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Background: Recent evidence supports the use of machine perfusion technologies (MP) for marginal liver grafts. Their effect on enhanced recovery, however, remains uncertain., Objectives: To identify areas in which MP might contribute to an ERAS program and to provide expert panel recommendations., Data Sources: Ovid MEDLINE, Embase, Scopus, Google Scholar, and Cochrane Central., Methods: Systematic review and meta-analysis following PRISMA guidelines and recommendations using the GRADE approach. CRD42021237713 RESULTS: Both hypothermic (HMP) and normothermic (NMP) machine perfusion demonstrated significant benefits in preventing postreperfusion syndrome (PRS) (HMP OR .33, .15-.75 CI; NMP OR .51, .29-.90 CI) and early allograft dysfunction (EAD) (HMP OR .51, .35-.75 CI; NMP OR .66, .45-.97 CI), while shortening LOS (HMP MD -3.9; NMP MD -12.41). Only NMP showed a significant decrease in the length of ICU stay (L-ICU) (MD -7.07, -8.76; -5.38 CI), while only HMP diminishes the likelihood of major complications. Normothermic regional perfusion (NRP) reduces EAD (OR .52, .38-.70 CI) and primary nonfunction (PNF) (OR .51, .27-.98 CI) without effect on L-ICU and LOS., Conclusions: The use of HMP decreases PRS and EAD, specifically for marginal grafts. This is supported by a shorter LOS and a lower rate of major postoperative complications (QOE; moderate | Recommendation; Strong). NMP reduces the incidence of PRS and EAD with associated shortening in L-ICU for both DBD and DCD grafts (QOE; moderate | Recommendation; High) This technology also shortens the length of hospital stay (QOE; low | Recommendation; Strong). NRP decreases the likelihood of EAD (QOE; moderate) and the risk of PNF (QOE; low) when compared to both DBD and SRR-DCD grafts preserved in SCS. (Recommendation; Strong)., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Dynamic preservation strategies are a promising option to improve graft quality before transplantation, and to extend preservation time for either logistic or treatment reasons. In contrast to normothermic oxygenated perfusion, which intends to mimic physiological conditions in the human body, with subsequent clinical application for up to 24 hrs, hypothermic perfusion is mainly used for a relatively short period with protection of mitochondria and subsequent reduction of oxidative injury upon implantation. The results from two randomized controlled trials, where recruitment has finished are expected this year. Both ex situ perfusion techniques are increasingly applied in clinical transplantation including recent reports on viability assessment, which could open the door for an increased liver utilization in the future., (Copyright © 2020 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.)

Outcomes for adult-to-adult living liver donors (LDs) are largely based on short-term data drawn from single-center studies. The aim of this study was to determine how living liver donation (LLD) impacts self-reported quality-of-life (QOL) up to 6 years after donation in a sample of residents from New York State. New York transplant programs are state-mandated to track LDs as part of a quality assurance and patient safety effort. Donor-reported QOL within 1 year of donation and longitudinal data over a 10-year period were analyzed. Self-reported surveys include the following domains: employment, finances, health/life insurance, activities of daily living, physical/emotional health, donor experience, relationships, and LD opinions. There were 220 LDs in New York (2004-2013) who completed a survey over the 10-year period with many donors completing surveys at several points in time. Overall, longterm LDs remain as comfortable about LLD as they were during the first year after donation (95%). The majority of LDs reported feeling as well as before LLD (72%). At 1 year after donation, 60% of subjects self-reported medical problems, and 30% reported emotional issues. However, the majority reported that they would willingly donate again. In conclusion, LDs remain satisfied with their decision to donate over time. A minority of LDs report longterm medical and emotional issues. The conclusions provide information for educational interventions to improve informed choice to those considering donation., (Copyright © 2018 by the American Association for the Study of Liver Diseases.)

The pervasive shortage of deceased donor liver allografts contributes to significant waitlist mortality despite efforts to increase organ donation. Ex vivo liver perfusion appears to enhance preservation of donor organs, extending viability and potentially evaluating function in organs previously considered too high risk for transplant. These devices pose novel challenges for organ allocation, safety, training, and finances. This white paper describes the American Society of Transplant Surgeons' belief that organ preservation technology is a vital advance, but its use should not change fundamental aspects of organ allocation. Additional data elements need to be collected, made available for organ assessment by transplant professionals to allow determination of organ suitability in the case of reallocation and incorporated into risk adjustment methodology. Finally, further work is needed to determine the optimal strategy for management and oversight of perfused organs prior to transplantation., (© 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.)

