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Decreasing the graft size in living donor liver transplantation (LDLT) increases the risk of early allograft dysfunction. Graft-to-recipient weight ratio (GRWR) of 0.8 is considered the threshold. There is evidence that smaller volume grafts may also provide equally good outcomes, the cut-off of which remains unknown. In this retrospective multicenter study, 92 adult LDLTs with a final GRWR ≤0.6 performed at 12 international liver transplant centers over a 3-year period were included. Perioperative data including preoperative status, portal flow hemodynamics (PFH) and portal flow modulation, development of small for size syndrome (SFSS), morbidity, and mortality was collated and analyzed. Thirty-two (36.7%) patients developed SFSS and this was associated with increased 30-day, 90-day, and 1-year mortality. The preoperative model for end-stage liver disease and inpatient status were independent predictors for SFSS (P < .05). Pre-liver transplant renal dysfunction was an independent predictor of survival (hazard ratio 3.1; 95% confidence intervals 1.1, 8.9, P = .035). PFH or portal flow modulation were not predictive of SFSS or survival. We report the largest ever multicenter study of LDLT outcomes using ultralow GRWR grafts and for the first time validate the International Liver Transplantation Society-International Living donor liver transplantation study group-Liver Transplantation Society of India consensus definition and grading of SFSS. Preoperative recipient condition rather than GRWR and PFH were independent predictors of SFSS. Algorithms to predict SFSS and LT outcomes should incorporate recipient factors along with GRWR., Competing Interests: Declaration of competing interest The authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation., (Copyright © 2024 American Society of Transplantation & American Society of Transplant Surgeons. Published by Elsevier Inc. All rights reserved.)

