Liver Transplant Program Research Articles

A Single-Center Report on Liver Transplantation: First Experiences from Shahid Beheshti University of Medical Sciences.

BACKGROUND In the Middle East, data on liver transplantation (LT) are limited, and reports on LT from this region are of specific value. The purpose of this study is to report our 8-year experiences and challenges with LTs in our center to improve the outcomes. METHODS 116 patients received whole organ graft from deceased donors, and orthotopic liver transplantation was performed at Taleghani hospital, between January 2009 and July 2017. The patients were prioritized according to Model for End-Stage Liver Disease (MELD) score and Child-Pugh classification. RESULTS The most common postoperative complication was sepsis (16%), although the most common surgical post LT complication was postoperative bleeding. The most common cause of death was primary graft dysfunction (21.9%). Following LT, 50% of the deaths (n = 16) occurred during the first 10 days. Cumulative survival rates were 78.4%, 77.6%, and 66.7% at 1 month, 1 year, and 5 years, respectively. CONCLUSION This report provides invaluable experience from a region where data on LT is largely missing due to the absence of official registration programs. The data could be used to improve the LT program in the region.

Genetic disease and intellectual disability as contraindications to transplant listing in the United States: A survey of heart, kidney, liver, and lung transplant programs.

Discrimination based on disability is prohibited in organ transplantation, yet studies suggest it continues in listing practices for intellectual disability and genetic diseases. It is not known if this differs between adult and pediatric programs, or by organ type. We performed an online, forced-choice survey of psychosocial listing criteria for adult and pediatric heart, kidney, liver, and lung transplant programs in the United States. Of 650 programs contacted, 343 (52.8%) submitted complete. A minority of programs had formal listing guidelines for any condition considered (Down Syndrome, Duchenne Muscular Dystrophy, Becker Muscular Dystrophy, DiGeorge Syndrome, and Wolf Hirschhorn Syndrome; and mild [IQ<70] and severe [IQ<35] intellectual disability), although a majority had encountered most. Pediatric programs were significantly (P<.02) more lenient in the level of contraindication to listing for all genetic conditions considered except Duchenne Muscular Dystrophy, and for mild and severe intellectual disability. Level of contraindication differed significantly by organ type (heart, lung, liver, and kidney) for Duchenne Muscular dystrophy (P=<.001), Becker Muscular Dystrophy (P<.001), DiGeorge Syndrome (P<.001), Wolf-Hirschhorn syndrome (P=.0012), and severe intellectual disability (P<.001). There is significant variation among transplant programs in availability of guidelines for as well as listing practices regarding genetic diseases and intellectual disability, differing by both adult vs pediatric program, and organ type. Programs with absolute contraindications to listing for specific genetic diseases or intellectual disability should reframe their approach, ensuring individualized assessments and avoiding elimination of patients based on membership in a particular group.

Liver transplantation in Italy in the era of COVID 19: reorganizing critical care of recipients

Transplant programs have been severely disrupted by the COVID-19 pandemic. Italy was one of the first countries with the highest number of deaths in the world due to SARS-CoV-2. Here we propose a management model for the reorganization of liver transplant (LT) activities and policies in a local intensive care unit (ICU) assigned to liver transplantation affected by restrictions on mobility and availability of donors and recipients as well as health personnel and beds. We describe the solutions implemented to continue transplantation activities throughout a given pandemic: management of donors and recipients’ LT program, ICU rearrangement, healthcare personnel training and monitoring to minimize mortality rates of patients on the waiting list. Transplantation activities from February 22, 2020, the data of first known COVID-19 case in Italy’s Emilia Romagna region to June 30, 2020, were compared with the corresponding period in 2019. During the 2020 study period, 38 LTs were performed, whereas 41 were performed in 2019. Patients transplanted during the COVID-19 pandemic had higher MELD and MELD-Na scores, cold ischaemia times, and hospitalization rates (p < 0.05); accordingly, they spent fewer days on the waitlist and had a lower prevalence of hepatocellular carcinoma (p < 0.05). No differences were found in the provenance area, additional MELD scores, age of donors and recipients, BMI, re-transplant rates, and post-transplant mortality. No transplanted patients contracted COVID-19, although five healthcare workers did. Ultimately, our policy allowed us to continue the ICU’s operations by prioritizing patients hospitalized with higher MELD without any case of transplant infection due to COVID-19.

