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).

Development, validation, and prognostic evaluation of a risk score for long-term liver-related outcomes in the general population: a multicohort study.

BACKGROUND: Liver cirrhosis is a major cause of death worldwide. Cirrhosis develops after a long asymptomatic period of fibrosis progression, with the diagnosis frequently occurring late, when major complications or cancer develop. Few reliable tools exist for timely identification of individuals at risk of cirrhosis to allow for early intervention. We aimed to develop a novel score to identify individuals at risk for future liver-related outcomes. METHODS: We derived the LiverRisk score from an international prospective cohort of individuals from six countries without known liver disease from the general population, who underwent liver fibrosis assessment by transient elastography. The score included age, sex, and six standard laboratory variables. We created four groups: minimal risk, low risk, medium risk, and high risk according to selected cutoff values of the LiverRisk score (6, 10, and 15). The model's discriminatory accuracy and calibration were externally validated in two prospective cohorts from the general population. Moreover, we ascertained the prognostic value of the score in the prediction of liver-related outcomes in participants without known liver disease with median follow-up of 12 years (UK Biobank cohort). FINDINGS: We included 14 726 participants: 6357 (43·2%) in the derivation cohort, 4370 (29·7%) in the first external validation cohort, and 3999 (27·2%) in the second external validation cohort. The score accurately predicted liver stiffness in the development and external validation cohorts, and was superior to conventional serum biomarkers of fibrosis, as measured by area under the receiver-operating characteristics curve (AUC; 0·83 [95% CI [0·78-0·89]) versus the fibrosis-4 index (FIB-4; 0·68 [0·61-0·75] at 10 kPa). The score was effective in identifying individuals at risk of liver-related mortality, liver-related hospitalisation, and liver cancer, thereby allowing stratification to different risk groups for liver-related outcomes. The hazard ratio for liver-related mortality in the high-risk group was 471 (95% CI 347-641) compared with the minimal risk group, and the overall AUC of the score in predicting 10-year liver-related mortality was 0·90 (0·88-0·91) versus 0.84 (0·82-0·86) for FIB-4. INTERPRETATION: The LiverRisk score, based on simple parameters, predicted liver fibrosis and future development of liver-related outcomes in the general population. The score might allow for stratification of individuals according to liver risk and thus guide preventive care. FUNDING: European Commission under the H20/20 programme; Fondo de Investigación Sanitaria de Salud; Instituto de Salud Carlos III; Spanish Ministry of Economy, Industry, and Competitiveness; the European Regional Development Fund; and the German Ministry of Education and Research (BMBF).

Dysglycemia in young women attenuates the protective effect against fatty liver disease.

Introduction: Sexual dimorphism has been reported in non-alcoholic fatty liver disease (NAFLD), similar to the sex differences evident with cardiovascular disease. Type 2 diabetes mellitus (T2D) significantly increases the risk and severity of NAFLD, but there is scarce information on whether T2D or altered glucose metabolism can modify the prevalence of NAFLD in men and women of reproductive age. Purpose: To investigate the relationship between age, sex and NAFLD in subjects with and without dysglycemia. Materials and methods: We analyzed 2,790 patients. NAFLD was characterized using established diagnostic criteria: one or more positive results on the fatty liver index and hepatic ultrasound. Liver fibrosis (liver stiffness measurement [LSM] ≥8.0 kPa) was assessed by Fibroscan®. For analysis purposes, we included both T2D and prediabetes under the predefined condition of dysglycemia. Results: The global prevalence of NAFLD was higher in men than in women (50% and 34%; P<0.001), and the prevalence increased with age in both sexes. Older women (≥ 50 years) had a higher prevalence than younger women (<50 years), both in the overall cohort and in non-dysglycemic subjects. In dysglycemic subjects, the prevalence of NAFLD was slightly higher in men (68% vs 61%, p=0.021); in younger subjects, there were no differences in the prevalence of NAFLD between men and women (68% vs 64%, respectively; p=0.635). We found an interaction between dysglycemia and female sex (odds ratio [OR] 1.6 95% confidence interval [CI] 1.0-2.4, p=0.030), and between and age ≥50 years (OR 0.6, 95% CI 0.3-1.0, p=0.046). The global prevalence of LSM ≥8.0 kPa was higher in men compared with women (8% vs 4%; p< 0.001). This prevalence increased with age, mainly in men. We did not find any association between liver fibrosis and age and gender. Conclusions: While the global prevalence of NAFLD is higher in men than in women across all ages, younger women with dysglycemia have a similar risk of developing NAFLD as men of a similar age. Therefore, the presence of dysglycemia may erase the protective effect of female sex against fatty liver disease.

