Figure 1. Ex vivo split liver transplantation into right trisegment and left lateral segment grafts. A, The hilar structures are divided after angiography and cholangiography. B, After parenchymal splitting, the allografts are ready for transplantation. C, Reperfusion of the right trisegment graft.
Figure 2. Split liver transplantations (SLTs) by year (1993-2010) performed at the University of California, San Francisco. A, Pediatric and adult recipients. B, Ex vivo and in situ SLTs.
Figure 3. Types of split grafts transplanted at the University of California, San Francisco (1993-2010). LL indicates left lobe; LLS, left lateral segment; RL, right lobe; and RTS, right trisegment.
Figure 4. Patient (A) and graft (B) survival rates for adult recipients of split liver transplantations (SLTs) at the University of California, San Francisco (UCSF). Comparison of ex vivo and in situ patient (C) and graft (D) survival rates for adult recipients of SLT at the UCSF.
Figure 5. Patient (A) and graft (B) survival rates for pediatric recipients of split liver transplantation (SLT) at the University of California, San Francisco (UCSF). Comparison of ex vivo and in situ patient (C) and graft (D) survival rates for pediatric recipients of SLT at the UCSF.
Vagefi PA, Parekh J, Ascher NL, Roberts JP, Freise CE. Outcomes With Split Liver Transplantation in 106 RecipientsThe University of California, San Francisco, Experience From 1993 to 2010. Arch Surg. 2011;146(9):1052-1059. doi:10.1001/archsurg.2011.218
Author Affiliations: Division of Transplant Surgery, Department of Surgery, University of California, San Francisco.
Background Split liver transplantation (SLT) allows for expansion of the deceased donor pool.
Objectives To assess outcomes and the impact of splitting technique (in situ vs ex vivo) in SLT recipients.
Design Single-center retrospective review (September 18, 1993, to July 1, 2010).
Setting University medical center.
Patients One hundred six SLT recipients.
Main Outcome Measures Postoperative graft and patient survival and postoperative complications.
Results In adults, 1-, 5-, and 10-year overall patient survival was 93%, 77%, and 73%, respectively; overall graft survival was 89%, 76%, and 65%, respectively; ex vivo split patient survival was 93%, 85%, and 74%, respectively; and ex vivo graft survival was 86%, 77%, and 63%, respectively. In situ split patient and graft survival was 94% at 1 year and 75% at 5 years. Postoperative complications included biliary (29%), vascular (11%), unplanned reexploratory surgery (11%), incisional hernia (8%), small-for-size syndrome (n = 1), need for shunt at the time of SLT (n = 1), and primary nonfunction (n = 1). In children, 1-, 5-, and 10-year overall patient survival was 84%, 75%, and 69%, respectively; overall graft survival was 77%, 63%, and 57%, respectively; ex vivo split patient survival was 83%, 73%, and 73%, respectively; and ex vivo graft survival was 75%, 59%, and 59%, respectively. In situ split patient and graft survival was 86% at 1 and 5 years. Postoperative complications included biliary (40%), vascular (26%), and primary nonfunction (n = 1).
Conclusions Split liver transplantation remains an excellent option for expansion of the deceased donor pool for adult and pediatric populations. Postoperative morbidity remains high; however, this is justifiable owing to limited resources.
The shortage of deceased donor livers is the most significant factor inhibiting further application of liver transplantation for patients with end-stage liver disease.1 The technical advance of split liver transplantation (SLT), whereby one liver is divided into 2 partial grafts for successful transplantation in 2 recipients, a child and an adult, emerged in 1988 after the study by Pichlmayr et al.2
Two types of SLT, ex vivo and in situ, have been described. Ex vivo SLT involves standard rapid en bloc multi-organ procurement followed by parenchymal and vessel dissection of the allograft on the back table. In contrast, in situ splitting involves hilar dissection and parenchymal transection before procurement, similar to a living donor liver operation. Given the infrequency with which splitting is performed, direct comparisons of the in situ and ex vivo techniques have been limited.3 The present study aimed to describe a large single-center experience with SLTs, most of which were performed ex vivo, with an emphasis on operative course, surgical morbidity, and long-term survival.