500 Consecutive Liver Transplants: The Outcomes of a New Transplantation Program in the Middle West of Brazil

IntroductionLiver transplantation is the standard treatment for end-stage liver disease. Brazil holds the third highest number of liver transplants performed per year, but center maldistribution results in high discrepancies in accessing this treatment. In 2012, an interstate partnership successfully implemented a new liver transplantation program in the middle west of Brazil. Here, we report the results of the first 500 liver transplants performed in this new program and discuss the impacts of a new transplant center in regional transplantation dynamics. MethodsWe reviewed data from the first 500 consecutive deceased donor liver transplants performed in the new program during an 8-year period. We analyzed data on patients’ clinical and demographic profiles, postoperative outcomes, and graft and recipient survival rates. Univariate survival analysis was conducted using log-rank tests to compare the groups. ResultsAlmost half (48%) of the procured organs and 40% of the recipients transplanted in our center were from outside our state. Recipient 30-day mortality was 9%. Overall recipient survival at 1 year and 5 years was 85% and 80%, respectively. Mortality was significantly associated with higher Model for End-Stage Liver Disease (P < .001) but not with the presence of hepatocellular carcinoma (P = .795). DiscussionThe new transplantation program treated patients from different regions of Brazil and became the reference center in liver transplantation for the middle west region. Despite the recent implementation, our outcomes are comparable to experienced centers around the world. This model can inspire the creation of new transplantation programs aiming to democratize access to liver transplantation nationwide.

Utilization of hepatitis C viremic donors for liver transplant recipients without hepatitis C. A veterans transplant center report.

We report our experience utilizing liver donors with HCV Viremia (RNA+) for HCV-negative recipients (HCV D+R-) at a Veterans Affairs (VA) transplant center. In 2018, we introduced an informed consent process for HCV D+R- liver transplants. Eight HCV D+R- liver transplants (LT) were performed. Median time from listing to LT was 189days (range 41-511). Median MELD at LT was 23.5 (median MELD at LT of 31 for center). All recipients developed HCV viremia after transplant. Median time to DAA initiation was 10days after viremia (range 3-25). After transplant, the DAAs used were Mavyret in five recipients and Epclusa in three, all for 12weeks. All eight patients completed DAA therapy and achieved negative HCV RNA by end of therapy (ETR) and seven reached sustained virologic response (SVR) by 12weeks after end of therapy. One patient died from chronic ischemic encephalopathy after ETR, before SVR. HCV D+R- is a practical strategy to expand the pool of donor organs. It shortened waiting time, allowing patients to receive transplants at lower MELD scores. VA liver transplant programs have provided universal and timely access to post-transplant HCV DAA therapy after donor-derived infection.

Liver Transplant for Nonresectable Colorectal Cancer Liver Metastases in South Africa: A Single-Center Case Series

Publication in 2013 of the first Secondary Cancer cohort study returned attention to liver transplant for nonresectable colorectal cancer, demonstrating excellent outcomes for a procedure that was historically contraindicated. The Wits Donald Gordon Medical Centre in Johannesburg, South Africa, hosts the largest liver transplant program in sub-Saharan Africa. The persistent shortage of deceased donor organs in our setting has compelled us to innovate solutions unique to our context, which allows us to perform as many transplants as possible and maximize our resource utilization. Therefore, we initiated a research study to transplant organs in patients with nonresectable colorectal carcinoma with expanded criteria using marginal deceased donor organs that would otherwise have been discarded. Institutional Review Board approval was obtained for this study. We used criteria from the 2013 Secondary Cancer cohort study to determine eligibility of patients with nonresectable colorectal carcinoma for liver transplant. Unlike the study from 2013, we utilized expanded criteria and marginal liver allografts for transplant. Five patients have undergone liver transplant for nonresectable colorectal carcinoma. At a median follow-up of 36 months (range, 10-52 months), 4 of the 5 (80%) patients are alive. The patient who died had progressive disease on chemotherapy pretransplant and was the only patient who tested positive for the Kirsten rat sarcoma viral oncogene homolog mutant. Recurrence occurred in all patients at a median time of 6 months after transplant (range, 3-13 months). To our knowledge, this is the only published case series of patients undergoing liver transplant for nonresectable colorectal carcinoma in Africa and is internationally unique in its use of expanded criteria and marginal grafts for this type of transplant. Despite the use of such grafts in our recipients, thus far, these outcomes align with those of the 2013 Secondary Cancer cohort studies from Norway.