LiverScreen project: study protocol for screening for liver fibrosis in the general population in European countries.

BACKGROUND: The development of liver cirrhosis is usually an asymptomatic process until late stages when complications occur. The potential reversibility of the disease is dependent on early diagnosis of liver fibrosis and timely targeted treatment. Recently, the use of non-invasive tools has been suggested for screening of liver fibrosis, especially in subjects with risk factors for chronic liver disease. Nevertheless, large population-based studies with cost-effectiveness analyses are still lacking to support the widespread use of such tools. The aim of this study is to investigate whether non-invasive liver stiffness measurement in the general population is useful to identify subjects with asymptomatic, advanced chronic liver disease. METHODS: This study aims to include 30,000 subjects from eight European countries. Subjects from the general population aged ≥ 40 years without known liver disease will be invited to participate in the study either through phone calls/letters or through their primary care center. In the first study visit, subjects will undergo bloodwork as well as hepatic fat quantification and liver stiffness measurement (LSM) by vibration-controlled transient elastography. If LSM is ≥ 8 kPa and/or if ALT levels are ≥1.5 x upper limit of normal, subjects will be referred to hospital for further evaluation and consideration of liver biopsy. The primary outcome is the percentage of subjects with LSM ≥ 8kPa. In addition, a health economic evaluation will be performed to assess the cost-effectiveness and budget impact of such an intervention. The project is funded by the European Commission H2020 program. DISCUSSION: This study comes at an especially important time, as the burden of chronic liver diseases is expected to increase in the coming years. There is consequently an urgent need to change our current approach, from diagnosing the disease late when the impact of interventions may be limited to diagnosing the disease earlier, when the patient is asymptomatic and free of complications, and the disease potentially reversible. Ultimately, the LiverScreen study will serve as a basis from which diagnostic pathways can be developed and adapted to the specific socio-economic and healthcare conditions in each country. TRIAL REGISTRATION: This study is registered on Clinicaltrials.gov ( NCT03789825 ).

Low Accuracy of FIB-4 and NAFLD Fibrosis Scores for Screening for Liver Fibrosis in the Population.

BACKGROUND & AIMS: Fibrosis-4 (FIB-4) and the nonalcoholic fatty liver disease fibrosis score (NFS) are the 2 most popular noninvasive blood-based serum tests proposed for widespread fibrosis screening. We therefore aimed to describe the accuracy of FIB-4 and NFS to detect elevated liver stiffness as an indicator of hepatic fibrosis in low-prevalence populations. METHODS: This study included a total of 5129 patients with concomitant measurement of FIB-4, NFS, and liver stiffness measurement (LSM) by Fibroscan (Echosens, France) from 5 independent population-based cohorts from Spain, Hong Kong, Denmark, England, and France; 3979 participants from the general population and 1150 from at-risk cohorts due to alcohol, diabetes, or obesity. We correlated LSM with FIB-4 and NFS, and calculated pre- and post-test predictive values of FIB-4 and NFS to detect elevated LSM at 8 kPa and 12 kPa cutoffs. The mean age was 53 ± 12 years, the mean body mass index was 27 ± 5 kg/m2, and 2439 (57%) were women. One in 10 patients (552; 11%) had liver stiffness ≥8 kPa, but 239 of those (43%) had a normal FIB-4, and 171 (31%) had normal NFS. The proportion of false-negatives was higher in at-risk patients than the general population. FIB-4 was false-negative in 11% of diabetic subjects, compared with 2.5% false-negatives with NFS. Waist circumference outperformed FIB-4 and NFS for detecting LSM ≥8 kPa in the general population. Almost one-third (28%-29%) of elevated FIB-4/NFS were false-positive in both the general population and at-risk cohorts. CONCLUSIONS: FIB-4 and NFS are suboptimal for screening purposes due to a high risk of overdiagnosis and a non-negligible percentage of false-negatives, especially in patients with risk factors for chronic liver disease. Waist circumference emerged as a potential first step to identify patients at risk for liver fibrosis in the general population.

