Adiponectin, leptin, and IGF-1 are useful diagnostic and stratification biomarkers of NAFLD

[EN] Background: Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease where liver biopsy remains the gold standard for diagnosis. Here we aimed to evaluate the role of circulating adiponectin, leptin, and insulin-like growth factor 1 (IGF-1) levels as non-invasive NAFLD biomarkers and assess their correlation with the metabolome. Materials and Methods: Leptin, adiponectin, and IGF-1 serum levels were measured by ELISA in two independent cohorts of biopsy-proven obese NAFLD patients and healthy-liver controls (discovery: 38 NAFLD, 13 controls; validation: 194 NAFLD, 31 controls) and correlated with clinical data, histology, genetic parameters, and serum metabolomics. Results: In both cohorts, leptin increased in NAFLD vs. controls (discovery: AUROC 0.88; validation: AUROC 0.83; p < 0.0001). The leptin levels were similar between obese and non-obese healthy controls, suggesting that obesity is not a confounding factor. In the discovery cohort, adiponectin was lower in non-alcoholic steatohepatitis (NASH) vs. non-alcoholic fatty liver (AUROC 0.87; p < 0.0001). For the validation cohort, significance was attained for homozygous for PNPLA3 allele c.444C (AUROC 0.63; p < 0.05). Combining adiponectin with specific serum lipids improved the assay performance (AUROC 0.80; p < 0.0001). For the validation cohort, IGF-1 was lower with advanced fibrosis (AUROC 0.67, p<0.05), but combination with international normalized ratio (INR) and ferritin increased the assay performance (AUROC 0.81; p < 0.01). Conclusion: Serum leptin discriminates NAFLD, and adiponectin combined with specific lipids stratifies NASH. IGF-1, INR, and ferritin distinguish advanced fibrosis.CR was funded by FEDER through the COMPETE program and by national funds through Fundação para a Ciência e a Tecnologia (PTDC/MED-FAR/29097/2017—LISBOA-01- 0145-FEDER-029097) and by European Horizon 2020 (H2020- MSCA-RISE-2016-734719). This work was also supported by Fundação para a Ciência e Tecnologia (PD/BD/135467/2017) and Portuguese Association for the Study of Liver/MSD 2017. JB was funded by Spanish Carlos III Health Institute (ISCIII) (PI15/01132, PI18/01075 and Miguel Servet Program CON14/00129 and CPII19/00008), co-financed by Fondo Europeo de Desarrollo Regional (FEDER), Instituto de Salud Carlos III (CIBERehd, Spain), La Caixa Scientific Foundation (HR17-00601), Fundación Científica de la Asociación Española Contra el Cáncer, and European Horizon 2020 (ESCALON project: H2020-SC1-BHC-2018-2020)

Adiponectin, Leptin, and IGF-1 Are Useful Diagnostic and Stratification Biomarkers of NAFLD

Background: Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease where liver biopsy remains the gold standard for diagnosis. Here we aimed to evaluate the role of circulating adiponectin, leptin, and insulin-like growth factor 1 (IGF-1) levels as non-invasive NAFLD biomarkers and assess their correlation with the metabolome.Materials and Methods: Leptin, adiponectin, and IGF-1 serum levels were measured by ELISA in two independent cohorts of biopsy-proven obese NAFLD patients and healthy-liver controls (discovery: 38 NAFLD, 13 controls; validation: 194 NAFLD, 31 controls) and correlated with clinical data, histology, genetic parameters, and serum metabolomics.Results: In both cohorts, leptin increased in NAFLD vs. controls (discovery: AUROC 0.88; validation: AUROC 0.83; p &lt; 0.0001). The leptin levels were similar between obese and non-obese healthy controls, suggesting that obesity is not a confounding factor. In the discovery cohort, adiponectin was lower in non-alcoholic steatohepatitis (NASH) vs. non-alcoholic fatty liver (AUROC 0.87; p &lt; 0.0001). For the validation cohort, significance was attained for homozygous for PNPLA3 allele c.444C (AUROC 0.63; p &lt; 0.05). Combining adiponectin with specific serum lipids improved the assay performance (AUROC 0.80; p &lt; 0.0001). For the validation cohort, IGF-1 was lower with advanced fibrosis (AUROC 0.67, p &lt; 0.05), but combination with international normalized ratio (INR) and ferritin increased the assay performance (AUROC 0.81; p &lt; 0.01).Conclusion: Serum leptin discriminates NAFLD, and adiponectin combined with specific lipids stratifies NASH. IGF-1, INR, and ferritin distinguish advanced fibrosis