The medical records of patients who underwent SLT between September 18, 1993, and July 1, 2010, at the University of California, San Francisco (UCSF), were retrospectively reviewed. This work was approved through the Committee for Human Research at UCSF. Long-term outcomes were assessed via office medical records; in cases in which this was impossible, survival was assessed via the Social Security Death Master File. Clinical medical records, operative notes, and pathologic reports were used to gather data. Additional recipient and donor data were supplied by the United Network for Organ Sharing (UNOS), as the contractor for the Organ Procurement and Transplantation Network, as of July 30, 2010.
Kaplan-Meier curves were used to analyze patient and graft survival. Comparisons between groups were accomplished via the log-rank test. Means, medians, standard deviations, and ranges summarize data distribution. Unless indicated otherwise, all data are expressed as mean (SD). Simple comparisons were made using the t test or the χ2 test. All calculations were completed using a commercially available statistical software package (STATA 10; StataCorp LP, College Station, Texas). P < .05 was deemed statistically significant.
The adult and pediatric ex vivo group (n = 79) consisted of all patients who received grafts split using the ex vivo technique. In the in situ group (n = 27), of the 20 adult recipients, 11 received imported in situ split grafts and 9 received grafts using an undocumented splitting technique but by procurement teams whose practice pattern consists of in situ splitting; of the 7 pediatric recipients, 2 received imported in situ split grafts and 5 received grafts using an undocumented splitting technique but by procurement teams whose practice pattern consists of in situ splitting.
In brief, the ex vivo split liver procedure at the UCSF was performed in the following manner (Figure 1). After traditional multi-organ procurement, care was taken to maintain the liver allograft submerged in an ice bath at all times. The biliary anatomy and arterial anatomy were initially delineated with contrast radiography. The hilar structures were approached posteriorly, with the bifurcation of the portal vein being identified first. The left portal vein was divided off the main portal trunk, leaving the main portal vein in continuity with the right portal vein branch. Biliary and arterial anatomy were further defined with the use of dilute methylene blue injected through the open end of the common bile duct or hepatic artery. The right hepatic artery was divided off the proper hepatic artery, leaving the left graft with the celiac trunk and the left hepatic artery. The left bile duct was taken off the main duct, leaving the right hepatic duct in continuity with the common bile duct. The left (± middle) hepatic vein was dissected free from the vena cava. For true right/left splitting, the middle hepatic vein was kept with the left lobe graft. The parenchymal division was accomplished using the fracture technique and a combination of ties, clips, and vascular staples. The cut surface was inspected for leaks via flushing of the hilar structures, with stasis achieved using silk ties or sutures. The cut surface was treated with argon beam coagulation and was covered with topical sealant before reperfusion. Transplantations were routinely performed without venovenous bypass. T-tubes were rarely used during our procedures.
Graft loss was defined as death or need for retransplantation. Complications were initially categorized as biliary, vascular, primary nonfunction, small for size, incisional hernia, or need for reexploratory surgery. Biliary complications were characterized as leak, stricture, or combined leak and stricture. The course of recipients with a biliary complication, including those with concomitant hepatic artery thrombosis (HAT), was further reviewed to determine the number of nonsurgical and surgical interventions. Nonsurgical interventions included maintenance of a postoperative drain for continued bilious output, drainage of perihepatic bilious abscesses, endoscopic retrograde cholangiopancreatography with or without stent placement, percutaneous transhepatic cholangiography with or without stent placement, dilation of biliary strictures, simple fistulography, tube checks, and tube removals. Vascular complications were characterized as stenosis or thrombosis and as early (<1 month after transplantation) or late (≥1 month after transplantation). The number and type of all surgical and nonsurgical interventions necessary to treat a vascular complication (including retransplantation) were recorded.
A total of 107 SLTs were identified in 107 patients. One pediatric patient received a temporary auxiliary SLT and was, thus, excluded from the final study cohort of 106 patients (Figure 2A). Forty ex vivo splits were performed at the UCSF, which generated 76 of 106 grafts transplanted (Figure 2B). Of the 76 grafts generated by ex vivo splitting at UCSF, there were 31 left lateral segment, 9 left lobe, 9 right lobe, and 27 right trisegment grafts. Of the 30 imported grafts, there were 6 left lateral segment, 1 right lobe, and 23 right trisegment grafts. Grafts split at the UCSF had a mean (SD) cold time of 10.2 (2.6) hours, whereas grafts imported had a mean (SD) cold time of 9.5 (2.1) hours (P = .19). The breakdown of all the 106 split grafts transplanted at the UCSF is demonstrated in Figure 3.
