Liver Articles: Short Takes

DBE van Wessel et al. JPGN 2017; 65: 370-74.  This retrospective study showed an increase in biliary atresia incidence in preterm infants compared with full-term: 1.06 per 10,000 compared with 0.52/10,000. In addition, 4-year transplant-free survival rates were significantly worse at 21%, whereas 4-year survival rates was 61%. Clearance of jaundice (with Kasai) was achieved in only 23%.

Related post: Biliary Atresia More Common in Preterm Infants

ES Björnsson et al. Clin Gastroenterol Hepatol 2017; 15: 1635-36. This study examined response to steroids in 18 patients with drug-induced autoimmune hepatitisKey findings: 14 patients had elevated antinuclear antibodies & there were none with elevated smooth muscle antibodies. Infliximab was most frequent agent (n=11) and nitrofurantoin was other frequent agent (n=3).  Overall, 40% improved after discontinuation of medication, the remainder had prompt responses to corticosteroids.  Relapse did not occur when corticosteroids were discontinued.  Among the infliximab group, there was no evidence of liver injury after transitioning to alternative tumor necrosis factor-α inhibitor.

M Balwani et al. Hepatology 2017; 66: 1314-22. Acute Hepatic Porphyrias -Review. Current recommendations include gene sequencing to confirm all biochemical cases. Biochemical tests are spot urine testing of porphobilinogen (PBG), 5-aminolevulinic acid (ALA), and porphyrins. A normal urine PBG in symptomatic patients “excludes the three most common acute hepatic porphyrias.”  For those with abnormal studies, this reference is a handy.

S Wirth et al. Hepatology 2017; 66: 1102-10.  This study examined the effectiveness of sofosbuvir and weigh-based ribavirin dosing in 12-17 year olds with genotype 2 & 3 Hepatitis C infection.  Duration of treatment was 12 weeks for genotype 2 and 24 weeks for type 3.  Overall, SVR12 was achieved in 51 of 52 (98%); one patient with genotype 3 did not achieve SVR12.

Related post: New HCV Treatment Effective in Adolescents (Genotype 1 study)

F Kanwal et al. Gastroenterol 2017; 153: 996-1005. This study, a retrospective cohort of 22,500 VA patients treated for hepatitis C infection, showed that direct-acting antivirals (DAAs) lowered, but did not eliminate, the risk of hepatocellular carcinoma (HCC). Among the 87% who achieved an SVR, the adjusted hazard ratio for HCC was 0.28.  This was true as well as among patients with cirrhosis.. Hazard ratio for those with compensated cirrhosis was 0.32 compared with 0.18 among those without cirrhosis.

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#NASPGHAN17 Selected Abstracts

Some of the abstracts that were presented at this year’s meeting –see below.  For a listing of the titles/authors presented, use this link: NASPGHAN Annual Mtg 2017

For complete abstracts: NASPGHAN 2017 Scientific Abstracts

Using a standardized approach along with a protocol for oral cleanouts and saline enemas if needed, the authors showed a marked decline in admissions for fecal impaction:

In this study, the authors found that low risk patients had a 91% likelihood of a negative scope.  However, on closer inspection, this rate OVERESTIMATES the likelihood of finding anything significant.  Most findings in the low risk group had questionable benefit from being identified on endoscopy including “acute colitis,” and H pylori.

The following abstract showed that in patients with EoE and not PPI-REE that topical steroids alone were as effective as PPI with topical steroids.

The following slides indicate the development of A4250, a bile acid transporter, which reduces pruritus. The presenter stated that this drug essentially is a chemical diversion which could replace biliary diversion for pruritic conditions like PFIC and Alagille syndrome.

#NASPGHAN17 Presentations at Annual Meeting: GGT in PSC, Nutrition for Intestinal Failure

This blog entry has abbreviated/summarized this presentation. Though not intentional, some important material is likely to have been omitted; in addition, transcription errors are possible as well.

Improvement in GGT Predicts Event-free Survival in Primary Sclerosing Cholangitis Regardless of Ursodeoxycholic Acic Treatment. 

Mark Deneau et al. (Grand Watkins Prize).

Key points:

  • PSC is difficult to study due to its rarity and due to its slow progression; thus surrogate biomarkers are needed.
  • Alkaline phosphatase is not a good biomarker in children
  • GGT level at one year after diagnosis was predictive of prognosis
  • Ursodeoxycholic acid does not appear to be effective

Optimizing Nutrition in Intestinal Failure

Justine Turner, University of Alberta

Key points:

  • Human milk is an ideal “formula” for infants, including those with intestinal failure
  • Oral feedings are important
  • Combination of bolus feeds and continuous feeds is reasonable
  • SMOFlipid allows higher lipid dose administration without hepatoxicity; this may improve cognitive outcomes
  • Amino acid based formulas have higher osmolality which can contribute to diarrhea

Patients with >50% of small bowel and >50% of colon were most likely to achieve enteral autonomy (GIFT registry)

 

 

#NASPGHAN17 Annual Meeting Notes (Part 2): Year in Review

This blog entry has abbreviated/summarized this presentation. Though not intentional, some important material is likely to have been omitted; in addition, transcription errors are possible as well.

