Dr. Jim Squires: Practical Approach to Pediatric PSC and Pointers on Unconjugated Hyperbilirubinemia (Part 1)

Recently Dr. Squires gave our group a terrific lecture. I have taken some notes and shared some slides. There may be inadvertent omissions and mistakes in my notes.

Key points:

2023 AASLD Practice Guidance is very helpful and Dr. Squires considers its advice akin to a ‘North Star’

There are several etiologies for the sclerosing cholangitis phenotype – including primary disorders and secondary causes.

Pancolitis is most common presentation of IBD with PSC, often with rectal sparing and backwash ileitis

PSC often has subclinical inflammation and poor growth. PUCAI scores typically underestimate IBD activity

Diagnosis can be challenging – but often “I know it when I see it”

MMP-7 is still being studied as a biomarker. Thus far, it appears a little better than GGT and Alk phos as a marker for biliary injury
ERCP should be avoided as part of diagnostic workup but is important for therapeutic intervention

Deneau et al (Hepatology 2017; 66: 518) study wit 781 children has a wealth of information on natural history. In children, 38% developed portal HTN and 25% developed biliary complications over 10 years. However, once these complications developed, the need for transplantation develops more quickly. Median survival with native liver after the development of portal HTN was 2.8 yrs and it was 3.5 yrs after development of biliary strictures

Cholangiocarcinoma is rare in pediatrics ~1%
ASC (overlap of AIH and PSC) is fairly common in children and often a manifestation of early PSC. Many evolve to PSC without overlap features. Dr. Squires counsels families that most patients will need multiple biopsies to help determine need for ongoing immunosuppression

In patients with IBD, some liver test abnormalities and autoimmune features may be transient. Some watchful waiting may be beneficial prior to extensive evaluation
Multiple factors can predispose to PSC, including EBV infection which is associated with OR 12. Genetics, environment, immune dysregulation, toxic bile acids, microbiome, leaky gut/inflammation are additional factors
SCOPE is very useful prognostic tool

Ursodeoxycholic acid (UDCA) is a first line therapy. However, if no response to treatment, it is likely not beneficial

Oral vancomycin has not been proven to improve liver outcomes in PSC thus far (not recommended by AASLD 2023 Practice Guidance). However, further studies are ongoing and it has been associated with improvement in IBD activity