Direct-acting antiviral (DAA) therapy has transformed the management of human immunodeficiency virus (HIV) and hepatitis C (HCV) coinfected patients with advanced liver disease. STOP-Coinfection was a multicenter prospective and retrospective, open-label study using sofosbuvir-based DAA therapy to treat HIV/HCV-coinfected participants pre- or post-liver transplant (LT). Sixty-eight participants with end-stage liver disease (Child-Turcotte-Pugh score ≥7 and Model for End-Stage Liver Disease score 6-29) were enrolled, 26 had hepatocellular carcinoma. Forty-two participants were treated pre-LT and 26 post-LT. All participants completed therapy without need for dose reduction or transfusion; eight required two or more courses of therapy. Ninety-three percent achieved a sustained virologic response and DAA therapy was well tolerated. Despite HCV cure, 12 end-stage liver disease participants required subsequent LT, 7 for decompensated liver disease. Thirteen participants died, 10 with decompensated liver disease pre-LT and three post-LT. Overall, transplant free survival was 42.8% at 4 years and post-LT survival was 87.9% at 5 years. We conclude that sofosbuvir-based DAA therapy is safe and highly effective in HCV-HIV patients with decompensated liver disease and post-LT, with post-LT survival rates comparable to other indications. This removes one of the last barriers to liver transplantation in this challenging cohort of recipients., (© 2020 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Living donation provides important access to organ transplantation, which is the optimal therapy for patients with end-stage liver or kidney failure. Paired exchanges have facilitated thousands of kidney transplants and enable transplantation when the donor and recipient are incompatible. However, frequently willing and otherwise healthy donors have contraindications to the donation of the organ that their recipient needs. Trans-organ paired exchanges would enable a donor associated with a kidney recipient to donate a lobe of liver and a donor associated with a liver recipient to donate a kidney. This article explores some of the ethical concerns that trans-organ exchange might encounter including unbalanced donor risks, the validity of informed consent, and effects on deceased organ donation., (© 2018 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Of the 1.6 million patients >70 years of age who died of stroke since 2002, donor livers were retrieved from only 2402 (0.15% yield rate). Despite reports of successful liver transplantation (LT) with elderly grafts (EG), advanced donor age is considered a risk for poor outcomes. Centers for Medicare and Medicaid Services definitions of an "eligible death" for donation excludes patients >70 years of age, creating disincentives to donation. We investigated utilization and outcomes of recipients of donors >70 through analysis of a United Network for Organ Sharing Standard Transplant Analysis and Research-file of adult LTs from 2002 to 2014. Survival analysis was conducted using Kaplan-Meier curves, and Cox regression was used to identify factors influencing outcomes of EG recipients. Three thousand one hundred four livers from donors >70, ≈40% of which were used in 2 regions: 2 (520/3104) and 9 (666/3104). Unadjusted survival was significantly worse among recipients of EG compared to recipients of younger grafts (P < .0001). Eight independent negative predictors of survival in recipients of EG were identified on multivariable analysis. Survival of low-risk recipients who received EG was significantly better than survival of recipients of younger grafts (P = .04). Outcomes of recipients of EG can therefore be optimized to equal outcomes of younger grafts. Given the large number of stroke deaths in patients >70 years of age, the yield rate of EGs can be maximized and disincentives removed to help resolve the organ shortage crisis., (© 2017 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Because results from single-center (mostly kidney) donor studies demonstrate interpersonal relationship and financial strains for some donors, we conducted a liver donor study involving nine centers within the Adult-to-Adult Living Donor Liver Transplantation Cohort Study 2 (A2ALL-2) consortium. Among other initiatives, A2ALL-2 examined the nature of these outcomes following donation. Using validated measures, donors were prospectively surveyed before donation and at 3, 6, 12, and 24 mo after donation. Repeated-measures regression models were used to examine social relationship and financial outcomes over time and to identify relevant predictors. Of 297 eligible donors, 271 (91%) consented and were interviewed at least once. Relationship changes were positive overall across postdonation time points, with nearly one-third reporting improved donor family and spousal or partner relationships and >50% reporting improved recipient relationships. The majority of donors, however, reported cumulative out-of-pocket medical and nonmedical expenses, which were judged burdensome by 44% of donors. Lower income predicted burdensome donation costs. Those who anticipated financial concerns and who held nonprofessional positions before donation were more likely to experience adverse financial outcomes. These data support the need for initiatives to reduce financial burden., (© 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Blood chimerism has been reported sporadically among visceral transplant recipients, mostly in association with graft-vs-host disease (GVHD). We hypothesized that a higher degree of mixed chimerism would be observed in multivisceral (MVTx) than in isolated intestinal (iITx) and isolated liver transplant (iLTx) recipients, regardless of GVHD. We performed a longitudinal prospective study investigating multilineage blood chimerism with flow cytometry in 5 iITx and 4 MVTx recipients up to one year posttransplant. Although only one iITx patient experienced GVHD, T cell mixed chimerism was detected in 8 out of 9 iITx/MVTx recipients. Chimerism was significantly lower in the four subjects who displayed early moderate to severe rejection. Pre-formed high-titer donor-specific antibodies, bound in vivo to the circulating donor cells, were associated with an accelerated decline in chimerism. Blood chimerism was also studied in 10 iLTx controls. Among nonsensitized patients, MVTx recipients exhibited greater T and B cell chimerism than either iITx or iLTx recipients. Myeloid lineage chimerism was present exclusively among iLTx and MVTx (6/13) recipients, suggesting that its presence required the hepatic allograft. Our study demonstrates, for the first time, frequent T cell chimerism without GVHD following visceral transplantation and a possible relationship with reduced rejection rate in MVTx recipients., (© Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Hypothermic machine preservation (HMP) remains investigational in clinical liver transplantation. It is widely used to preserve kidneys for transplantation with improved results over static cold storage (SCS). At our center, we have used HMP in 31 adults receiving extended criteria donor (ECD) livers declined by the originating United Network for Organ Sharing region ("orphan livers"). These cases were compared to ECD SCS cases in a matched cohort study design. Livers were matched for donor age, recipient age, cold ischemic time, donor risk index and Model for End-Stage Liver Disease (MELD) score. HMP was performed for 3-7 h at 4-8 °C using our previously published protocol. Early allograft dysfunction rates were 19% in the HMP group versus 30% in the control group (p = 0.384). One-year patient survival was 84% in the HMP group versus 80% in the SCS group (p = NS). Post hoc analysis revealed significantly less biliary complications in the HMP group versus the SCS group (4 vs. 13, p = 0.016). Mean hospital stay was significantly shorter in the HMP group (13.64 ± 10.9 vs. 20.14 ± 11.12 days in the SCS group, p = 0.001). HMP provided safe and reliable preservation in orphan livers transplanted at our center., (© Copyright 2014 The American Society of Transplantation and the American Society of Transplant Surgeons.)

