UNASSIGNED: Non-alcoholic fatty liver disease (NAFLD) is characterized by ectopic deposition of fat in the liver, in the absence of other secondary causes of fat buildup. The relationship between NAFLD, including alanine aminotransferase (ALT), and glycated haemoglobin (HbA1c), is important for predicting the severity of disease and prognosis. This study aims to investigate the association of HbA1c in type 2 diabetes mellitus (T2DM) patients with NAFLD via measuring the ALT levels.
UNASSIGNED: This retrospective cross-sectional study enroled 130 patients with T2DM and NAFLD. The association between levels of HbA1c and ALT in patients of NAFLD with controlled and uncontrolled T2DM, respectively, was investigated. Stratification was done based on gender and diabetic control, using HbA1c levels as a marker of glycemic control. Serum ALT levels were also compared in both groups.
UNASSIGNED: The mean age of the participants was 50.2±5.7 years. The total participants were 130, of which 77 (59.3%) were females and 53 (40.7%) were males. The numbers of patients having uncontrolled T2DM (HbA1c>7%), and controlled T2DM (HbA1c <7%) were 78 (60%) and 52 (40%), respectively. Moreover, 46 (35.3%) females and 32 (24.7%) males had uncontrolled T2DM, and 31 (23.8%) females and 21 (16.2%) males had controlled T2DM. The mean ALT level for uncontrolled and controlled T2DM in female patients was found to be 24.6±3.4 and 13.5±2.4, respectively, (P <0.05). For male patients, it was found to be 54.0±4.9 and 29.1±5.4, respectively (P=0.008).
UNASSIGNED: There is a positive association between elevated HbA1c and ALT levels in T2DM patients with NAFLD.

OBJECTIVE: Non-alcoholic fatty liver disease (NAFLD), now termed metabolic dysfunction-associated fatty liver disease (MAFLD), is a growing health concern associated with obesity and type 2 diabetes. Bariatric surgery offers potential benefits, but its impact on MAFLD remains incompletely understood, with scarce long-term follow-up prospective studies. Moreover, being liver biopsy the gold standard for liver condition measurement, the need for non-invasive techniques that allow the assessment of MAFLD development after bariatric surgery is imperative. OWLiver® Care and OWLiver® represent two serum lipidomic tests, featuring panels comprising 11 and 20 triglycerides, respectively.
METHODS: We conducted a prospective study involving 80 Caucasians to assess the effects of bariatric surgery on MAFLD using non-invasive diagnostics and to identify baseline predictors of MAFLD remission. Serum samples were collected before surgery and at a 3-year follow-up.
RESULTS: After 3 years, the proportion of patients exhibiting a healthy liver escalated from 5.0% at baseline to 26.3%. Conversely, the percentage of steatohepatitis declined from 35.1% to a mere 7.6%. Younger age, female gender, and the absence of type 2 diabetes were associated with MAFLD remission. However, age stood as the only independent variable associated with this favorable liver evolution (R2 = 0.112).
CONCLUSIONS: Bariatric surgery demonstrates mid-term benefits in improving MAFLD, with younger age as a baseline predictor of remission. Non-invasive diagnostic methods, like OWLiver®, are valuable tools for monitoring MAFLD evolution. Further research with larger populations and longer follow-up periods is warranted to refine personalized treatment approaches.

BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) has been traditionally associated with insulin resistance and obesity. Recently, pollutants have been shown to contribute to the development of MASLD. Given the global burden of MASLD, understanding whether pollutants are merely associated with steatosis or contribute to its progression to advanced chronic liver disease (ACLD) and hepatocellular carcinoma (HCC) is critical. Workers exposed to occupational toxicants represent an ideal population for assessing the potentially hazardous consequences of professional exposure. Confirming a link between occupational exposure and ACLD/HCC may not only provide further elements in understanding MASLD, but also contribute to preventive strategies for exposed workers.
OBJECTIVE: This study aimed to assess the prevalence of self-reported occupational exposure to toxicants in patients with MASLD.
METHODS: This hospital-based prospective pilot study included 201 patients with MASLD. Data on workplace toxicant exposure were collected systematically using a structured questionnaire. Subsequently, patients with ACLD and/or HCC (n = 55) were compared to controls (n = 146). Logistic regression analysis and propensity score models were used to investigate the associations between self-reported occupational exposure and ACLD and/or HCC.
RESULTS: Patients with ACLD/HCC reported exposure to metals, halogenated refrigerants, pain/resins, and fuel emissions more often than the controls. After controlling for confounders, durations of 21-30 years and >30 years of occupational exposure to toxicants showed odds ratios (ORs) of 2.31 (95 % confidence interval [CI]: 1.09-4.88, p = 0.029) and 4.47 (95 % CI: 2.57-7.78, p<0.001), respectively.
CONCLUSIONS: In this pilot study, patients with MASLD complications were more likely to report workplace toxicant exposure. Our results warrant future multicentre confirmatory studies, as implementing prevention policies may reduce the risk of life-threatening diseases among exposed populations.

Non-alcoholic fatty liver disease (NAFLD) is a very common liver disease associated with obesity, unhealthy diet, and lack of physical exercise. Short-term aerobic or resistance exercise has been shown to result in reduced liver fat in patients with NAFLD; however, the impact of the combination of these types of exercise has received less attention. This study investigated the effect of a short-term (7 days) concurrent exercise training program performed daily on liver steatosis indices, as well as the glycemic and lipidemic profile of overweight/obese sedentary volunteers. Twenty adult patients (age: 47.3 ± 12.3 yrs, body mass index: 32.4 ± 3.4 kg/m2) with NAFLD, detected by ultrasound and hematological indices, participated in the study. Pre- and post-exercise intervention assessment included body weight (BW), waist circumference (WC), hip/waist ratio (H/W), Homeostasis Model Assessment Insulin Resistance (HOMA-IR), blood lipids, and steatosis indices. Fatty Liver Index, Lipid Accumulation Index, WC, H/W, triglycerides, and total cholesterol were improved (p < 0.05) post-exercise, while no differences (p > 0.05) were observed in BW, HOMA-IR, HDL, LDL, Hepatic Steatosis Index, and Framingham Steatosis Index compared to pre-exercise values. It is concluded that a 7-day combined exercise program can have beneficial effects on hepatic steatosis and central adiposity indices, independently of weight loss, in patients with NAFLD.

It is unclear whether health-related quality of life (HRQoL) is impaired in patients with nonalcoholic fatty liver disease (NAFLD) without advanced fibrosis and how this compares with the general population. We aimed to assess HRQoL in patients with NAFLD in comparison to the general population and any associations of fibrosis severity and metabolic comorbidities with impairments in HRQoL.
We prospectively enrolled 513 consecutive patients with NAFLD who completed the EuroQol 5-dimensional questionnaire (EQ-5D) and Chronic Liver Disease Questionnaires (CLDQ). Demographic and clinical information, liver biopsy results, and/or liver stiffness (LS) by transient elastography were recorded. A general population sub-cohort of the Health Survey for England 2018 was used as a comparator (n = 5483), and a 1:1 propensity-score (PS) matching was performed, according to age, sex, body mass index, and type 2 diabetes mellitus (T2DM).
EQ-5D-5L utility was significantly lower in 466 PS-matched patients with NAFLD compared with PS-matched controls (0.77 ± 0.27 vs 0.84 ± 0.19; P < .001), even in those without advanced fibrosis (F ≤2 or LS <8kPa) (0.80 ± 0.24 vs 0.84 ± 0.19; P = .024). HRQoL measures (EQ-5D-5L, EQ-VAS, CLDQ) did not differ between patients with NAFLD with and without advanced fibrosis. LS was independently associated with lower EQ-5D-5L in all patients with NAFLD but not in those without advanced fibrosis. In the latter, lower EQ-5D-5L was associated with female sex, T2DM, and depression.
Patients with NAFLD, even those without advanced fibrosis, have worse HRQoL compared with the general population. In patients with NAFLD without advanced fibrosis, HRQoL is independently associated with non-liver comorbidities but not LS. Multi-disciplinary management is therefore required in NAFLD, irrespective of fibrosis severity.

