Liver-intestinal Transplantation Research Articles

265.4: The first report of three-way macrochimerism and alloreactivity using single cell profiling in a patient receiving multivisceral transplantation following loss of an initial liver-intestine transplant.

265.4: The first report of three-way macrochimerism and alloreactivity using single cell profiling in a patient receiving multivisceral transplantation following loss of an initial liver-intestine transplant.

Excess waitlist mortality among candidates for multivisceral liver-intestine transplant in acuity circle allocation

Candidates for multivisceral transplant (MVT) have experienced decreased access to transplant in recent years. Using Organ Procurement and Transplantation Network data, transplant and waiting list outcomes for MVT (ie, liver-intestine, liver-intestine-pancreas, and liver-intestine-kidney-pancreas) candidates listed between February 4, 2018, and February 3, 2022, were analyzed, including model for end-stage liver disease/pediatric end-stage liver disease and exception scores by era (before and after acuity circle [AC] implementation on February 4, 2020) and age group (pediatric and adult). Of 284 MVT waitlist registrations (45.6% pediatric), fewer had exception points at listing post-AC compared to pre-AC (10.0% vs 19.1%), and they were less likely to receive transplant (19.1% vs 35.9% at 90 days; 35.7% vs 57.2% at 1 year). Of 177 MVT recipients, exception points at transplant were more common post-AC compared to pre-AC (30.8% vs 20.2%). Postpolicy, adult MVT candidates were more likely to be removed due to death/too sick compared with liver-alone candidates (13.5% vs 5.6% at 90 days; 24.2% vs 9.8% at 1 year), whereas no excess waitlist mortality was observed among pediatric MVT candidates. Under current allocation policy, multivisceral candidates experience inferior waitlist outcomes compared with liver-alone candidates. Clarification of guidance around submission and approval of multivisceral exception requests may help improve their access to transplantation and achieve equity between multivisceral and liver-alone candidates on the liver transplant waiting list.

124: The first report of three-way macrochimerism in a patient receiving multivisceral transplantation following loss of an initial liver-intestine transplant

124: The first report of three-way macrochimerism in a patient receiving multivisceral transplantation following loss of an initial liver-intestine transplant

OPTN/SRTR 2021 Annual Data Report: Intestine

There has been just over 30 years of experience in clinical intestine transplant. A rise in demand until 2007 with improving transplant outcomes preceded a subsequent fall in demand due, at least in part, to improvements in pretransplant care of patients with intestinal failure. Over the past 10 to 12 years, there has been no suggestion of an increase in demand and, particularly for adult transplant, there may be a continued trend toward fewer additions to the waiting list and fewer transplants, especially in those needing combined intestine-liver transplant. In addition, over the same period there has been no noticeable improvement in graft survival, with 1- and 5-year graft failure rates averaging 21.6% and 52.5%, respectively, for intestine-alone transplants and 28.6% and 47.2%, respectively, for combined intestine-liver allografts.

Outcome of Total Colonic Aganglionosis Involving the Small Bowel Depends on Bowel Length, Liver Disease, and Enterocolitis.

Total colonic aganglionosis involving the small bowel is a rare form of Hirschsprung disease. We aim to analyse the long-term outcomes, digestive autonomy, and complications, to suggest recommendations for prevention and treatment. All patients born between 2000 and 2015 followed in our centre were retrospectively included. We analysed the length of aganglionosis, surgical procedures, growth, duration of parenteral nutrition (PN), enterocolitis, liver disease, intestinal transplantation. Twenty-five patients were followed for a median of 10.9 years. Fifteen patients had less than 80 cm of ganglionic small bowel (SB) with a median of 20 cm. Ten patients had more than 80 cm of ganglionic sB with a median of 115 cm. The median PN duration was significantly shorter for patients with more than 80 cm: 0.9 versus 7.5 years in those with less than 80 cm (P < 0.001). No patient with less than 80 cm was weaned off PN, except 1 who underwent intestinal transplantation. Ten patients with less than 80 cm develop enterocolitis on the excluded segment, leading to emergency entero-colectomy in 5. Liver disease was more frequent in patients with less than 80 cm (11 vs 0). Three patients required combined liver-intestine transplantation; 2 underwent an isolated intestinal transplantation. Digestive autonomy was possible in most patients with more than 80 cm of ganglionic SB. The more severe complication was enterocolitis. Liver disease compromised long-term survival without transplantation. Both complications should be prevented by early diversion and enterectomy of the whole aganglionic segment. Follow-up in or together with a multidisciplinary intestinal rehabilitation centre is suggested.

