Elizabeth A. Pomfret

Report of a national conference on liver allocation in patients with hepatocellular carcinoma in the United States.

A national conference was held to better characterize the long‐term outcomes of liver transplantation (LT) for patients with hepatocellular carcinoma (HCC) and to assess whether it is justified to continue the policy of assigning increased priority for candidates with early‐stage HCC on the transplant waiting list in the United States. The objectives of the conference were to address specific HCC issues as they relate to liver allocation, develop a standardized pathology report form for the assessment of the explanted liver, develop more specific imaging criteria for HCC designed to qualify LT candidates for automatic Model for End‐Stage Liver Disease (MELD) exception points without the need for biopsy, and develop a standardized pretransplant imaging report form for the assessment of patients with liver lesions. At the completion of the meeting, there was agreement that the allocation policy should result in similar risks of removal from the waiting list and similar transplant rates for HCC and non‐HCC candidates. In addition, the allocation policy should select HCC candidates so that there are similar posttransplant outcomes for HCC and non‐HCC recipients. There was a general consensus for the development of a calculated continuous HCC priority score for ranking HCC candidates on the list that would incorporate the calculated MELD score, alpha‐fetoprotein, tumor size, and rate of tumor growth. Only candidates with at least stage T2 tumors would receive additional HCC priority points. Liver Transpl 16:262–278, 2010.

A Report of the Vancouver Forum on the Care of the Live Organ Donor: Lung, Liver, Pancreas, and Intestine Data and Medical Guidelines

An international conference of transplant physicians, surgeons, and allied health professionals was held in Vancouver, Canada, on September 15 and 16, 2005 to address the care of the live lung, liver, pancreas, and intestine organ donor. The Vancouver Forum was convened under the auspices of the Ethics Committee of The Transplantation Society. Forum participants included over 100 leaders in organ transplantation, representing many countries from around the world, including participants from the following continents: Africa, Asia, Australia, Europe, North and South America. The objective of the Vancouver Forum was to develop an international standard of care for the live lung, liver, pancreas and intestinal organ donor. This Vancouver Forum followed a conference convened in Amsterdam on the care of the live kidney donor (1, 2). There were four organ specific work groups at the Vancouver Forum: lung, liver, pancreas and intestine. Each organ work group addressed the following topics in concert and reported their findings in a plenary presentation to all participants:

ASTS recommended practice guidelines for controlled donation after cardiac death organ procurement and transplantation

The American Society of Transplant Surgeons (ASTS) champions efforts to increase organ donation. Controlled donation after cardiac death (DCD) offers the family and the patient with a hopeless prognosis the option to donate when brain death criteria will not be met. Although DCD is increasing, this endeavor is still in the midst of development. DCD protocols, recovery techniques and organ acceptance criteria vary among organ procurement organizations and transplant centers. Growing enthusiasm for DCD has been tempered by the decreased yield of transplantable organs and less favorable posttransplant outcomes compared with donation after brain death. Logistics and ethics relevant to DCD engender discussion and debate among lay and medical communities. Regulatory oversight of the mandate to increase DCD and a recent lawsuit involving professional behavior during an attempted DCD have fueled scrutiny of this activity. Within this setting, the ASTS Council sought best‐practice guidelines for controlled DCD organ donation and transplantation. The proposed guidelines are evidence based when possible. They cover many aspects of DCD kidney, liver and pancreas transplantation, including donor characteristics, consent, withdrawal of ventilatory support, operative technique, ischemia times, machine perfusion, recipient considerations and biliary issues. DCD organ transplantation involves unique challenges that these recommendations seek to address.

Survival Benefit‐Based Deceased‐Donor Liver Allocation

Currently, patients awaiting deceased‐donor liver transplantation are prioritized by medical urgency. Specifically, wait‐listed chronic liver failure patients are sequenced in decreasing order of Model for End‐stage Liver Disease (MELD) score. To maximize lifetime gained through liver transplantation, posttransplant survival should be considered in prioritizing liver waiting list candidates. We evaluate a survival benefit based system for allocating deceased‐donor livers to chronic liver failure patients. Under the proposed system, at the time of offer, the transplant survival benefit score would be computed for each patient active on the waiting list. The proposed score is based on the difference in 5‐year mean lifetime (with vs. without a liver transplant) and accounts for patient and donor characteristics. The rank correlation between benefit score and MELD score is 0.67. There is great overlap in the distribution of benefit scores across MELD categories, since waiting list mortality is significantly affected by several factors. Simulation results indicate that over 2000 life‐years would be saved per year if benefit‐based allocation was implemented. The shortage of donor livers increases the need to maximize the life‐saving capacity of procured livers. Allocation of deceased‐donor livers to chronic liver failure patients would be improved by prioritizing patients by transplant survival benefit.

