OPTN/SRTR 2020 Annual Data Report: Intestine.

Despite small increases in additions to the intestine transplant wait- list, total waitlist numbers, overall intestine transplant rates, and overall transplants performed from 2019 to 2020, the trend over the last decade is still toward less intestine transplant activity. Waitlist mortality continues to fall for pediatric populations and is relatively stable for adults. While 1- year graft survival continues to improve, there has been no noticeable improvement in 3- and 5-year graft survival. Immunosuppression practices continue to favor use of an induction agent followed by tacrolimus-based regimens. Patient survival at 5 years is currently identical for isolated intestines and liver-inclusive allograft recipients.

OPTN/SRTR 2019 Annual Data Report: Intestine.

Intestine transplant can be life-saving and can improve quality of life for patients with intestinal failure. Medical and surgical advances in treatment of intestinal failure over the past 10 to 15 years have resulted in fewer patients being added to the waiting list for intestine transplant alone or for intestine transplant in combination with liver transplant (and sometimes other organs). Consequently, fewer transplants are being performed. The numbers of listings and transplants fell to new lows in 2019. The number of programs performing transplants in at least one patient in 2019 was the lowest in the last decade, equal to 2014, at 15. Graft failure plateaued over the past decade, but early graft loss has increased in the past 2 years, notably in recipients of a combined liver and intestine allograft. Five-year patient survival for transplants in 2012-2014 varied little by graft type.

OPTN/SRTR 2018 Annual Data Report: Intestine.

Despite medical and surgical advances in treatment of intestinal failure, intestine transplant still plays an important role. However, the number of new patients added to the intestine transplant waiting list has decreased over the past decade, reaching a low of 135 in 2018. The number of intestine donors also decreased, reaching a low of 106 in 2018, and the number of intestine transplants performed declined to its lowest level, 104, of which 59% were intestine-liver transplants. Graft failure has plateaued over the past decade. Patient survival for transplants in 2011-2013 varied by age and transplant type. Patient survival was lowest for adult intestine-liver recipients (1-and 5-year survival 66.7% and 49.1%, respectively) and highest for pediatric intestine recipients (1-and 5-year survival 89.1% and 76.4%, respectively).

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).

OPTN/SRTR 2016 Annual Data Report: Intestine.

Despite improvements in medical and surgical treatment of intestinal failure, intestine transplant continues to play an important role. In 2016, a total of 147 intestine transplants were performed, 80 intestine-without-liver and 67 intestine-liver. Over the past decade, the age distribution of candidates waitlisted for intestine and intestine-liver transplant shifted from primarily pediatric to increasing proportions of adults. In 2016, 58.2% 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 41.9% of candidates on the list at any time during the year, with a stable proportion of those aged 18-34 years and a decrease in those aged 35 years or older. By age, pretransplant mortality rate was highest for adult candidates at 11.7 per 100 waitlist years and lowest for children aged younger than 6 years at 2.2 per 100 waitlist years. For intestine transplants with or without a liver in 2009-2011, 1- and 5-year graft survival was 72.0% and 54.1%, respectively, for recipients aged younger than 18 years, and 70.5% and 44.1%, respectively, for recipients aged 18 years or older.

OPTN/SRTR 2015 Annual Data Report: Intestine.

Intestine and intestine-liver transplant remains important in the treatment of intestinal failure, despite decreased morbidity associated with parenteral nutrition. In 2015, 196 new patients were added to the intestine transplant waiting list, with equal numbers waiting for intestine and intestine-liver transplant. Among prevalent patients on the list at the end of 2015, 63.3% were waiting for an intestine transplant and 36.7% were waiting for an intestine-liver transplant. The pretransplant mortality rate decreased dramatically over time for all age groups. Pretransplant mortality was notably higher for intestine-liver than for intestine transplant candidates (respectively, 19.9 vs. 2.8 deaths per 100 waitlist years in 2014-2015). By age, pretransplant mortality was highest for adult candidates, at 19.6 per 100 waitlist years, and lowest for children aged younger than 6 years, at 3.6 per 100 waitlist years. Pretransplant mortality by etiology was highest for candidates with non-congenital types of short-gut syndrome. Numbers of intestine transplants without a liver increased from a low of 51 in 2013 to 70 in 2015. Intestine-liver transplants increased from a low of 44 in 2012 to 71 in 2015. Short-gut syndrome (congenital and non-congenital) was the main cause of disease leading to intestine and to intestine-liver transplant. Patient survival was lowest for adult intestine-liver recipients and highest for pediatric intestine recipients.

