JE Squires et al. JPGN 2020; 70: 79-86. Using a prospective, longitudinal database, this study from ChiLDReN network with 93 children with biliary atresia and native liver found that NO increased prevalence of neurodevelopmental delays. Markers of advanced liver disease (high bilirubin/GGT for those ≤5 yrs, and portal hypertension for those >5 years) did negatively affect neurodevelopmental measures.
C Jaramillo et al. JPGN 2020; 70: 87-92. This pilot study with 21 patients found that degree of fibrosis, quantified by collagen hybridizing peptide, at time of Kasai, was associated with the risk of requiring a liver transplantation by age 4 years. Total bilirubin >2 mg/dL and Albumin ❤ g/dL at 3 months post-Kasai were also associated significantly with need for liver transplantation.
H-S Chen et al. Hepatology 2019; 70: 1903-12. In this study from Taiwan with 182 children (median age of 10.6 at enrollment) with hepatitis B and a normal ALT, a baseline anti-HBc titer of >500 IU/mL was associated with spontaneous HBeAg seroconversion with hazard ratio of 2.81. Over the median follow-up of 19.8 years, 85 subjects (46.7%) had HBeAg seroconversion. Thus, anit-HBc reflects anti-HBV immune response in the HBeAg-positive patients with normal ALT.
A recent study (A Chandrakumar et al. J Pediatr 2019; 215: 144-51) followed 190 children with inflammatory bowel disease from 2011 to 2018 in a longitudinal population-based cohort in Manitoba and examined the development of primary sclerosing cholangitis (PSC). The diagnosis of PSC was made on discretion of the treating physician; thus, only a subset of patients underwent extensive evaluations for PSC.
9 developed PSC-UC (9/95) and overall 11 developed PSC-IBD (11/190)
Among children with PSC-UC, 8 had high GGT (>50) at baseline and only 1 had a normal GGT at baseline.
All UC patients who developed PSC were diagnosed withing 6 months of their UC diagnosis.
At baseline, 22 patients with UC had an elevated GGT and 73 had a normal GGT. Thus, about one-third of patients with an elevated GGT developed PSC (possibly more as all patients were not subjected to extensive testing)
My view: This study reinforces two concepts: 1) GGT is valuable as a screening test 2) PSC (often asymptomatic) is fairly common in UC and needs to be considered especially in the first year of diagnosis. What this study does not do is help us figure out what should be done about children with asymptomatic PSC as there are no proven therapies.
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A recent clinical practice update (CL Bowlus et al. Clin Gastroenterol Hepatol 2019; 17: 2416-22) makes several recommendations on surveillance for hepatobiliary cancers in patients with primary sclerosing cholangitis (PSC).
I will highlight the most important recommendation for pediatric hepatologists:
Best practice advice 6: Surveillance for cholangiocarcinoma should not be performed in PSC patients with small-duct PSCs or those younger than age 20.
In the text, the authors note that “in pediatric PSC patients, cholangiocarcinoma is very rare, with only 8 of 781 (1%) …developing cholangiocarcinoma” (MR Deneau et al. Hepatology 2017; 66: 518-27)
Here are the other recommendations:
Best practice advice 1 Surveillance for cholangiocarcinoma and gallbladder cancer should be considered in all adult patients with PSC regardless of disease stage, especially in the first year after diagnosis and in patients with ulcerative colitis and those diagnosed at an older age.
Best practice advice 2 Surveillance for cholangiocarcinoma and gallbladder cancer should include imaging by ultrasound, computed tomography, or magnetic resonance imaging, with or without serum carbohydrate antigen 19-9, every 6 to 12 months
Best practice advice 3 Endoscopic retrograde cholangiopancreatography with brush cytology should not be used routinely for surveillance of cholangiocarcinomas in PSC.
Best practice advice 4 Cholangiocarcinomas should be investigated by endoscopic retrograde cholangiopancreatography with brush cytology with or without fluorescence in situ hybridization analysis and/or cholangioscopy in PSC patients with worsening clinical symptoms, worsening cholestasis, or a dominant stricture.
Best practice advice 5 Fine-needle aspiration of perihilar biliary strictures should be used with caution in PSC patients considered to be liver transplant candidates because of concerns for tumor seeding if the lesion is a cholangiocarcinoma.
Best practice advice 7 The decision to perform a cholecystectomy in PSC patients with a gallbladder polyp should be based on the size and growth of the polyp, as well as the clinical status of the patient, with the knowledge of the increased risk of gallbladder cancer in polyps greater than 8 mm.
Best practice advice 8 Surveillance for hepatocellular carcinoma in PSC patients with cirrhosis should include ultrasound, computed tomography, or magnetic resonance imaging, with or without α-fetoprotein every 6 months.
A recent study (KB Schwarz et al. JPGN 2019; 69: 588-94) highlights the chronic hepatitis B virus (HBV) phenotypes from a large pediatric North American cohort (n=371).
Immune-tolerant HBV was define by HBe-Ag-positivity along with normal ALT levels.
Inactive carrier were HBe-Ag-negative with low HBV DNA/normal ALT.
Chronic hepatitis B (HBeAg positive and HBeAg negative) had high HBV DNA and abnormal ALT values.
Indeterminant HBV had characteristics did not allow them to classified in these four categories.
If local laboratory normative values were used 36% of children would have been classified as immune-tolerant*. However, this drops down to 12% if updated upper limits of normal (ULN) are used based on Figure 3.
Using updated ULN, 62% had immune active HBeAg+ disease, 12% with immune-tolerant HBV, 4% with immune-active HBeAg-negative disease, 6% with inactive carrier, and 16% indeterminant HBV.
*There are a few discrepancies between Figure 3 and the abstract data. The abstract states that 82% would be considered to have chronic hepatitis B (this is 62% in figure 3). The abstract states that 35% were immune-tolerant based on local lab values.
The data presented were cross-sectional data at time of patient enrollment.
My take: this study shows that very few children in this cohort were immune tolerant based on more precise ULN values. The authors note that the cohort who were immune tolerant were largely drawn from Asian children (most often infected perinatally).