Clinical epidemiology of non-alcoholic fatty liver disease in children and adolescents. The LiverKids: Study protocol.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is rapidly increasing alongside overweight and obesity, not only in adults but also in children and adolescents. It is unknown what impact the development of NAFLD in childhood may have in later life. The importance of early detection and treatment lies in its potential for progression to cirrhosis, liver cancer and liver-related death, as well as its associated extrahepatic comorbidities. Vibration-Controlled Transient Elastography (VCTE) with Controlled Attenuation Parameter (CAP) is an effective, non-invasive and safe diagnostic method to estimate the degree of fibrosis and steatosis in the liver, but little is known about its applicability in the paediatric population. AIMS: 1) To assess the prevalence of significant liver fibrosis (Liver Stiffness Measurement (LSM) ≥6.5 kPa) using VCTE, and that of non-alcoholic fatty liver disease (≥225 dB/m) using CAP in children and adolescents. 2) To determine the optimal cut-off points of the CAP to achieve maximum concordance with the Magnetic Resonance Imaging (MRI) findings in the diagnosis of mild, moderate and severe NAFLD in children and adolescents. METHODS: Cross-sectional population-based study which will include 2,866 subjects aged between 9 and 16 years. Participants will undergo: anamnesis, physical examination, blood extraction, VCTE, MRI and questionnaires on socio-demographic data, personal and family medical history and lifestyle assessment. APPLICABILITY AND RELEVANCE: The study aims to establish the foundations for the use of VCTE in children and adolescents in order to achieve early diagnosis of NAFLD. Moreover, it will serve to understand in further detail the disease and to identify the risk groups of children and adolescents who may be at risk of developing it. Ultimately, this will help determine to which subgroups of the population we need to target resources for prevention and early detection of this entity, as well as possible intervention for its treatment. TRIAL REGISTRATION: The LiverKids study is registered on Clinicaltrials.gov (NCT05526274).

Abdominal obesity and dsyglycemia are risk factors for liver fibrosis progression in NAFLD subjects: A population-based study.

Objective: To investigate longitudinal changes in the liver stiffness measurement (LSM) in the general adult population without known liver disease and to describe its association with metabolic risk factors, with a special focus on subjects with non-alcoholic fatty liver disease (NAFLD) and dysglycemia. Material and Methods: A longitudinal adult population-based cohort study was conducted in Catalonia. LSM was measured by transient elastography (TE) at baseline and follow-up (median: 4.2 years). Subgroup with NAFLD and dysglycemia were analyzed. Moderate-to-advanced liver fibrosis was defined as LSM ≥8.0 kPa and LSM ≥9.2 kPa respectively. Results: Among 1.478 subjects evaluated, the cumulative incidence of LSM ≥8.0 kPa and ≥9.2 kPa at follow-up was 2.8% and 1.9%, respectively. This incidence was higher in NAFLD (7.1% for LSM ≥8.0 kPa and 5% for LSM ≥9.2 kPa) and dysglycemia (6.2% for LSM ≥8.0 kPa and 4.7% for LSM ≥9.2 kPa) subgroups. In the global cohort, the multivariate analyses showed that dysglycemia, abdominal obesity and atherogenic dyslipidemia were significantly associated with progression to moderate-to-advanced liver fibrosis. Female sex was negatively associated. In subjects with NAFLD, abdominal obesity and dysglycemia were associated with changes in LSM to ≥8.0 kPa and ≥9.2 kPa at follow-up. A decline in LSM value to <8 kPa was observed in 64% of those subjects with a baseline LSM ≥8.0 kPa. Conclusions: In this population study, the presence of abdominal obesity and dysglycemia were the main risk metabolic factors associated with moderate-to-advanced liver fibrosis development over time in general populations as well as in subjects with NAFLD.

TSH Levels as an Independent Risk Factor for NAFLD and Liver Fibrosis in the General Population.