Position Statement of Transplant Activity in the Middle East in Era of COVID-19 Pandemic.

Position Statement of Transplant Activity in the Middle East in Era of COVID-19 Pandemic.

The life of Roger Williams

In this brief obituary, we celebrate the life and achievements of Professor Roger Williams, who set up the UK's first liver transplant programme and championed excellence in hepatology for six decades.

BUILDING A SELF-SUFFICIENT LIVER TRANSPLANT PROGRAM IN MONGOLIA

Introduction: The first liver transplant (LT) in Mongolia was performed in 2011. Since then, 93 more LTs have been performed. The aim of this study is to describe the establishment of a LT program with supervised learning and gradual program autonomy in a lower-middle income country (LMIC). Materials and Methods: This is a retrospective study. Patients that received a LT between September 2011 and March 2020 were included. Demographic, transplant, and outcome data were collected. In 2011, a partnership was established with an experienced liver transplant team from Korea to perform the first LT in Mongolia. During the first 4 years, all LTs were performed with the experienced team, with gradually increasing involvement of the Mongolian team. Patients were classified as having been transplanted in the Initial Period (2011-2016), where most transplants were performed with the mentoring team, or the Current Period (2017-2020), performed mostly by the local team. Primary endpoints were patient and graft survival at 1-year. Safety outcomes included complication rates. Results and Discussion: A total of 94 liver transplants were performed on 92 patients (88 adult and 4 pediatric) over the last 10 years. 30 patients received a LT during the initial period and 62 during the current period. LT activity has grown from 3 transplants performed in 2011 to 26 in 2019 (Fig 1).Fig. 1. Since 2017, 87.3% of all LTs have been performed independently. 48.9% (45/92) of patients were female with a median age of 40.5 (IQR: 35-49) years old. The mean MELD at the time of transplant was 14.4±4.9 and the most common diagnosis was hepatitis B(HBV) (n=63) (Table 1).The majority of transplants were performed using right lobes from living donors (93.6%). All pediatric patients received a left lobe from living donors. Nine (9.5%) patients had vascular complications, the most common being hepatic venous outflow obstruction (6.3%). Biliary complications were observed in 18 (19.1%) cases, most of which were biliary strictures (Table 2).1-year survival was 93.9% (95% CI: 87.4-100), during the current period vs 93.3% (95% CI: 84.8-100) during the initial period (p = 0.6) (Fig 2A). Similarly, graft survival was 91.9% (95% CI: 84.5-99.9) for the current period and 90.3% (95% CI: 80.4-100; p = 0.75) for the initial period (Fig 2B).Fig. 2. At 1 year, there were 5 deaths and 1 re-transplant. Conclusion: The establishment of an independent LT program in a LMIC with outcomes similar to well established programs is feasible, and significantly increases access to life-saving procedures for patients with end-stage liver disease. LT volume increased five-fold after graduation to program autonomy. Further increases in capacity, however, are needed to meet the country’s demand. Greater utilization of deceased donors may be key to achieving this, in addition to strategies such as split liver transplants for children.