More data are needed regarding the long-term impact of the histological progression of non-alcoholic fatty liver disease (NAFLD) on long-term outcomes, including end-stage liver disease (ESLD) and mortality.
We included Swedish adults with biopsy-confirmed non-cirrhotic NAFLD and ≥2 liver biopsies >6 months apart (1969-2017; n = 718). NAFLD was categorized at initial biopsy as simple steatosis, non-fibrotic steatohepatitis (NASH), or non-cirrhotic fibrosis. NAFLD progression was defined by histological changes between biopsies (i.e. incident NASH, incident fibrosis, fibrosis progression, cirrhosis). Using Cox regression, we estimated multivariable adjusted hazard ratios (aHRs) and 95% CIs for incident ESLD (i.e. hospitalization for decompensated cirrhosis, hepatocellular carcinoma or liver transplantation) and mortality, according to NAFLD progression vs. stable/regressed disease.
At initial biopsy, 497 patients (69.2%) had simple steatosis, 90 (12.5%) had non-fibrotic NASH, and 131 (18.2%) had non-cirrhotic fibrosis. Over a median of 3.4 years between biopsies, 30.4% (218/718) experienced NAFLD progression, including 12.5% (62/497) with incident non-fibrotic NASH, 24.0% (141/587) with incident fibrosis, and 5.6% (40/718) with cirrhosis. Compared to stable/regressed disease, NAFLD progression was associated with significantly higher rates of developing incident ESLD (23.8 vs. 11.4/1,000 person-years [PY]; difference = 12.4/1,000 PY; aHR 1.65, 95% CI 1.17-2.32). While the highest ESLD incidence occurred with progression to cirrhosis (difference vs. stable/regressed disease = 56.3/1,000 PY), significant excess risk was also found with earlier transitions, including from simple steatosis to incident fibrosis (difference vs. stable/regressed disease = 18.9/1,000 PY). In contrast, all-cause mortality rates did not appear to differ when NAFLD progression was compared to stable/regressed disease (difference = 4.7/1,000 PY; aHR 0.99, 95% CI 0.78-1.24).
In a nationwide, real-world cohort of patients with paired NAFLD biopsies, histological disease progression contributed to significantly higher rates of developing incident ESLD, but did not appear to impact all-cause mortality.
Currently, data are scarce regarding the long-term impact of histological progression or regression of non-alcoholic fatty liver disease (NAFLD) on subsequent risk of adverse clinical outcomes, including the development of end-stage liver disease and mortality. This is particularly important because randomized-controlled trials of NAFLD therapeutics currently focus on short-term histological endpoints as presumed surrogates for those major clinical outcomes. Thus, the results from this study can help inform the optimal design of future NAFLD therapeutic trials, while also providing the necessary evidence base for public health policies focused on preventing the development and progression of NAFLD.

BACKGROUND: The effect of vitamin D status on steatosis has not been fully elucidated. In this study, we planned to investigate this interaction using a large-scale population-based cohort.
METHODS: Patients diagnosed with simple steatosis (K76.0) and non-alcoholic steatohepatitis (NASH) (K75.8) by using the International Classification of Diseases 10th Revision (ICD-10) coding system, and who had 25-hydroxyvitamin D (25OHD) measurements at the diagnosis, were included in the study. Control group comprised subjects without liver diseases. Age, gender, alanine aminotransferase (ALT) and 25OHD levels, and the date of the measurements were recorded.
RESULTS: We compared ALT and 25OHD measurements between the patient and control groups, and between the simple steatosis and NASH subgroups. 25OHD levels were lower and ALT levels were higher in the patient group (p < 0.001, effect size = 0.028, and p < 0.001, effect size = 0.442, respectively). Logistic regression analysis showed that when 25OHD levels decrease by 1 ng/dL, it increases the risk of being in the patient group by 3.7%.
CONCLUSIONS: Our results suggest that vitamin D status may be related to the development of non-alcoholic fatty liver disease (NAFLD). Although this relationship is weak, it may be important in the pathogenesis of steatosis.