With increasing demand for donor organs for transplantation, machine perfusion (MP) promises to be a beneficial alternative preservation method for donor livers, particularly those considered to be of suboptimal quality, also known as extended criteria donor livers. Over the last decade, numerous studies researching MP of donor livers have been published and incredible advances have been made in both experimental and clinical research in this area. With numerous research groups working on MP, various techniques are being explored, often applying different nomenclature. The objective of this review is to catalog the differences observed in the nomenclature used in the current literature to denote various MP techniques and the manner in which methodology is reported. From this analysis, we propose a standardization of nomenclature on liver MP to maximize consistency and to enable reliable comparison and meta-analyses of studies. In addition, we propose a standardized set of guidelines for reporting the methodology of future studies on liver MP that will facilitate comparison as well as clinical implementation of liver MP procedures., (© 2016 The Authors. American Journal of Transplantation published by Wiley Periodicals, Inc. on behalf of 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.)

Macrovesicular steatosis in greater than 30% of hepatocytes is a significant risk factor for primary graft nonfunction due to increased sensitivity to ischemia reperfusion (I/R) injury. The growing prevalence of hepatic steatosis due to the obesity epidemic, in conjunction with an aging population, may negatively impact the availability of suitable deceased liver donors. Some have suggested that metabolic interventions could decrease the fat content of liver grafts prior to transplantation. This concept has been successfully tested through nutritional supplementation in a few living donors. Utilization of deceased donor livers, however, requires defatting of explanted organs. Animal studies suggest that this can be accomplished by ex vivo warm perfusion in a time scale of a few hours. We estimate that this approach could significantly boost the size of the donor pool by increasing the utilization of steatotic livers. Here we review current knowledge on the mechanisms whereby excessive lipid storage and macrosteatosis exacerbate hepatic I/R injury, and possible approaches to address this problem, including ex vivo perfusion methods as well as metabolically induced defatting. We also discuss the challenges ahead that need to be addressed for clinical implementation., (© Copyright 2012 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.)

Background: Protein C is a natural thrombin antagonist produced by hepatocytes. Its levels are low in liver failure and predispose patients to increased risk for thrombosis. Little is known about the relationship between protein C activity and hepatic function after orthotopic liver transplantation (OLT)., Methods: We measured protein C activity of 41 patients undergoing liver transplantation by the Staclot method (normal range, 70%-130%) preoperatively and then daily on postoperative days (POD) 0-5., Results: The mean protein C activity was low before OLT (34.3 ± 4.3%) and inversely correlated with the preoperative Model for End-Stage Liver Disease score (Spearman's r = -0.643; P < .0001). Mean activity increased significantly on POD 1 (58.9 ± 4.5%), and remained above preoperative levels through POD 5. Ten patients developed metabolic liver dysfunction defined by a serum total bilirubin >5 mg/dL on POD 7. These patients had significantly lower protein C activity from POD 3 (47.2 ± 9.6% vs 75.9 ± 5.8%; P = .01) to POD 5. Preoperative protein C activity correlated inversely with the severity of liver failure as indicated by preoperative MELD score., Conclusion: Protein C activity recovered rapidly in patients with good allograft function but remained significantly lower in patients who had limited metabolic function as evidenced by increased total bilirubin levels., (Copyright © 2012 Elsevier Inc. All rights reserved.)

In solid organ transplantation, the disparity between donor supply and patients awaiting transplant continues to increase. The organ shortage has led to relaxation of historic contraindications to organ donation. A large percentage of deceased organ donors have been subjected to traumatic injuries, which can often result in intervention that leads to abdominal packing and intensive care unit resuscitation. The donor with this "open abdomen" (OA) presents a situation in which the risk of organ utilization is difficult to quantify. There exists a concern for the potential of a higher risk for both bacterial and fungal infections, including multidrug-resistant (MDR) pathogens because of the prevalence of antibiotic use and critical illness in this population. No recommendations have been established for utilization of organs from these OA donors, because data are limited. Herein, we report a case of a 21-year-old donor who had sustained a gunshot wound to his abdomen, resulting in a damage-control laparotomy and abdominal packing. The donor subsequently suffered brain death, and the family consented to organ donation. A multiorgan procurement was performed with respective transplantation of the procured organs (heart, liver, and both kidneys) into 4 separate recipients. Peritoneal swab cultures performed at the time of organ recovery grew out MDR Pseudomonas aeruginosa on the day after procurement, subsequently followed by positive blood and sputum cultures as well. All 4 transplant recipients subsequently developed infections with MDR P. aeruginosa, which appeared to be donor-derived with similar resistance patterns. Appropriate antibiotic coverage was initiated in all of the patients. Although 2 of the recipients died, mortality did not appear to be clearly associated with the donor-derived infections. This case illustrates the potential infectious risk associated with organs from donors with an OA, and suggests that aggressive surveillance for occult infections should be pursued., (© 2012 John Wiley & Sons A/S.)