Impact of the acuity circle model for liver allocation on multivisceral transplant candidates

Liver allocation was updated on February 4, 2020, replacing a Donor Service Area (DSA) with acuity circles (AC). The impact on waitlist outcomes for patients listed for combined liver-intestine transplantation (multivisceral transplantation [MVT]) remains unknown. The Organ Procurement and Transplantation Network/United Network for Organ Sharing database was used to identify all candidates listed for both liver and intestine between January 1, 2018 and March 5, 2021. Two eras were defined: pre-AC (2018-2020) and post-AC (2020-2021). Outcomes included 90-day waitlist mortality and transplant probability. A total of 127 adult and 104 pediatric MVT listings were identified. In adults, the 90-day waitlist mortality was not statistically significantly different, but transplant probability was lower post-AC. After risk-adjustment, post-AC was associated with a higher albeit not statistically significantly different mortality hazard (sub-distribution hazard ratio[sHR]: 8.45, 95% CI: 0.96-74.05; p=.054), but a significantly lower transplant probability (sHR: 0.33, 95% CI: 0.15-0.75; p=.008). For pediatric patients, waitlist mortality and transplant probability were similar between eras. The proportion of patients who underwent transplant with exception points was lower post-AC both in adult (44% to 9%; p=.04) and pediatric recipients (65% to 15%; p=.002). A lower transplant probability observed in adults listed for MVT may ultimately result in increased waitlist mortality. Efforts should be taken to ensure equitable organ allocation in this vulnerable patient population.

National survey on deceased donor organ transplantation during the COVID-19 pandemic in Japan

PurposeWe investigated the status of deceased organ donation and transplantation through a questionnaire distributed to transplant centers in Japan during the COVID-19 pandemic.MethodsThe questionnaire was distributed electronically to 206 transplant centers for heart (n = 11), lung (n = 10), liver (n = 25), kidney (n = 130), pancreas (n = 18), and small intestine (n = 12) transplantation. Organ donations and organ transplantation data were extracted from the Japan Organ Transplant Network website.ResultsWe received questionnaire responses from 177 centers (response rate, 86%). In 2020, the number of brain-dead donors (BDDs) decreased to 68 (69% of the year-on-year average) and the number of donors after cardiac death (DCDs) decreased to 9 (32% of the year-on-year average). Eighty-five (48%) transplant centers (heart, n = 0; lung, n = 0; liver, n = 4; kidney, n = 78; pancreas, n = 22; and small intestine, n = 0) suspended transplant surgeries in response to the COVID-19 pandemic. Consequently, the number of organ transplantations from deceased donors was significantly lower in 2020 than in 2019.ConclusionAlthough the COVID-19 pandemic has had less impact in Japan than in other countries, it has affected transplantation activity significantly, suspending transplantation surgeries in 48% of the transplantation centers, including 78% of the kidney transplantation centers, and reducing the number of organ donations to 61% of the year-on-year average.

