The epidemiology and natural history of pediatric primary sclerosing cholangitis (PSC), autoimmune sclerosing cholangitis (ASC), and autoimmune hepatitis (AIH) are not well characterized. Using multiple, overlapping search strategies followed by a detailed records review, we identified all cases of pediatric PSC, ASC, AIH, and inflammatory bowel disease (IBD) in a geographically isolated region of the United States. We identified 607 cases of IBD, 29 cases of PSC, 12 cases of ASC, and 44 cases of AIH. The mean age at diagnosis was 13.0 years for PSC, 11.3 years for ASC, and 9.8 years for AIH. The incidence and prevalence of PSC, ASC, and AIH were 0.2 and 1.5 cases, 0.1 and 0.6 cases, and 0.4 and 3.0 cases per 100,000 children, respectively. The mean duration of follow-up was 5.9 years. The probability of developing complicated liver disease within 5 years of the diagnosis of liver disease was 37% [95% confidence interval (CI) 5 21%-58%] for PSC, 25% (95% CI 5 7%-70%) for ASC, and 15% (95% CI 5 7%-33%) for AIH. The 5-year survival rates with the native liver were 78% (95% CI 5 54%-91%) for PSC, 90% (95% CI 5 47%-99%) for ASC, and 87% (95% CI 5 71%-95%) for AIH. Cholangiocarcinoma developed in 2 of the 29 PSC patients (6.9%). PSC occurred in 9.9% of patients with ulcerative colitis (UC) and in 0.6% of patients with Crohn's disease (CD). ASC occurred in 2.3% of UC patients and 0.9% of CD patients. AIH occurred in 0.4% of UC patients and in 0.3% of CD patients. Liver disease occurred in 39 of 607 IBD patients (6.4%) overall. Conclusion: Immune-mediated liver diseases are important sources of morbidity in children. Using a populationbased design, this study quantifies the burden and natural history of immune-mediated liver disease in children. (HEPATOLOGY 2013;58:1392-1400

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BACKGROUND There is a gap of knowledge in the long-term outcomes of patients who have complete recovery of kidney function after an episode of acute kidney injury (AKI). We sought to determine if complete recovery of kidney function after an episode of AKI is associated with development of incident stage 3 chronic kidney disease (CKD) and mortality in patients with normal baseline kidney function. DESIGN Retrospective cohort study. SETTING & PARTICIPANTS 3,809 patients from an integrated healthcare delivery system that had a hospitalization between January 1, 1999 and December 31, 2009 with follow-up through March 31, 2010. PREDICTOR AKI defined by ICD-9 codes and using the Acute Kidney Injury Network (AKIN) definition with complete recovery defined by reduction in serum creatinine to less than 1.10 times the baseline value. OUTCOMES AND MEASUREMENTS Incident stage 3 CKD persistent for 3 months and all-cause mortality. RESULTS After a median follow-up of 2.5 years, incident stage 3 CKD occurred in 15% and 3% of those with and without AKI, respectively, with an unadjusted HR of 5.93 (95% CI, 4.49-7.84) and a HR of 3.82 (95% CI, 2.81-5.19) in propensity score-stratified analyses. Deaths occurred in 35% and 24% of those with and without AKI, respectively, with an unadjusted HR of 1.46 (95% CI, 1.27-1.68). In the propensity score stratified analyses, HR decreased to 1.08 (95% CI, 0.93-1.27). LIMITATIONS Measurements of albuminuria were not available. CONCLUSIONS Complete recovery of kidney function after an episode of AKI in subjects with normal baseline kidney function is associated with an increased risk of development of incident stage 3 CKD but not all-cause mortality.

Background Pregnancy in kidney disease is considered high risk but the degree of this risk is unclear. We tested the hypothesis that kidney disease in pregnancy is associated with adverse maternal and fetal outcomes. Study Design Retrospective study comparing pregnant women with and without kidney disease. Setting & Participants Using data from an integrated healthcare delivery system from 2000 through 2013, 778 women met the criteria for kidney disease. Using a pool of 74,105 women without kidney disease, we selected 778 women to use for matches for the women with kidney disease. These women were matched 1:1 by age, race, and history of diabetes, chronic hypertension, liver disease and connective tissue disease. Predictor Kidney disease was defined using the NKF-KDOQI definition for chronic kidney disease or ICD-9 codes prior to pregnancy or serum creatinine >1.2 mg/dL and/or proteinuria in first trimester. Outcomes & Measurements Maternal outcomes included preterm delivery, delivery via cesarean section, preeclampsia/eclampsia, length of stay at hospital (>3 days) and maternal death. Fetal outcomes included low birth weight (weight <2500 g), small for gestational age, number of admissions to neonatal intensive care unit (NICU) and infant death. Results Compared to women without kidney disease, those with kidney disease had 52% increased odds of preterm delivery (OR, 1.52; 95% CI, 1.16-1.99) and 33% increased odds of delivery via cesarean section (OR, 1.33; 95% CI, 1.06-1.66). Infants born to women with kidney disease had 71% increased odds of admission to NICU or infant death compared to infants born to women without kidney disease (OR, 1.71; 95% CI, 1.17-2.51). Kidney disease was also associated with two-fold increased odds of low birth weight (OR, 2.38; 95% CI, 1.64-3.44). Kidney disease was not associated with increased risk of maternal death. Limitations Data on level of kidney function and cause of death not available. Conclusions Kidney disease in pregnancy is independently associated with adverse maternal and fetal outcomes when other comorbid conditions are controlled by matching.

