). Similarly, nine studies[12, 13, 21–27] reported detailed data for estimated blood loss between the two groups. We found that intraoperative blood loss was significantly less in LLDH group [patients 1346; WMD: -56.09 mL; 95%CI: -100.28-(-11.90) mL; P = 0.01]. There was significant heterogeneity of difference in operation time and blood loss between the studies (P < 0.1).
Six studies[12, 13, 22–24, 27] reported on length of hospital stay, which was found to be significantly shorter in the LLDH group versus the OLDH group [patients 737; WMD: -1.75 d; 95%CI: -3.01-(-0.48) d; P = 0.007] with significant heterogeneity (P < 0.1). No significant difference was observed between the groups regarding other outcomes, such as overall complication (trials 8; patients 853; OR: 0.72; 95%CI: 0.47–1.11; P = 0.14), bile leakage (trials 4; patients 256; OR: 0.59; 95%CI: 0.15–2.24; P = 0.43), postoperative bleeding (trials 3; patients 575; OR: 1.97; 95%CI: 0.54–7.22; P = 0.31), pulmonary complication (trials 3; patients 575; OR: 0.95; 95%CI: 0.22–4.04; P = 0.94), wound complication (trials 5; patients 627; OR: 0.55; 95%CI: 0.20–1.51; P = 0.25), time to dietary intake (trials 2; patients 132; WMD: -0.03; 95%CI: -1.18–1.12; P = 0.96) and period of analgesic use (trials 2; patients 80; WMD: -0.52; 95%CI: -1.11–0.06; P = 0.08).
The funnel plot was based on the operation time, intraoperative blood loss and hospital stay, and the appearance was symmetrical. The Egger test gave a P value of 0.072 for operation time, a P value of 0.804 for intraoperative blood loss and a P value of 0.781 for hospital stay, indicating no evidence of publication bias (Figs 6–8).
Although OLDH is still the standard procedure for LDLT, LLDH has been designed to perform a less invasive donor operation. LLDH is a challenging technique for surgeons because the liver is an unpaired organ with the need for parenchymal transection. Rare but catastrophic complications have been reported in LLDH[29, 30]. On the contrary, increased experience in donor surgery and technical advancements have reduced the incidence of donor morbidity and mortality[29, 31]. In spite of these advancements, LLDH has not been accepted by many surgeons, mainly for reasons of unassured safety. However, the difference in perioperative outcomes between LLDH and OLDH has not been assessed in a randomized controlled trial.
Our results demonstrated that LLDH was associated with significantly longer operative time, which could be explained by the frequent installation and removal of laparoscopic devices, mobilization and dissection the lobe of the liver under laparoscopy as well as surgeons’ experience and initial learning curve[26, 27]. Meanwhile, the operative time difference between LLDH and OLDH might correlate with the type of hepatectomy. Marubashi et al. reported that operative time in the left-lobe laparoscopy-assisted hybrid donor hepatectomy was associated with the maximal distance between the surface of the right lobe and the portal vein bifurcation. Decreasing the operating time was not a crucial aim in LLDH, but operating time was indeed both related to the warm ischemia time and some rare complications such as gas embolism. The meta-analysis also revealed decreased blood loss for LLDH compared to OLDH. This finding was probably attributed to the more meticulous dissection under image magnification and smaller incision on the abdominal wall provided by the laparoscopic approach as well as the hemostatic effect of pneumoperitoneum on the hepatic vein branches.
The efficacy of the LDLT should prioritize the donor safety. A recent worldwide survey revealed that the donor mortality rate was 0.20% (23/11553), with 19 of these 23 deaths related to the surgical procedure. In this analysis, we found no mortality in neither of the donor groups. However, the LLDH group reported five cases that conversed to open surgery, three of which the causative data were available. One case was converted to open donation in left lateral sectionectomy when a left portal branch injury occurred, and other two cases of conversion due to a right hepatic vein injury and an inferior vena cava injury in right hepatectomy. Additionally, we found no significant difference in postoperative morbidity between the two groups with regards to developing overall complication, bile leakage, bleeding, pulmonary complication and wound complication. These results pointed towards the feasibility of LLDH.
