Serum Metabolites Are Associated With HFpEF in Biopsy-Proven Nonalcoholic Fatty Liver Disease.

Background Nonalcoholic fatty liver disease (NAFLD) and heart failure with preserved ejection fraction (HFpEF) share common risk factors, including obesity and diabetes. They are also thought to be mechanistically linked. The aim of this study was to define serum metabolites associated with HFpEF in a cohort of patients with biopsy-proven NAFLD to identify common mechanisms. Methods and Results We performed a retrospective, single-center study of 89 adult patients with biopsy-proven NAFLD who had transthoracic echocardiography performed for any indication. Metabolomic analysis was performed on serum using ultrahigh performance liquid and gas chromatography/tandem mass spectrometry. HFpEF was defined as ejection fraction >50% plus at least 1 echocardiographic feature of HFpEF (diastolic dysfunction, abnormal left atrial size) and at least 1 heart failure sign or symptom. We performed generalized linear models to evaluate associations between individual metabolites, NAFLD, and HFpEF. Thirty-seven out of 89 (41.6%) patients met criteria for HFpEF. A total of 1151 metabolites were detected; 656 were analyzed after exclusion of unnamed metabolites and those with >30% missing values. Fifty-three metabolites were associated with the presence of HFpEF with unadjusted P value <0.05; none met statistical significance after adjustment for multiple comparisons. The majority (39/53, 73.6%) were lipid metabolites, and levels were generally increased. Two cysteine metabolites (cysteine s-sulfate and s-methylcysteine) were present at significantly lower levels in patients with HFpEF. Conclusions We identified serum metabolites associated with HFpEF in patients with biopsy-proven NAFLD, with increased levels of multiple lipid metabolites. Lipid metabolism could be an important pathway linking HFpEF to NAFLD.

Rate of and Factors Associated with Palliative Care Referral among Patients Declined for Liver Transplantation.

Background: End-stage liver disease (ESLD) is associated with high morbidity and mortality, with liver transplantation as the only existing cure. Despite reduced quality of life and limited life expectancy, referral to palliative care (PC) rarely occurs. Moreover, there is scarcity of data on the appropriate timing and type of PC intervention needed. Aim: To evaluate PC utilization and documentation in ESLD patients declined or delisted for transplant at a tertiary care medical center with a large liver transplantation program. Methods: We performed a retrospective cohort study of all patients discussed in Liver Transplant Committee (LTC) at our academic medical center between August 2018 and May 2020 in the United States. Patients declined or delisted for liver transplantation were included. Baseline demographics, model for end-stage liver disease (MELD) score, decompensation events, and reason for transplant ineligibility were recorded. The primary outcome was PC referral. Secondary outcomes included survival from LTC decision, time from LTC decision to PC referral, and code status in relation to PC referral. Results: Of 769 patients discussed at LTC, 135 were declined for transplantation. Thirty-seven (27%) received referral to PC. When adjusting for body mass index and age, MELD score of 21-30 had odds ratio (OR) of 4.5 (95% confidence interval [CI]: 1.7-12.3) and MELD score >30 had OR of 12.8 (95% CI: 3.9-47.7) for PC referral when compared with MELD score <20. When adjusting for MELD score, presence of ascites had OR of 4.6 (95% CI: 1.1-19.1) and presence of multiple complications had OR of 2.2 (95% CI: 2.2-3.8). Conclusions: Only 37 (27%) patients delisted or declined for liver transplantation were referred to PC. MELD score and degree of decompensation were important factors associated with referral. Continued exploration of these data could help guide future studies and help determine timing and criteria for PC referral.

Association of Health Literacy and Numeracy With Lupus Knowledge and the Creation of the Lupus Knowledge Assessment Test.

OBJECTIVE: Limited health literacy and numeracy are associated with worse patient-reported outcomes and higher disease activity in systemic lupus erythematosus (SLE), but which factors may mediate this association is unknown. We sought to determine the association of health literacy and numeracy with SLE knowledge. METHODS: Patients with SLE were recruited from an academic center clinic. Participants completed validated assessments of health literacy (Newest Vital Sign [NVS]; n = 96) and numeracy (Numeracy Understanding in Medicine Instrument, Short Version [S-NUMI]; n = 85). They also completed the Lupus Knowledge Assessment Test (LKAT), which consists of 4 questions assessing SLE knowledge that were determined through consensus expert opinion for their wide applicability and importance related to self-management of the disease. Descriptive statistics and multivariable logistic regression modeling were used to analyze the results. RESULTS: In our SLE cohort (n = 125), 33% (32/96) had limited health literacy and 76% (65/85) had limited numeracy. The majority correctly identified that hydroxychloroquine prevented SLE flares (91%); however, only 23% of participants correctly answered a numeracy question assessing which urine protein to creatinine (UPC) ratio was > 1000 mg/g. The mean LKAT score was 2.7 out of 4.0. Limited health literacy, but not numeracy, was associated with lower knowledge about SLE as measured by the LKAT, even after adjusting for education. CONCLUSION: Patients with SLE with limited health literacy had lower knowledge about SLE. The LKAT could be further refined and/or used as a screening tool to identify patients with knowledge gaps. Further work is needed to improve patients' understanding of proteinuria and investigate whether literacy-sensitive education can improve care.