BACKGROUND: In addition to hyperglycemia, hypoglycemia, and glycemic variability, reduced time in targeted blood glucose range (TIR) is associated with increased risk of death in critically ill patients. This relation between TIR and mortality may be confounded by diabetic status and antecedent glycemic control. METHODS: This study retrospectively analyzed critically ill patients managed with the same IV insulin protocol at multiple centers. The percentage of TIR between 70 and 139 mg/dL was calculated. Patients with diabetic ketoacidosis, patients who had < 10 blood glucose readings, and patients with repeat admissions were excluded. The highest recorded glycosylated hemoglobin value in the preceding 3 months or up to 1 month following admission were used as a surrogate for the patient's preexisting glucose control. Stratified regression analyses were performed for 30-day mortality, with covariates of age, sex, TIR $ 80%, Acute Physiology Score, and Charlson Comorbidity Index. RESULTS: A total of 9,028 patients, 53.2% of whom had diabetes, were studied. Median TIR was 84.1% for nondiabetic patients and 64.5% for patients with diabetes. Mortality was lower in those with TIR > 80% compared with those with TIR # 80% (12.4% vs 19.2%; P < .001). TIR > 80% was independently associated with reduced mortality in nondiabetic patients (OR, 0.52; P < .001), patients with diabetes (OR, 0.69; P ¼ .001), and patients with wellcontrolled disease (OR, 0.50; P < .001) but not in patients with poorly controlled disease (OR, 0.86; P ¼ .40). CONCLUSIONS: TIR was independently associated with mortality in critically ill patients, particularly those with good antecedent glucose control.

Moderate glucose control (90-140 mg/dL) may confer greater mortality in critically ill patients without diabetes compared with tight glucose control (80-110 mg/dL). A single glucose target does not appear optimal for all critically ill patients. These data have important implications for the design of future interventional trials as well as for the glycemic management of critically ill patients.

IntroductionBoth patient- and context-specific factors may explain the conflicting evidence regarding glucose control in critically ill patients. Blood glucose variability appears to correlate with mortality, but this variability may be an indicator of disease severity, rather than an independent predictor of mortality. We assessed blood glucose coefficient of variation as an independent predictor of mortality in the critically ill.MethodsWe used eProtocol-Insulin, an electronic protocol for managing intravenous insulin with explicit rules, high clinician compliance, and reproducibility. We studied critically ill patients from eight hospitals, excluding patients with diabetic ketoacidosis and patients supported with eProtocol-insulin for < 24 hours or with < 10 glucose measurements. Our primary clinical outcome was 30-day all-cause mortality. We performed multivariable logistic regression, with covariates of age, gender, glucose coefficient of variation (standard deviation/mean), Charlson comorbidity score, acute physiology score, presence of diabetes, and occurrence of hypoglycemia < 60 mg/dL.ResultsWe studied 6101 critically ill adults. Coefficient of variation was independently associated with 30-day mortality (odds ratio 1.23 for every 10% increase, P < 0.001), even after adjustment for hypoglycemia, age, disease severity, and comorbidities. The association was higher in non-diabetics (OR = 1.37, P < 0.001) than in diabetics (OR 1.15, P = 0.001).ConclusionsBlood glucose variability is associated with mortality and is independent of hypoglycemia, disease severity, and comorbidities. Future studies should evaluate blood glucose variability.

Background and Aims We sought to explore associations between serum 25-hydroxyvitamin D [25(OH)D] levels and non-alcoholic fatty liver disease [NAFLD] in an integrated healthcare delivery system in the U.S. Methods and Results 607 NAFLD cases were randomly matched 1:1 with controls for age, sex, race and season of measurement. Conditional logistic regression was used to evaluate if serum 25(OH)D levels were associated with increased odds of NAFLD (diagnosed by ultrasound) after adjusting for body mass index and history of diabetes, renal, peripheral vascular and liver diseases (model 1) and also for hypertension (model 2). Mean (SD) serum 25(OH)D level was significantly lower in the group with NAFLD as compared with that in the matched control group (75±17 vs. 85±20 nmol/L [30±7 vs. 34±8 ng/mL], P<0.001). Inadequate 25(OH)D status progressively increased the odds of NAFLD when classified categorically as sufficient (25(OH)D 75 nmol/L [>30 ng/mL], reference group), insufficient (37–75 nmol/L [15–30 ng/mL]; adjusted odds ratio [OR]: 2.40, 95% confidence interval [CI]: 0.90–6.34) or deficient (<37 nmol/L [<15 ng/mL]; adjusted OR: 2.56, 95% CI: 1.27–5.19). When modeled as a continuous variable, increased log10 25(OH)D was inversely associated with the risk of prevalent NAFLD (adjusted OR: 0.25, 95% CI: 0.064–0.96, P=0.02). Conclusion Compared with matched controls, patients with NAFLD have significantly decreased serum 25(OH)D levels, suggesting that low 25(OH)D status might play a role in the development and progression of NAFLD.