This blog entry has abbreviated/summarized the presentations. Though not intentional, some important material is likely to have been omitted; in addition, transcription errors are possible as well. I’ve attached the course syllabus as well:
PG Course Syllabus – FINAL
Primary Sclerosing Cholangitis –Dennis Black (Le Bonheur Children’s Hospital)
- Up-to-date review provided
- GWAS (genome-wide association study) identified 16 significant risk loci which account for only 7.3% of overall risk; environmental influences need to be worked out
- Pediatric studies –total of 328 patients reported to date
Is pediatric disease the same disease as in adults?
- Incidence in pediatrics: 0.23/100,000 incidence vs 1.1/100,000 in adults
- Mean age at diagnosis 13 years in pediatrics.
- 30% of pediatric patients have overlap with autoimmune hepatitis which is higher than in adult patients.
Other pointers:
- Discussed “Autoimmune cholangitis.” Imaging needed in autoimmune hepatitis to look for primary sclerosing cholangitis.
- IBD Association with PSC: IBD occurs in about 55% of PSC patients. If PSC diagnosed first, usually with right-sided colitis. If IBD diagnosed first, than pancolitis is more commonly noted.
- Add IgG4 as part of workup to rule out IgG4 cholangiopathy (sensitive to immunosuppression).
Treatment:
- Supportive care for cholestasis (vitamins, pruritus management, etc
- Monitoring for complications (rare cases of cholangiocarcinoma in pediatric population). 14 drugs tested to date –mainly in adults. “All without proven positive impact on long-term outcome.”
- Ursodeoxycholic acid –widely used but controversial because higher doses associated with worsened outcomes in adult study (Lindor et al). Ongoing study in pediatric population with ursodeoxycholic acid.
- Vancomycin (Aliment Pharm 37: 2013; 604. Adults n=35). Both Flagyl and Vanc seemed to be helpful. Uncontrolled pediatric studies with vancomycin reviewed. Vancomycin study in the works for pediatric/adults.
- No prospective randomized controlled trials in children and very little data in adults. Hard endpoints –very difficult in children/not practical in children (eg. portal hypertension, transplant, death).
PSC and Transplantation: PSC 2.6% of total transplants –long-term outcome is similar.
Related Blog Posts:
The Jaundiced Infant –Saul Karpen (Emory)
- “We don’t estimate jaundice very well… Our eyes do an awful job.”
- Breastmilk Jaundice: Archives of Disease in Childhood 1978; 53: 506-16. Only 12 of 853 had jaundice beyond 3 weeks of life.
- Cholestasis. One of the best studies looking at etiology was recently published: Hoerning A, et al Front Pediatr. 2014; 2: 65. N=82. Only 1 patient had CMV. 41% had biliary atresia.
Biliary atresia (BA):
- Reviewed study indicating that liver biopsy was most accurate means of making diagnosis of biliary atresia (blog comment: this study result may not be accurate in all settings as the interpretation relies on the ability/reliability of pathologist). High utility of stool pigment & ultrasound (including flow).
- In retrospective study (Pediatrics 2011; 128 e1428-33), all the BA patients had elevated direct bilirubin by 24-48 hrs of life.
- Genetic panels and whole exome sequencing (~$4-7K) are happening now. Cost-effective.
Take-home message: Molecular understanding possible for conjugated/unconjugated hyperbilirubinemias. Direct bilirubin >1 is abnormal
Related blog posts:
Acute Liver Failure –Estella Alonso (Children’s Hospital of Chicago) (pg 43)
Points:
- Few patients receive a full diagnostic workup (J Pediatr 2009;155:801‐6)–especially with regard to metabolic and autoimmune disorders.
- Reviewed etiologies –most frequently “indeterminant” especially in younger patients. Acetaminophen is most frequent etiology in teenagers and adults.
- Systemic inflammation is common in acute liver failure (Bucuvalas, J JPGN 2013;56: 311–315). Soluble IL2 receptor alpha –significantly higher in patients that died. Immune regulation important aspect regarding survival. Should steroids be used in cases with high inflammation?
Prognosis: Squires et al. J Pediatr 2006;148:652-8, Lee et al. JPGN 2005;40:575-81, Baliga et al. Liver Transpl 2004;10:1364-71
- 33% ‐53% survival with native liver
- 61% survival including LT
- 70%‐80% after LT
- Multiorgan failure is most common etiology of death. Bleeding is “a rare cause of mortality.”
Management:
- Reviewed including coagulopathy/bleeding, cardiovascular collapse, hepatic encephalopathy/cerebral edema
- Pediatric N-acetylcysteine Trial Squires, et al Hepatology 2013;57:1542‐9 N=182. Patients with NAC seemed to do worse, but not statistically proven. This study has stopped the widespread use of NAC in acute liver failure.
- Discussed approach to neurological complications in ALF. Hussain et al, JPGN 2014;58:449‐56. Retrospective study (n=18). Early EEGs obtained. Hypertonic saline may be more effective than mannitol. Hypothermia may be helpful adjunct.
- Timing of Transplantation discussed (pg 54 in syllabus). Difficult to predict spontaneous survival.
Related blog posts:
Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications/diets (along with potential adverse effects) should be confirmed by prescribing physician/nutritionist. This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.
This Year’s Pumpkin
gutsandgrowth 