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Background: Magnetic resonance elastography (MRE) is an accurate biomarker of liver fibrosis; however, limited data characterize its association with outcomes. We aimed to evaluate the association between liver stiffness (LS) on MRE and liver-related outcomes. Methods: This is a longitudinal, retrospective analysis of subjects at risk of NAFLD who had MRE assessment. LS was estimated using MRE, and liver fat was assessed using magnetic resonance imaging proton density fat fraction. Univariable and multivariable survival and regression analyses were used to assess the association between LS on MRE and liver-related outcomes including a cumulative primary outcome of hepatic decompensation, hepatocellular carcinoma (HCC), or death. Results: In all, 265 patients (68% women) with a mean age of 50 (±18) years and 44% Hispanic ethnicity and 45.3% with NAFLD were included. A total of 76 liver-related events or death occurred, and there was 453 person-years of follow-up time in 97 patients with available follow-up. Each 1-kPa increase in LS was associated with 2.20-fold (95% CI: 1.70–2.84, p < 0.001) increased odds of prevalent hepatic decompensation or HCC. A positive MEFIB index, a combination of MRE ⩾ 3.3 kPa and FIB-4 ⩾ 1.6, had a strong association with the primary outcome compared with those without, HR = 21.8 (95% CI: 4.28–111.4, p < 0.001). The MEFIB index had a sensitivity of 75% and specificity of 90%, and a negative score was associated with 98% negative predictive value for incident liver-related events or death. Conclusion: LS assessed by MRE is associated with hepatic decompensation and death, and the MEFIB combination of MRE with FIB-4 may have high negative predictive value for liver-related events.

Introduction: Two-dimensional shear wave elastography (2D-SWE) and vibration-controlled transient elastography (VCTE) provide noninvasive assessment of hepatic fibrosis. We compared performance of 2D-SWE and VCTE for fibrosis detection in nonalcoholic fatty liver disease (NAFLD). Methods: We performed a prospective study of adults with NAFLD who underwent 2D-SWE, VCTE, and liver biopsy analysis (using Nonalcoholic Steatohepatitis Clinical Research Network scoring system). The primary outcome was hepatic fibrosis (stage ⩾ 1); secondary outcomes included dichotomized fibrosis stages. Area under receiver operating characteristic curve (AUROC) analyses were used to compare 2D-SWE and VCTE performance. Results: A total of 114 adults with a median BMI of 31.2 kg/m2 were included. The VCTE was better than 2D-SWE for the detection of fibrosis (AUROC: 0.81 versus 0.72, p = 0.03). The VCTE detected fibrosis stage 2, 3, or 4 with AUROCs of 0.86 (95% CI, 0.80–0.93), 0.91 (95% CI, 0.82–0.99), and 0.96 (95% CI, 0.91–1.00). The 2D-SWE detected fibrosis stage 2, 3, or 4 with AUROCs of 0.84 (95% CI, 0.76–0.92), 0.88 (95% CI, 0.81–0.96), and 0.93 (95% CI, 0.86–0.99). Conclusion: In a prospective study including more than 100 adults with NAFLD, we found VCTE to be more accurate than 2D-SWE in detecting fibrosis; these modalities, however, are comparable in assessing for higher stages of fibrosis.

Serum alanine aminotransferase (ALT) is a marker of liver injury. The 2005 American Gastroenterology Association Future Trends Committee report states that serum ALT levels remain constant with age. This study examines the association between serum ALT and age in a community-dwelling cohort in the United States. A cross-sectional study of 2,364 (54% female) participants aged 30-93 years from the Rancho Bernardo Study cohort who attended a research clinic visit in 1984-87. Demographic, metabolic co-variates, ALT, bilirubin, gamma glutamyl transferase (GGT), albumin, and adiposity signaling biomarkers (leptin, IL-6, adiponectin, ghrelin) were measured. Participants were divided into four-groups based upon age quartile, and multivariable-adjusted least squares of means (LSM) were examined (p for trend <0.05). ALT decreased with increasing age, with mean ALT levels (IU/L) of 23, 21, 20, and 17 for those between quartile ages 30-62, 63-71, 72-77, and 78-93 years (p<0.0001). Trends of decreasing LSM ALT with age and the decreasing prevalence of categorically defined elevated serum ALT with age remained robust after adjusting for sex, alcohol use, metabolic syndrome components, and biomarkers of adiposity (p-value <0.0001), and was not materially changed after adjusting for bilirubin, GGT, and albumin. ALT levels decrease with age in both men and women independent of metabolic syndrome components, adiposity signaling biomarkers, and other commonly used liver function tests. Further studies are needed to understand the mechanisms responsible for a decline in ALT with age, and to establish the optimal cut-point of normal ALT in the elderly.

