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We examined transient elastography assessed hepatic steatosis and fibrosis distributions and relationships with body composition in a representative United States population sample. Liver stiffness and controlled attenuation parameter (CAP) were assessed on 4870 non-Hispanic White, non-Hispanic Black, non-Hispanic Asian, and Hispanic men and women aged 20 years and over in the National Health and Nutrition Examination Survey (NHANES) 2017–2018. Participants underwent anthropometry and dual-energy x-ray absorptiometry (DXA). Compared to women, men had higher mean CAP (274.2 dB/m vs 254.4 dB/m) and liver stiffness (6.4 kPa vs 5.5 kPa). CAP and liver stiffness increased through middle age and markedly with BMI. In multivariate-adjusted analysis, CAP in the upper quartile was associated with increased age, BMI, waist-to-hip ratio, diabetes, hypertension, alanine aminotransferase (ALT) and C-reactive protein and decreased HDL cholesterol. After adjustment, non-Hispanic Blacks had lower CAP and non-Hispanic Asians had higher CAP. In multivariate-adjusted analysis, liver stiffness in the upper quartile was associated with male sex, increased age, BMI, diabetes, hepatitis C virus positivity, ALT and CAP. Lower stiffness among Non-Hispanic Asians was not significant after adjustment for BMI. DXA trunk and extremity fat mass were positively related to both CAP and liver stiffness with multivariate adjustment (P <.001 for each). Results were similar with CAP and liver stiffness as continuous characteristics. In the United States population, increased anthropometric and DXA body composition measures were associated with higher CAP and liver stiffness. Racial-ethnic differences observed merit further research to elucidate the burden of obesity and liver health disparities. [ABSTRACT FROM AUTHOR]

Background & Aims: Physiological changes that occur during puberty might affect pathologic features of nonalcoholic fatty liver disease (NAFLD). We investigated associations between pubertal development and clinical and histopathologic features of NAFLD. Methods: We studied 186 children (age <18 years, 143 boys) with biopsy-proven NAFLD. The population was divided into 3 groups on the basis of Tanner stage (prepuberty, puberty, and postpuberty). Clinical characteristics and histologic features were compared among groups. Multivariable regression models were used to adjust for potential confounders. Results: After adjusting for other factors, hyperuricemia and low levels of high-density–lipoprotein cholesterol were more prevalent among children who entered puberty with lower levels of quantitative insulin sensitivity check index (P < .05). The degree of steatosis, numbers of Mallory–Denk bodies, and diagnostic categories of NAFLD differed among groups (P < .05). There were potential sex differences in associations between stages of puberty and lobular inflammation, hepatocyte ballooning, and borderline steatohepatitis of zone 3; these were therefore not included in multivariable analyses of the overall population. After adjustment for different sets of confounders, patients at or beyond puberty were less likely to have high-grade steatosis, severe portal inflammation, borderline steatohepatitis (zone 1), or a high stage of fibrosis than patients who had not entered puberty (P < .05). On the contrary, the prevalence of Mallory–Denk body was greater among postpuberty subjects (P = .06). Conclusions: Steatosis, portal inflammation, and fibrosis are less severe during or after puberty than before puberty among subjects with NAFLD. Postpubescent individuals have a lower prevalence of borderline steatohepatitis of zone 1 but are more likely to have Mallory–Denk bodies. These findings indicate that puberty affects the pathologic features of NAFLD. [Copyright &y& Elsevier]

Background & Aims: Gastroparesis can be diabetic or idiopathic, yet little is known about differences in their presentation. We compared clinical characteristics, symptoms, and gastric emptying in patients with type 1 or type 2 diabetic (DG) or idiopathic (IG) gastroparesis. Methods: We analyzed data from 416 patients with gastroparesis who were enrolled in the National Institute of Diabetes and Digestive and Kidney Diseases Gastroparesis Registry; 254 had IG (most were female and white), and 137 had DG (78 had type 1 and 59 had type 2). Registry data included detailed histories, physical examinations, results from gastric emptying scintigraphy, and responses to validated symptom questionnaires. Results: Patients with type 2 diabetes mellitus (DM) were an average of 13 years older at the onset of symptoms of gastroparesis and heavier than patients with IG. Patients with type 1 DM had more hospitalizations in the past year than patients with IG. Symptoms that prompted evaluation more often included vomiting for DG and abdominal pain for IG. Patients with DG had more severe retching and vomiting than those with IG, whereas patients with IG had more severe early satiety and postprandial fullness subscores. Compared with IG, gastric retention was greater in patients with type 1 DM. More than 50% of patients with type 1 DM had severe retention (>35% at 4 hours); they took prokinetic agents more frequently and were more likely to receive gastric electric stimulation. Conclusions: There are similarities and differences in clinical characteristics of DG and IG. Gastroparesis is a heterogeneous disorder; its etiology affects symptoms and severity. Long-term studies are needed to determine whether the differences in symptoms and gastric emptying affect progression and treatment responses. [ABSTRACT FROM AUTHOR]

