Lots of Allergy & Autoimmunity Issues Following Solid Organ Transplantation

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

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More on Time to Split (2018)

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)

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.

Liver Shorts May 2018

VL NG et al. J Pediatr 2018; 196: 139-47. This study with 148 children examined the neurodevelopmental outomes of young children with biliary atresia (ChiLDRen Study). Key finding: Children with their native livers were at increased risk for neurodevelopmental delays at 12 and 24 months.  This risk was more than 4-fold increased among those with unsuccessful Kasai procedure.

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WS Lee et al. J Pediatr 2018; 196: 14-20. Updated review on hepatopulmonary synddrome (HPS) and portopulmonary hypertension (POPH).  Figure 1 graphically shows the difference in pathophysiology.  HPS hallmark is intrapulmonary vascular dilatation.  POPH is characterized by progressive remodeling of the wall (thickening & vasoconstriction) of small pulmonary arteries.

Related blog posts:

JA Woo Baidal et al. Hepatology; 2018; 67: 1339-47. This prospective cohort study with 528 children showed that increased Vitamin E intake in early childhood, based on validated food questionnaires, correlated with lower ALT values in mid-childhood.  Children with higher intakes “had lower odds of elevated mid-childhood ALT” (adjusted odds ratio of 0.62) when comparing quartiles 2-4 to the lowest quartile.  The authors note that Vitamin E is present in foods that are more often consumed in “healthful diets, such as wheat germ, almonds, spinach, and broccoli, as well as cooking oils.”

J Pfeiffenberger et al. Hepatology 2018; 67: 1261-69. The retrospective multicenter study with 282 pregnancies in 136 women with Wilson’s disease (WD), showed good outcomes. Aggravation of neurologic symptoms was rare (1%) (though tended to persist), liver test abnormalities (6%) resolved in all cases after delivery. Birth defect rate of 3% and spontaneous abortion rate of 26%; rthough, patients receiving treatment with zinc and D-penicillamine had lower spontaneous abortion rates, (10% and 17%, respectively) than those without treatment.  Chelation therapy resulted in no increase in the rate of birth defects compared to the general population.

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F Bril et al. Clin Gastroenterol Hepatol 2018; 16: 558-66. This prospective study of adults with biopsy-proven NASH (52 with diabetes and 49 with prediabetes) found that pioglitazone treatment was associated with a reduction in the primary outcome, NAFLD activity score by 2 or more points, in 48% of those with type 2 diabetes and 46% of those with prediabetes. And, with a resolution of NASH in 44% and 26% respectively.

 

Big Creek Greenway near McFarland

When Should a Spleen Guard Be Recommended?

A survey (O Waisbourd-Zinman, et al. JPGN 2018; 66: 447-49) of 44 pediatric hepatologists (with 935 years of clinical practice) examined the issue of splenic rupture and spleen guards.  ~90% of those surveyed reported following at least 30 patients with portal hypertension and splenomegaly.

  • In total, the hepatologists could recall 13 cases of splenic rupture among patients with portal hypertension/splenomegaly due to cirrhosisalmost all of these occurred after a fall or in a motor vehicle accident.  Only one of these falls happened during a sports-related event (soccer).
  • 11 cases were serious. 9 of these cases resulted in shock with subsequent splenectomy, embolization, and/or death. Death reported in 2 cases.
  • In this survey,  61% of hepatologists recommended “absolute restriction from activity with high risk of blunt abdominal trauma;” whereas 23% indicated that activities with risk of blunt trauma were acceptable if wearing a spleen guard.
  • To prevent splenic rupture in patients with portal hypertension/splenomegaly, among the participating hepatologists, the majority identified the following ‘high risk’ sports: football (95%), hockey (82%), and wrestling (66%).  A smaller percentage advocated a spleen guard for skiing (42%), soccer (41%), basketball (30%) and other sports.

While I did not participate in this survey, the one patient with chronic liver disease that I followed who had a splenic rupture had fallen down a flight of steps; fortunately, he recovered with supportive care.

My take: This survey shows that there is wide variability in the use of spleen guards.  In almost all cases of splenic rupture, this was precipitated by severe trauma.  Though, patients with portal hypertension may avoid high contact sports and thus the risks are for these sports is unclear.

Related blog post:

Foggy Morning in Sandy Springs

Wilson’s Disease –Pediatric Guideline

P Socha et al. JPGN 2018; 334-4. This ESPGHAN position paper makes recommendations for Wilson’s disease. This is a helpful paper, though the AASLD Wilson’s guideline is more comprehensive. A couple of pointers from the JPGN publication:

  • The authors recommend molecular testing if available and using liver copper measurement “if molecular testing is inconclusive”
  • Screen siblings of any new patients
  • Urinary copper excretion in the 200-500 mcg per 24 hours is consistent with adequacy of treatment
  • With treatment, liver function tests improve over 2-6 months. “If increased transaminases remain or relapse despite treatment, poor compliance should be suspected.”

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January 2018 -Sunrise in Sandy Springs

TPN Prior to Liver Transplantation for Biliary Atresia

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