Interleukin-6 (IL-6) may have a protective role in acute liver disease but a detrimental effect in chronic liver disease. It is unknown whether IL-6 is associated with risk of liver-related mortality in humans. To determine if IL-6 is associated with an increased risk of all-cause, cardiovascular disease (CVD), cancer, and liver-related mortality. A prospective cohort study included 1843 participants who attended a research visit in 1984-87. Multiple covariates were ascertained including serum IL-6. Multivariable-adjusted Cox proportional hazards regression analyses were used to examine the association between serum IL-6 as a continuous (log transformed) variable with all-cause, CVD, cancer, and liver-related mortality. Patients with prevalent CVD, cancer and liver disease were excluded for cause-specific mortality. The mean (± standard deviation) age and body-mass-index (BMI) of participants was 68 (± 10.6) years and 25 (± 3.7) Kg/m(2), respectively. During the 25,802 person-years of follow-up, the cumulative all-cause, CVD, cancer, and liver-related mortality were 53.1% (N = 978), 25.5%, 11.3%, and 1.3%, respectively. The median (± IQR) length of follow-up was 15.3 ± 10.6 years. In multivariable analyses, adjusted for age, sex, alcohol, BMI, diabetes, hypertension, total cholesterol, HDL, and smoking, one-SD increment in log-transformed serum IL-6 was associated with increased risk of all-cause, CVD, cancer, and liver-related mortality, with hazard ratios of 1.48 (95% CI, 1.33-1.64), 1.38 (95% CI, 1.16-1.65), 1.35 (95% CI, 1.02-1.79), and 1.88 (95% CI, 0.97-3.67), respectively. CRP adjustment attenuated the effects but the association between IL-6 and all-cause and CVD mortality remained statistically significant, independent of CRP levels. In community-dwelling older adults, serum IL-6 is associated with all-cause, CVD, cancer, and liver-related mortality.

The effect of dietary cholesterol on cognitive function is debatable. While eggs contain high levels of dietary cholesterol, they provide nutrients beneficial for cognitive function. This study examined the effects of egg consumption on change in cognitive function among 890 ambulatory adults (N = 357 men; N = 533 women) aged ≥55 years from the Rancho Bernardo Study who attended clinic visits in 1988–1991 and 1992–1996. Egg intake was obtained in 1988–1991 with a food frequency questionnaire. The Mini-Mental Status Exam (MMSE), Trails B, and category fluency were administered at both visits to assess cognitive performance. Sex-specific multiple regression analyses tested associations of egg intake with changes in cognitive function after adjustment for confounders. The mean time between visits was 4.1 ± 0.5 years; average ages were 70.1 ± 8.4 in men and 71.5 ± 8.8 in women (p = 0.0163). More men consumed eggs at higher levels than women; while 14% of men and 16.5% of women reported never eating eggs, 7.0% of men and 3.8% of women reported intakes ≥5/week (p = 0.0013). In women, after adjustment for covariates, egg consumption was associated with less decline in category fluency (beta = −0.10, p = 0.0241). Other associations were nonsignificant in women, and no associations were found in men. Results suggest that egg consumption has a small beneficial effect on semantic memory in women. The lack of decline observed in both sexes suggests that egg consumption does not have detrimental effects and may even have a role in the maintenance of cognitive function.

Background/Objectives: Eggs are an excellent nutritional source. However, historical associations of dietary cholesterol with serum cholesterol and cardiovascular disease, along with restrictive dietary guidelines may have been barriers to egg consumption. This study examines trends over time, patterns, and predictors of egg consumption in individuals followed for 48 years, and current barriers to usage. Methods: Participants were 6326 men and women enrolled in the Rancho Bernardo Study in 1972–1974 when asked about the number of eggs consumed/week. Subsequent egg intake was collected with food frequency questionnaires during clinic visits in 1988–1991 (n = 1627) and 1992–1996 (n = 1385), and with the original question on a 2021 mailed survey (n = 710), when barriers to intake were also queried. Results: The mean (±SD) number of eggs consumed was 3.6 ± 3.0 in 1972–1974, 1.8 ± 2.1 in 1988–1991, 1.8 ± 2.2 in 1992–1996, and 3.4 ± 3.5 in 2021. Comparisons within 5-year categories of enrollment age (<20, 20–24, 25–29, 30–34, 35–39, >40) showed no differences in egg intake between 1972 and 1974, and when older in 2021. Men consumed more eggs than women at all timepoints (p’s < 0.0001). High cholesterol and taking cholesterol-lowering medication were associated with lower egg consumption in 1972–1974 (p’s < 0.0001), but were not associated in 2021. Over 22% reported limiting egg intake in 2021; the majority cited cholesterol content of eggs or having high cholesterol as barriers. Conclusions: Egg consumption was responsive to dietary guidelines, decreasing over time then increasing by 2021 to levels similar to those of the early 1970s. Despite the abandonment of these guidelines, they continue to have a negative impact for a segment of society, suggesting the need for additional education on the health benefits of eggs.

