Evolving practice and changing phenotype in pediatric autoimmune liver disease: Outcomes from an Australian center

Autoimmune liver disease (AILD) incorporates primary sclerosing cholangitis (PSC), autoimmune hepatitis (AIH), and autoimmune sclerosing cholangitis (ASC). ASC is a condition that includes overlap of AIH and PSC. We investigate changes in practice in relation to diagnosis and phenotype over 2 time periods.Retrospective chart review was conducted from January 2000 to 2016. Data were divided into two 8-year cohorts, CI and C2.Data were collected in 75 children, 29 in 2000-2007 (C1) and 46 in 2008-2016 (C2). Presenting AILD type was AIH in 59%, ASC in 10%, and PSC in 31%. Final AILD type was AIH in 53%, ASC in 16%, and PSC in 31%. When comparing C1 to C2, those with AIH decreased (65% vs 45%) and those with ASC increased (14% vs 18%). Use of magnetic resonance cholangio-pancreatography increased from 34% in C1 to 65% in C2. Advanced liver disease on biopsy was noted in 53% of all children at presentation. Only 5 female children progressed to liver transplant (3 ASC-IBD [inflammatory bowel disease]; 1 PSC-IBD; 1 AIH). Colonoscopy performance increased from 48% in C1 to 63% in C2 with diagnosis of AILD-IBD increasing from 31% to 52%. Right-sided disease was present in 46% and macroscopic rectal sparing in 36% of those with ulcerative colitis. Colectomy was required in 3 children with large duct PSC-IBD.PSC and ASC are increasing in relevance along with IBD and reflect increasing performance of magnetic resonance cholangio-pancreatography and colonoscopy. Large duct PSC and ASC with IBD are risk factors for colectomy and along with female gender, for liver transplant

Utility of proactive infliximab levels in paediatric Crohn's disease

Infliximab (IFX) has an established role in Crohn's disease (CD), with serum trough levels of IFX (TLI) increasingly used to optimise dosing. We report the utility of routine, proactive TLI in children on combination therapy with immunosuppression (IS) from a single paediatric centre.This is a retrospective chart review of all children with CD receiving IFX therapy conducted betweenJanuary 2014-May 2017. Clinical phenotype, duration of therapy, TLI (µg/mL), drug antibodies, type of IS, biomarkers and changes in management were recorded.60 children (8-17 years; median 14.1 years) had 206 TLIs recorded. 56/60 (93%) were on IS, with 5/60 (8%) developing antidrug antibodies (ADAs). 63/206 TLIs were recorded duringan episode of relapse (median 3.0 µg/mL) vs 143/206 TLIs recorded in remission (median 5.2 µg/mL). For children with TLI 7 µg/mL, 7/63 (11%) were in relapse vs 46/143 (32%) in remission. Change in management resulted from 43/206 (21%) TLIs in 31/60 (52%) children: 21 dose escalations, 12 de-escalations and 10 changed to adalimumab. Of 31 postinduction TLIs, 15/17 (88%) children with TLI >7 µg/mL achieved clinical and biochemical remission for the duration of therapy (median 14 months), while 4/5 (80%) children with TL

Transient liver elastography in unsedated control children: Impact of age and intercurrent illness

Transient elastography (TE) is a rapid, non-invasive, reproducible assessment of liver fibrosis by liver stiffness measurement (LSM). Uncertainty remains regarding utility in children, unsedated an

Supersonic shear-wave elastography and APRI for the detection and staging of liver disease in pediatric cystic fibrosis

Background: Current diagnostic methods for the diagnosis of Cystic fibrosis (CF)-associated liver disease (CFLD) are non-specific and assessment of disease progression is difficult prior to the advent of advanced disease with portal hypertension. This study investigated the potential of Supersonic shear-wave elastography (SSWE) to non-invasively detect CFLD and assess hepatic fibrosis severity in children with CF. Methods: 125 children were enrolled in this study including CFLD (n = 55), CF patients with no evidence of liver disease (CFnoLD = 41) and controls (n = 29). CFLD was diagnosed using clinical, biochemical and imaging best-practice guidelines. Advanced CFLD was established by the presence of portal hypertension and/or macronodular cirrhosis on ultrasound. Liver stiffness measurements (LSM) were acquired using SSWE and diagnostic performance for CFLD detection was evaluated alone or combined with aspartate aminotransferase-to-platelet ratio index (APRI). Results: LSM was significantly higher in CFLD (8.1 kPa, IQR = 6.7–11.9) versus CFnoLD (6.2 kPa, IQR = 5.6–7.0; P < 0.0001) and Controls (5.3 kPa, IQR = 4.9–5.8; P < 0.0001). LSM was also increased in CFnoLD versus Controls (P = 0.0192). Receiver Operating Characteristic (ROC) curve analysis demonstrated good diagnostic accuracy for LSM in detecting CFLD using a cut-off = 6.85 kPa with an AUC = 0.79 (Sensitivity = 75%, Specificity = 71%, P < 0.0001). APRI also discriminated CFLD (AUC = 0.74, P = 0.004). Classification and regression tree modelling combining LSM + APRI showed 14.8 times greater odds of accurately predicting CFLD (AUC = 0.84). The diagnostic accuracy of SSWE for discriminating advanced disease was excellent with a cut-off = 9.05 kPa (AUC = 0.95; P < 0.0001). Conclusions: SSWE-determined LSM shows good diagnostic accuracy in detecting CFLD in children, which was improved when combined with APRI. SSWE alone discriminates advanced CFLD