In recent years different minimal access strategies have been designed in order to perform living donor liver surgery for adult recipients with less morbidity. Techniques involve shortening the length of the incision with or without previous laparoscopic mobilization of the liver. Herein we present two cases of totally laparoscopic living donor left hepatectomy, with and without removal of the middle hepatic vein, respectively. We describe in detail the anatomical and technical aspects of the procedure focusing on relevant points to enhance safety., (© Copyright 2013 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Hypothermic machine perfusion (HMP) is in its infancy in clinical liver transplantation. Potential benefits include diminished preservation injury (PI) and improved graft function. Molecular data to date has been limited to extrapolation of animal studies. We analyzed liver tissue and serum collected during our Phase 1 trial of liver HMP. Grafts preserved with HMP were compared to static cold stored (SCS) transplant controls. Reverse transcription polymerase chain reaction (RT-PCR), immunohistochemistry and transmission electron microscopy (TEM) were performed on liver biopsies. Expression of inflammatory cytokines, adhesion molecules and chemokines, oxidation markers, apoptosis and acute phase proteins and the levels of CD68 positive macrophages in tissue sections were evaluated. RT-PCR of reperfusion biopsy samples in the SCS group showed high expression of inflammatory cytokines, adhesion molecules and chemokines, oxidative markers and acute phase proteins. This upregulation was significantly attenuated in livers that were preserved by HMP. Immunofluorescence showed larger numbers of CD68 positive macrophages in the SCS group when compared to the HMP group. TEM samples also revealed ultrastructural damage in the SCS group that was not seen in the HMP group. HMP significantly reduced proinflammatory cytokine expression, relieving the downstream activation of adhesion molecules and migration of leukocytes, including neutrophils and macrophages when compared to SCS controls., (© Copyright 2012 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Abdominal tumors involving both roots of the celiac and superior mesenteric artery are deemed unresectable by conventional surgical methods. We performed three cases of multivisceral ex vivo surgery involving temporary removal of the entire abdominal viscera followed by vascular reconstruction, ex vivo tumor resection and autotransplantation of excised organs. We achieved a complete tumor resection with negative margins in all cases. All patients have survived with no tumor recurrence to date at 17-, 27- and 38-month follow-up. Postoperative complications included diarrhea, sphincter of Oddi dysfunction and arterial stenosis; all responded to directed treatments. Multivisceral ex vivo surgery applying techniques of deceased donor multivisceral transplantation is feasible in achieving local control of otherwise unresectable abdominal tumors. This surgery is best suitable for locally invasive tumors unresectable because of location and vascular involvement., (© Copyright 2012 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Deviations in the processes of healthcare delivery that affect patient outcomes are recognized to have an impact on the cost of hospitalization. Whether deviations that do not affect patient outcome affects cost has not been studied. We have analyzed process of care (POC) events that were reported in a large transplantation service (n = 3,012) in 2005, delineating whether or not there was a health consequence of the event and assessing the impact on hospital resource utilization. Propensity score matching was used to adjust for patient differences. The rate of POC events varied by transplanted organ: from 10.8 per 1000 patient days (kidney) to 17.3 (liver). The probability of a POC event increased with severity of illness. The majority (81.5%) of the POC events had no apparent effect on patients' health (63.6% no effect and 17.9% unknown). POC events were associated with longer length of stay (LOS) and higher costs independent of whether there was a patient health impact. Multiple events during the same hospitalization were associated with the highest impact on LOS and cost. POC events in transplantation occur frequently, more often in sicker patients and, although the majority of POC events do not harm the patient, their effect on resource utilization is significant., (© 2010 The Authors Journal compilation © 2010 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Hypothermic machine perfusion (HMP) is widely used to preserve kidneys for transplantation with improved results over cold storage (CS). To date, successful transplantation of livers preserved with HMP has been reported only in animal models. In this, the first prospective liver HMP study, 20 adults received HMP-preserved livers and were compared to a matched group transplanted with CS livers. HMP was performed for 3-7 h using centrifugal perfusion with Vasosol solution at 4-6 degrees C. There were no cases of primary nonfunction in either group. Early allograft dysfunction rates were 5% in the HMP group versus 25% in controls (p = 0.08). At 12 months, there were two deaths in each group, all unrelated to preservation or graft function. There were no vascular complications in HMP livers. Two biliary complications were observed in HMP livers compared with four in the CS group. Serum injury markers were significantly lower in the HMP group. Mean hospital stay was shorter in the HMP group (10.9 +/- 4.7 days vs. 15.3 +/- 4.9 days in the CS group, p = 0.006). HMP of donor livers provided safe and reliable preservation in this pilot case-controlled series. Further multicenter HMP trials are now warranted.

