INTRODUCTION: Estimating the severity of liver steatosis by controlled attenuation parameter (CAP) and liver fibrosis by transient elastography (TE) using the FibroscanTM machine provides a noninvasive method to establish the presence of nonalcoholic fatty liver disease (NAFLD) and assess its severity. The use of CAP/TE is becoming routine practice in adults yet limited data exists in children with suspected NAFLD. The aim of this study was to assess the feasibility and utility of measuring CAP/TE by FibroscanTM in a cohort of children with suspected NAFLD. METHODS: All children referred with a clinical suspicion of NAFLD (elevated alkaline phosphatase (ALT) or fatty infiltration on ultrasonography) who had CAP/TE measured were included. FibroscanTM testing was performed on a standardized machine with an experienced operator utilizing a medium (M) or extra-large (XL) probe. Standard criteria for having valid measurements were applied (IQR < 30% with >70% success rate). Severity of steatosis was evaluated based on the following cutoffs for CAP: <225 db/m (no steatosis), 225-250 db/m (mild steatosis), 250-300 db/m (moderate steatosis), >300 db/m (severe steatosis). Severity of liver stiffness was evaluated using the following TE cutoffs: <6 kPa (no fibrosis), 6-10 kPa (mild to moderate fibrosis), >10 kPa (advanced fibrosis). Baseline clinical and laboratory parameters were also collected. RESULTS: 119 children with suspected NAFLD were referred to the clinic between May 2017 and April 2019. The mean age at time of assessment was 13.0 (± 3.0) years. The majority were males (68%), obese (87%) and of Hispanic ethnicity (77%). The M probe was used to successfully complete 64% of scans whereas the XL probe was required for 36% of scans. 4/116 (3%) had a CAP < 225 indicating no steatosis. 15/116 (13%) of patients fell within the mild steatosis range (CAP 225-250), 31/116 (27%) with moderate steatosis (CAP 250-300) and the majority, 66/116 (57%), of patients having severe steatosis with CAP values > 300. On TE, 50% had no fibrosis, 45% with mild to moderate fibrosis and 7% with advanced fibrosis. Linear regression analysis demonstrated a weakly positive correlation between baseline ALT and TE measurements (correlation coefficient (r) was 0.24; P value < 0.05; Figure 1.1). CONCLUSION: CAP/TE provides a reliable way to confirm the diagnosis of NAFLD and assess its severity in children. Larger pediatric studies that assess the correlation with liver histology and disease progression are needed.

INTRODUCTION: Lysosomal acid lipase deficiency (LAL-D) is a rare autosomal recessive disease caused by mutations in the lysosomal acid lipase (LIPA) gene and characterized by cholesteryl ester accumulation in the liver and other body parts. Depending on the lipase enzyme residual activity level, severity of LAL-D can be low enough and patients may present with nonspecific symptoms; LAL-D can then be easily confused with more common causes of hepatic steatosis such as nonalcoholic fatty liver disease leading to underdiagnosis or even misdiagnosis well into adulthood. Here we present two cases of patients whose diagnoses of LAL-D were delayed for several years due to initial misdiagnosis. CASE DESCRIPTION/METHODS: A 59-year-old male, initially presented in childhood with hepatomegaly and elevated liver enzymes and was diagnosed with type 3 glycogen storage disease due to findings of liver biopsy done in 1975. He presented to our practice with worsening fatigue, muscle wasting and abdominal distension despite being on cornstarch therapy. His labs showed ALT of 75 U/L (0-44), AST of 73 U/L (0-40), and LDL cholesterol of 302 mg/dL (<110). LAL activity was low at 4 pmol/h/punch and liver biopsy showed diffuse microvesicular steatosis and foamy macrophages with stage 2 fibrosis confirming the diagnosis of LAL-D. His diagnosis was missed for at least 44 years from his initial liver biopsy. The second patient, a 14-year-old male, was not diagnosed for 8 years after repeatedly presenting to the emergency room with abdominal pain, diarrhea, and mild elevation in ALT for years. He required a cholecystectomy at the age of 13 years and the surgeon noted an “orange” liver. A biopsy showed diffuse microvesicular steatosis with stage 3 fibrosis suggestive of lipid storage disorder. His labs at presentation to our clinic were: ALT of 225, AST of 111, LDL cholesterol at 192. Genetic testing confirmed the diagnosis of LAL-D (E8SJM homozygous) and he was started on sebelipase alfa enzyme replacement with normalization of ALT and LDL cholesterol. DISCUSSION: Gastroenterologists should suspect the diagnosis of LAL-D in any patient presenting with hepatomegaly, fatty infiltration of the liver and elevated LDL. Prompt diagnosis of LAL-D could have helped decrease morbidity and improve these patients' quality of life by initiating sebelipase alfa enzyme replacement therapy to reduce the known long-term complications of advanced liver fibrosis such as cirrhosis and liver failure, and the many effects of progressive atherosclerosis.

INTRODUCTION: The currently accepted criteria to define therapeutic response to primary biliary cholangitis (PBC) consists of alkaline phosphatase (ALP) (<180 U/L) and bilirubin (<1.0 mg/dL). New data suggests that normalization of ALP (<120 U/L) and bilirubin (<0.5 mg/dL) is associated with better overall outcomes. PBC patients are usually maintained on first line therapy of ursodeoxycholic acid (UDCA), obeticholic acid (OCA) or combination of both agents. The aim of the study was to determine the percentage of PBC patients that achieve the accepted (ALP < 180, bilirubin < 1) and ideal (ALP < 120, bilirubin < 0.5) treatment responses in a real-world setting. METHODS: All adult patients in this multi-center study had a diagnosis of PBC via ICD-9 and ICD-10 codes. Other chronic liver disease cases and those with significant alcohol consumption were excluded. Baseline demographics, clinical characteristics and laboratory data were collected. Therapy starting time was noted, assessing their lab values at baseline compared to a recent workup. A two-sided t test was done to compare continuous variables and a P value < 0.05 was considered statistically significant. RESULTS: 76 adult PBC patients were included in the final analysis. The mean age at the last follow up was 61.8 years (±11.3). 96% were female, 47% were White and 51% were of Hispanic ethnicity. 93% were on UDCA therapy alone with daily dosages between 750-1500 mg. Only 7% received both UDCA and OCA. The mean baseline ALP was 286 U/L and the mean follow up ALP was 172 U/L (±84.6), 52 U/L above the ideal value (P < 0.05). The mean baseline bilirubin was 1.04 mg/dL and the mean follow up bilirubin was 0.8 mg/dL (±1.2), 0.3 mg/dL above the ideal value (P < 0.05). 62% reached the accepted ALP value, 86% reached the accepted bilirubin value, and 57% reached the accepted level. 30% of patients achieved the ideal ALP value and 26% achieved the ideal bilirubin level with 20% reaching the ideal response. The rates for accepted and ideal responses were 80% and 40%, respectively, for those on UDCA and OCA. CONCLUSION: The majority of PBC patients in real-life settings did not achieve the ideal treatment response of ALP < 120 U/L and bilirubin < 0.5 mg/dL. Furthermore, a significant percentage did not achieve the accepted treatment response of ALP < 180 U/L and bilirubin < 1.0 mg/dL. Only a small percentage received combination therapy with UDCA/OCA. There's a need to increase awareness among healthcare providers on the optimal responses to PBC treatment.