Intestine.

Intestine and intestine-liver transplant plays an important role in the treatment of intestinal failure, despite decreased morbidity associated with parenteral nutrition. In 2014, 210 new patients were added to the intestine transplant waiting list. Among prevalent patients on the list at the end of 2014, 65% were waiting for an intestine transplant and 35% were waiting for an intestine-liver transplant. The pretransplant mortality rate decreased dramatically over time for all age groups. Pretransplant mortality was highest for adult candidates, at 22.1 per 100 waitlist years compared with less than 3 per 100 waitlist years for pediatric candidates, and notably higher for candidates for intestine-liver transplant than for candidates for intestine transplant without a liver. Numbers of intestine transplants without a liver increased from a low of 51 in 2013 to 67 in 2014. Intestine-liver transplants increased from a low of 44 in 2012 to 72 in 2014. Short-gut syndrome (congenital and other) was the main cause of disease leading to both intestine and intestine-liver transplant. Graft survival improved over the past decade. Patient survival was lowest for adult intestine-liver recipients and highest for pediatric intestine recipients.

OPTN/SRTR 2013 Annual Data Report: intestine.

Despite improvements in medical and surgical treatment of intestinal failure over the past decade, intestine transplant continues to play an important role. Of 171 new patients added to the intestine transplant waiting list in 2013, 49% were listed for intestine-liver transplant and 51% for intestine transplant alone or with an organ other than liver. The pretransplant mortality rate decreased dramatically over time for all age groups, from 30.3 per 100 waitlist years in 2002-2003 to 6.9 for patients listed in 2012-2013. The number of intestine transplants decreased from 91 in 2009 to 51 in 2013; intestine-liver transplants decreased from 135 in 2007 to a low of 44 in 2012, but increased slightly to 58 in 2013. Ages of intestine and intestineliver transplant recipients have changed substantially; the number of adult recipients was double the number of pediatric recipients in 2013. Graft survival improved over the past decade. Graft failure in the first 90 days posttransplant occurred in 14.1% of intestine recipients and in 11.2% of intestine-liver recipients in 2013. The number of recipients alive with a functioning intestine graft has steadily increased since 2002, to 1012 in 2013; almost half were pediatric intestine-liver transplant recipients.

OPTN/SRTR 2012 Annual Data Report: intestine.

Advances in the medical and surgical treatments of intestinal failure have led to a decrease in the number of transplants over the past decade. In 2012, 152 candidates were added to the intestinal transplant waiting list, a new low. Of these, 64 were listed for intestine-liver transplant and 88 for intestinal transplant alone or with an organ other than liver. Historically, the most common organ transplanted with the intestine was the liver; this practice decreased substantially from a peak of 52.9% in 2007 to 30.0% in 2012. Short-gut syndrome, which encompasses a large group of diagnoses, is the most common etiology of intestinal failure. The pretransplant mortality rate decreased dramatically over time for all age groups, from 51.0 per 100 wait-list years in 1998-1999 to 6.7 for patients listed in 2010-2012. Numbers of intestinal and intestine-liver transplants steadily decreased from 198 in 2007 to 106 in 2012. By age, intestinal transplant recipients have changed substantially; the number of adult recipients now approximately equals the number of pediatric recipients. Graft survival has improved over the past decade. Graft failure in the first 90 days after transplant occurred in 15.7% of 2011-2012 intestinal transplant recipients, compared with 21% in 2001-2002.

OPTN/SRTR 2011 Annual Data Report: intestine.

Since 2006, the number of new intestinal transplant candidates listed each year has declined, likely reflecting increased medical and surgical treatment for intestinal failure. Historically, intestinal transplant occurred primarily in the pediatric population; in 2011, 41% of prevalent candidates on the waiting list were aged 18 years or older. The most common etiology of intestinal failure remains short-gut syndrome, which encompasses several diagnoses. The proportion of candidates with high medical urgency status decreased and time on the waiting list increased in 2011. The overall rate of transplant decreased from a peak of 92.7 transplants per 100 wait-list years in 2005 to 49.2 in 2011. The number of intestines recovered and transplanted per donor has decreased since 2007, possibly due to fewer listed patients. Almost 50% of deceased donor intestines were transplanted with another organ in 2011. Historically, the most common organ transplanted with the intestine was the liver, but in 2011 it was the pancreas. Graft survival has continued to improve over the past decade, and the number of recipients alive with a functioning intestinal graft has steadily increased since 1998. Hospitalization is common, occurring in 84.8% of recipients by 6 months posttransplant and in almost all by 4 years.