Background & Aims: In overnourished individuals, impaired peripheral fat storage (ie, reduced fat mass in extremities) can increase delivery of surplus calories to the organs other than peripheral adipose tissues, including the liver (ie, lipid overload), and facilitate disease progression in patients with nonalcoholic fatty liver disease (NAFLD). We investigated whether peripheral and/or abdominal adipose depot size correlates with stage of hepatic fibrosis in patients with NAFLD in sex- and/or menopausal stage–specific manners. Methods: We performed a cross-sectional analysis of 537 adult patients with NAFLD. Peripheral adipose depot size was defined as the sum of z-scores of 2 anthropometric parameters (middle upper arm circumference and hip circumference, relative to total body size) and expressed as extremity size. Abdominal adipose depot size was defined as waist circumference. Peripheral and abdominal adipose depot sizes were associated with fibrosis stage(s) (F0–F4) using multivariable analyses separately for men and pre- and post-menopausal women. Results: After adjusting for caloric intake and energy expenditure during physical activity (MET; hours/week), peripheral and/or abdominal adipose depot sizes were differentially associated with fibrosis stages in men and pre- and post-menopausal women. Men with smaller extremity size, premenopausal women with larger extremity size, and postmenopausal women with larger abdominal size were more likely to have higher stages of fibrosis. Conclusions: In patients with NAFLD, regional anthropometric measures are associated with fibrosis severity in a sex- and menopausal stage–specific manner. Unlike premenopausal women, men with NAFLD who have small peripheral adipose depots are at an increased risk of having advanced fibrosis. [ABSTRACT FROM AUTHOR]

Background & Aims Sex and sex hormones can affect responses of patients with nonalcoholic fatty liver disease (NAFLD) to metabolic stress and development of hepatocyte injury and inflammation. Methods We collected data from 3 large U.S. studies of patients with NAFLD (between October 2004 and June 2013) to assess the association between histologic severity and sex, menopause status, synthetic hormone use, and menstrual abnormalities in 1112 patients with a histologic diagnosis of NAFLD. We performed logistic or ordinal logistic regression models, adjusting for covariates relevant to an increase of hepatic metabolic stress. Results Premenopausal women were at an increased risk of lobular inflammation, hepatocyte ballooning, and Mallory-Denk bodies than men and also at an increased risk of lobular inflammation and Mallory-Denk bodies than postmenopausal women ( P < .01). Use of oral contraceptives was associated with an increased risk of lobular inflammation and Mallory-Denk bodies in premenopausal women, whereas hormone replacement therapy was associated with an increased risk of lobular inflammation in postmenopausal women ( P < .05). Conclusions Being a premenopausal woman or a female user of synthetic hormones is associated with increased histologic severity of hepatocyte injury and inflammation among patients with NAFLD at given levels of hepatic metabolic stress. [ABSTRACT FROM AUTHOR]