With respect to postoperative recovery, the length of hospital stay after surgery was shorter in the LLDH group. This might be ascribed to the surgeons’ postoperative protocols. However, our results revealed no significant difference between LLDH and OLDH regarding the period of analgesic use and time to dietary intake. Thus, combined with the previous results about the postoperative complications, the laparoscopic method of incision seemed to be in favor of reducing hospital stay.
Although our analysis overcomes the drawbacks of each individual study and may provide the most convincing results so far, it has some potential limitations. First, significant heterogeneity was found in certain outcome measures, which might have resulted from differences in study designs, sample sizes, geographical variations, donors’ baseline characteristics, surgical techniques and surgeons’ learning curve. For example, there was no randomized trials on our topic, all of them were observational. Also, both cohort studies and case-control studies were included in this meta-analysis. The six case-control studies involved in our meta-analysis were all hospital based[12, 21–23, 26, 27]. Meanwhile, several studies with small sample size brought some concerns regarding the reliability of their results[12, 13, 21–26]. To address this issue, we applied the random-effects model to determine the overall estimate of variability.
Second, we did a mixed analysis and did not differentiate laparoscopy-assisted hybrid donor hepatectomy or totally laparoscopic donor hepatectomy, as well as left hepatectomy or right hepatectomy. Because most studies had mixed results only and the data in each group was insufficient for analysis.
Third, it should be noted that donors who underwent LLDH were a selected population. For example, LLDH should only be performed in cases with a favorable anatomy, whereas OLDH was preferred for urgent LDLT from some surgeon’s view point.
Fourth, the outcome of the operation time had some sensitivity. In view of the mainly influencing factors, we tried subgroup analyses classified by year or type of hepatectomy. However, it was unable to adequately explore sources of this heterogeneity, and meta-regression was not possible for the small number of studies. Therefore, the meta-analysis results of operation time should be carefully concluded. Fortunately, it did not affect the pooled results of intraoperative blood loss and hospital stay.
Finally, although the Egger test showed no evidence of publication bias on the main outcome measures, for comparisons of the time to dietary intake and period of analgesic use, the analysis was based on only 2 studies. Under these circumstances, a single study might have great impact on the pooled results, so the potential bias due to publication could not be minimized. Based on these limitations, more future prospective studies should be needed.
In conclusion, our meta-analysis suggests that LLDH is a safe and effective alternative to OLDH for donors. The promising use of LLDH could further minimize its invasiveness and benefit donors’ postoperative recovery. Further prospective randomized controlled studies may add more information to ascertain the advantages of LLDH in LDLT.
S1 Fig. Forest plot results not shown in the manuscript.
S2 File. The 341 irrelevant articles in Selection flow diagram.
- Conceptualization: WLW SSZ.
- Formal analysis: MLZ SY.
- Investigation: JX CH HLC.
- Methodology: WLW SSZ.
- Project administration: WLW.
- Supervision: WLW SSZ.
- Writing – original draft: JX CH HLC.
- 1. Raia S, Nery JR, Mies S. Liver transplantation from live donors. Lancet. 1989;2(8661):497. pmid:2570198.
- 2. Hashikura Y, Makuuchi M, Kawasaki S, Matsunami H, Ikegami T, Nakazawa Y, et al. Successful living-related partial liver transplantation to an adult patient. Lancet. 1994;343(8907):1233–4. pmid:7909905.
- 3. Lo CM, Fan ST, Liu CL, Wei WI, Lo RJ, Lai CL, et al. Adult-to-adult living donor liver transplantation using extended right lobe grafts. Annals of surgery. 1997;226(3):261–9; discussion 9–70. pmid:9339932; PubMed Central PMCID: PMC1191019.
- 4. Kawasaki S, Makuuchi M, Matsunami H, Hashikura Y, Ikegami T, Nakazawa Y, et al. Living related liver transplantation in adults. Annals of surgery. 1998;227(2):269–74. pmid:9488526; PubMed Central PMCID: PMC1191245.