Population screening for liver fibrosis: Toward early diagnosis and intervention for chronic liver diseases.

Cirrhosis, highly prevalent worldwide, develops after years of hepatic inflammation triggering progressive fibrosis. Currently, the main etiologies of cirrhosis are non-alcoholic fatty liver disease and alcohol-related liver disease, although chronic hepatitis B and C infections are still major etiological factors in some areas of the world. Recent studies have shown that liver fibrosis can be assessed with relatively high accuracy noninvasively by serological tests, transient elastography, and radiological methods. These modalities may be utilized for screening for liver fibrosis in at-risk populations. Thus far, a limited number of population-based studies using noninvasive tests in different areas of the world indicate that a significant percentage of subjects without known liver disease (around 5% in general populations and a higher rate -18% to 27%-in populations with risk factors for liver disease) have significant undetected liver fibrosis or established cirrhosis. Larger international studies are required to show the harms and benefits before concluding that screening for liver fibrosis should be applied to populations at risk for chronic liver diseases. Screening for liver fibrosis has the potential for changing the current approach from diagnosing chronic liver diseases late when patients have already developed complications of cirrhosis to diagnosing liver fibrosis in asymptomatic subjects providing the opportunity of preventing disease progression.

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.

Interaction between metabolic syndrome and alcohol consumption, risk factors of liver fibrosis: A population-based study.

BACKGROUND AND AIMS: Alcohol and metabolic syndrome (MS) coexist frequently as cofactors of liver disease. Previous studies suggest a deleterious effect of MS in advanced alcohol-related liver disease (ArLD). However, it is unknow whether MS can increase the risk of liver fibrosis in early stages of ArLD. The aim of this study was to investigate the effect of MS on liver fibrosis in subjects with alcohol consumption from a population-based cohort. METHODS: The number of subjects include 1760(58%) of 3014 who were randomly selected from the community consumed alcohol and were classified as current drinkers, divided in moderate (n = 1222) or high-risk drinkers (n = 275) (>21 units/week men, >14 units/week women for high-risk drinkers), or former drinkers (n = 263). Liver fibrosis was estimated by measuring liver stiffness(LS) with transient elastography (TE). RESULTS: Prevalence of significant LS using cutoff values of TE of 8 and 9.1kPa was increased in high-risk compared with moderate or former drinkers and lifetime abstainers. In subjects with alcohol consumption, LS was associated with male gender, AST, ALT, years of consumption, and MS. In high-risk drinkers, MS and intensity of consumption were the only factors associated with significant LS (OR 3.7 and 4.6 for LS ≥ 8 kPa and 3.9 and 9.2 kPa for LS ≥ 9.1 kPa, respectively). Presence of significant liver fibrosis in the liver biopsy was higher among high-risk as compared with moderate or former drinkers. CONCLUSION: MS increases the risk of liver fibrosis in subjects with alcohol consumption. Among high-risk drinkers, only MS and consumption of high amount of alcohol are associated with risk of liver fibrosis.

Atherogenic dyslipidemia, but not hyperglycemia, is an independent factor associated with liver fibrosis in subjects with type 2 diabetes and NAFLD: a population-based study.