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.

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.

Introduction: Cold storage (CS) is the standard preservation technique for liver transplantation (LTx). Hypothermic machine perfusion (HMP) is an alternative preservation technique that provides a continuous supply of substrates and removes waste products. HMP improves early graft function in kidney transplantation, especially for marginal organs: To our knowledge there have been no reports HMP in human LTx. The aim of this study was to develop a reproducible technique for liver HMP prior to initiating a clinical trial., Methods: For the discard protocol, between May 2001 and March 2002, 10 nontransplantable human livers were obtained. We designed a model of atraumatic, centrifugal HMP of the portal vein (PV) and hepatic artery (HA) via donor vascular conduit. Livers were perfused at 3 degrees C to 5 degrees C with Vasosol solution for 5 to 10 hours using a modified Medtronic Portable Bypass System. Perfusion variables (temp, flow, pressure) where recorded every 30 minutes. During the study, we also validated our techniques in an animal model. For the animal protocol; six swine were used as liver donors and randomized to 12 hours of CS in UW (n = 3) or 12 hours of HMP using Vasosol solution (n = 3). LTx was performed in six swine. Animals survived until postoperative day 5., Results: For the discard protocol, mean HMP time was 6.7 +/- 1.8 hours. Target flow was 0.7 mL/g liver/min. PV and HA pressure ranged from 3 to 5 and 12 to 18 mm Hg, respectively. All grafts were maintained at 3 degrees C to 5 degrees C during HMP. For the animal protocol, all recipients had good liver function and survived to postoperative day 5. AST and TBili were similar between CS and HMP., Conclusions: Our method of liver HMP appears to be a safe and reliable method to preserve livers. A clinical trial is now underway to evaluate this technique in human LTx.

Objectives: The safety of donors is paramount in adult living donor liver transplantation. Our goal is to compare the pattern of recovery of hepatic synthetic function and aminotransferases in healthy adult donors with and without complications., Methods: We reviewed 47 consecutive patients undergoing right donor hepatectomy at our center. Laboratory data were collected through the first 2 postoperative weeks and results from donors with and without complications were compared., Results: Donor morbidity was 25% and there were no donor deaths. Total bilirubin peaked on postoperative day 3, whereas aminotransferases and international normalized ratio peaked on postoperative day 1. Peak total bilirubin was higher in patients with fluid collections (n = 7) compared with those without fluid collections (n = 40), 4.6 mg/dL and 2.3 mg/dL, respectively, P = 0.02. On postoperative day 3 the peak total bilirubin was greater than 3.0 mg/dL in 86% of donors with fluid collections and 15% of donors without fluid collections, (P = 0.0005) whereas aminotransferases and alkaline phosphatase were not significantly different between these 2 groups., Conclusions: After right donor hepatectomy a total bilirubin greater than 3.0 mg/dL on postoperative day 3 should prompt an evaluation for a fluid collection, even if other liver tests are normal or declining.

Publications about liver transplantation (LTX) for autoimmune hepatitis (AIH) have started to emerge, but many issues remain unresolved. We reviewed data on 32 patients transplanted for AIH to determine how pretransplantation and posttransplantation characteristics correlate with recipient outcome, including disease recurrence. Recipients were 37+/- 14 years old; 30 of 32 were women. Most had chronic disease (8 +/- 6 years); 25% had fulminant failure. The majority had ascites (91%), jaundice (88%), elevated prothrombin time (18 +/- 3 seconds), and hypoalbuminemia (2.7 +/- 0.6 g/dL). All had hypergammaglobulinemia (3.0 +/- 1.0 g/dL) and autoantibodies (72% antinuclear, 74% smooth muscle). Only one was HLA A1-B8-DR3 positive. Other autoimmune disorders affected 25% of patients; half improved after transplantation. Actuarial survival was 81% at 1 and 2 years posttransplantation. There was a high frequency of rejection (75% of recipients had 1.7 +/- 0.8 episodes), and 39% of rejections required OKT3. Among 24 recipients with long-term follow-up (27 +/- 14 months), histologically proven recurrent AIH occurred in 25%, 15 +/- 2 months posttransplantation; half (3 patients) required retransplantation 11 +/- 3 months after diagnosis. After retransplantation 2 of 3 patients had re-recurrence within 3 months; 1 received a third LTx. Recurrence occurred in 6 of 18 patients transplanted for chronic disease vs. 0 of 6 transplanted as fulminants (P = not significant [NS]). Patients with and without recurrence had similar rejection profiles. In summary, results of LTx for AIH are excellent. However, AIH patients have a high frequency of rejection and often require OKT3. Furthermore, severe recurrent AIH sometimes develops, particularly in chronic versus fulminant AIH patients and in those already retransplanted for recurrence. Multicenter studies could elucidate the best posttransplantation immunosuppressive regimens for AIH patients.