Recurrent hepatitis C (HCV) and biliary complications (BC) are major causes of post liver transplant morbidity and mortality. The impact of these complications may be additive or synergistic. We performed a retrospective cohort study to analyze the effects of HCV and BC on all patients transplanted at two institutions over 6 years. BC was defined by imaging findings in the setting of abnormal liver function tests that required intervention. The primary outcomes were graft and patient survival over a mean 3.4 years. 709 patients (619 deceased, 90 living donor) were included, 337 with HCV and 372 without. BC was diagnosed more frequently in patients with HCV, 26% versus 18% (p = 0.008). One-year and overall patient and graft survival were significantly lower in patients with HCV, but BC impacted only 1-year graft survival. The combination of BC and HCV had no additional impact on survival or fibrosis rates on 1-year protocol biopsies. Multivariate analysis revealed HCV (HR 2.1) and HCC (HR 1.9) to be independent predictors of mortality. Since BC are diagnosed more frequently in HCV patients and only affect early graft loss, it is likely that recurrent HCV rather than BC accounts for the majority of adverse graft outcomes.

Although living donor liver transplantation (LDLT) has been shown to decrease waiting-list mortality, little is known of its financial impact relative to deceased donor liver transplantation (DDLT). We performed a retrospective cohort study of the comprehensive resource utilization, using financial charges as a surrogate measure-from the pretransplant through the posttransplant periods-of 489 adult liver transplants (LDLT n = 86; DDLT n = 403) between January 1, 2000, through December 31, 2006, at a single center with substantial experience in LDLT. Baseline characteristics differed between LDLT versus DDLT with regards to age at transplantation (p = 0.02), male gender (p < 0.01), percentage Caucasians (p < 0.01) and transplant model for end-stage liver disease (MELD) score (p < 0.01). In univariate analysis, there was a trend toward decreased total transplant charges with LDLT (p = 0.06), despite increased surgical charges associated with LDLT (p < 0.01). After adjustment for the covariates that were associated with financial charges, there was no significant difference in total transplant charges (p = 0.82). MELD score at transplant was the strongest driver of resource utilization. We conclude that at an experienced transplant center, LDLT imposes a similar overall financial burden than DDLT, despite the increased complexity of living donor surgery and the addition of the costs of the living donor. We speculate that LDLT optimizes transplantation by transplanting healthier and younger recipients.

Living donor liver transplantation (LDLT) may have better immunological outcomes compared to deceased donor liver transplantation (DDLT). The aim of this study was to analyze the incidence of acute cellular rejection (ACR) after LDLT and DDLT. Data from the adult-to-adult living donor liver transplantation (A2ALL) retrospective cohort study on 593 liver transplants done between May 1998 and March 2004 were studied (380 LDLT; 213 DDLT). Median LDLT and DDLT follow-up was 778 and 713 days, respectively. Rates of clinically treated and biopsy-proven ACR were compared. There were 174 (46%) LDLT and 80 (38%) DDLT recipients with >/=1 clinically treated episodes of ACR, whereas 103 (27%) LDLT and 58 (27%) DDLT recipients had >/=1 biopsy-proven ACR episode. A higher proportion of LDLT recipients had clinically treated ACR (p = 0.052), but this difference was largely attributable to one center. There were similar proportions of biopsy-proven rejection (p = 0.97) and graft loss due to rejection (p = 0.16). Longer cold ischemia time was associated with a higher rate of ACR in both groups despite much shorter median cold ischemia time in LDLT. These data do not show an immunological advantage for LDLT, and therefore do not support the application of unique posttransplant immunosuppression protocols for LDLT recipients.