Thyroid hormones may be a risk factor for the development of non-alcoholic fatty liver disease (NAFLD) and its progression to liver fibrosis. The aim of this study is to investigate the relationship between thyroid stimulating hormone (TSH) levels, NAFLD, and liver fibrosis in the general population. A descriptive cross-sectional study was performed in subjects aged 18-75 years randomly selected from primary care centers between 2012 and 2016. Each subject underwent clinical evaluation, physical examination, blood tests and transient elastography. Descriptive and multivariate logistic regression analyses were used to identify factors associated with NAFLD and fibrosis. We included 2452 subjects (54 ± 12 years; 61% female). Subjects with TSH ≥ 2.5 µIU/mL were significantly associated with obesity, atherogenic dyslipidemia, metabolic syndrome (MetS), hypertransaminasemia and altered cholesterol and triglycerides. The prevalence of NAFLD and liver fibrosis was significantly higher in subjects with TSH ≥ 2.5 (µIU/mL). We found a 1.5 times increased risk of NAFLD, 1.8 and 2.3 times increased risk of liver fibrosis for cut-off points of ≥8.0 kPa and ≥9.2 kPa, respectively, in subjects with TSH ≥ 2.5 µIU/mL compared with TSH < 2.5 µIU/mL (control group), independent of the presence of MetS. These findings remained significant when stratifying TSH, with values ≥ 10 µIU/mL.

Risk of Liver Fibrosis According to TSH Levels in Euthyroid Subjects.

Alterations in thyroid function may contribute to the development of liver fibrosis especially in subjects with non-alcoholic fatty liver disease. This study aimed to investigate the risk of liver fibrosis according to low-normal thyroid function in the general population. We performed a descriptive cross-sectional study in subjects from 18-75 years randomly selected from 16 primary health care centers from 2017-2019. Each subject underwent clinical evaluation, physical examination, blood analysis and transient hepatic elastography. Descriptive and multivariate logistic regression analyses were used to identify factors associated with fibrosis. We included 1096 subjects (60 ± 11 years; 61% women); 70% had strict-normal thyroid function and 30% had low-normal thyroid function. Low-normal thyroid function was associated with a higher liver stiffness (LS) values: 5.2 vs. 4.8 kPa (p = 0.001) and a greater prevalence of fibrosis: 6.1 vs. 3% (p = 0.016) and 4.3 vs. 2.1% (p = 0.044) for the cut-off points of ≥8.0 kPa and ≥9.2 kPa, respectively. After adjustment for potential confounding factors, the risk of fibrosis in subjects with low-normal thyroid function was OR 1.54 (p = 0.213). In conclusion, low-normal thyroid function is associated with higher LS values and a greater risk of liver fibrosis in the general population, being dependent on other metabolic factors.

Relationship between hypothyroidism and non-alcoholic fatty liver disease in the Spanish population. / Relación entre el hipotiroidismo y el hígado graso no alcohólico en una población española.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the most prevalent liver disease in developed countries and is considered the hepatic component of metabolic syndrome (MetS). Recently hypothyroidism has been associated with NAFLD but has never been studied in Spain. OBJECTIVES: To analyze the relationship between hypothyroidism (clinical and subclinical) and NAFLD. To determine the association between MetS with NAFLD and hypothyroidism. METHODS: Cross-sectional, retrospective, population study in subjects ≥45 years from primary care centres in Catalonia included in the SIDIAP database. The data was collected between 2009 and 2013. VARIABLES: socio-demographic data, comorbidities, toxic habits, physical examination, analytical tests and diagnosis of MetS. Descriptive analysis and application of statistical tests for the comparison of variables. RESULTS: Sample of 10,116 individuals with a mean age of 61(10) and a predominance of females (63.6%). The prevalence of hypothyroidism was 9.1%, with no significant differences according to the presence of NAFLD (p=.631). Hypothyroidism was associated with higher triglyceride levels and a greater prevalence of obesity (p=.003). Greater alteration of AST was detected in individuals with elevated TSH (p=.012) and decreased levels of T4L (p=.037). Alterations in thyroid hormone levels were not associated with a higher prevalence of NAFLD (TSH p=.072 and T4L p=.447). Hypothyroidism was not considered a risk factor for the development of NAFLD (OR .75; 95% CI: .39-1.44; p=.38). CONCLUSIONS: No association was found between hypothyroidism and NAFLD. Prospective studies are needed to clarify a possible relationship between these two diseases.