OBJECTIVE: To provide evidence-based recommendations regarding the diagnosis and management of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) to endocrinologists, primary care clinicians, health care professionals, and other stakeholders.
METHODS: The American Association of Clinical Endocrinology conducted literature searches for relevant articles published from January 1, 2010, to November 15, 2021. A task force of medical experts developed evidence-based guideline recommendations based on a review of clinical evidence, expertise, and informal consensus, according to established American Association of Clinical Endocrinology protocol for guideline development.
UNASSIGNED: This guideline includes 34 evidence-based clinical practice recommendations for the diagnosis and management of persons with NAFLD and/or NASH and contains 385 citations that inform the evidence base.
CONCLUSIONS: NAFLD is a major public health problem that will only worsen in the future, as it is closely linked to the epidemics of obesity and type 2 diabetes mellitus. Given this link, endocrinologists and primary care physicians are in an ideal position to identify persons at risk on to prevent the development of cirrhosis and comorbidities. While no U.S. Food and Drug Administration-approved medications to treat NAFLD are currently available, management can include lifestyle changes that promote an energy deficit leading to weight loss; consideration of weight loss medications, particularly glucagon-like peptide-1 receptor agonists; and bariatric surgery, for persons who have obesity, as well as some diabetes medications, such as pioglitazone and glucagon-like peptide-1 receptor agonists, for those with type 2 diabetes mellitus and NASH. Management should also promote cardiometabolic health and reduce the increased cardiovascular risk associated with this complex disease.

This is a meeting report of the 3rd Translational Hepatology Meeting held in Alicante, Spain, in October 2021. The meeting, which was organized by the Spanish Association for the Study of the Liver (AEEH), provided an update on the recent advances in the field of basic and translational hepatology, with a particular focus on the molecular and cellular mechanisms and therapeutic targets involved in metabolic-associated fatty liver disease (MAFLD), metabolic-associated steatohepatitis (MASH), cirrhosis and end-stage hepatocellular carcinoma (HCC).

Nonalcoholic fatty liver disease (NAFLD) is one of the major seeds of liver cirrhosis and hepatocellular carcinoma. There is no convenient reliable non-invasive early diagnostic tool available for NAFLD/NASH diagnosis and stratification. Recently, the role of cytosolic sensor, stimulator of interferon genes (STING) signaling pathway in pathogenesis of nonalcoholic steatohepatitis (NASH) has been evidenced in research. We have selected EDN1/TNF/MAPK3/EP300/hsa-miR-6888-5p/lncRNA RABGAP1L-DT-206 RNA panel from bioinformatics microarrays databases related to STING pathway and NAFLD/NASH pathogenesis. We have used reverse-transcriptase real-time polymerase chain reaction to assess the expression of the serum RNAs panel in NAFLD/NASH without suspicion of advanced fibrosis, NAFLD/with NASH patients with suspicion of advanced fibrosis and controls. Additionally, we have assessed the diagnostic performance of the Ribonucleic acid (RNA) panel. We have detected upregulation of the EDN1 regulating RNAs panel expression in NAFLD/NASH cases compared to healthy controls. We concluded that this circulatory RNA panel could enable us to discriminate NAFLD/NASH cases from controls, and also NAFLD/NASH cases (F1, F2) from advanced fibrosis stages (F3, F4).