Dataset Information

Baseline Tyrosine Level Is Associated with Dynamic Changes in FAST Score in NAFLD Patients under Lifestyle Modification.

ABSTRACT: Noninvasive risk stratification is a challenging issue in the management of patients with nonalcoholic fatty liver disease (NAFLD). This study aimed to identify multiomics-based predictors of NAFLD progression, as assessed by changes in serial FibroScan-aspartate aminotransferase (FAST) scores during lifestyle modification. A total of 266 patients with available metabolomics and genotyping data were included. The follow-up sub-cohort included patients with paired laboratory and transient elastography results (n = 160). The baseline median FAST score was 0.37. The PNPLA3 rs738409 genotype was significantly associated with a FAST score > 0.35. Circulating metabolomics significantly associated with a FAST score > 0.35 included SM C24:0 (odds ratio [OR] = 0.642; 95% confidence interval [CI], 0.463-0.891), PC ae C40:6 (OR = 0.477; 95% CI, 0.340-0.669), lysoPC a C18:2 (OR = 0.570; 95% CI, 0.417-0.779), and tyrosine (OR = 2.743; 95% CI, 1.875-4.014). A combination of these metabolites and PNPLA3 genotype yielded a c-index = 0.948 for predicting a FAST score > 0.35. In the follow-up sub-cohort (median follow-up = 23.7 months), 47/76 patients (61.8%) with a baseline FAST score > 0.35 had a follow-up FAST score ≤ 0.35. An improved FAST score at follow-up was significantly associated with age, serum alanine aminotransferase, and tyrosine. In conclusion, baseline risk stratification in NAFLD patients may be assisted using a multiomics-based model. Particularly, patients with increased tyrosine may benefit from an earlier switch to pharmacologic approaches.

SUBMITTER: Kim HY

PROVIDER: S-EPMC10058052 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature

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Baseline Tyrosine Level Is Associated with Dynamic Changes in FAST Score in NAFLD Patients under Lifestyle Modification.

Kim Hwi Young HY Kim Da Jung DJ Lee Hye Ah HA Cho Joo-Youn JY Kim Won W

Metabolites 20230317 3

Noninvasive risk stratification is a challenging issue in the management of patients with nonalcoholic fatty liver disease (NAFLD). This study aimed to identify multiomics-based predictors of NAFLD progression, as assessed by changes in serial FibroScan-aspartate aminotransferase (FAST) scores during lifestyle modification. A total of 266 patients with available metabolomics and genotyping data were included. The follow-up sub-cohort included patients with paired laboratory and transient elastog ...[more]

PMID: 36984884

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Project description:Background and aimsThe NASH Clinical Research Network histologic scoring system, the gold-standard NASH histology assessment for clinical trials, has demonstrated intrarater and interrater variability. An expert panel in a previous systematic Research and Development/University of California Los Angeles (RAND/UCLA) study determined that existing histologic scoring systems do not fully capture NASH disease activity and fibrosis, and standardized definitions of histologic features are needed. We evaluated the reliability of existing and alternate histologic measures and their correlations with a disease activity visual analog scale to propose optimal components for an expanded NAFLD activity score (NAS).Approach and resultsFour liver pathologists who were involved in the prior RAND/UCLA study underwent standardized training and multiple discussions with the goal of improving agreement. They were blinded to clinical information and scored histologic measures twice, ≥2 weeks apart, for 40 liver biopsies representing the full spectrum of NAFLD. Index intraclass correlation coefficient (ICC) estimates demonstrated intrarater (0.80-0.85) and interrater (0.60-0.72) reliability. Hepatocyte ballooning items had similar interrater ICCs (0.68-0.79), including those extending scores from 0-2 to 0-4. Steatosis measures (interrater ICCs, 0.72-0.80) correlated poorly with disease activity. Correlations with disease activity were largest for hepatocyte ballooning and Mallory-Denk bodies (MDBs), with both used to develop the expanded NAS (intrarater ICC, 0.90; interrater ICC, 0.80). Fibrosis measures had ICCs of 0.70-0.87.ConclusionsAfter extensive preparation among a group of experienced pathologists, we demonstrated improved reliability of multiple existing histologic NAFLD indices and fibrosis staging systems. Hepatocyte ballooning and MDBs most strongly correlated with disease activity and were used for the expanded NAS. Further validation including evaluation of responsiveness is required.

Project description:Observational studies have shown that non-alcoholic fatty liver disease (NAFLD) is strongly associated with metabolic dysfunction. However, there is a paucity of research on whether changes in indicators of serum metabolism contribute to the development of NAFLD. This study was conducted with 4084 participants who underwent healthy physical examinations at Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China, in 2022 and 2023. Baseline and follow-up measurements, including anthropometric data, abdominal ultrasound and blood samples were collected. The diagnosis of NAFLD was based on the 2010 Chinese Guidelines on Diagnosis and Treatment of NAFLD. Multiple logistic regression was utilized to analyze the odds ratios (ORs) for the 1-year risk of NAFLD in connection with both baseline metabolic indicators and changes in metabolic indicators observed over the course of 1 year. A total of 3425 study participants who were free of NAFLD at baseline, including 1146 men and 2279 women, were included in the final analysis. The mean age was 34.43 ± 7.20 years. Participants who developed NAFLD were older, male and had higher levels of body mass index (BMI), blood pressure, fasting blood glucose (FBG), triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), free triiodothyronine (fT3), uric acid (UA), alanine aminotransferase (ALT) and aspartate aminotransferase (AST); and lower levels of high-density lipoprotein cholesterol (HDL-C) and free thyroxine (fT4) (all P values < 0.05). The multivariable model showed that baseline BMI, diastolic blood pressure (DBP), TG, TC, HDL-C, LDL-C, UA, fT4, fT3, ALT and changes in TG, HDL-C, and UA were associated with the 1-year risk of developing NAFLD. The risk of NAFLD increased by 56% [OR 1.56, 95% Confidence Interval (CI) 1.32-1.87] and 40% (OR 1.40, 95% CI 1.19-1.64) for each standard deviation (SD) increase in altered TG values (1.01 mmol/L) and altered UA values (55 µmol/L) respectively. Conversely, for each SD (0.27 mmol/L) increase in HDL-C change, the 1-year risk of incident NAFLD was reduced by 50% (OR 0.50, 95% CI 0.40-0.62). The present study suggested that increases in TG and UA, and decreases in HDL-C, significantly increase the risk of developing NAFLD. Therefore, more attention should be paid to these factors in the management and prevention of NAFLD.

Dataset Information

Baseline Tyrosine Level Is Associated with Dynamic Changes in FAST Score in NAFLD Patients under Lifestyle Modification.

Publications

Baseline Tyrosine Level Is Associated with Dynamic Changes in FAST Score in NAFLD Patients under Lifestyle Modification.

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