This study examines the prospective association of egg consumption with multiple domains of cognitive function in older, community-dwelling men and women followed for 16.3 years. Participants were 617 men and 898 women from the Rancho Bernardo Cohort aged 60 and older, who were surveyed about egg intake/week in 1972–1974, and attended a 1988–1991 research visit, where cognitive function was assessed with 12 tests. Analyses showed that egg intake ranged from 0–24/week (means: men = 4.2 ± 3.2; women = 3.5 ± 2.7; p < 0.0001). In men, covariate-adjusted regressions showed that egg intake was associated with better performance on Buschke total (p = 0.04), long-term (p = 0.02), and short-term (p = 0.05) recall. No significant associations were observed in women (p’s > 0.05). Analyses showed that in those aged <60y in 1972–1974, egg intake was positively associated with scores on Heaton copying (p < 0.04) and the Mini-Mental Status Exam (MMSE; p < 0.02) in men and category fluency (p < 0.05) in women. Egg intake was not significantly associated with odds of poor performance on MMSE, Trails B, or category fluency in either sex. These reassuring findings suggest that there are no long-term detrimental effects of egg consumption on multiple cognitive function domains, and for men, there may be beneficial effects for verbal episodic memory. Egg consumption in middle age may also be related to better cognitive performance later in life.

Background. Ectopic fat deposition in the pancreas and its relationship with hepatic steatosis and insulin resistance have not been compared between patients with nonalcoholic fatty liver disease (NAFLD) and healthy controls. Aim. Using a novel magnetic resonance imaging (MRI) based biomarker, the proton-density-fat-fraction (MRI-PDFF), we compared pancreatic fat content in patients with biopsy-proven NAFLD to healthy controls and determined whether it is associated with insulin resistance and liver fat content. Methods. This nested case-control study was derived from two prospective studies including 43 patients with biopsy-proven NAFLD and 49 healthy controls who underwent biochemical testing and MRI. Results. Compared to healthy controls, patients with NAFLD had significantly higher pancreatic MRI-PDFF (3.6% versus 8.5%, P value <0.001), and these results remained consistent in multivariable-adjusted models including age, sex, body mass index, and diabetes (P value =0.03). We found a strong correlation between hepatic and pancreatic MRI-PDFF (Spearman correlation, P = 0.57, P value <0.001). Participants with increased insulin resistance determined by homeostatic-model-of-insulin-resistance (HOMA-IR) greater than 2.5 had higher pancreatic (7.3% versus 4.5%, P value =0.015) and liver (13.5% versus 4.0%, P value <0.001) MRI-PDFF. Conclusion. Patients with NAFLD have greater pancreatic fat than normal controls. Insulin resistance is associated with liver and pancreatic fat accumulation.

The presence of cirrhosis in nonalcoholic-fatty-liver-disease (NAFLD) is the most important predictor of liver-related mortality. Limited data exist concerning the diagnostic accuracy of gut-microbiome-derived signatures for detecting NAFLD-cirrhosis. Here we report 16S gut-microbiome compositions of 203 uniquely well-characterized participants from a prospective twin and family cohort, including 98 probands encompassing the entire spectrum of NAFLD and 105 of their first-degree relatives, assessed by advanced magnetic-resonance-imaging. We show strong familial correlation of gut-microbiome profiles, driven by shared housing. We report a panel of 30 features, including 27 bacterial features with discriminatory ability to detect NAFLD-cirrhosis using a Random Forest classifier model. In a derivation cohort of probands, the model has a robust diagnostic accuracy (AUROC of 0.92) for detecting NAFLD-cirrhosis, confirmed in a validation cohort of relatives of proband with NAFLD-cirrhosis (AUROC of 0.87). This study provides evidence for a fecal-microbiome-derived signature to detect NAFLD-cirrhosis.

Abstract Eggs are an excellent nutritional source. However, the historical association of dietary cholesterol with serum cholesterol and thus, cardiovascular disease, along with restrictive dietary guidelines may have served as a barrier to egg consumption. This study examines trends over time, and predictors and patterns of egg consumption in older individuals followed for over 45 years. Participants were 6326 men and women enrolled in the Rancho Bernardo Study in 1972-74 when they were asked about the number of eggs consumed/week. Subsequent egg intake information was collected with food frequency questionnaires from subsamples attending clinic visits in 1988-91 (N=1627) and 1992-96 (N=1385), and with the original question on a 2021 mailed survey (N=710). Mean(□SD) eggs consumed was 3.6□3.0 in 1972-74, 1.8□2.1 in 1988-91, 1.8□2.2 in 1992-96, and 3.4□3.5 in 2021. Comparisons within 5-year categories of baseline age (< 20, 20-24, 25-29, 30-34, 35-39, >40) showed no differences in egg intake between 1972-74 and when older in 2021. Men consumed more eggs than women at all timepoints (p’s< 0.0001). Those with higher education (p< 0.0001) and diabetes (p=0.0009) consumed more eggs; those with high cholesterol or taking cholesterol lowering medication consumed fewer eggs in 1972-74 (p’s< 0.0001), but there were no differences by these factors by 2021. Egg consumption appears responsive to dietary guidelines, decreasing over time then increasing by 2021 to levels similar to the early 1970s. Among those young and middle-aged at baseline, egg intake patterns were similar 45 years later, when older. Cholesterol and cholesterol-lowering medication use are no longer factors in egg intake.