It is critical to balance waitlist mortality against posttransplant mortality. Our objective was to devise a scoring system that predicts recipient survival at 3 months following liver transplantation to complement MELD-predicted waitlist mortality. Univariate and multivariate analysis on 21,673 liver transplant recipients identified independent recipient and donor risk factors for posttransplant mortality. A retrospective analysis conducted on 30,321 waitlisted candidates reevaluated the predictive ability of the Model for End-Stage Liver Disease (MELD) score. We identified 13 recipient factors, 4 donor factors and 2 operative factors (warm and cold ischemia) as significant predictors of recipient mortality following liver transplantation at 3 months. The Survival Outcomes Following Liver Transplant (SOFT) Score utilized 18 risk factors (excluding warm ischemia) to successfully predict 3-month recipient survival following liver transplantation. This analysis represents a study of waitlisted candidates and transplant recipients of liver allografts after the MELD score was implemented. Unlike MELD, the SOFT score can accurately predict 3-month survival following liver transplantation. The most significant risk factors were previous transplantation and life support pretransplant. The SOFT score can help clinicians determine in real time which candidates should be transplanted with which allografts. Combined with MELD, SOFT can better quantify survival benefit for individual transplant procedures.

Patients considering living donor liver transplantation (LDLT) need to know the risk and severity of complications compared to deceased donor liver transplantation (DDLT). One aim of the Adult-to-Adult Living Donor Liver Transplantation Cohort Study (A2ALL) was to examine recipient complications following these procedures. Medical records of DDLT or LDLT recipients who had a living donor evaluated at the nine A2ALL centers between 1998 and 2003 were reviewed. Among 384 LDLT and 216 DDLT, at least one complication occurred after 82.8% of LDLT and 78.2% of DDLT (p = 0.17). There was a median of two complications after DDLT and three after LDLT. Complications that occurred at a higher rate (p < 0.05) after LDLT included biliary leak (31.8% vs. 10.2%), unplanned reexploration (26.2% vs. 17.1%), hepatic artery thrombosis (6.5% vs. 2.3%) and portal vein thrombosis (2.9% vs. 0.0%). There were more complications leading to retransplantation or death (Clavien grade 4) after LDLT versus DDLT (15.9% vs. 9.3%, p = 0.023). Many complications occurred more commonly during early center experience; the odds of grade 4 complications were more than two-fold higher when centers had performed 40). In summary, complication rates were higher after LDLT versus DDLT, but declined with center experience to levels comparable to DDLT.

Living donor liver transplantation evolved in response to donor shortage. Current guidelines recommend potential living donors (LD) have a body mass index (BMI) <30. With the current obesity epidemic, locating nonobese LD is difficult. From September 1999 to August 2003, 68 LD with normal liver function test (LFTs) and without significant comorbidities underwent donor hepatectomy at our center. Post-operative complications were collected, including wound infection, pneumonia, hernia, fever, ileus, biliary leak, biliary stricture, thrombosis, bleeding, hepatic dysfunction, thrombocytopenia, deep venous thrombosis, pulmonary embolism, difficult to control pain, depression and anxiety. Complication rates for LD with BMI >30 (n = 16) and BMI <30 (n = 52) were compared. The incidence of wound infection increased with BMI, 4% for nonobese and 25% for obese LD (p = 0.024). There were no statistically significant differences for all other complications. No LD died. Recipient survival was 100% with obese LD and 80% with nonobese LD (p = 0.1). Select donors with a BMI >30 may undergo donor hepatectomy with acceptable morbidity and excellent recipient results. Updating current guidelines to include select LD with BMI >30 has the potential to safely increase the donor pool.

Studies comparing adult living donor liver transplantation to deceased donor liver transplantation have focused on post-transplant survival. Our aim was to focus on the impact of living donor liver transplant on waiting time mortality and overall mortality. We analyzed the affect of living donor liver transplantation on waiting time mortality and overall mortality (from listing until last follow up) in a cohort of 116 transplant candidates. Fifty-eight candidates who had individuals present as potential living donors (volunteer group) were matched by MELD score to 58 liver transplant candidates who did not have individuals present as a potential living donor (no volunteer group). Twenty-seven percent of candidates in the no volunteer group and 62% of candidates in the volunteer group underwent liver transplantation, p = 0.0003. One-year waiting list mortality for the volunteer group and no volunteer group was 10% and 20%, respectively, p = 0.03. Patient survival from the time of listing to last follow up was similar between the two groups. In our study group, living donor liver transplantation is associated with a higher rate of liver transplantation and lower waiting time mortality. In the era of living donor liver transplantation, estimates of patient survival should incorporate waiting time mortality.