Adult nonalcoholic fatty liver disease (NAFLD) is characterized by absent or mild portal chronic inflammation (CI); in children, portal CI may be predominant. This study correlated clinical features with portal CI. Centrally-graded biopsies and temporally-related clinical parameters from 728 adults and 205 children. From the Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) were evaluated. Mild, more than mild and no portal CI were found in 60%, 23% and 16% of adult biopsies and 76%, 14% and 10% of pediatric biopsies. Autoantibodies, and elevated alanine aminotransferase were not associated with portal CI. Clinical features associated with "more than mild" in adults were older age (P < 0.0001), female gender (P ‫؍‬ 0.001), higher body mass index (P < 0.0001), elevated insulin levels (P ‫؍‬ 0.001), higher homeostasis model assessment of insulin resistance score (HOMA-IR) (P < 0.0001), and medications used for NAFLD (P ‫؍‬ 0.0004), diabetes (P < 0.0001), and hypertension (P < 0.0001). "More than mild" in the pediatric biopsies correlated with younger age (P ‫؍‬ 0.01), but not with body mass index, insulin or HOMA-IR. In both groups, lobular and portal inflammation scores had no association, but there was an association with definite steatohepatitis (P < 0.0001). Features associated in the adult biopsies with "more than mild" were steatosis amount (P ‫؍‬ 0.01) and location (P < 0.0001), ballooning (P < 0.0001), and advanced fibrosis (P < 0.0001). In the pediatric biopsies, "more than mild" was associated with steatosis location (P ‫؍‬ 0.0008) and fibrosis score (P < 0.0001), specifically, the portal/periportal fibrosis or greater fibrosis) (P < 0.01). Conclusion: Increased portal CI is associated with many clinical and pathologic features of progressive NAFLD in both adults and children, but not with ALT, autoantibodies, or lobular inflammation. More than mild portal CI in liver biopsies of untreated NAFLD may be considered a marker of advanced disease. (HEPATOLOGY 2009;49:809-820.)

Children with systolic blood pressures above the criterion values established in this longitudinal study are at increased risk of hypertension and the metabolic syndrome later in life.

In persons at high risk for diabetes, insulin at the dosage used in this study does not delay or prevent type 1 diabetes.

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the UnitedStates. The association between NAFLD and quality of life (QOL) remains unclear. These data are important to estimate the burden of illness in NAFLD. The aim was to report QOL scores of adults with NAFLD and examine the association between NAFLD severity and QOL. QOL data were collected from adults with NAFLD enrolled in the Nonalcoholic Steatohepatitis Clinical Research Network using the Short Form 36 (SF-36) survey, and scores were compared with normative U.S. population scores. Liver biopsy histology was reviewed by a central pathology committee. A total of 713 subjects with NAFLD (male ‫؍‬ 269, female ‫؍‬ 444) were included. Mean age of subjects was 48.3 years; 61% had definite nonalcoholic steatohepatitis (NASH), and 28% had bridging fibrosis or cirrhosis. Diabetes was present in 27% of subjects. Subjects with NAFLD had worse physical (mean, 45.2) and mental health scores (mean, 47.6) compared with the U.S. population with (mean, 50) and without (physical, 55.8; mental, 52.5) chronic illness. Subjects with NASH reported lower physical health compared with subjects with fatty liver disease without NASH (44.5 versus 47.1, P ‫؍‬ 0.02). Subjects with cirrhosis had significantly (P < 0.001) poorer physical health scores (38.4) than subjects with no (47.6), mild (46.2), moderate (44.6), or bridging fibrosis (44.6). Cirrhosis was associated with poorer physical health after adjusting for potential confounders. Mental health scores did not differ between participants with and without NASH or by degree of fibrosis. Conclusion: Adults with NAFLD have a significant decrement in QOL. Treatment of NAFLD should incorporate strategies to improve QOL, especially physical health. (HEPATOLOGY 2009;49:1904-1912

Objectives-To determine the age of significant divergence in body mass index (BMI) and waist circumference in adults with and without the metabolic syndrome, and to provide age-and sexspecific childhood values that predict adult metabolic syndrome.Study design-Part 1 of this study is a retrospective cohort study of 92 men and 59 women (mean age, 51 years) who had metabolic syndrome and 154 randomly selected adults matched for age and sex who did not have the syndrome. Part 2 is a study of predictive accuracy in a validation sample of 743 participants.Results-The first appearance of differences between adults with and without metabolic syndrome occurred at ages 8 and 13 for BMI and 6 and 13 for waist circumference in boys and girls, respectively. Odds ratios (ORs) for the metabolic syndrome at 30 years and older ranged from 1.4 to 1.9 across age groups in boys and from 0.8 to 2.8 across age groups in girls if BMI exceeded criterion values in childhood. The corresponding ORs for waist circumference ranged from 2.5 to 31.4 in boys and 1.7 to 2.5 in girls. These ORs increased with the number of examinations.Conclusions-Children with BMI and waist circumference values exceeding the established criterion values are at increased risk for the adult metabolic syndrome.The availability of long-term serial data from the Fels Longitudinal Study presents opportunities to directly link obesity, centralized fat pattern, and the metabolic syndrome in adulthood to body mass index (BMI) and waist circumference measured decades earlier in the same individuals as children and to establish criterion values for BMI and waist Copyright © 2008 NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript circumference that predict obesity, centralized fat patterns, and the metabolic syndrome later in life. Recently, we derived age-and sex-specific childhood blood pressures that predict hypertension and the metabolic syndrome in adulthood using a random-effects model in a discovery sample and validated these criterion values in a larger sample using logistic regression. 1 In the present study, we apply a similar approach to ascertaining age-and sexspecific values in childhood for BMI and waist circumference that predict the metabolic syndrome later in life. Currently, there is no agreement on the definition of the metabolic syndrome in children or adolescents. In recent reports, investigators have used arbitrary thresholds for levels of fasting plasma triglycerides, fasting plasma HDL cholesterol, and fasting plasma glucose, coupled with age-and sex-specific ≥90th percentiles for waist circumference and blood pressure from the National Health and Nutrition Examination Survey (NHANES) III to assess the prevalence of the metabolic syndrome in children and adolescents. [4][5][6] In this study, we take a different approach to ascertaining the onset of the metabolic syndrome in children by linking the adult metabolic syndrome directly to childhood risk factors measured in the same individuals decades earlier. This dire...