LIVER TRANSPLANTATION AT BASKENT UNIVERSITY

Background: The only potentially lifesaving intervention for acute liver failure or end-stage liver disease is liver transplant. All over the world, the common indications for liver transplant include hepatitis B, hepatitis C, alcoholic cirrhosis, and hepatocellular carcinoma. However, some more unusual liver diseases, such as liver-based metabolic abnormalities and tumor metastasis, can be treated with liver transplant. The aim of this study was to evaluate the outcomes of liver transplant at our center. Methods: The liver transplantation program at Baskent University began in December 1988. After this transplantation the first LDLT in children in Turkey, the Middle and Near East, and Europe was performed in March 1990, the first LDLT in adult in the World was performed in April 1990, first combined liver-kidney transplantation was performed in the World in May 1992 at Baskent University. We retrospectively analyzed the results of 672 patients who underwent liver transplant from 1988 to October 2020 at our liver transplant center in Turkey. Results: Four hundred fifty-eight of the patients were living donor LT, 214 of them were deceased donor LT. Thee-hundred and eleven (46.2%) of the patients were pediatric, 361 (53,8%) of them were adult. The most common etyology for pediatric liver transplantation was biliary atresia (20%) and, hepatitis B (57%) for adult liver transplantation. In the pediatric group, 5-year surviv al rates of patients was 90%, and 10-year survival rates of patients was 81%, in the adult group, the 5-year survival rate was 79.3% and the 10-year survival rate was 74%. Conclusions: In our center, we perform living-donor liver transplants more than deceased-donor liver transplant because of the paucity of organ donation. Considering acceptable postoperative complications, liver transplant is a lifesaving treatment for liver failure. Careful evaluation of recipients before transplant plays a critical step in curative treatment.

THE IMPACT OF LIVING-UNRELATED TRANSPLANT ON ESTABLISHING DECEASED-DONOR LIVER PROGRAM IN SYRIA

Liver transplant is the criterion standard for patients with end-stage liver disease. Yet there is no liver transplant in Syria. Traveling abroad for a liver transplant is a luxury few Syrians can afford. There is currently an on-going debate whether to start a liver transplant program using living or deceased donors. In 2003, a new law was enacted, authorizing the use of organs from volunteer strangers and deceased donors. Despite the positive aspects of this law (allowing unrelated donors to increase the number of transplants in the country); the negative aspects also were obvious. The poor used the law to sell their organs to the rich, and this model is in violation of the Istanbul Declaration. To better document transplant communities' perceptions on organ donation, an e-mail survey was sent to a nationally representative sample of physicians (n = 115) that showed that 58% of respondents did not support the start of liver transplant from live donors, as they fear a considerable risk for the donor and the recipient. Seventy-one percent of respondents believe that unrelated kidney donation has contributed to tarnishing the reputation of transplant, and 56% believe that a deceased-donor program can run in parallel with unrelated organ donations. The interest in deceased-donor program has been affected negatively by the systematic approach of using poor persons as the source of the organ. This lack of interest has affected starting a liver program that relies on deceased donors; especially the need for kidneys is more than livers. Health authorities in Syria were inclined to initiate a liver transplant program from live donors, despite the risks of serious morbidities and mortality. In conclusion then, paid kidney donation in actual effect is actually a hindrance to establishing a deceased-donor liver program.

Self-limited HBV infection of the recipient does not reactivate after liver transplantation: Observations from a 30-year liver transplant program.

A self-limited hepatitis B infection can reactivate in patients under immunosuppression or chemotherapy (reappearance of hepatitis B surface antigen (HBsAg) or HBV-DNA). Exact circumstances of HBV reactivation in patients undergoing liver transplantation (LT) for end-stage liver diseases (ESLD) unrelated to HBV are unknown, and recommendations on HBV prophylaxis remain unclear. Among 1273 liver transplants, 168 patients with a self-limited HBV hepatitis B infection prior to LT were identified from our prospective liver transplant database. Patients with underlying chronic HBV infection and recipients of an anti-HBc-positive liver were not included in the analysis. Demographic, laboratory, serological, and virological data were analyzed retrospectively. Appearance of HBsAg or HBV-DNA was defined as reactivation. The median follow-up after LT was 12.0years (0.6-30.7years). The rate of HBV reactivation was 0% independent of antiviral prophylaxis (n=7; 4.2%), the etiology of ESLD, hepatitis C treatment, or the anti-HBs concentration. The overall patient survival with a history of a self-limited HBV infection before LT did not significantly differ from the rest of the cohort. Antiviral treatment with nucleos(t)ide analogues post-liver transplantation in order to prevent HBV reactivation in patients with a resolved self-limited hepatitis B infection prior to LT seems to be omittable since the main viral reservoir is removed by the hepatectomy. These findings may clarify the current uncertainty in the recommendations regarding the risk of HBV reactivation in patients with self-limited hepatitis B prior to LT.