- 5. Marcos A, Fisher RA, Ham JM, Shiffman ML, Sanyal AJ, Luketic VA, et al. Right lobe living donor liver transplantation. Transplantation. 1999;68(6):798–803. pmid:10515380.
- 6. Yersiz H, Renz JF, Farmer DG, Hisatake GM, McDiarmid SV, Busuttil RW. One hundred in situ split-liver transplantations: a single-center experience. Annals of surgery. 2003;238(4):496–505; discussion 6–7. pmid:14530721; PubMed Central PMCID: PMC1360108.
- 7. Otte JB. Paediatric liver transplantation—a review based on 20 years of personal experience. Transplant international: official journal of the European Society for Organ Transplantation. 2004;17(10):562–73. pmid:15592713.
- 8. Thuluvath PJ, Yoo HY. Graft and patient survival after adult live donor liver transplantation compared to a matched cohort who received a deceased donor transplantation. Liver transplantation: official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society. 2004;10(10):1263–8. pmid:15376301.
- 9. Kulik LM, Fisher RA, Rodrigo DR, Brown RS Jr., Freise CE, Shaked A, et al. Outcomes of living and deceased donor liver transplant recipients with hepatocellular carcinoma: results of the A2ALL cohort. American journal of transplantation: official journal of the American Society of Transplantation and the American Society of Transplant Surgeons. 2012;12(11):2997–3007. pmid:22994906; PubMed Central PMCID: PMC3523685.
- 10. Samstein B, Cherqui D, Rotellar F, Griesemer A, Halazun KJ, Kato T, et al. Totally laparoscopic full left hepatectomy for living donor liver transplantation in adolescents and adults. American journal of transplantation: official journal of the American Society of Transplantation and the American Society of Transplant Surgeons. 2013;13(9):2462–6. Epub 2013/09/17. pmid:24034709.
- 11. Cherqui D, Soubrane O, Husson E, Barshasz E, Vignaux O, Ghimouz M, et al. Laparoscopic living donor hepatectomy for liver transplantation in children. Lancet. 2002;359(9304):392–6. pmid:11844509.
- 12. Soubrane O, Cherqui D, Scatton O, Stenard F, Bernard D, Branchereau S, et al. Laparoscopic left lateral sectionectomy in living donors: safety and reproducibility of the technique in a single center. Ann Surg. 2006;244(5):815–20. Epub 2006/10/25. pmid:17060776; PubMed Central PMCID: PMCPMC1856581.
- 13. Marubashi S, Wada H, Kawamoto K, Kobayashi S, Eguchi H, Doki Y, et al. Laparoscopy-assisted hybrid left-side donor hepatectomy. World J Surg. 2013;37(9):2202–10. Epub 2013/06/06. pmid:23736986.
- 14. Buell JF, Cherqui D, Geller DA, O'Rourke N, Iannitti D, Dagher I, et al. The international position on laparoscopic liver surgery: The Louisville Statement, 2008. Annals of surgery. 2009;250(5):825–30. pmid:19916210.
- 15. Ishizawa T, Hasegawa K, Kokudo N. Laparoscopy-Assisted Hybrid Left-side Donor Hepatectomy: Is it Truly Less Invasive for Living Donors? World J Surg. 2013. pmid:24142331.
- 16. Stroup DF, Berlin JA, Morton SC, Olkin I, Williamson GD, Rennie D, et al. Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group. JAMA: the journal of the American Medical Association. 2000;283(15):2008–12. pmid:10789670.
- 17. Cook DA, Reed DA. Appraising the Quality of Medical Education Research Methods: The Medical Education Research Study Quality Instrument and the Newcastle-Ottawa Scale-Education. Academic medicine: journal of the Association of American Medical Colleges. 2015. pmid:26107881.
- 18. Galbraith RF. A note on graphical presentation of estimated odds ratios from several clinical trials. Statistics in medicine. 1988;7(8):889–94. pmid:3413368.