OBJECTIVE: To investigate the prevalence and risks factors associated with the presence of liver fibrosis in subjects with nonalcoholic fatty liver disease (NAFLD) with and without type 2 diabetes mellitus (T2D). DESIGN AND METHODS: This study was part of a population-based study conducted in the Barcelona metropolitan area among subjects aged 18-75 years old. Secondary causes of steatosis were excluded. Moderate-to-advanced liver fibrosis was defined as a liver stiffness measurement (LSM) ≥ 8.0 kPa assessed by transient elastography. RESULTS: Among 930 subjects with NAFLD, the prevalence of moderate-to-advanced liver fibrosis was higher in subjects with T2D compared those without (30.8% vs 8.7%). By multivariable analysis, one of the main factors independently associated with increased LSM in subjects with NAFLD was atherogenic dyslipidemia but only in those with T2D. The percentage of subjects with LSM ≥ 8.0 kPa was higher in subjects with T2D and atherogenic dyslipidemia than in those with T2D without atherogenic dyslipidemia both for the cut-off point of LSM ≥8.0 kPa (45% vs 24% P = 0.002) and ≥13 kPa (13% vs 4% P = 0.020). No differences were observed in the prevalence of LSM ≥8.0 kPa regarding glycemic control among NAFLD-diabetic subjects. CONCLUSIONS: Factors associated with moderate-to-advanced liver fibrosis in NAFLD are different in subjects with and without T2D. Atherogenic dyslipidemia was associated with the presence of moderate-to-advanced liver fibrosis in T2D with NAFLD but not in non-diabetic subjects. These findings highlight the need for an active search for liver fibrosis in subjects with T2D NAFLD and atherogenic dyslipidemia.

Significant decrease in the prevalence of hepatitis C infection after the introduction of direct acting antivirals.

BACKGROUND AND AIM: Accurate information on the epidemiology of hepatitis C and B infection is mandatory to establish a national/regional plan. We aim to update the prevalence of hepatitis C and B infection in Catalonia using point-of-care tests to analyze the risk factors related and to implement a linkage-to-care circuit. METHODS: This is a community-based study. A random list of adult individuals was retrieved from censuses of primary care centers. Point-of-care tests for anti-hepatitis C virus (HCV) and HBV surface antigen (HBsAg) and a questionnaire for risk factor assessment were performed. Positive results were validated and a circuit for linkage-to-care was established. RESULTS: A total of 3328 individuals were included. The anti-HCV and HBsAg overall prevalence were lower than expected [1.02%, 95% confidence interval (CI) 0.65-1.39; and 0.52%, 95% CI 0.26-0.77, respectively]. Anti-HCV positive subjects were mostly (88%) autochthonous. The prevalence increased with age; only 12% were under age 40. The associated risk factors were drug use, blood transfusion, relative with HCV, and diabetes. Notably, the prevalence of active infection was only 0.49% (95% CI 0.23-0.74), 40% less than previously reported, reflecting the impact of direct acting antiviral therapy. Differently, HBsAg positive subjects were mostly foreign migrants (53%) with no other risk factors. Despite the implementation of a linkage-to-care circuit, one third of HBsAg positive subjects were lost. CONCLUSIONS: The prevalence of HCV infection was lower than previously reported, showing a strong impact of direct acting antiviral therapy in the last years. Because of hepatitis B universal vaccination, HBV infection in Catalonia is mainly associated with migrant population. Linkage-to-care in patients with hepatitis B was challenging and warrants additional efforts.

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.

Alcohol-related liver disease. Clinical practice guidelines. Consensus document sponsored by AEEH. / Enfermedad hepática por alcohol. Guías de práctica clínica. Documento de consenso auspiciado por la AEEH.