Safety and immunogenicity of varicella-zoster virus vaccine in pediatric liver and intestine transplant recipients.

Primary varicella-zoster virus (VZV) infections following organ transplantation may cause significant morbidity. We examined the safety and immunogenicity of Varivax after transplantation as a potential prophylactic tool. Pediatric liver and intestine transplant recipients without history of chickenpox received one dose of Varivax. VZV humoral and cellular immunity were assessed before and > or =12 weeks after vaccination. Adverse events (AE) and management of exposure to wild type VZV were monitored. Sixteen VZV-naïve subjects, 13-76 months of age, at 257-2045 days after transplantation were immunized. Five children developed mild local AE of short duration. Four subjects developed fever and four developed non-injection site rashes, three of whom received acyclovir. Liver enzymes did not increase during the month after vaccination. Eighty-seven percent and 86% of children developed humoral and cellular immunity, respectively. There were five reported exposures to varicella in four children, none of which resulted in chickenpox. One subject received VZV-immunoglobulin and another subject with liver enzyme elevations after exposure received acyclovir; all remained asymptomatic. Varivax was safe and immunogenic in pediatric liver and intestine transplant recipients. Larger studies are needed to establish the efficacy and role of varicella vaccination after transplantation.

Lack of utility of intestinal fatty acid binding protein levels in predicting intestinal allograft rejection.

INTRODUCTION: The enterocyte-specific protein, intestinal fatty acid binding protein (I-FABP), is detectable in serum only after intestinal injury. Previous studies in animals suggest that I-FABP might be a useful marker of intestinal allograft rejection. MATERIALS AND METHODS: I-FABP was repetitively measured in nine intestinal transplant recipients and correlated with findings of surveillance endoscopy. RESULTS: Average interval between I-FABP determination and biopsy was 3.4 days (SD=4.2 days). Average number of rejection episodes per patient totalled 1.6+/-1.2. General linear modeling demonstrated no tendency for increases in serum FABP to precede histologic graft rejection (P=0.263). Restriction of the analysis to I-FABP determinations 1 day before or on the day of biopsy failed to affect these results. Minor increases in I-FABP were often associated with histologically normal grafts, whereas rejection often occurred when I-FABP was not detectable. DISCUSSION: Serum I-FABP levels do not predict clinical intestinal allograft rejection.

Extracorporeal liver perfusion using human and pig livers for acute liver failure.

BACKGROUND: Patients with fulminant hepatic failure (FHF) often die awaiting liver transplantation. Extracorporeal liver perfusion (ECLP) has been proposed as a method of "bridging" such patients to transplantation. We report the largest experience to date of ECLP using human and porcine livers in patients with acute liver failure. METHODS: Patients with FHF unlikely to survive without liver transplantation were identified. ECLP was performed with human or porcine livers. Patients underwent continuous perfusion until liver transplantation or withdrawal of support. Two perfusion circuits were used: direct perfusion of patient blood through the extracorporeal liver and indirect perfusion with a plasma filter between the patient and the liver. FINDINGS: Fourteen patients were treated with 16 livers in 18 perfusion circuits. Nine patients were successfully "bridged" to transplantation. ECLP stabilized intracranial pressure (ICP) and cerebral perfusion pressure (CPP). Arterial ammonia levels fell from a median of 146 to 83 micromol/liter within 12 hr and this reduction was maintained at least 48 hr. Pig and human ECLP lowered ammonia levels equally. Serum bilirubin levels also fell from a median of 385 to 198 micromol/liter over the first 12 hr but the response was not sustained as well with porcine livers. There was no immunological benefit to using the the filtered perfusion circuit. INTERPRETATION: These data demonstrate that ECLP is safe and can provide metabolic support for comatose patients with fulminant hepatic failure for up to 5 days. While labor and resource intensive, this technology is available to centers caring for patients with acute liver failure and deserves wider evaluation and application.

Disaccharidase activities and fat assimilation in pediatric patients after intestinal transplantation.