Background: Short-term outcomes of liver transplantation are well reported. Little is known, however, about long-term results in liver recipients surviving > or =5 years. We sought to analyze long-term complications in liver recipients surviving > or =5 years after transplant, to assess their medical condition and to compare findings to the general population., Methods: We analyzed the chart and database records of all patients (n=139) who underwent liver transplantation at a major transplant center before January 1, 1991. Outcome measures included the presence of diabetes, hypertension, heart, renal or neurological disease, osteoporosis, incidence of de novo malignancy or fracture, or other pathology, body mass index, serum cholesterol and glucose, liver function, blood pressure, frequency of laboratory and clinic follow-up, current pharmacological regimen, and late rejection episodes., Results: Ninety-six patients (70%) survived > or =5 years. Compared to numbers expected based on U.S. population rates, transplant recipients had significantly higher overall prevalences of hypertension (standardized prevalence ratio [SPR]=3.07, 95% confidence interval [CI], 2.35-3.93) and diabetes (SPR=5.99, 95% CI, 4.15-8.38), and higher incidences of de novo malignancy (standardized incidence ratio [SIR]=3.94, 95% CI, 2.09-6.73), non-Hodgkin's lymphoma (SIR=28.56, 95% CI, 7.68-73.11), non-melanoma skin cancer (estimated SIR> or =3.16) and fractures in women (SIR=2.05, 95% CI, 1.12-3.43). Forty-one of 87 (47.1%) patients were obese, and 23 patients (27.4%) had elevated serum cholesterol levels (> or =240 mg/dl, 6.22 mmol/L), compared to 33% and 19.5% of U.S. adults, respectively. Prevalences of heart or peptic ulcer disease were not significantly higher., Conclusions: Liver transplantation is being performed with excellent 5-year survival. Significant comorbidities exist, however, which appear to be related to long-term immunosuppression.

As patient survival after orthotopic liver transplantation (OLT) improves, late complications, including late graft failure, more commonly occur and retransplantation (re-OLT) is required more often. Survival after re-OLT is poorer than after primary OLT, and given the organ shortage, it is essential that we optimize our use of scarce donor livers. We sought to identify variables that predict poor outcome after late re-OLT. Among adults who underwent OLT between September 1989 and October 1997, we identified transplant recipients who survived greater than 6 months (n = 964) and analyzed those who required late re-OLT (>/=6 months after primary OLT). We recorded the indication for the initial OLT and interval from OLT to re-OLT. We also analyzed data collected at the time of re-OLT, including age, sex, indications for primary OLT and re-OLT, United Network for Organ Sharing status, preoperative laboratory values (white blood cells, platelets, hemoglobin, albumin, bilirubin, creatinine, and prothrombin time), Child-Pugh-Turcotte score, number of rejection episodes before re-OLT, and interval between OLT and re-OLT. In addition, we analyzed surgical factors (including procedure performed and use of packed red blood cells, fresh frozen plasma, and platelets), postoperative immunosuppression, and donor factors (age, ischemic time). Forty-eight patients (5%) underwent late re-OLT at a median of 557 days (range, 195 to 2,559 days) post-OLT. Survival rates after re-OLT at 90 days, 1 year, and 5 years were 71%, 60%, and 42%, respectively. Patients surviving 90 days or greater after re-OLT had an 85% chance of surviving to 1 year. Sepsis was the leading cause of death (15 of 25 deaths; 60%). Recipient age older than 50 years (P =.04), preoperative creatinine level greater than 2 mg/dL (P =.004), and use of intraoperative blood products (packed red blood cells, P =.001; fresh frozen plasma, P =.002; platelets, P =.004) had significant impacts on survival. Late re-OLT was associated with increased mortality. Careful patient selection, with particular attention to recipient age and renal function, may help improve results and optimize our use of scarce donor livers.