Pediatric Home Parenteral Nutrition in France: A six years national survey

Home Parenteral Nutrition (HPN) is the cornerstone management for children suffering from chronic intestinal failure (CIF). In France, HPN is organized from a network of 7 certified centers located in University Hospitals spread across the national territory. This study aims to review the data involving children on HPN over a 6-years period in France to outline the global and continuous improvement in care.This cross-sectional study included all children enrolled in any of the 7 French HPN certified centers from January 1st, 2014 to December 31st, 2019. Data was recorded from annual databases provided by each center regarding: age at inclusion, indication and duration of HPN, type of intravenous lipid emulsion (ILE), outcome [PN weaning off, transfer to adult center, death, intestinal transplantation (ITx)], rate of catheter-related bloodstream infections (CRSBIs) for 1000 days of HPN, Taurolidine lock procedure (TLP) use and prevalence of cholestasis defined as conjugated bilirubin ≥20 μmol/l.The number of patients increased by 43.6% from 268 in 2014 to 385 in 2019. According to the year of follow up, the indications for HPN were short bowel syndrome (SBS) (42.3-46.6%), congenital enteropathies (CE) (18.5-22.8%), chronic intestinal pseudo-obstruction syndrome (CIPOS) (13.0-16.3%), long segment Hirschsprung's disease (LSHD) (9.7-13.3%), Crohn's disease (CD) (1.6-2.6%) and other non-primary digestive diseases (NPDD) such as immune deficiency, cancer or metabolic disease (4.0-9.2%). The median age at discharge on HPN decreased from 11.7 months in 2014 to 8.3 months in 2019 (p < .001). By December 31st, 2019, 44.8% of children had left the HPN program after a median duration ranging between 39.9 and 66.4 months. Among these patients, 192 (74.2%) were weaned off PN (94.7% SBS), 41 (15.8%) were transferred to adult centers for CIPOS (42%), SBS (31%) or CE (27%), 21 died (8.1%) - mostly in relation to cancer or immune deficiency - and 5 were transplanted (1.9%): 4 underwent combined liver-intestine transplantation for LSHD (n = 2), SBS, CE and one multivisceral Tx for CIPOS. The use of a composite fish-oil based ILE increased from 67.4% in 2014 to 88.3% in 2019 (p < 0.001). CRBSIs dropped from 1.04 CRSBIs per 1000 days HPN in 2014 to 0.61 in 2019 (p < 0.001) while meantime, the percentage of children receiving TLP increased from 29.4% to 63.0% (p < 0.001). The prevalence of cholestasis (conjugated bilirubin ≥ 20 μmol/l) was low and stable between 4.1 and 5.9% of children during the study period.In France, the number of children enrolled in a HPN program continuously increased over a 6 years period. SBS is the leading cause of CIF requiring HPN. The rate of CRBSIs dropped dramatically as the use of TLP increased. Mortality rate was low and mainly in relation to the underlying disease (cancer, immune deficiency). Cholestasis and intestinal Tx remained very rare.

2020 position statement and recommendations of the European Liver and Intestine Transplantation Association (ELITA): management of hepatitis B virus‐related infection before and after liver transplantation

Prophylaxis of HBV recurrence is critical after liver transplantation in HBV patients. Despite new prophylactic schemes, most European LT centres persist on a conservative approach combining hepatitis B immunoglobulin (HBIG) and nucleos(t)ides analogues (NA). This setting prompted the European Liver Intestine Transplantation Association (ELITA) to look for a consensus on the prevention of HBV recurrence. Based on a 4-round Delphi process, ELITA investigated 16 research questions and established 50 recommendations. Prophylaxis should be driven according to 3 simplified risk groups: Low and high virological risk patients, with undetectable and detectable HBV DNA pre-LT, respectively, and special populations (HDV, HCC, poorly adherent patients). In low-risk patients, short-term (4weeks) combination of third-generation NA+ HBIG, or third generation NA monotherapy can be considered as prophylactic options. In high-risk patients, HBIG can be discontinued once HBV DNA undetectable. Combined therapy for 1year is advised. HBV-HCC patients should be treated according to their virological risk. In HDV/HBV patients, indefinite dual prophylaxis remains the gold standard. Full withdrawal of HBV prophylaxis following or not HBV vaccination should only be attempted in the setting of clinical trials. Organs from HBsAg+ve donors may be considered after assessment of risks, benefits, and patient consent. They should not be used if HDV is present. In poorly adherent patients, dual long-term prophylaxis is recommended. Budget impact analysis should be taken into account to drive prophylactic regimen. These ELITA recommendations should stimulate a more rational and homogeneous approach to HBV prophylaxis across LT programs.