- 19. Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. Bmj. 2003;327(7414):557–60. pmid:12958120; PubMed Central PMCID: PMC192859.
- 20. Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. Bmj. 1997;315(7109):629–34. pmid:9310563; PubMed Central PMCID: PMC2127453.
- 21. Baker TB, Jay CL, Ladner DP, Preczewski LB, Clark L, Holl J, et al. Laparoscopy-assisted and open living donor right hepatectomy: A comparative study of outcomes. Surgery. 2009;146(4):817–25. pmid:19789043
- 22. Kim KH, Jung DH, Park KM, Lee YJ, Kim DY, Kim KM, et al. Comparison of open and laparoscopic live donor left lateral sectionectomy. Br J Surg. 2011;98(9):1302–8. Epub 2011/07/01. pmid:21717424.
- 23. Choi HJ, You YK, Na GH, Hong TH, Shetty GS, Kim DG. Single-port laparoscopy-assisted donor right hepatectomy in living donor liver transplantation: sensible approach or unnecessary hindrance? Transplant Proc. 2012;44(2):347–52. Epub 2012/03/14. pmid:22410013.
- 24. Zhang X, Yang J, Yan L, Li B, Wen T, Xu M, et al. Comparison of laparoscopy-assisted and open donor right hepatectomy: a prospective case-matched study from china. Journal of gastrointestinal surgery: official journal of the Society for Surgery of the Alimentary Tract. 2014;18(4):744–50. Epub 2013/12/07. pmid:24307217.
- 25. Choi Y, Yi NJ, Lee KW, Suh KS. Section 17. Laparoscopic and minimal incisional donor hepatectomy. Transplantation. 2014;97 Suppl 8:S69–75. pmid:24849839
- 26. Makki K, Chorasiya VK, Sood G, Srivastava PK, Dargan P, Vij V. Laparoscopy-assisted hepatectomy versus conventional (open) hepatectomy for living donors: when you know better, you do better. Liver transplantation: official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society. 2014;20(10):1229–36. Epub 2014/06/26. pmid:24961992.
- 27. Suh SW, Lee KW, Lee JM, Choi Y, Yi NJ, Suh KS. Clinical outcomes of and patient satisfaction with different incision methods for donor hepatectomy in living donor liver transplantation. Liver transplantation: official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society. 2015;21(1):72–8. Epub 2014/10/29. pmid:25348280.
- 28. Demirbas T, Bulutcu F, Dayangac M, Yaprak O, Guler N, Oklu L, et al. Which incision is better for living-donor right hepatectomy? Midline, J-shaped, or Mercedes. Transplant Proc. 2013;45(1):218–21. pmid:23375303.
- 29. Middleton PF, Duffield M, Lynch SV, Padbury RT, House T, Stanton P, et al. Living donor liver transplantation—adult donor outcomes: a systematic review. Liver transplantation: official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society. 2006;12(1):24–30. pmid:16498709.
- 30. Cheah YL, Simpson MA, Pomposelli JJ, Pomfret EA. Incidence of death and potentially life-threatening near-miss events in living donor hepatic lobectomy: a world-wide survey. Liver transplantation: official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society. 2013;19(5):499–506. pmid:23172840.
- 31. Kim SJ, Na GH, Choi HJ, Yoo YK, Kim DG. Surgical outcome of right liver donors in living donor liver transplantation: single-center experience with 500 cases. J Gastrointest Surg. 2012;16(6):1160–70. pmid:22426687.
- 32. Kaneko H, Otsuka Y, Tsuchiya M, Tamura A, Katagiri T, Yamazaki K. Application of devices for safe laparoscopic hepatectomy. HPB: the official journal of the International Hepato Pancreato Biliary Association. 2008;10(4):219–24. pmid:18773101; PubMed Central PMCID: PMC2518297.
- 33. Dagher I, Lainas P, Carloni A, Caillard C, Champault A, Smadja C, et al. Laparoscopic liver resection for hepatocellular carcinoma. Surg Endosc. 2008;22(2):372–8. pmid:17704878.