Serum Bile Acid, Vitamin E, and Serotonin Metabolites Are Associated With Future Liver-Related Events in Nonalcoholic Fatty Liver Disease.

Identifying patients at higher risk for poor outcomes from nonalcoholic fatty liver disease (NAFLD) remains challenging. Metabolomics, the comprehensive measurement of small molecules in biological samples, has the potential to reveal novel noninvasive biomarkers. The aim of this study was to determine if serum metabolite profiles in patients with NAFLD associate with future liver-related events. We performed a retrospective single-center cohort study of 187 participants with biopsy-proven NAFLD. Metabolomic analysis was performed on serum using ultrahigh performance liquid chromatography/tandem mass spectrometry and gas chromatography/mass spectrometry. We identified liver-related events (variceal bleeding, ascites, spontaneous bacterial peritonitis, hepatic encephalopathy, hepatocellular carcinoma, hepatopulmonary or hepatorenal syndrome) by manual chart review between index biopsy (2007-2013) and April 1, 2018. Generalized linear models and Cox proportional hazards models were used to test the association of metabolites with liver-related events and time to first liver-related event, controlling for covariates and fibrosis stage. Over a mean ± SD follow-up of 6.9 ± 3.2 years, 11 participants experienced 22 liver-related events. Generalized linear models revealed 53 metabolites significantly associated with liver-related events (P < 0.05). In Cox proportional hazards modeling, 69 metabolites were significantly associated with time to future liver-related events (P < 0.05), seven of which met the false discovery rate threshold of 0.10: vitamin E metabolites gamma-carboxyethyl-hydroxychroman (gamma-CEHC) and gamma-CEHC glucuronide; primary bile acid metabolite taurochenodeoxycholate; serotonin metabolite 5-hydroxyindoleacetate; and lipid metabolites (i) 2-hydroxyglutarate, (ii) 3beta,17beta-diol disulfate 1, and (iii) eicosenoyl sphingomyelin. Conclusion: Metabolites of a primary bile acid, vitamin E, and serotonin were associated with future liver-related events. Our results suggest metabolite pathways may be useful for predicting which patients with NAFLD are at higher risk for hepatic decompensation.

The association between anti-Müllerian hormone and vitamin 25(OH)D serum levels and polycystic ovarian syndrome in adolescent females.

BACKGROUND: High anti-Müllerian hormone (AMH) levels and 25-hydroxyvitamin D [25(OH)D] deficiency have been associated with polycystic ovarian syndrome (PCOS) in adult women, and implicated in its pathogenesis. Herein we determined if the level of both AMH and 25(OH)D are altered in adolescent females with clinical features of PCOS. METHODS: This is a cross-sectional study utilizing a retrospective chart review of 128 patients aged 12-20 referred to an academic adolescent gynecology and endocrinology clinic for an evaluation of suspected PCOS. Unadjusted comparisons of AMH and 25(OH)D distributions between subjects with and without PCOS were performed using the Wilcoxon Rank Sum test. Quantile regression was used to compare the median AMH and 25(OH)D between subject groups; adjusting for race, ethnicity, BMI, insurance type, age, and season when bloodwork was performed. RESULTS: Seventy-four subjects were classified as having PCOS by meeting ≥2 of the three Rotterdam diagnostic criteria, and 47 subjects met only one Rotterdam diagnostic criteria, and were used as the comparative non-PCOS group. There were statistically significant unadjusted differences in median levels of AMH and 25(OH)D. In the adjusted analyses, median AMH was significantly higher in the PCOS group compared to the non-PCOS group (+ 2.39 ng/mL, 95% CI 0.43, 4.35, p = 0.018); 25(OH)D was significantly lower in the PCOS group (- 9.01 ng/mL, 95% CI -14.49, - 3.53 p = 0.001). In our sample, adolescents in both groups had insufficient 25(OH)D level (22 ng/mL) and elevated BMI (32.2 kg/m2). CONCLUSIONS: Adolescents with PCOS display high levels of AMH and low 25(OH)D levels. Since traditional clinical markers of PCOS may be physiologic in adolescents, AMH and 25(OH)D may be used as surrogate markers of PCOS risk in adolescents.