Roger Williams: global leader in liver disease

Photo: Chris Young/PA In 2013 Roger Williams, who helped to develop the UK’s first liver transplant programme, said, “I still do my 12 hours a day.” He was then well...

Liver Transplantation in an ICU Dominated by COVID‐19

Potential conflict of interest: Nothing to report. To the Editor: The letter from D'Antiga about concerns of transplanting patients in the context of coronavirus disease 2019 (COVID‐19) pandemic is very interesting.(1) COVID‐19 is the name of the infection caused by the severe acute respiratory syndrome coronavirus 2 (SARS‐Cov‐2) virus. This illness originated in December 2019 in Wuhan, China. Since then, it has been identified in more than 150 countries. The first case of COVID‐19 in Portugal was on March 2, 2020. The intensive care unit (ICU) at Curry Cabral Hospital (CCH) in Lisbon, Portugal, has been supporting the local liver transplantation (LT) program (catchment area of approximately 4 million people), which runs an average of 100 procedures per year. This is a medical and surgical ICU with a regular capacity of 18 beds (10 beds of level 3 care and 8 beds of level 2 care) that are staffed by certified intensivists and specialized nurses. The ICU at CCH has been designated by the Portuguese Health Minister as one of the first ICUs to treat critically ill patients with COVID‐19 given its proximity to the local infectious disease division. As of March 20, we admitted 11 patients with acute respiratory distress syndrome due to COVID‐19 at the ICU, about a third of all critically ill patients with COVID‐19 at that point in Portugal. All of them required invasive mechanical ventilation, and 1 patient died. To improve the safety of both patients and staff, the capacity of the ICU has been provisionally adjusted to 14 level 3 care beds that are divided into 2 independent sectors: COVID‐19 positive (10 beds) and COVID‐19 negative (4 beds). Although almost all elective surgical procedures have been canceled, the ICU still has to provide care to emergent LT candidates. The ICU admits an average of 15 patients with acute liver failure (ALF) and 30 with acute‐on‐chronic liver failure (ACLF) per year. Given the current case mix and capacity of the ICU, we have introduced the following measures to our standard of care: Test emergent LT candidates with polymerase chain reaction for SARS‐Cov‐2 with pharynx swab. If clinical suspicion is high and pharynx swab has come back negative, a second pharynx swab and, if feasible, respiratory secretions are collected for testing. Discuss early with the LT team the need to maintain relatively stable patients with ALF or ACLF in the ICU while awaiting transplant. Collaborate with other ICUs inside the hospital or in other hospitals in the region to transfer other medical or surgical critically ill patients to optimize availability for emergent LT candidates. Patients and staff from each sector of the ICU use different circuits inside the ICU to minimize the risk of contagion. Taking into account the rapidly evolving nature of the COVID‐19 pandemic worldwide, which threatens to overstretch the capacity of health systems, especially that of critical care resources, there are concerns that the quality of care for patients with ALF or ACLF may be impaired. Furthermore, the risks of treating patients with a highly contagious virus close to patients with severe liver disease who are potentially subjected to transplantation and immunosuppression are difficult to weigh at the present time. Therefore, we urge clinicians to share their experiences in organizing care for emergent LT candidates in the ICU in the era of COVID‐19.

Predicting Liver Transplant Patient Outcomes. Is a Validated Model Enough?

Predicting Liver Transplant Patient Outcomes. Is a Validated Model Enough?

Experience of National Medical Center of Specialties “La Raza” in the endoscopical management of bile duct complications after liver transplantation

IntroductionLiver transplantation is a standardized treatment for the management of chronic liver failure, as well as, in selected cases of unresectable tumors and acute liver failure. Transplant programs show improvements that impact in the whole survival, however, bile duct complications remain the main cause of morbidity and mortality in transplant programs worldwide. Material and methodsFor statistical purposes, the liver transplant program activity has been divided into 2 Phases, the first one from 2009 to 2017 and the second from 2018 to the present. The files of patients with at least 6 months of follow-up were included. ResultsThroughout the program there is a record of 22 transplants, according to the division mentioned in two Phases, with a total of 9 transplants in 9 years in Phase 1 and 12 transplants in 2 years in Phase 2. With 33% (3) of complications for Phase 1 and 25% (3) for Phase 2.In all patients the management was endoscopic. ConclusionsBile duct complications are associated with identifiable risk factors, however, the patient's evolution is multifactorial. Both the decrease in the frequency of complications and the effectiveness in their management show improvement according to the establishment of the multidisciplinary team of Liver Transplantation.