O-42: Pediatric Composite Liver-intestine Transplantation with Native Splenopancreatic Preservation: Immunologic Complications and Long-term Outcomes

Introduction: Combined liver-intestine transplantation is the only proven treatment for the moribund child with intestinal failure and decompensated liver disease. Native splenopancreatic preservation may provide immunologic benefits that results in improved long-term outcomes. Methods: All pediatric patients who underwent combined liver-intestine transplantation with native splenopancreatic preservation at our institution from November 2003 until June 2019 were included in this study. Freedom from rejection and survival were estimated using the Kaplan-Meier method. Risk factors for graft loss and death were identified using Cox proportional hazard regression analysis. Results: Pediatric recipients included 68 infants with a median follow up of 9.8 years. Recipient median age was 1.3 years old with a median weight of 9.3kg and were more commonly male. Short gut syndrome was the most etiology of intestinal failure. Donors were generally younger (median age 0.4 years old) and smaller (median weight 6.9kg) than recipients. The most common cause of donor death was intracranial hemorrhage. Early rejection (<1 year) occurred in 10 (15%) and late rejection (>1 year) in 9 (13%) recipients. De novo donor specific antibody developed in 17 (25%) recipients. PTLD occurred in 4 (5.9%) and GVHD in 4 (5.9%) recipients. The 10-year survival with a functioning graft was 80.4% in this group. Multivariate Cox regression analysis identified inpatient status at time of transplant, donor-recipient weight ratio >0.9, and development of GVHD as statistically significant risk factors for graft loss and death after transplant. Conclusions: In this large pediatric cohort of combined liver-intestine transplant recipients with native splenopancreatic preservation there was a relatively low rate of immunologic complications and excellent long-term outcomes.

P-83: Laparoscopic Sleeve Gastrectomy for Obesity after Combined Liver-intestinal Transplantation is Feasible and Safe

P-83: Laparoscopic Sleeve Gastrectomy for Obesity after Combined Liver-intestinal Transplantation is Feasible and Safe

O-14: Portal Hypertensive Complications after Pediatric Combined Liver-intestine Transplantation from Late Vascular Compromise of Native Portacaval Shunt: Clinical Presentation and Management

O-14: Portal Hypertensive Complications after Pediatric Combined Liver-intestine Transplantation from Late Vascular Compromise of Native Portacaval Shunt: Clinical Presentation and Management

An Extraordinary Cause of Dyspnea and Weight Loss

Question: A 42-year-old male 10 years post liver–intestine transplantation was referred from a regional hospital to our institute with unintentional weight loss (15 kg over 6 months), progressive exertional dyspnea, and what was thought to be a loud pansystolic murmur. Past medical history is significant for short bowel syndrome with total parenteral nutrition dependence complicated by intestinal failure associated liver disease, diminishing venous access, and a distant history of a right nephrectomy as a child.

Review article: diagnosis and management of intestinal failure-associated liver disease in adults.

Hepatic disturbances in the context of intestinal failure and parenteral nutrition (PN) are frequently encountered and carry a significant burden of morbidity and sometimes mortality. The term intestinal failure-associated liver disease (IFALD) refers to liver injury due to intestinal failure and associated PN, in the absence of another evident cause of liver disease, encompassing a spectrum of conditions from deranged liver enzymes, steatosis/ steatohepatitis, cholestasis as well as progressive fibrosis, cirrhosis and end-stage liver disease. To present an up to date perspective on the diagnosis/definition, aetiologies and subsequent management of IFALD and to explore future consideration for the condition, including pharmacological therapies RESULTS: In adults using long-term PN for benign chronic intestinal failure, 1%-4% of all deaths are attributed to IFALD. The aetiology of IFALD is multifactorial and can be broadly divided into nutritional factors (eg lipid emulsion type) and patient-related factors (eg remaining bowel anatomy). Given its multifaceted aetiology, the management of IFALD requires clinicians to investigate a number of factors simultaneously. Patients with progressive liver disease should be considered for combined liver-intestine transplantation, although multivisceral grafts have a worse prognosis. However, there is no established non-invasive method to identify progressive IFALD such that liver biopsy, where appropriate, remains the gold standard. A widely accepted definition of IFALD would aid in diagnosis, monitoring and subsequent management. Management can be complex with a number of factors to consider. In the future, dedicated pharmacological interventions may become more prominent in the management of IFALD.