Acute hepatitis A virus infection in Turkey

Anti-HAV IgM positive serum samples from acute phase hepatitis A patients from various areas in Turkey were tested for viral RNA by RT-PCR (reverse transcriptase polymerase chain reaction), using primer pairs from two different regions of the HAV genome. The PCR products amplified from both genomic regions underwent phylogenetic analyses. A comparison of the regions showed the same genotyping results, and the RT-PCR-2 in the 5'NCR demonstrated greater sensitivity compared to RT-PCR-1 in the VP1-P2A region. The majority of the isolates belonged to genotype IB and are related closely to each other; however, two isolates related even more strongly to the HAV HM175 strain. Two (n = 37) RT-PCR positive sera were classified under genotype IA. A surprising finding emerged for the mean levels of serum transaminases AST and ALT: higher levels were found in patients under 10 years of age compared to older patients. Anti-HAV IgM levels were determined quantitatively and, in addition, the HAV-RNA genome equivalents were ascertained by real time RT-PCR. No evidence was found for an association between viral load and the higher transaminase levels in the younger group. J. Med Virol. 80.785-790, 2008. (C) 2008 Wiley-Liss, Inc

Long-Term Humoral Immune Response against SARS-CoV-2 after Natural Infection and Subsequent Vaccination According to WHO International Binding Antibody Units (BAU/mL)

The new WHO reference standard allows for the definition of serum antibodies against various SARS-CoV-2 antigens in terms of binding antibody units (BAU/mL) and thus to compare the results of different ELISA systems. In this study, the concentration of antibodies (ABs) against both the S- and the N-protein of SARS-CoV-2 as well as serum neutralization activity were evaluated in three patients after a mild course of COVID-19. Serum samples were collected frequently during a period of over one year. Furthermore, in two individuals, the effects of an additional vaccination with a mRNA vaccine containing the S1-RBD sequence on these antibodies were examined. After natural infection, the antibodies (IgA, IgG) against the S1-protein remained elevated above the established cut-off to positivity (S-IgA 60 BAU/mL and S-IgG 50 BAU/mL, respectively) for over a year in all patients, while this was not the case for ABs against the N-protein (cut-off N-IgG 40 BAU/mL, N-IgA 256 BAU/mL). Sera from all patients retained the ability to neutralize SARS-CoV-2 for more than a year. Vaccination resulted in a rapid boost of antibodies to S1-protein but, as expected, not to the N-protein. Most likely, the wide use of the WHO reference preparation will be very useful in determining the individual immune status of patients after an infection with SARS-CoV-2 or after vaccination

Clinical, genetic, and epidemiological survey of Polish children and adolescents with severe obesity : A study protocol of the Polish-German study project on severe early-onset obesity

Severe early-onset obesity (SEOO) in children is a common feature of monogenic obesity. Nowadays, mutations in at least 50 genes are known to be related to monogenic obesity, and many others are tested. Part of them is involved in the leptin–proopiomelanocortin pathway. The aim of the project is to establish the Polish database of severely obese children and adolescents and to evaluate the prevalence of monogenic forms of obesity in this cohort, with a special focus on leptin–proopiomelanocortin pathway abnormalities. The secondary project aim is to identify new population-specific mutations in obesity-related genes in severely obese Polish children and adolescents. This is a prospective multi-center clinical study performed in four Polish centers. The estimated sample size is 500 patients aged 1–18 years, with severe obesity, hyperphagia, and food-seeking behaviors. In each patient, the medical history regarding the obesity duration in the patient and obesity and its complication existence in the family will be taken. Next, the questionnaire regarding the symptom characteristic of specific mutations, which we are going to test, will be performed. Hyperphagia will be assessed on the basis of age-specific questionnaires. The physical examination with anthropometric measurement, basic biochemical and hormonal tests, and leptin and biologically active leptin measurements will be performed. Finally, genetic analysis will be performed using next-generation sequencing with sequencing libraries prepared to include obesity-related genes. The genotyping findings will be confirmed with the use of classic sequencing (Sanger’s method). In the future, the pathogenicity of new mutations in obesity-related genes identified in our cohort is planned to be confirmed by functional testing in vitro. Nowadays, there are no data regarding the prevalence of severe obesity or monogenic obesity in Polish children. This project has the potential to improve understanding of obesity etiology and may contribute to implementing attribute mutation-specific treatment. Moreover, it may lead to a finding of new, population-specific mutations related to SEOO