COVID-19 and liver transplantation.

The effect of coronavirus disease 2019 (COVID-19) on liver transplantation programmes and recipients is still not completely understood but overall involves the risk of donor-derived transmission, the reliability of diagnostic tests, health-care resource utilization and the effect of immunosuppression. This Comment reviews the effect of COVID-19 on liver transplantation and summarizes recommendations for donor and recipient management.

Strategies for liver transplantation during the SARS-CoV-2 outbreak: Preliminary experience from a single center in France.

Liver transplantation (LT) during the ongoing severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) pandemic is challenging given the urgent need to reallocate resources to other areas of patient care. Available guidelines recommend reorganizing transplant care, but data on clinical experience in the context of SARS‐CoV‐2 pandemic are scarce. Thus, we report strategies and preliminary results in LT during the peak of the SARS‐CoV‐2 pandemic from a single center in France. Our strategy to reorganize the transplant program included 4 main steps: optimization of available resources, especially intensive care unit capacity; multidisciplinary risk stratification of LT candidates on the waiting list; implementation of a systematic SARS‐CoV‐2 screening strategy prior to transplantation; and definition of optimal recipient‐donor matching. After implementation of these 4 steps, we performed 10 successful LTs during the peak of the pandemic with a short median intensive care unit stay (2.5 days), benchmark posttransplant morbidity, and no occurrence of SARS‐CoV‐2 infection during follow‐up. From this preliminary experience we conclude that efforts in resource planning, optimal recipient selection, and organ allocation strategy are key to maintain a safe LT activity. Transplant centers should be ready to readapt their practices as the pandemic evolves.

Deceased Donor Liver Transplantation in India in the COVID-19 Era: Current Scenario and Future Perspectives

Coronavirus disease 2019 (COVID-19) has been recently declared a global pandemic. As of June 5, 2020, over 75,000 cases have been reported with nearly 2500 deaths in India alone. COVID-19 has severely impacted deceased donor liver transplant (DDLT) programs throughout the world. Acceptance of deceased liver donors has decreased worldwide because of the unknown risks associated with COVID-19 transmission or postoperative infection in the immediate post-transplant period, along with the risks to the health care workers in a multidisciplinary setting. In India, DDLT has come to a standstill in the setting of a national lockdown. Many national guidelines have emerged on how to safely perform transplant as well on immunosuppressive regimens and care of patients posttransplant. Here, we take a look at the current situation and summarize the different guidelines and future perspectives of DDLT in India in the COVID-19 era.

Challenges for Liver Transplantation During Recovery From the COVID-19 Pandemic: Insights and Recommendations

The coronavirus disease 2019 (COVID-19) pandemic is placing an increasing burden on liver transplant (LT) services worldwide. At the peak of the pandemic, many LT services worldwide reduced or halted their activities. With the gradual easing of lockdowns, LT teams face new challenges when restarting activities. The numbers of LTs are likely to drop in the immediate post-COVID era.Prolonged and intermittent lockdowns are likely to lead to a shortage of supplies, especially in poor resource settings. Special attention is needed to avoid nosocomial COVID-19 infection among cirrhotic patients awaiting transplant, post-transplant patients, and members of transplant teams. LT programs may have to revise existing strategies in selecting donors and recipients for transplants.Redesigning service provision, restructuring outpatient care, carefully screening and selecting donors and recipients, and performing LT with limited resources will have to be initiated in the post-COVID era if long-term recovery of LT services is to be expected. Costs involved with LT are likely to increase, considering the change in protocols of testing, quarantining, and interstate traveling.This paper discusses the different elements affecting and the widespread impact of the COVID-19 pandemic on LT and strategies to minimize the impact of these factors and to adapt so LT services can meet the health care needs during this pandemic and beyond.