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<p><strong>BACKGROUND: </strong>Congestive hepatopathy is a recognized complication of Fontan physiology. Data regarding the incidence of hepatopathy and risk factors are lacking.</p>
<p><strong>METHODS AND RESULTS: </strong>Liver biopsies and cardiac catherizations were performed as part of an evaluation offered to all patients ≥10 years after Fontan. Quantitative determination of hepatic fibrosis was performed using Sirius red staining with automated calculation of collagen deposition per slide (%CD). Biopsies from included subjects were compared to stained specimens from controls without known fibrotic liver disease. Patient characteristics, echocardiographic findings, and hemodynamic measures were evaluated as potential risk factors. The cohort consisted of 67 patients (31 female) at mean age of 17.3±4.5 years and mean time from Fontan of 14.9±4.5 years. Right ventricular morphology was present in 37 subjects. Median %CD by Sirius red staining was 21.6% (range 8.7% to 49.4%) compared to 2.6% (range 2.2% to 3.0%) in controls. There was a significant correlation between time from Fontan and degree of Sirius red staining (r=0.33, P<0.01). Serum liver enzymes and platelet count did not correlate with %CD. The median inferior vena cava pressure was 13 mm Hg (range 6-24 mm Hg) and did not correlate with %CD. There was no difference in %CD based on ventricular morphology or severity of atrioventricular valve insufficiency.</p>
<p><strong>CONCLUSIONS: </strong>In this cohort of predominantly asymptomatic children and adolescents electively evaluated after a Fontan operation, all exhibited evidence for hepatic fibrosis as measured by collagen deposition in the liver. Time from Fontan was the only factor significantly associated with collagen deposition. These findings demonstrate that liver fibrosis is an inherent feature of Fontan physiology and that the degree of fibrosis increases over time.</p>
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<p>The Fontan operation is a widely used palliative procedure in patients with single ventricle anatomy that results in liver injury. As timely identification of liver fibrosis may result in management changes to Fontan patients, the aim of our study was to identify clinically meaningful semi-quantitative/quantitative pathologic parameters for biopsy assessment. We performed a retrospective review of 74 liver needle biopsies from Fontan patients. Fibrosis was assessed using quantitative % collagen deposition (%CD) by Sirius red image analysis, METAVIR, congestive hepatic fibrosis score (CHFS), sinusoidal fibrosis (SF) score, and sinusoidal dilation score. Contemporaneous laboratory, hemodynamic, and ultrasound data were collected. Centrilobular and peri-sinusoidal fibrosis was observed in all cases, with 39.2% high grade. Portal fibrosis was observed in 93.2%, with 36.2% high grade (METAVIR F3-F4). Cirrhosis was observed in 5.4%. %CD was increased over control tissue (p<0.001) and correlated with time from Fontan (r=0.3, p=0.009) and prothrombin time (PT) (r=0.25, p=0.034). Mildly elevated PT/INR was the only measure of liver function consistently associated with multiple high-grade fibrosis scores (METAVIR p=0.046, SF p=0.018). Abnormal liver echotexture on ultrasound was associated with high grade CHFS (p=0.03). Pathologic gradings and %CD correlated with each other (r=0.48-0.8, p<0.001). Hepatic fibrosis in Fontan patients in our study is universally present, appears to be time dependent, and correlates with few laboratory measurements of liver function. Careful assessment of needle liver biopsies lends a more meaningful measure of liver fibrosis in the Fontan patient than clinical and laboratory data, allowing for appropriate changes to patient management.</p>
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<p><strong>OBJECTIVES: </strong>To determine whether the addition of hepatitis B virus (HBV) vaccine to national immunization programs improved vaccination rates among refugee children, a marginalized population with limited access to care.</p>
<p><strong>METHODS: </strong>The sample included 2291 refugees younger than 19 years who completed HBV screening after arrival in the United States. Children were categorized by having been born before or after the addition of the 3-dose HBV vaccine to their birth country's national immunization program. The outcome was serological evidence of immunization.</p>
<p><strong>RESULTS: </strong>The odds of serological evidence of HBV immunization were higher for children born after the addition of HBV vaccine to their birth country's national immunization program (adjusted odds ratio = 2.54; 95% confidence interval = 2.04, 3.15).</p>
<p><strong>CONCLUSIONS: </strong>National HBV vaccination programs have contributed to the increase in HBV vaccination coverage observed among US-bound refugee children.</p>
<p><strong>PUBLIC HEALTH IMPLICATIONS: </strong>Ongoing public health surveillance is needed to ensure that vaccine rates are sustained among diverse, conflict-affected, displaced populations. (Am J Public Health. Published online ahead of print June 16, 2016: e1-e3. doi:10.2105/AJPH.2016.303203).</p>