Malignant hepatic vascular tumors in adults: Characteristics, diagnostic difficulties and current management.

Malignant vascular tumors of the liver include rare primary hepatic mesenchymal tumors developed in the background of a normal liver parenchyma. Most of them are detected incidentally by the increased use of performing imaging techniques. Their diagnosis is challenging, involving clinical and imaging criteria, with final confirmation by histology and immunohistochemistry. Surgery represents the mainstay of treatment. Liver transplantation (LT) has improved substantially the prognosis of hepatic epithelioid hemangioendothelioma (HEHE), with 5-year patient survival rates of up to 81%, based on the European Liver Intestine Transplantation Association-European Liver Transplant Registry study. Unfortunately, the results of surgery and LT are dismal in cases of hepatic angiosarcoma (HAS). Due to the disappointing results of very short survival periods of approximately 6-7 mo after LT, because of tumor recurrence and rapid progression of the disease, HAS is considered an absolute contraindication to LT. Recurrences after surgical resection are high in cases of HEHE and invariably present in cases of HAS. The discovery of reliable prognostic markers and the elaboration of prognostic scores following LT are needed to provide the best therapeutic choice for each patient. Studies on a few patients have demonstrated the stabilization of the disease in a proportion of patients with hepatic vascular tumors using novel targeted antiangiogenic agents, cytokines or immunotherapy. These new approaches, alone or in combination with other therapeutic modalities, such as surgery and classical chemotherapy, need further investigation to assess their role in prolonging patient survival. Personalized therapeutic algorithms according to the histopathological features, behavior, molecular biology and genetics of the tumors should be elaborated in the near future for the management of patients diagnosed with primary malignant vascular tumors of the liver.

OPTN/SRTR 2017 Annual Data Report: Intestine.

Despite improvements in medical and surgical treatment of intestinal failure, intestine transplant continues to play an important role. In 2017, 109 intestine transplants were performed, 62 in adults and 47 in children, reflecting the changed age distribution over the past decade of candidates waitlisted for intestine and intestine-liver transplant from largely pediatric to increasing proportions of adults. In 2017, 56.0% of candidates on the intestine list at any time during the year were aged younger than 18 years, with a decrease over time in those aged younger than 6 years and an increase in those aged 6-17 years. Adults accounted for 44.0% of candidates on the list at any time during the year, with an increase since 2013 in those aged 18-34 years and a decrease in those aged 35 years or older. By age, the pretransplant mortality rate was highest for adult candidates at 7.9 per 100 waitlist-years and lowest for pediatric candidates at 3.7 per 100 waitlist-years. Patient survival varied by age and type of transplant, and was lowest for adult intestine-liver recipients (1- and 5-year survival 66.7% and 42.6%, respectively) and highest for pediatric intestine recipients (1- and 5-year survival 86.2% and 75.4%, respectively).

Hereditary Hemorrhagic Telangiectasia

Hereditary Hemorrhagic Telangiectasia

Vascular tumours of the liver: a particular story.