Background: Hepatic artery thrombosis (HAT) can be a devastating complication of orthotopic liver transplantation (OLT), but early diagnosis may allow successful revascularization and graft salvage., Methods: We reviewed data on 1,026 liver transplants at our institution. For patients in whom HAT was diagnosed within 30 days after OLT, we recorded indications for ultrasonography and liver function tests at diagnosis, management of HAT, and graft and patient survival., Results: Thirty-two patients (3.1%) developed HAT at 6.8+/-6.6 days (range, 1-29 days) after OLT. Twelve patients (37.5%) were asymptomatic at diagnosis. In 11 of these 12, HAT was diagnosed on routine duplex at 2.0+/-1.55 days after OLT; in the 12th patient, HAT was noted during re-exploration for unrelated bleeding on postoperative day 3. Eleven of 12 patients (91.6%) were revascularized; one patient (8.4%) received no treatment with no sequelae. Of the 11 who were revascularized, 9 (81.8%) had graft salvage and 2 (18.2%) received a second transplant, with one death. Twenty patients (62.5%) were symptomatic. In these 20, HAT was diagnosed at 9.85+/-6.93 days after OLT. Symptoms were: elevated liver function test results (serum glutamic oxaloacetic transaminase: 722+/-1792 U/ml, serum glutamic pyruvic transaminase: 678+/-963 U/ml, and bilirubin: 10.2+/-6.2 mg/dl) in 13 patients (65%); bile leak in 4 patients (20%), and sepsis in 3 (15%). Five of the 20 patients (25%) were revascularized; of these 5, 2 (40%) had graft salvage, 2 (40%) received a second transplant with 1 death, and 1 (20%) died of a liver abscess. Twelve symptomatic patients (60%) had immediate re-OLT; 10/12 are alive, 1 died of sepsis, and 1 died late of unrelated causes. Three symptomatic patients had no treatment; two died of biliary sepsis and one survived. Overall graft salvage was 83.3% in asymptomatic patients and 15% in patients with symptoms (P<0.001). Graft salvage in asymptomatic patients undergoing revascularization was 81.8%, versus 40% in symptomatic patients (P=NS). One-year patient survival was 91.7% in asymptomatic patients and 65% in symptomatic patients (with one late death excluded) (P=NS)., Conclusions: Routine postoperative duplex ultrasonography should be performed early after liver transplantation. We believe that emergent revascularization of hepatic artery thrombosis in asymptomatic patients and retransplantation in symptomatic patients lead to improved graft salvage and patient survival with a relatively low incidence of late biliary complications.

Background: We evaluated the utility of CD3 cell counts for monitoring OKT3 induction immunosuppression and for predicting early rejection in liver recipients., Methods: In 32 adults in whom OKT3 and steroids were used to induce immunosuppression, CD3 cell subsets were labeled with CD3 (IgG1)-fluorescein isothiocyanate monoclonal antibody and assayed by flow cytometry before orthotopic liver transplantation and within 2-4 days, 5-7 days, and 8-10 days after transplantation. Trough OKT3 levels were measured at the same points in 10 patients. Early rejection (before postoperative [POD] day 21) was proven by elevated liver function tests and biopsy. Six patients were excluded for death, retransplantation, or early cessation of OKT3., Results: Eight of 26 patients (30.8%) had early rejection and 18 (69.2%) had no early rejection. All had depletion of CD3 cells to <10.2% of baseline at POD 2-4. On POD 8-10, the mean CD3 count in rejectors was 213.31+/-184.98/mm3 vs. 22.71+/-32.42/mm3 in nonrejectors (P<0.001). By POD 8-10, five of eight (62.5%) patients who rejected had CD3 count recovery to >75% of baseline. No nonrejecting patient recovered to >26% of baseline (P<0.001). OKT3 levels did not correlate with CD3 recovery or rejection., Conclusions: The incidence of early rejection correlates strongly with recovery of CD3 counts by POD 10. Higher baseline CD3 counts do not predict early rejection.

The hepatotoxic effects of isoniazid have been well described, but there have been no reports on the incidence of isoniazid-induced liver disease in patients who have received an orthotopic liver transplant. We retrospectively reviewed the records of 13 patients who received isoniazid after liver transplantation for either chemoprophylaxis or as part of a multidrug regimen for the treatment of Mycobacterium tuberculosis infection. Five of the 13 patients developed biochemical and histologic evidence of isoniazid hepatotoxicity. All five patients were on a multidrug regimen which included the administration of rifampin. No hepatotoxicity occurred in patients who received isoniazid alone or in conjunction with ethambutol for chemoprophylaxis. In conclusion, the incidence of isoniazid hepatotoxicity increased when the drug was used in conjunction with rifampin for the treatment of M. tuberculosis infection.