BACKGROUND: Intestinal transplantation has become an accepted therapy for short bowel syndrome and other types of intestinal failure. In order to assess digestive capabilities and feeding practices in a group of 22 pediatric patients after intestinal transplantation, we assessed mucosal disaccharidase activities and assimilation of total dietary lipid and vitamin E. Twelve of the patients had undergone contemporaneous liver transplantation. METHODS: Mucosal biopsies were assayed for disaccharidase activities between 15 and 412 days after transplantation in 7 of the 22 when all were receiving some enteral nutrition and were free of rejection. Coefficients of lipid absorption were determined in those patients receiving total enteral feeding (two-thirds polymeric/one-third elemental) between 43 and 1032 days after transplantation; oral vitamin E tolerance tests were done at about the same time. RESULTS: Activities of lactase, sucrase, maltase, and palatinase consistently exceeded reference ranges (P<0.05). Mean coefficient of lipid absorption equaled 86+/-12% and was not influenced by duration of time after transplantation. No patient required dietary lipid restriction. No significant absorption of vitamin E was demonstrated until 160 days after transplantation. Vitamin E absorption did correlate with length of time elapsed after surgery (r=0.64, P<0.0011). CONCLUSIONS: The results of this investigation show that, in the absence of histologic or clinical indications of allograft rejection, pediatric intestinal transplant recipients do not have primary disaccharidase deficiencies. Similarly, absorption of usual dietary lipid content is adequate once weaning from parenteral nutrition is complete. In contrast, early assimilation of vitamin E is poor. Vitamin E absorption subsequently improves, but the mechanism is obscure.

Correlation of mucosal disaccharidase activities with histology in evaluation of rejection following intestinal transplantation.

Following intestinal transplantation, we have found that recovery from severe rejection may be difficult to identify. In this study we sought to ascertain whether concurrent determination of mucosal disaccharidase activities and histologic assessment improves the accuracy of diagnosis of rejection. Histologic changes were graded blindly using a standard set of diagnostic criteria, and these changes were compared over time to maltase, sucrase, lactase, and palatinase activities in four pediatric patients under treatment for severe rejection. The histologic criteria, which included magnitude of enterocyte loss, degree of granulation tissue, severity of villus atrophy, and frequency of apoptosis and cryptitis, were found to correlate with one another over time irrespective of outcome (r = 0.72 to r = 0.85). Enzyme activities were also correlated with each other over time (r = 0.64 to r = 0.80). However, the correlation between histologic diagnosis and enzyme activity was weaker (r = -0.48 to r = -0.57). Furthermore, neither histologic nor enzyme evaluation early in the course of rejection predicted ultimate clinical outcome. The results of this investigation show that determination of mucosal disaccharidase activity provides no additional useful information concerning efficacy of anti-rejection therapy as compared to histologic analysis alone.

Copper associated childhood cirrhosis.

Several papers have reported severe liver disease in association with massive hepatic copper accumulation, which do not seem to be either of the recognised copper associated liver diseases, namely Wilson's disease and Indian childhood cirrhosis. A further case is reported in which novel copper kinetic studies were carried out using the stable isotope 65Cu, showing that this patient did not suffer from Wilson's disease. It is suggested that these cases can be divided into two groups on the basis of age, clinical course, and history of excessive copper ingestion. The benefits of using 65Cu for in vivo studies of copper metabolism is discussed.

Cholestasis in infancy: 2.

Neonates with cholestasis present in several ways but all cases need to be investigated. Prompt diagnosis is imperative as age at treatment can be a major factor affecting the prognosis. The modes of presentation of infants with conjugated hyperbilirubinaemia are discussed and a plan for the investigation of such infants is suggested.

Liver histology in the arthrogryposis multiplex congenita, renal dysfunction, and cholestasis (ARC) syndrome: report of three new cases and review.

We report three cases from two unrelated families of infants with arthrogryposis multiplex congenita, cholestatic jaundice, and renal Fanconi's syndrome. In both families the parents were consanguineous. All three children died by 7 months of age. This association was first reported in 1973 by Lutz-Richner and Landolt and again in another family by Nezelof et al in 1979. However, because of differing liver histology the two sibships were considered to have two separate conditions. Based on the histological findings in one of our cases we propose that all cases described so far represent variation within a single syndrome.

Cholestasis in infancy: 1.

Although conjugated hyperbilirubinaemia is not common in infants its presence carries serious implications in the majority of cases. It is therefore important that those responsible for the care of sick infants have a good understanding of the causes of cholestasis in infancy. Early diagnosis facilitates early treatment which is the key to optimal management in many such children. In the first of two articles, the major causes of cholestasis in infancy are discussed.