Vascular tumours of the liver represent an underrated chapter of medical and surgical hepatology. These tumours cover a wide spectrum ranging from the frequent and most benign hepatic haemangioma (HH), via the rare and intermediately aggressive hepatic epithelioid haemangioendothelioma (HEHE) to the rare and most malignant hepatic haemangiosarcoma (HHS). In contrast to the treatment algorithms for hepatocellular and cholangiocellular cancer, the diagnostic and therapeutic approaches to HEHE and HHS are not well developed. The related uncertainty is explained by their rare occurrence and their protean clinical, morphological (imaging) and histopathological presentation and behaviour. This article gives an update about these particular tumours based on the analysis of the recent literature and of the studies on vascular tumours published by the European Liver Intestine Transplantation Association (ELITA)-European Liver Transplant Registry (ELTR). It focuses also on the place of liver transplantation (LT) in the respective therapeutic algorithms. The differential diagnosis between these vascular and other tumour types may be very difficult. Correct diagnosis is of utmost importance and is based on a high index of clinical suspicion and on the integration of clinical, radiological, histological [including immunohistochemistry (IHC) and molecular biology findings]. Surgery, be it partial or total hepatectomy (LT), should be proposed whenever possible, because it is the therapeutic mainstay. In HEHE, LT provides excellent results, with long-term disease-free survivals (DFS) reaching 75%. Good results can be obtained even in case of (frequent) extrahepatic spread. Based on the extensive ELITA-ELTR study a HEHE-LT prognostic score has been proposed in order to estimate the risk of recurrence after LT. In contrast, results of surgery and LT are extremely poor for HHS, for the almost invariably rapid recurrence (within 6 months) and related death within 2 years. LT remains a contraindication for HHS. Due to the still important recurrence rate after surgical resection (25% in HEHE and almost 100% in HHS), there is an urgent need to develop pharmacological treatments targeting angiogenic and non-VEGF angiogenic pathways. To date, some prospective pilot studies and case reports have shown some short-term stabilisation of the disease in small groups of patients. In order to make progress, combination of surgery, anti-angiogenic and immunotherapy seems worthwhile. To complete the panel of vascular liver tumours, infantile haemangioendothelioma, haemangiopericytoma, nodular regenerative hyperplasia (NRH) and hepatic small vessel neoplasms (HSVN) are also discussed.

Grafting's Function in Patients with Liver Intestinal and Multivisceral Transplantation

Introduction There are few studies of the intestinal graft function in medium and long term. Objectives Assess the functional status of the graft in transplantation patients, once the immediate post-transplant has been overcome. Methodology Patients who received a liver-intestinal or multivisceral transplantation were prospectively evaluated through cross-sectional data collection during a review. Clinical, analytical and functional variables are analyzed. Unstable patients with intercurrent processes were excluded. Results Twenty-six patients were analyzed, 65.38% of them male. 21 with multivisceral graft (80.76%) and 5 liver-intestinal (19.23%). 7 multivisceral grafts were retransplantation (26.92%). The average age at transplantation was 1.73 + / 3.22 years (range: 7 months - 13 years). The average time post-transplant was 3.78 +/- 3.69 years (range 1.5 - 14 years). The indication for transplant was volvulus (19.23%), necrotizing enterocolitis (15.38%), gastroschisis (15.38%), pseudo-obstruction (11.53%), atresia (7.69%) intestinal ischemia (7.69%), epithelial dysplasia (7.69%), MartínezFrías syndrome (3.84%), mitochondrial disease (3.84%) and Hirschsprung's disease (3.84%). 96.15% of patients are autonomous oral-enteral. 1 (3.85%) maintains home parenteral nutrition. 15.38% receive enteral nocturnal nutrition. 3 patients (11.53%) maintain ostomy.Fecal alpha 1-antitrypsin was normal in 92.30% of patients. Fecal elastase was normal at 100%. Faecal fat excretion was normal in 84.61% of patients, only 4 (15.38%) with a moderate steatorrhea. Blood parameters were normal in 100% of patients, including serum citrulline levels with a mean of 37.16 μmol / L (range 21-74). Conclusion 1. Patients with liver-intestinal and multivisceral transplantation have good graft function in medium and long term. 2. Most maintain digestive autonomy. 3. Although in some patients steatorrhea is observed, pancreatic function is normal in 100% of patients with a multivisceral transplantation that includes a pancreatic graft.

Organ Transplantation in Argentina.

Organ Transplantation in Argentina.