Tag Archives: liver transplantation

Liver Shorts November 2018

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J Ge et al. Hepatology 2018; 68: 1101-10.  This study reviewed liver donation offers between 2010 to 2014.  This study found that 5.6% of men (293/5202) and 6.2% of women (179/2899) received a pediatric donor as a first offer.  Women, but not men, who received a pediatric first offer had a lower risk of waitlist mortality than with those who received adult organ offers. The authors recommend that “offers of pediatric donor liver be prioritized to women, who are generally shorter stature, once alllocation to the entire…pediatric waitlist pool has occurred.”

CA Chapin et al. Hepatology 2018; 68: 1087-1100.  This study found that patients with indeterminate pediatric acute liver failure (iPALF) have a unique pattern of dense CD8+ T-cell infiltrate that is also perforin-positive adn CD103-positive.  These CD8+ cells are a biomarker for immune dysregulation. These CD8+ dense pattern was found in the 27 of 33 patients with iPALF; 3 had moderate and 3 had minimal staining pattern (per table 2).  The dense CD8+ pattern was seen in 3 of 9 with autoimmune hepatitis and in 1 of 14 with other liver diseases.

E-D Pfister et al. Liver Transplantation 2018; 24: 1186-98.  This study examined patient (n=338) and graft survival in the pediatric population (median age 14.0 years) with Wilson’s disease (1968-2013).  Overall, patient survival was 87% at 1 year, 84% at 5 years, and 81% at 10 years.  Though, the survival was much improved since 2009.

JA Bezzerra et al. Hepatology 2018; 68: 1163-73. This review summarized a research workshop (June 2017) focused on the clinical and research challenges for biliary atresia.

Banff

More Acceptance (of livers), Better Outcomes

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An important metric of liver transplantation outcome is not readily available: acceptance of organ offers.  A recent study (E Mitchell et al. Liver Transplantation 2018; 24: 803-809) showed a great deal of variability among pediatric liver transplantation centers in this metric.

The authors examined data from 2007-2015 with 4088 unique patients and 27,094 match runs. The range in organ acceptance rates was 5.1% to 14.6% with a median of 8.9%.

Key finding:

  • “Center-level acceptance rates were associated with wait-list mortality, with a >10% increase in the risk of wait-list mortality for every 1% decrease in a centers adjusted liver offer acceptance rate (odds ratio, 1.10, CI 1.01-1.19)

As noted in a previous post, Pediatric Liver Transplantation -Past Time to Split, larger centers generally have higher acceptance rates.

My take: This study adds to the literature regarding the inequities that some patients unknowingly face when listed in some centers.

Related article: HPJ van der Doef et al. Liver Transplantation 2018; 24: 810-9.  This article describes the wait-list mortality of young patients with biliary atresia.  Those listed before age 6 months and with higher MELD scores (>20) were at increased risk. Recognition of these factors may help improve allocation.

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Hate it when this happens!

Lots of Allergy & Autoimmunity Issues Following Solid Organ Transplantation

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A recent retrospective cross-sectional cohort study (N Marcus et al. J Pediatr 2018; 196: 154-60, editorial page 10) identified 273 transplant recipients with a median followup of 3.6 years. This cohort included 111 liver transplant recipients, 103 heart transplant recipients, 52 kidney transplant recipients, and 7 multivisceral transplant recipients.

Key findings:

  • 92 (34%) developed allergy or autoimmunity after transplantation.
  • Allergic problems included eczema (n=44), food allergy (n=22), eosinophilic gastrointestinal disease (n=11), and asthma (n=28)
  • Autoimmunity problems developed in 6.6% (18) including autoimmune cytopenias (n=10). Two patients died due to autoimmune hemolytic anemia and hemophagocytic lymphohistiocytosis.
  • Allergic problems typically developed during the first year after transplantation and rarely after 5 years following transplantation.
  • ~20% required a change in immunosuppression
  • ~50% improved with time

In the editorial, the Dr. Helen Evans notes that the increasing reporting of atopic/allergic disorders could be due to recognition but could also be due, in part, to the widespread adoption of tacrolimus instead of cyclosporine for immunosuppression.

My take: Many have said that organ transplantation, which is life-saving, substitutes one problem for another.  This is an example of an additional burden, often related to immunosuppression, that patients and families have to manage afterwards.

Chattahoochee River, Island Ford

More on Time to Split (2018)

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As noted in a blog last year (More on its Past Time to Split), increased use of split livers can reduce liver transplantation waitlist mortality in children.  Further justification for this approach is evident from a new study (DB Mogul et al. J Pediatr 2018; 196: 148-53, editorial pg 12) indicated that outcomes following split liver organs are equivalent to whole organ liver organs.