New OPTN/UNOS Policy for Liver Transplant Allocation: Standardization of Liver Imaging, Diagnosis, Classification, and Reporting of Hepatocellular Carcinoma

A new liver allocation policy featuring improved imaging criteria for hepatocellular carcinoma exceptions has been developed and approved by the Organ Procurement and Transplantation Network–United Network for Organ Sharing, in late 2011; radiologists in accredited transplantation centers in the United States are now challenged to implement the policy.

Liver regeneration and surgical outcome in donors of right-lobe liver grafts.

Introduction. Previous studies of healthy live‐liver donors have suggested that complete liver regeneration occurs within a matter of weeks; however, there have been no long‐term studies evaluating liver regeneration and few studies documenting long‐term donor outcome. Materials and Methods. Fifty‐one donors who provided right‐lobe grafts underwent volumetric spiral computed tomography scans preoperatively and postoperatively at time intervals of 1 week and 1, 3, 6, and 12 months. Patient demographics, surgical data, and postoperative outcome were correlated with liver regeneration data. Donor surgical outcome was followed prospectively and recorded in a comprehensive database. Results. Thirty‐three males and 18 females (mean age 36.0±9.6 years) provided 51 right‐lobe grafts. Mean follow‐up was 9.8±3.4 months. No donor operation was aborted, and surgical morbidity and mortality rates were 39% and 0%, respectively. Donor remnant liver volume was 49.4±5.7% of the original total liver volume (TLV). Overall liver regeneration was 83.3±9.0% of the TLV by 1 year. Female donors had significantly slower liver regrowth when compared with males at 12 months (79.8±9.3% vs. 85.6±8.2%, P<0.01). There was no effect of age, body mass index, operative time, estimated blood loss, postoperative complications, or perioperative liver function tests on liver regeneration. Discussion. Liver regeneration continues throughout the first postoperative year. Only one donor achieved complete liver regeneration during this time period; however, all donors have maintained normal liver function without long‐term complications. Longer follow‐up is needed to determine whether donors ever achieve original TLV.

Simultaneous Liver-Kidney Transplantation Summit: Current State and Future Directions

Although previous consensus recommendations have helped define patients who would benefit from simultaneous liver–kidney transplantation (SLK), there is a current need to reassess published guidelines for SLK because of continuing increase in proportion of liver transplant candidates with renal dysfunction and ongoing donor organ shortage. The purpose of this consensus meeting was to critically evaluate published and registry data regarding patient and renal outcomes following liver transplantation alone or SLK in liver transplant recipients with renal dysfunction. Modifications to the current guidelines for SLK and a research agenda were proposed.

Incidence of death and potentially life‐threatening near‐miss events in living donor hepatic lobectomy: A world‐wide survey

The incidence of morbidity and mortality after living donor liver transplantation (LDLT) is not well understood because reporting is not standardized and relies on single‐center reports. Aborted hepatectomies (AHs) and potentially life‐threatening near‐miss events (during which a donors life may be in danger but after which there are no long‐term sequelae) are rarely reported. We conducted a worldwide survey of programs performing LDLT to determine the incidence of these events. A survey instrument was sent to 148 programs performing LDLT. The programs were asked to provide donor demographics, case volumes, and information about graft types, operative morbidity and mortality, near‐miss events, and AHs. Seventy‐one programs (48%), which performed donor hepatectomy 11,553 times and represented 21 countries, completed the survey. The average donor morbidity rate was 24%, with 5 donors (0.04%) requiring transplantation. The donor mortality rate was 0.2% (23/11,553), with the majority of deaths occurring within 60 days, and all but 4 deaths were related to the donation surgery. The incidences of near‐miss events and AH were 1.1% and 1.2%, respectively. Program experience did not affect the incidence of donor morbidity or mortality, but near‐miss events and AH were more likely in low‐volume programs (≤50 LDLT procedures). In conclusion, it appears that independently of program experience, there is a consistent donor mortality rate of 0.2% associated with LDLT donor procedures, yet increased experience is associated with lower rates of AH and near‐miss events. Potentially life‐threatening near‐miss events and AH are underappreciated complications that must be discussed as part of the informed consent process with any potential living liver donor. Liver Transpl 19:499–506, 2013.

