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Aims: We sought to examine whether disturbances in central and peripheral circadian rhythms were related to the experience of fatigue in patients with chronic liver disease (CLD). Methods: Fatigued and non-fatigued patients with compensated CLD were enrolled in a prospective pilot study. Patients underwent a one week evaluation of free-living sleep and physical activity patterns, followed by a 24-hour admission, during which they underwent serial blood sampling, polysomnography, a 6-minute walk test and continuous core temperature measurements under standardized conditions. Blood samples were analyzed for liver tests, melatonin levels, lipids, and cortisol. Circadian rhythms were analyzed using single cosinor analyses. Results: Six fatigued and six non-fatigued patients were studied; five participants had cirrhosis. Fatigue severity was positively associated higher peak melatonin levels (rho=0.59, p=0.04) and a delay in night-time melatonin peak and inversely associated with sleep efficiency (rho=−0.63, p=0.04). Polysomnography, 6-minute walk test, and core temperature measurements did not differ significantly between the fatigued and non-fatigued patients. Although liver enzymes, bilirubin and albumin demonstrated a circadian pattern, it was not associated with fatigue. Fatigued patients showed a blunted and delayed cortisol rhythm and fatigue was strongly correlated with cortisol amplitude (rho=−0.77, p=0.004) and phase (r=−0.66, p=0.02). Conclusion: Subtle aberrations in melatonin and adrenal circadian rhythms, as well as reduced sleep efficiency, likely contribute to fatigue in patients with CLD. These abnormalities may ultimately be a therapeutic target to improve quality of life for fatigued patients with CLD.

Purpose Celiac disease (CD) is a disorder in which gluten ingestion triggers an autoimmune response causing inflammation and damage to the small intestine. With improved awareness and screening availability, prevalence and variation in clinical presentation have subsequently increased. Thus, our study identified the disease characteristics and presentation patterns of pediatric CD in southern West Virginia. Methods We retrospectively reviewed charts for pediatric patients (age <18 years) diagnosed with CD during a 10-year period at a tertiary care hospital. Results A total of 59 patients met inclusion criteria. The mean age of diagnosis was 10.0+4.6 years, with 61% of patients being female. One-third of cases were asymptomatic and diagnosed from screenings of patients with hypothyroidism or type 1 diabetes mellitus. In symptomatic patients (n=40), abdominal pain was the most common presenting symptoms (78%), followed by constipation (30%). Classical symptoms of diarrhea and failure to thrive/unexplained weight loss were less common (n=9). At diagnosis, anti-tissue transglutaminase (tTG) IgA antibodies and deamidated gliadin peptide IgG antibodies were both positive in 88% of cases, and endomysial antibodies were positive in 70% cases. One-year post-diagnosis clinic follow-up rate was 63%. A gluten-free diet improved symptoms and tTG IgA serology levels in all patients with follow-up. Conclusion Our data fills in the gap of the paucity of information available about CD in children from Appalachia. A high index of suspicion is required to screen and diagnose CD as many patients are either asymptomatic or lack classical findings. A gluten-free diet is a highly effective treatment, although follow-up after initial diagnosis remains a challenge.

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