Alcohol-related liver disease (ARLD) is the most prevalent cause of advanced liver disease and liver cirrhosis in Europe, including Spain. According to the World Health Organization the fraction of liver cirrhosis attributable to alcohol use in Spain is 73.8% among men and 56.3% among women. ARLD includes various stages such as steatohepatitis, cirrhosis and hepatocellular cancer. In addition, patients with underlying ARLD and heavy alcohol intake may develop alcoholic hepatitis, which is associated with high mortality. To date, the only effective treatment to treat ARLD is prolonged withdrawal. There are no specific treatments, and the only treatment that increases life expectancy in alcoholic hepatitis is prednisolone. For patients with alcoholic hepatitis who do not respond to treatment, some centres offer the possibility of an early transplant. These clinical practice guidelines aim to propose recommendations on ARLD taking into account their relevance as a cause of advanced chronic liver disease and liver cirrhosis in our setting. This paper aims to answer the key questions for the clinical practice of Gastroenterology, Hepatology, as well as Internal Medicine and Primary Health Centres, making the most up-to-date information regarding the management and treatment of ARLD available to health professionals. These guidelines provide evidence-based recommendations for the clinical management of this disease.

Prevalence of Early Chronic Kidney Disease and Main Associated Factors in Spanish Population: Populational Study.

The aim of this study was to determine the prevalence of early chronic kidney disease (EKD) (stages 1 and 2) and the factors associated. This was a populational study including individuals from 18-75 years randomly selected from 18 Primary Healthcare centers in the area of Barcelonès Nord and Maresme (Catalunya, Spain). Variables: anamnesis, physical examination, blood pressure, and analysis. EKD was defined with by a glomerular filtration rate (GFR) ≥60 mL/min/1.73 m2 and albumin/creatinine ratio (ACR) ≥17 mg/g in men and ≥25 mg/g in women confirmed with two determinations. 2871 individuals: 43% men, mean age 55 years (19-75), 32.2% obese, 50.5% abdominal obesity, 21.1% hypertensive, and 10.6% diabetic. Prevalence of EKD: With one determination 157 individuals (5.5%), 110 men (9%) and 47 women (2.8%); with two determinations 109 individuals (3.8%), 85 men (7%), and 24 women (1.5%). Factors independently associated with the multivariate logistic regression model: Man (OR 3.35), blood pressure ≥ 135/85 mmHg (OR 2.29), BMI ≥ 30 kg/m2 (OR 2.48), glycemia ≥ 100 mg/dL (OR 1.73), smoker (OR 1.67) and age (OR 1.04). The prevalence varies if the diagnosis is established based on one or two analytical determinations, overestimated if only one determination is made and depends on the value chosen to define urine albumin excretion.

Transient elastography for screening of liver fibrosis: Cost-effectiveness analysis from six prospective cohorts in Europe and Asia.

BACKGROUND & AIMS: Non-alcoholic fatty liver disease and alcohol-related liver disease pose an important challenge to current clinical healthcare pathways because of the large number of at-risk patients. Therefore, we aimed to explore the cost-effectiveness of transient elastography (TE) as a screening method to detect liver fibrosis in a primary care pathway. METHODS: Cost-effectiveness analysis was performed using real-life individual patient data from 6 independent prospective cohorts (5 from Europe and 1 from Asia). A diagnostic algorithm with conditional inference trees was developed to explore the relationships between liver stiffness, socio-demographics, comorbidities, and hepatic fibrosis, the latter assessed by fibrosis scores (FIB-4, NFS) and liver biopsies in a subset of 352 patients. We compared the incremental cost-effectiveness of a screening strategy against standard of care alongside the numbers needed to screen to diagnose a patient with fibrosis stage ≥F2. RESULTS: The data set encompassed 6,295 participants (mean age 55 ±â€¯12 years, BMI 27 ±â€¯5 kg/m2, liver stiffness 5.6 ±â€¯5.0 kPa). A 9.1 kPa TE cut-off provided the best accuracy for the diagnosis of significant fibrosis (≥F2) in general population settings, whereas a threshold of 9.5 kPa was optimal for populations at-risk of alcohol-related liver disease. TE with the proposed cut-offs outperformed fibrosis scores in terms of accuracy. Screening with TE was cost-effective with mean incremental cost-effectiveness ratios ranging from 2,570 €/QALY (95% CI 2,456-2,683) for a population at-risk of alcohol-related liver disease (age ≥45 years) to 6,217 €/QALY (95% CI 5,832-6,601) in the general population. Overall, there was a 12% chance of TE screening being cost saving across countries and populations. CONCLUSIONS: Screening for liver fibrosis with TE in primary care is a cost-effective intervention for European and Asian populations and may even be cost saving. LAY SUMMARY: The lack of optimized public health screening strategies for the detection of liver fibrosis in adults without known liver disease presents a major healthcare challenge. Analyses from 6 independent international cohorts, with transient elastography measurements, show that a community-based risk-stratification strategy for alcohol-related and non-alcoholic fatty liver diseases is cost-effective and potentially cost saving for our healthcare systems, as it leads to earlier identification of patients.

