Molecular characterization of hepatitis B virus (HBV) in African children living in Australia identifies genotypes and variants associated with poor clinical outcome.

Migration from sub-Saharan Africa is contributing to the rising incidence of chronic hepatitis B (CHB) infection and its complications in Australia. African CHB is associated with unique genotypes, such as E and A1, which are associated with reduced vaccine efficacy and early-onset hepatocellular carcinoma, respectively, although the prevalence of these genotypes outside Africa is poorly described. Treatment-naïve children of African origin with CHB were recruited at the Royal Children's Hospital Melbourne. Population-based sequencing of the complete HBV genome, or the clinically relevant basal core promoter (BCP)/precore (PC) region, was performed, and the HBV genotype/subgenotype assigned by phylogenetic analysis. HBV was characterized in serum from 67 children, median age 12.5 years. HBV genotype E was most frequent (70 %), with genotype D [25 %; subgenotypes D6 (formerly D7)/D3/D2)] and subgenotype A1 (5 %) also being identified. Despite their young age, over 50 % of the children were HBeAg-negative and had seroconverted to anti-HBe, with this being associated with canonical BCP/PC mutations in the majority of cases. The profile of HBV in African children living in Australia was characterized by early HBeAg seroconversion and infection with HBV variants associated with poor clinical outcome, as well as genotypes previously associated with reduced vaccine efficacy or rapid progression to liver cancer. These findings have important ramifications for patient monitoring and treatment guidelines in the Australian paediatric setting.

Can celiac serology alone be used as a marker of duodenal mucosal recovery in children with celiac disease on a gluten-free diet?

OBJECTIVES: Assessment of treatment response in children with celiac disease (CD) after commencing a strict gluten-free diet (GFD) is generally based on the resolution of clinical features and normalization of serology. Recent adult studies have shown that serologic markers do not correlate with mucosal recovery. We aimed (i) to determine whether anti-tissue transglutaminase immunoglobulin (Ig)A (tTG) and anti-deamidated gliadin peptide IgG (DGP) antibodies are sensitive and specific markers of mucosal recovery in children with CD on a GFD for at least 12 months, and (ii) to determine whether a validated dietary questionnaire of compliance can identify patients with mucosal recovery. METHODS: A total of 150 children with biopsy-proven CD were prospectively evaluated with duodenal biopsies at ≥12 months on GFD, paired with repeat tTG and DGP serology. The biopsies were reviewed in a blinded manner by two histopathologists and graded by Marsh criteria. A validated questionnaire of dietary compliance was also administered. RESULTS: Of 150 children recruited, 27 (18%) had positive serology, 97 (65%) had negative serology, and 26 (17%) had equivocal serology. Of the 97 children with negative serology, none had Marsh type 3 enteropathy. Of the 27 patients with positive serology, only 6 had Marsh type 3 changes. The sensitivity and specificity of serology as a marker of significant mucosal pathology was 75 and 85%, respectively, with a positive predictive value of 22% but a negative predictive value of 98%. Of the 129 (86%) questionnaires completed, 88% reported good or excellent compliance with a GFD (negative predictive value 97%). CONCLUSIONS: This study suggests that follow-up using two serological tests in children with CD on a GFD may obviate the need for repeat mucosal biopsy in the majority of patients. A standardized dietary questionnaire may be useful in identifying patients who require further evaluation.