Objective: To investigate the histological spectrum of nonalcoholic fatty liver disease (NAFLD) in children with normal, mildly elevated (26-50 U/L boys, 23-44 U/L girls), or elevated (>50 U/L in boys, >44 U/L in girls) serum alanine aminotransferase (ALT) levels. Study design: The Nonalcoholic Steatohepatitis Clinical Research Network enrolls children aged 5-18 years with NAFLD. We analyzed baseline clinical and histological data from 91 children with suspected NAFLD and normal or mildly elevated ALT and liver biopsy analysis within 180 days of ALT measurement, and compared them with data from 392 children with elevated ALT. Results: Seventeen of the 91 children with suspected NAFLD (19%) had a normal ALT level, and 74 (81%) had a mildly elevated ALT level. Overall, 45% of the biopsy specimens analyzed had steatosis ≥33%, 22% had grade ≥2 lobular inflammation, 81% had portal inflammation, 29% had ballooned hepatocytes, 35% had “suspicious/borderline” steatohepatitis, 8% had definite nonalcoholic steatohepatitis, 34% had an NAFLD activity score ≥4, and 46% had fibrosis (38% mild/moderate and 8% bridging/cirrhosis). Marked steatosis (50% vs 24%) and fibrosis (54% vs 12%) were significantly more common in the patients with mildly elevated ALT compared with those with normal ALT, with no difference in ballooning, inflammation, or NAFLD activity score ≥4 between the 2 groups. Fibrosis stage 3/4 was seen in none of the children with normal ALT, in 9% of those with mildly elevated ALT, and in 15% of those with elevated ALT. Conclusion: Liver biopsy specimens from children with NAFLD with normal or mildly elevated ALT levels show significant histological abnormalities, including advanced fibrosis in children with mildly elevated ALT. Thus, measurement of ALT may underestimate liver injury in NAFLD. The use of appropriate ALT cutoff levels can help identify children at risk for more severe disease. [Copyright &y& Elsevier]

Background & Aims: Gastroparesis can lead to food aversion, poor oral intake, and subsequent malnutrition. We characterized dietary intake and nutritional deficiencies in patients with diabetic and idiopathic gastroparesis. Methods: Patients with gastroparesis on oral intake (N = 305) were enrolled in the National Institute of Diabetes and Digestive and Kidney Diseases Gastroparesis Registry and completed diet questionnaires at 7 centers. Medical history, gastroparesis symptoms, answers to the Block Food Frequency Questionnaire, and gastric emptying scintigraphy results were analyzed. Results: Caloric intake averaged 1168 ± 801 kcal/day, amounting to 58% ± 39% of daily total energy requirements (TER). A total of 194 patients (64%) reported caloric-deficient diets, defined as <60% of estimated TER. Only 5 patients (2%) followed a diet suggested for patients with gastroparesis. Deficiencies were present in several vitamins and minerals; patients with idiopathic disorders were more likely to have diets with estimated deficiencies in vitamins A, B6, C, K, iron, potassium, and zinc than diabetic patients. Only one-third of patients were taking multivitamin supplements. More severe symptoms (bloating and constipation) were characteristic of patients who reported an energy-deficient diet. Overall, 32% of patients had nutritional consultation after the onset of gastroparesis; consultation was more likely among patients with longer duration of symptoms and more hospitalizations and patients with diabetes. Multivariable logistic regression analysis indicated that nutritional consultation increased the chances that daily TER were met (odds ratio, 1.51; P = .08). Conclusions: Many patients with gastroparesis have diets deficient in calories, vitamins, and minerals. Nutritional consultation is obtained infrequently but is suggested for dietary therapy and to address nutritional deficiencies. [ABSTRACT FROM AUTHOR]

Background & Aims: Idiopathic gastroparesis (IG) is a common but poorly understood condition with significant morbidity. We studied characteristics of patients with IG enrolled in the National Institute of Diabetes and Digestive and Kidney Diseases Gastroparesis Clinical Research Consortium Registry. Methods: Data from medical histories, symptom questionnaires, and 4-hour gastric emptying scintigraphy studies were obtained from patients with IG. Results: The mean age of 243 patients with IG studied was 41 years; 88% were female, 46% were overweight, 50% had acute onset of symptoms, and 19% reported an initial infectious prodrome. Severe delay in gastric emptying (>35% retention at 4 hours) was present in 28% of patients. Predominant presenting symptoms were nausea (34%), vomiting (19%), an abdominal pain (23%). Women had more severe nausea, satiety, constipation, and overall gastroparesis symptoms. Patients who experienced acute-onset IG had worse nausea than those with insidious onset. Overweight patients had more bloating and gastric retention at 2 hours but less severe loss of appetite. Patients with severely delayed gastric emptying had worse vomiting and more severe loss of appetite and overall gastroparesis symptoms. Severe anxiety and depression were present in 36% and 18%, respectively. A total of 86% met criteria for functional dyspepsia, primarily postprandial distress syndrome. Conclusions: IG is a disorder that primarily affects young women, beginning acutely in 50% of cases; unexpectedly, many patients are overweight. Severe delay in gastric emptying was associated with more severe symptoms of vomiting and loss of appetite. IG is a diverse syndrome that varies by sex, body mass, symptom onset, and delay in gastric emptying. [Copyright &y& Elsevier]