Recommendations for the detection, diagnosis and follow-up of patients with non-alcoholic fatty liver disease in primary and hospital care. / Recomendaciones para la detección, diagnóstico y seguimiento de los pacientes con enfermedad por hígado graso no alcohólico en atención primaria y hospitalaria.

Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases, with a prevalence of 20-30% in the general population and 60-80% in at-risk populations. In a not negligible percentage of patients, NAFLD progresses from steatosis to different stages of fibrosis and cirrhosis. Due to its high prevalence, NAFLD has become a significant health problem that requires specific action in detection, diagnosis, follow-up and treatment. Furthermore, given that NAFLD presents an increased risk of cardiovascular morbidity and mortality, a multidisciplinary approach is required for its treatment and follow-up. Patients with early stages of the disease, without fibrosis, can be diagnosed and receive treatment in the Primary Care setting, while those with more advanced liver disease benefit from specialised follow-up in the hospital setting to prevent and treat liver complications. This consensus document, prepared by the Catalan Societies of Digestology, Primary Care, Endocrinology, Diabetes and Internal Medicine, arises from the need to design strategies to guide patient flows between Primary and Hospital Care in order to offer patients with NAFLD the best care according to the stage of their disease. The consensus document describes the most commonly used non-invasive diagnostic methods for patient diagnosis and two algorithms have been designed for patient management in both Primary Care and Hospital Care.

Range of Normal Liver Stiffness and Factors Associated With Increased Stiffness Measurements in Apparently Healthy Individuals.

BACKGROUND & AIMS: Transient elastography (TE) is a noninvasive technique used to measure liver stiffness to estimate the severity of fibrosis. The range of liver stiffness measurements (LSMs) in healthy individuals is unclear. We performed a systematic review to determine the range of LSMs, examined by TE, in healthy individuals and individuals who are susceptible to fibrosis. METHODS: We collected data from 16,082 individuals, in 26 cohorts, identified from systematic searches of Embase, Ovid MEDLINE, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews for studies of liver stiffness measurements. Studies analyzed included apparently healthy adults (normal levels of liver enzymes, low-risk alcohol use patterns, and negative for markers of viral hepatitis). The presence of diabetes, hypertension, dyslipidemia, or steatosis, based on ultrasound examination, was known for most participants. We performed a meta-analysis of data from individual participants. The cohort was divided into 4 groups; participants with a body mass index <30 kg/m2 were examined with the medium probe and those with a body mass index ≥30 kg/m2 were examined with the extra-large probe. Linear regression models were conducted after adjusting for potential confounding factors of LSMs. We performed several sensitivity analyses. RESULTS: We established LSM ranges for healthy individuals measured with both probes-these did not change significantly in sensitivity analyses of individuals with platelets ≥150,000/mm3 and levels of alanine aminotransferase ≤33 IU/L in men or ≤25 IU/L in women. In multivariate analysis, factors that modified LSMs with statistical significance included diabetes, dyslipidemia, waist circumference, level of aspartate aminotransferase, and systolic blood pressure at examination time. Significant increases in LSMs were associated with the metabolic syndrome in individuals examined by either probe. Diabetes in obese individuals increased the risk of LSMs in the range associated with advanced fibrosis. CONCLUSIONS: In a systematic review and meta-analysis of data from individual participants, we established a comprehensive set of LSM ranges, measured by TE in large cohorts of healthy individuals and persons susceptible to hepatic fibrosis. Regression analyses identified factors associated with increased LSMs obtained by TE with the medium and extra-large probes.