This first slide shows the growth in NASPGHAN membership:

Year in Review

Melvin Heyman  Editor, JPGN

This lecture reviewed a number of influential studies that have been published in the past year.  After brief review of the study, Dr. Heyman summarized the key take-home point.

 

#NASPGHAN17 Annual Meeting Notes (Part 1): Neurostimulation for RAP, PSC-IBD, Organoids

This blog entry has abbreviated/summarized these presentations. Though not intentional, some important material is likely to have been omitted; in addition, transcription errors are possible as well.

William Balistreri Prize: Katja Kovaic et al. Neurostimulation for functional abdominal pain disorders in children –a randomized, double-blind, sham-controlled trial. This study enrolled 104 patients.  Lancet Gastroenterol Hepatol 2017; 2: 7272-37.

Summary slide:

Fellow Research Award: Symptoms Underestimate Endoscopic Activity in PSC-IBD. Amanda Ricciuto et al. Hospital for Sick Children.

Key points:

  • In patients with IBD-PSC, clinical remission based on clinical symptoms is not reliable indicator of histologic remission.
  • Patients with PSC-IBD are more likely to have active endoscopic disease even when in “clinical remission”
  • Calprotectin levels (not PUCAIs) are helpful in confirming clinical remission.  A calprotectin <93 mcg/g was optimal level in determining clinical remission
  • Better control of disease could improve clinical outcomes (eg. colon cancer, liver progression)

Keynote Address: Organoids: Current and future promise for changing treatment of gastrointestinal and liver disorders.  James Wells Cincinnati Children’s Hospital Medical Center.

This was a terrific lecture.

  • Example of use of pluripotent stem cell usage: Diabetes. Phase 1 study has been started.
  • Organoids are in essence miniature versions of organs in a dish and with complex combination of cell types.
  • Organoids allow easier testing on these tissues for treatment and diagnosis of diseases
  • Organoids will allow for personalized testing of medications.  Some patients will respond differently.  This technology could be used to grow a specific organoid for a specific person and determine response on the organoid before giving to the patient.
  • Can engraft organoids into mice which can provide blood supply and allow larger organoids.
  • Clinical projects for organoids: Hirschsprung’s,  H pylori, Clostridium difficile, Short bowel syndrome, Fatty liver disease

NASPGHAN Postgraduate Course 2017 (Part 3): Biliary Atresia, NAFLD, SMOFlipid, Pancreatic Pain

This blog entry has abbreviated/summarized these presentations. Though not intentional, some important material is likely to have been omitted; in addition, transcription errors are possible as well.

Here is a link to postgraduate course syllabus: NASPGHAN PG Syllabus – 2017

Biliary Atresia: Update on diagnostic and prognostic biomarkers and therapeutic interventions

Cara Mack    Children’s Hospital of Colorado

Key points:

  • 84% of biliary atresia is isolated; 16% are syndromic with other defects
  • Direct bilirubin is (mildly) elevated at birth in patients with biliary atresia
  • Total bilirubin 3 months after Kasai predicts outcome. If <2 mg/dL, then unlikely to need a transplant in the first 2 years of life.
  • Reviewed biomarkers including Th1, Autotaxin, IL-8

Therapeutic interventions:

  • Nutritional support. Better nutrition improves outcomes after liver transplantation.
  • Fat soluble vitamin supplementation
  • Cholangitis prevention. Some studies have shown that prophylactic antibiotics may reduce incidence of cholangitis.
  • No therapeutic interventions that delay progression of this disease

 

 

CHILDREN Cohort Mgt of Vitamin Supplementation

Steroids are not helpful after Kasai procedure

Diagnosis and Management of Pediatric NAFLD 2017

Stavra Xanthokos   Cincinnati Children’s Hospital Medical Center

Key points:

  • NAFLD is #2 cause of liver transplantation in adults and on its way to becoming #1
  • ALT is still the best screening tool; NASPGHAN guidelines recommends screening overweight/obese children 9-11 years of age
  • Ultrasound has poor sensitivity and specificity for NAFLD; it is helpful for detecting gallbladder disease
  • Bariatric surgery has been effective for NAFLD

 

SMOFlipid and the Pediatric Patient

Peter Wales  Hospital for Sick Children (Toronto)

Slides are not available in syllabus

Key points:

  • Improving outcomes noted in the intestinal failure population
  • Dr. Wales reviewed proposed improvements with Omega-3 lipids -less cholestasis, less hepatitis, and less fibrosis
  • Compared improvements with lipid minimization (1 g/kg/day) compared to newer agents: omegaven and SMOFlipid. Additional studies are needed due to limitations of previous studies
  • Discussed SMOFlipid vs. Intralipid trial at 5 centers in Canada. N=24.
  • At SickKids: SMOFlipid for all preterms at admission & for term infants after 2 weeks of PN. Dosing 2-2.5 g/kg & now accounts for 85% of lipid usage at institution
  • None of the lipid products were designed for preterm infants. Intralipid has a pediatric indication and other products are used off label
  • Lipid restriction probably affects brain size/development; thus, a lipid agent that allows for higher doses likely will be beneficial for developmental outcomes.  The retina can be used as a biomarker of the brain affects of lipids.

Painful Chronic Pancreatitis: Management/therapeutic interventions

Vikesh Singh  Johns Hopkins University School of Medicine

Slides are not available in syllabus

 

 

More on It’s Past Time to Split

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