Forty-three of the 63 adult recipients (68.3%) received grafts split ex vivo. Of the 43 ex vivo split grafts, 40 of the splits were performed at the UCSF, with the remaining 3 ex vivo split grafts having been imported from outside centers. The remainder of the cohort (the in situ group) was composed of 20 adult recipients, all of whom received imported split grafts. The demographics, UNOS listing, types of grafts transplanted, and operative course for adult recipients of split livers are detailed in Table 1. The indications for SLT in the adult population are given in Table 2. Of the 63 adult recipients, 17 had hepatocellular carcinoma.
The 1-, 5-, and 10-year overall adult patient survival was 93%, 77%, and 73%, respectively (Figure 4A); overall adult graft survival was 89%, 76%, and 65%, respectively (Figure 4B); ex vivo split adult patient survival was 93%, 85%, and 74%, respectively (Figure 4C); and ex vivo split adult graft survival was 86%, 77%, and 63%, respectively (Figure 4D). In situ split adult patient and graft survival were both 94% at 1 year and 75% at 5 years (Figure 4C and D). There was no significant difference in survival between adult male vs adult female recipients (P = .08), adult recipients of grafts split ex vivo vs in situ (P = .55), adult recipients with vs without hepatitis C (P = .34), adult recipients with vs without hepatocellular carcinoma (P = .38), or adult recipients receiving different grafts (right trisegment, right lobe, left lobe, or left lateral segment grafts) (P = .45).
Table 3 lists the incidence and management of complications after adult SLT. Six patients later required surgical biliary revision, which was performed 0, 0, 1, 1, 5, and 60 months after SLT. These surgical revisions were performed for 3 bile leaks, 2 combined leaks and strictures, and 1 biliary stricture. The 2 cases of hepatic artery stenosis were treated successfully with interventional radiology angioplasty. Two of the 3 early HAT recipients underwent retransplantation. Using biliary and vascular complications as a common end point, simple analysis did not demonstrate a significant difference in the rates of complications between the ex vivo group and the in situ group (37% vs 20%, P = .17).
All the SLT donors succumbed to brain death. Demographics for split liver donors are given in Table 1. Head trauma represented the most common cause of donor death (70%), followed by cerebrovascular accident or stroke (17%), anoxia (10%), and other (3%).
Thirty-six of 43 pediatric recipients (83.7%) received grafts split ex vivo, all of which were performed at the UCSF. The remaining 7 pediatric recipients (the in situ group) received imported split grafts. The demographics, UNOS listing, types of grafts transplanted, and operative course for pediatric recipients of split livers are detailed in Table 1. The indications for SLT in the pediatric population are given in Table 2. Only 1 of the 43 pediatric recipients had hepatocellular carcinoma. No venovenous bypass and no T-tubes were used.
The 1-, 5-, and 10-year overall pediatric patient survival was 84%, 75%, and 69%, respectively (Figure 5A); overall pediatric graft survival was 77%, 63%, and 57%, respectively (Figure 5B); ex vivo split pediatric patient survival was 83%, 73%, and 73%, respectively (Figure 5C); and ex vivo split pediatric graft survival was 75%, 59%, and 59%, respectively (Figure 5D). In situ split pediatric patient and graft survival were both 86% at 1 and 5 years (Figure 5C and D). Again, no significant difference in survival was noted between pediatric recipients of grafts split ex vivo vs in situ (P = .87).