Effect of orthotopic liver transplantation on the progression of familial amyloidotic polyneuropathy.

BACKGROUND Familial amyloidotic polyneuropathy (FAP) is an autosomal dominant inherited disease associated with a mutant form of the protein transthyretin (TTR). It is characterized clinically by the systemic deposition of amyloid fibrils resulting in organ dysfunction and, ultimately, death. The majority of TTR is produced in the liver, and transplantation of the liver has been shown to ameliorate this source of mutant TTR, arresting the progression of this fatal disease. METHODS Thirteen patients with FAP have undergone successful liver transplant surgery at our center since 1992. The impact of liver transplantation on amyloid-related polyneuropathy, cardiovascular, and gastrointestinal dysfunction is reported in this study. Three patients who died before cardiovascular and neurological follow-up are excluded from the analysis. RESULTS Ten of 13 patients (77%) remain alive an average of 49 months (range, 17-64 months) after transplantation. Three patients suffered sudden death, with autopsy documentation of amyloid deposits involving the conduction system of the heart. Liver transplantation was performed more quickly, required less blood, and a shorter postoperative hospital stay in these patients, compared with patients with cirrhosis. Neurological and nutritional symptoms improved in the majority of affected patients. Those patients with echocardiographic evidence of ventricular wall and valve thickening before transplantation progressed postoperatively despite neurologic improvement. CONCLUSIONS Liver transplantation offers the only cure for the genetic defect causing FAP and appears to result in subjective and objective improvement in neurological dysfunction. Patients with preexisting cardiovascular abnormalities progress despite transplantation; therefore, consideration for combined heart-liver transplantation may be warranted in this subset of patients.

Measurement of choline and choline metabolite concentrations using high-pressure liquid chromatography and gas chromatography-mass spectrometry

We have developed a reproducible and sensitive procedure for the isolation and measurement of choline, phosphocholine, glycerophosphocholine, phosphatidylcholine, lysophosphatidylcholine and acetylcholine in a single 100-mg sample of biological tissue. Tissues were spiked with 14C-methyl- and 2H-methyl- or 15N-choline labeled internal standards for each compound. They were extracted with chloroform/methanol/water and the aqueous and organic phases were dried. The organic phase was resuspended in chloroform/methanol (1/1, v/v) and an aliquot was applied to a silica-gel thin-layer chromatography plate. The plate was developed in chloroform/methanol/water (65/30/4, v/v). Segments which cochromatographed with external standards of phosphatidylcholine and lysophosphatidylcholine were stained, scraped, and hydrolyzed in 6 M methanolic-HCl at 80 degrees C for 60 min, liberating free choline. The aqueous phase was resuspended in methanol/water and injected onto a silica HPLC column. Choline and its metabolites were eluted using a binary nonlinear gradient of acetonitrile/ethanol/acetic acid/1 M ammonium acetate/water/0.1 M sodium phosphate (800/68/2/3/127/10, v/v changing to 400/68/44/88/400/10, v/v). Peaks were detected with an on-line radiometric detector, collected, and dried under vacuum. Each choline ester was digested in 6 M HCl at 80 degrees C to form choline. Choline was then converted to the propionyl ester and demethylated with sodium benzenethiolate. This volatile derivative was then isolated using gas chromatography and measured with a mass selective detector. Deuterated internal standards were used to correct for variations in recovery. Choline, glycerophosphocholine, phosphocholine, phosphatidylcholine, lysophosphatidylcholine, and acetylcholine were measured in rat liver, heart, muscle, kidney, plasma, red blood cells, and brain and in human plasma.(ABSTRACT TRUNCATED AT 250 WORDS)