The authors examined two time periods: 2002-2009 and 2010-2015 using the Scientific Registry of Transplant Recipients. n=5715

Key findings:

  • 1-year survival from split liver transplant (SLT) improved during the later period compared to the initial period: 95% versus 89%. n=1626 (28.5% of all transplants)
  • 1-year survival from living donor liver transplant (LDLT) improved during the later period compared to the initial period: 98% versus 93%. n=661 (11.6% of all transplants)
  • 1-year survival from whole liver transplant (WLT) was essentially unchanged during the later period compared to the initial period: 95% versus 94%. n=3428 (60% of all transplants)

These data show that survival after transplant is no longer worsened by SLT and may be higher for LDLT than WLT.

The editorial by Dr. Bae Kim and Dr. Vakili note that there have been several proposals to encourage more use of SLTs.  One that was developed “would prioritize children <2 years old before local/regional adults except for those who were status 1 or who had a MELD score above 30.”  At this point, these efforts to favor SLT allocation have not been adopted by UNOS Board of Directors.

My take (borrowed from editorial): “The question should no longer be ‘To split or not to split?’ but rather ‘Why should we let children die when we can now split livers safely?'”

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Chattahoochee River

 

 

Are Long-Term Liver Transplant Survivors Destined to Have Low Bone Density? (No)

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Briefly noted: A recent study (L Ee et al. JPGN 2018; 66: 797-801) provides some good news for children who have had liver transplantation (LTx).

Among 42 patients (64% with biliary atresia) who had undergone LTx at a median age of 2.2 years and were long-term survivors (median time since LTx 10.1 yrs), mean bone mineral density (BMD) were normal.  Lumbar BMD z-score -0.15 and total body BMD -0.76.  Pathologic fractures were noted in 2 patients; these occurred within 18 months of transplantation.

My take: this study indicates that over time, most patients are not likely to have very low bone density.

TPN Prior to Liver Transplantation for Biliary Atresia

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Briefly noted:

D Wendel et al. JPGN 2018; 66: 212-7.  This single center retrospective review examined patients who received home TPN prior to liver transplantation.   These 18 patients, which represented 41% of their entire transplant cohort of 44 between 2010-2015, all had biliary atresia. Key findings:

  • Malnutrition improved or resolved in all but one patient
  • 8 catheter-related infections were noted (3.8/1000 catheter days)
  • There were no deaths in patients receiving TPN

My take: While there is an increased burden of care with TPN, improved nutrition may improve long-term outcomes.

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Amber Cove, Dominican Republic

 

 

Challenging Assumptions: Self-Management Adolescent Skills and Poor Outcomes

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If you think that teaching more self-management to adolescents will lead to better outcomes, you might be wrong.  A recent study (RA Annunziato et al. J Pediatr 2018; 193: 128-33) shows that adolescents who reported greater self-management, following liver transplantation, had worse outcomes.

In this study of 9-17 year olds and their parents (213 dyads), the key finding was based on a score derived from the REFILS survey.  REFILS is an acronym for “Responsibility and Familiarity with Illness Survey.”  This survey was curtailed from 22 items to the following 13 items:

  • Understands key aspects of liver disease
  • Discusses management plan with team
  • Self-manages liver regimen
  • Knows names/dose of medications
  • Keeps track of medications
  • Correctly takes medications
  • Calls pharmacy for refills
  • Knows different types of providers
  • Knows date of next appointment
  • Makes appointments
  • Know insurance details
  • Understands insurance plan
  • Keeps healthcare records

Key finding:

  • “Negative outcomes were more likely to occur if patients reported that they are ‘in charge.’ A higher [REFILS] score, which denotes a higher level of (self-reported) management, was significantly and consistently correlated with worse adherence and organ rejection.”

The implication is that the transition of responsibilities from the parent/caregiver to the adolescent “may in fact not always be indicated or advisable…education about self-care might actually be harming patients…It is probably prudent to discourage rather than encourage adolescents from assuming self-care in some cases.”

My take: While adolescents and young adults are capable in many aspects, there are hardly any that I would trust to care for our dog (see below) for any protracted period.  Thus, in my view, without close parental supervision, entrusting the life of a liver transplant recipient to an adolescent is risky.

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Charlie

How Successful is Liver Transplantation for Fatty Liver Disease?

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A recent guideline update (ZM Younossi. Liver Transplantation 2018; 24: 166-70) provides some useful information about nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH), and liver transplantation (LT).

Key points:

  • “Despite metabolic comorbidities, posttransplant outcomes of NASH patients are generally good.  In fact, 1-, 3-, and 5-year patient and graft survival rates are …similar to other liver diseases.”
  • NASH/NAFLD can recur following LT…”NASH with significant fibrosis (stage ≥2) occurs in approximately 5% of recipients by 5 years after transplantation.”
  • Additional issues to manage after LT, include weight management, and metabolic conditions including diabetes, hypertension, dyslipidemia, and hypertension.  All of these conditions can be affected by specific immunosuppressants.  For example, calcineurin inhibitors and corticosteroids can exacerbate type 2 diabetes mellitus.

My take: This article indicates better LT outcomes than I expected in patients with NASH/NAFLD.

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Bright Angel Trail

More on It’s Past Time to Split

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In followup to this morning’s post, Pediatric Liver Transplantation: It’s Past Time to Split, one reader pointed out an abstract by Emily R. Perito et al.presented at this year’s AASLD which showed that pediatric deaths would decrease if more livers were split.

