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BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver disease and cirrhosis. NAFLD is mediated by changes in lipid metabolism and known risk factors include obesity, metabolic syndrome, and diabetes. The aim of this study was to better understand differences in the lipid composition of individuals with NAFLD compared to controls, by performing direct infusion lipidomics on serum biospecimens from a cohort study of adults in Mexico. METHODS: A nested case-control study was conducted with a sample of 98 NAFLD cases and 100 healthy controls who are participating in an on-going, longitudinal study in Mexico. NAFLD cases were clinically confirmed using elevated liver enzyme tests and liver ultrasound or liver ultrasound elastography, after excluding alcohol abuse, and 100 controls were identified as having at least two consecutive normal alanine aminotransferase (ALT) and aspartate aminotransferase (AST) (< 40 U/L) results in a 6-month period, and a normal liver ultrasound elastography result in January 2018. Samples were analyzed on the Sciex Lipidyzer Platform and quantified with normalization to serum volume. As many as 1100 lipid species can be identified using the Lipidyzer targeted multiple-reaction monitoring list. The association between serum lipids and NAFLD was investigated using analysis of covariance, random forest analysis, and by generating receiver operator characteristic (ROC) curves. RESULTS: NAFLD cases had differences in total amounts of serum cholesterol esters, lysophosphatidylcholines, sphingomyelins, and triacylglycerols (TAGs), however, other lipid subclasses were similar to controls. Analysis of individual TAG species revealed increased incorporation of saturated fatty acyl tails in serum of NAFLD cases. After adjusting for age, sex, body mass index, and PNPLA3 genotype, a combined panel of ten lipids predicted case or control status better than an area under the ROC curve of 0.83. CONCLUSIONS: These preliminary results indicate that the serum lipidome differs in patients with NAFLD, compared to healthy controls, and suggest that assessing the desaturation state of TAGs or a specific lipid panel may be useful clinical tools for the diagnosis of NAFLD.

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Alcoholic hepatitis (AH) is a condition of acute liver inflammation in the setting of heavy alcohol use that is often managed with corticosteroids in severe cases. Among non-responders to steroids, however, prognosis is poor with up to 75% mortality within 6 months after treatment failure. Early liver transplantation (LT) can achieve an acceptable short-term survival, and initial studies have demonstrated 3-year survival rates of up to 84%. However, the practice of early LT in severe AH remains controversial with concerns over the 6-month rule of sobriety and risk of alcohol relapse post-transplant. Proponents of LT advocate for better understanding of alcohol use as a disorder rather than self-inflicted cause of illness, aim to redefine the misguided application of the 6-month rule, and point out similar relapse rates among patients with early LT and those with greater than 6 months abstinence before transplant. Opponents of LT emphasize the correlation between alcohol relapse and graft failure and mortality, public resistance and potential for distrust among donors, and arguments that transplant centers need to establish improved models to predict relapse and standardize candidate selection criteria across centers. Here we review recent literature on this controversy and provide recommendations for moving forward to consensus.

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BACKGROUND AND RATIONALE: The post-Liver Transplant Quality of Life (pLTQ) questionnaire, developed in the United States, is a disease-targeted instrument designed to evaluate health-related quality of life (HRQoL) in liver transplant recipients. Our study sought to validate a version of the pLTQ for use in the Brazilian population. Translation and cross-cultural adaptation were carried out in accordance with international standard practices for questionnaire validation. Validity was measured by means of convergent validity (correlations between pLTQ domains and WHOQOL-Bref domains). Reliability was assessed by measurement of internal consistency (Cronbach's alpha coefficient), reproducibility (intraclass correlation coefficient), sensitivity to change (effect size), and floor and ceiling effects. RESULTS: The study sample comprised 160 liver transplant recipients, with a mean age of 56.9 ± 10.4 years, treated at a tertiary hospital in Southern Brazil. The sample was largely male (62.5%), and the predominant indication for liver transplant was hepatocellular carcinoma (49.4%). Only two questionnaire items were modified during the translation and cross-cultural validation stage. The mean total pLTQ score was 5.58 ± 0.9, with < 20% floor/ceiling effect. Correlations between pLTQ and WHOQOL-Bref domains were acceptable (r = 0.37-0.40). For similar dimensions, the correlations between WHOQOL-Bref and pLTQ were statistically significant (p ≤ 0.001). Cronbach's alpha for the total score was 0.91 (95% CI 0.89-0.93), with a range of 0.51 to 0.77 across domains. Reproducibility was 0.90, and sensitivity to change was 0.84. CONCLUSION: In conclusion, the Brazilian Portuguese versión of the pLTQ exhibited good psychometric performance, suggesting that it can be a useful tool in the Brazilian cultural context.

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