Table 3 details the incidence and management of complications after pediatric SLT. Twelve pediatric patients went on to require surgical biliary revision, all performed within 5 months of transplantation except for 1, which was performed 20 months after transplantation. These 12 surgical revisions were performed for 7 biliary leaks, 4 biliary strictures, and 1 combined leak and stricture. The 2 recipients with hepatic artery stenosis underwent interventional radiology angioplasty; however, 1 recipient required subsequent surgical revision of the hepatic artery anastomosis. Three of 4 recipients with early HAT required retransplantation, as did 2 of 3 with late HAT. The remaining recipient with early HAT underwent interventional radiology angioplasty with tissue plasminogen activator infusion and did not require retransplantation. The 1 case of portal vein thrombosis was successfully managed with surgical thrombectomy. The 1 case of hepatic vein stenosis was successfully managed with interventional radiology angioplasty. When looking at biliary and vascular complications as a common end point, simple analysis did not demonstrate any significant difference in complications between the ex vivo and in situ split groups (54% vs 43%, P = .59). Although 63% of pediatric recipients underwent reexploratory surgery, this was undertaken with a policy for planned reexploration for pediatric recipients on postoperative day 7.
All the SLT donors succumbed to brain death. Demographics for split liver donors are given in Table 1. Head trauma represented the most common cause of death (69%), followed by cerebrovascular accident and stroke (14%), anoxia (12%), and other (5%).
The donor organ shortage remains the largest limiting factor in the successful application of liver transplantation to those on the waiting list.1 The more extreme shortage of pediatric donors, and the size discrepancy between the typical pediatric liver transplant recipient and the adult deceased donor, necessitated an evolution in surgical technique during the past 3 decades that exploited the segmental anatomy of the liver and its regenerative capacity. These innovations included reports of reduced-sized liver transplantation (with discarding of the remnant liver) in 1984,4,5 SLT in 1988,2 and living related liver transplantation in 1990.6
Although reduced-sized liver transplantation provided more liver allografts for pediatric recipients, this came at the cost of shifting a donor organ away from the adult deceased donor pool and, thus, from a potential adult recipient.7 Living liver donation emerged as an advance that allowed for transplantation of the pediatric recipient without the loss of an allograft for an adult recipient on the waiting list; however, living donation carried with it the risk of morbidity and mortality to the live donor. In contrast, SLT, whereby a deceased donor liver allograft was divided to generate 2 allografts suitable for transplantation, obviated any risk posed to a live donor and benefited a pediatric and an adult recipient.
The present retrospective review demonstrates that SLT remains a viable option for expansion of the deceased donor liver pool, with excellent patient and graft survival for pediatric and adult recipients. Paramount to the successful application of SLT, careful recipient and donor selection is required. The criteria at UCSF for optimal donor selection include the following: younger than 40 years, body mass index (calculated as weight in kilograms divided by height in meters squared) less than 30, sodium level less than 155 mEq/L (to convert to millimoles per liter, multiply by 1.0), no more than single-agent vasopressor requirements, normal liver function test results, less than 7 days' hospitalization, and less than 30 minutes of arrest. Recipient selection requires appropriate size matching to minimize the risk of small-for-size syndrome postoperatively. We attempted to keep the graft weight to recipient weight ratio at greater than 1.0% for all such transplants. Furthermore, the use of most split allografts is reserved for adult recipients who are not critically ill. Indeed, of the 63 adult recipients, only 2 were listed as UNOS status 1/1a, and only 3 had a listed Model for End-Stage Liver Disease score of 40 (this status and score designate the sickest patients). In contrast, and given the scarcity of whole-organ pediatric donors that necessitates SLT or living liver donation, 22 of 43 pediatric recipients were listed as UNOS status 1/1a, with an additional 3 patients with a Pediatric End-Stage Liver Disease score of 40. Indeed, the greater acuity of the pediatric recipient may contribute to the higher rate of morbidity observed in this population.