ABSTRACT #137

Increasing split liver transplantation in the U.S. could decrease pediatric deaths on the liver transplant waiting list

Emily R. Perito1,3, Garrett Roll2, Jennifer L. Dodge2,

Background: In the United Kingdom, defaulting to split liver transplantation (LT) with suitable deceased donor grafts has virtually eliminated pediatric waitlist (WL) mortality. In the US, only <2% of LTs are split, but 1 in 10 infants die on the WL.

Methods: Using UNOS STAR data, livers for potential split LT were identified from all transplanted, deceased-donor livers 2010-15 who fit strict criteria: age 18-40y, BMI<30, recovered in US after donor brain death, 0-1 vasopressors, a <155meq/L, AST/ALT<100IU/L, bilirubin<3mg/dL, <7d hospitalized, cardiac arrest≤30min, HBV/HCV neg, not CDC high-risk, steatosis≤10% if biopsied, not multi-organ transplant, and no bloodstream infection. Livers allocated to patients high-risk for split LT were also removed: status 1A or MELD/PELD≥40 at WL removal, re-transplant, in the ICU, BMI>34, or >300mi from donor hospital. Pediatric WL deaths included deaths and removals for too sick to transplant, never relisted.

Results: Of 35,461 livers transplanted 2010-15, 6.7% were potentially utilizable for split LT based on donor characteristics. Of these, 95% were transplanted whole (n=2,253). 50% went to recipients deemed possibly high-risk for split LT. This left 1,116 potential livers for split LT (FIGURE); 78% of their primary recipients were listed as willing to accept a segmental liver, and 97% to accept cold ischemia time≥6h (CIT, median 12h). Median donor risk index for this subset was 1.06 (max 1.67). During the same 5y, 261 children died after ≥3d on the WL (median 57d, IQR 15-161)—87% of all pediatric WL deaths. Of these, 56% were <2y of age, 26% 2-12y, 18% 13-18y. Median weight was 9.2kg (IQR 5.9-29.4kg). 36% died at centers that reported doing no pediatric split LTs (15%) or ≤1/year (22%).

Conclusions: Increased utilization of split LT could decrease US pediatric WL mortality—without decreasing LT access for adults. Barriers are significant, but changes to  allocation policy, increasing centers with splitting experience, and splitting on normothermic perfusion could increase access and reduce WL mortality.

Jose Garza, Chelly Dykes, Elvis, and Jay Hochman at Cincinnati Children’s Reception

Pediatric Liver Transplantation: Past Time to Split

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A recent study (EK Hsu et al. Gastroentorol 2017; 153: 988-95, editorial 888-89) exposes some deep flaws in organ transplantation in U.S.

The retrospective study examined children on the U.S liver transplant wait-list from 2007-14.  This included 3852 pediatric candidates.  Key findings:

  • Of 27,831 adults who underwent transplantation, 1667 (6%) received livers from pediatric donors (<18 years)
  • Of children who died or were delisted, the centers caring for 173 (55%) had received an offer of 1 or more livers that was subsequently transplanted into another pediatric recipient.  The remaining 45% died or delisted with no offers. High-volume (>15 transplants per year) centers were more likely to accept an organ than a low-volume center (<5 transplants per year).
  • Only 29% of children received a split graft.  When a splittable adult liver graft was allocated to an adult the chance of it being used as a split was 0.6%.

Background:

  • Children have much lower survival rate than adults on waiting list. Of adults who died or delisted, 85% receive at least one transplant offer; whereas, nearly half of all children never even receive an offer.  Children who died/delisted had wait-time of 33 days compared with 92 days for adults who died/delisted.
  • Less than 10% of all liver transplant recipients are pediatric transplants.  Per editorial, “a measure that improves pediatric access by 20% would only reduce adult access by 2%.”
  • There are more than 100 pediatric liver transplant centers in U.S. Certainly, this improves convenience; however, per editorial:  “three-fourths are very low volume centers, performing <5 liver transplantations per year…Death on waiting list” occur 5 times more at low-volume transplantation centers.
  • In this study, only 29% of children received split livers; in comparison, in the UK, >80% receive either a split graft or living donor graft.

The editorial points out that splittable livers that are allocated to adults are virtually never split; this is either due to inconvenience or lack of expertise.  A small increase in liver splitting would dramatically lower the pediatric mortality wait list.  There is no incentive in the current system to split a liver/save a child’s life.

My take: The data from this study points out glaring problems in pediatric liver transplantation.

  1. Children are dying due to lack of prioritization.  Pediatric livers are going to adults.
  2. There is practically no splitting when liver organs are allocated to an adult.  Incentives to increase organ splitting would save many children from dying waiting for an organ.
  3. Large volume pediatric centers are much more likely to accept a liver offer for patients waiting at their centers.  There is an increased wait-list mortality at very low volume centers, perhaps due to lack of expertise and passing up viable organs.  Do hepatologists/surgeons at these centers explain this risk to families at their centers?

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