Split liver transplantation has yet to gain wide acceptance; it remains an underused technique for expansion of the deceased donor pool, with an estimated use of only 3% in deceased donor liver transplantations.8 The latter has been attributed to the technical complexity of liver splitting and the inferior results reported in an initial series.7 With experience, large single-center series9,10 have demonstrated excellent results with SLT that are comparable with results obtained with whole-liver allografts. Recent data8 have demonstrated that 54% of split grafts are performed ex vivo, with the remaining 46% performed in situ. However, there remain few studies that directly compare the outcomes of in situ vs ex vivo split liver allografts3 because most centers that perform SLT use a single surgical technique for optimization and standardization of results.11- 14 Both techniques present advantages and disadvantages. Proponents of in situ splitting favor dissection within the donor to minimize cold ischemia time and graft rewarming, both of which may occur with ex vivo splitting.13 Furthermore, they report easier identification of crucial vascular and biliary structures and hemostasis of the cut edge before revascularization. However, in situ splitting requires an accomplished transplant surgeon to travel to the donor hospital and furthermore necessitates prolonged operative times in brain-dead donors, who often demonstrate some degree of hemodynamic instability. These longer operative times often occur in the setting of multiple procurement teams because these donors tend to yield a full complement of thoracic and abdominal organs. In addition, an advantage of ex vivo splitting is that it allows for careful and complete inspection of the vascular and biliary structures using angiography, cholangiography, or the instillation of dilute methylene blue. The use of these imaging techniques not only facilitates splitting but also, more important, helps determine the allograft's suitability for splitting.
Results of a national survey have demonstrated that morbidity and mortality are comparable between the 2 methods of SLT except for postoperative hemorrhage, which was higher in recipients who had received grafts split using the ex vivo technique.8 We concur with the Paul Brousse team that both techniques are applicable for the expansion of the deceased donor liver pool and do not have to be viewed as opposing each other.15 Indeed, it is the greater application of SLT, using the technique with which a center is most comfortable and most experienced, that will result in the greatest number of split grafts benefitting the most recipients.
Our experience with SLT, especially with ex vivo splitting, demonstrates survival outcomes comparable with those of published studies for in situ, whole-organ, and living donor allografts and a surprisingly low rate of primary nonfunction.9,13 Indeed, the sole case of primary nonfunction in the adult and pediatric recipient populations shared their liver allograft from the same donor (Table 3). Retrospective review of this donor's history did not identify any factors that may have contributed to the recipients' outcome after transplantation. Postoperative morbidity, composed of vascular and biliary complications, remains high for pediatric and adult recipients of SLTs. In this study, we were vigilant to include any invasive diagnostic or therapeutic intervention for the management of a biliary or vascular postoperative complication, which may not necessarily have been reported by previous centers (inclusion of biliary complications in the setting of HAT, simple fistulograms, and tube or stent removals). Thus, this may explain our high rate of postoperative morbidity. With a worsening shortage of deceased donor organs for an expanding waiting list, a higher risk of morbidity may be justifiable. Indeed, the complication rate for recipients of living donor liver allografts has been demonstrated to be higher than that for recipients of whole-organ allografts,16 which is further compounded by the morbidity and mortality risk imposed on the living donor.17 The transference of risk from the living donor back to the liver recipient by the application of SLT rather than living liver donation may justify the increased recipient morbidity associated with SLT. Indeed, despite the higher risk of morbidity associated with SLT, it has been demonstrated that SLT results in a net gain in life-years and more recipients undergoing successful transplantation.18
In summary, we present a large single-center experience with SLT. All the splits performed at the UCSF were performed via the ex vivo technique for splitting. We demonstrated excellent graft and patient survival with grafts transplanted using either splitting method. Increased awareness of the techniques for SLT and refinements in true right/left splitting for application of SLT to 2 adult recipients may help further expand the deceased donor organ pool and decrease the reliance on living donor liver transplantation.
Correspondence: Parsia A. Vagefi, MD, Division of Transplant Surgery, Department of Surgery, University of California, San Francisco, 505 Parnassus Ave, PO Box 0780, San Francisco, CA 94143 (firstname.lastname@example.org).
Accepted for Publication: May 17, 2011.
Author Contributions:Study concept and design: Vagefi and Freise. Acquisition of data: Vagefi. Analysis and interpretation of data: Vagefi, Parekh, Ascher, Roberts, and Freise. Drafting of the manuscript: Vagefi, Parekh, and Freise. Critical revision of the manuscript for important intellectual content: Vagefi, Ascher, Roberts, and Freise. Statistical analysis: Vagefi and Parekh. Administrative, technical, and material support: Vagefi and Freise. Study supervision: Ascher, Roberts, and Freise.
Financial Disclosure: None reported.
Previous Presentation: This paper was presented at the 82nd Annual Meeting of the Pacific Coast Surgical Association; February 21, 2011; Scottsdale, Arizona, and is published after peer review and revision.