Overview

Over a 5-year follow-up period, we aim to conduct a study among twins aged 15-44 years from the Polish population with the following objectives:

1. To determine the incidence and risk factors for the development of de novo metabolic dysfunction-associated steatotic liver disease (MASLD), liver fibrosis, or cirrhosis. We also intend to evaluate the progression of hepatic steatosis from early to advanced stages or toward fibrosis/cirrhosis.
2. To determine the prevalence and identify predictive factors for the onset and progression of features, diseases, or complications of metabolic syndrome (MS) other than liver disease, particularly within the spectrum of metabolic, nutritional, cardiovascular, endocrine, oncological, psychological, and other disorders typically associated with MS.
3. To assess the association between previous COVID-19 infection or long-COVID features and the occurrence of MASLD, liver fibrosis, or cirrhosis due to MASLD, as well as other features, diseases, or complications of MS.
4. To evaluate the prevalence of malignancies in a young twin population (aged 15-44 years) with MS or with risk factors for MS.
5. To investigate the contribution of genetic and environmental factors and gut microbiota composition to the development and progression of structural liver changes (steatosis, fibrosis, cirrhosis) in MASLD, as well as other features and complications of MS in twins discordant for the MS phenotype.
6. To assess the role of genetic and environmental components in the occurrence and severity of MS phenotype discordance in monozygotic twins.

Eligibility

Inclusion Criteria

1. Age between 15 and 44 years. 2. Provision of informed consent to participate in the study. 3. Twin with a living co-twin. 4. Positive family history in first- and second-degree relatives of metabolic syndrome (MS), associated diseases, or the most common complications of the syndrome.

________________________________________ Exclusion Criteria

Permanent exclusion criteria:

1. Co-twin does not consent to participate in the study.
2. Inability to obtain medical history of biological family members.
3. Presence of advanced liver fibrosis, cirrhosis, or liver cancer.
4. Known liver genetic disorders, autoimmune hepatitis, celiac disease, hemochromatosis, primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), cystic fibrosis, or Wilson's disease.
5. Current or chronic alcohol consumption >20 g of ethanol/day in women and >30 g/day in men.
6. Short bowel syndrome.
7. Cyanotic congenital heart defect.
8. Myasthenia.
9. Central nervous system degenerative diseases such as Alzheimer's disease, Parkinson's disease, or Huntington's disease.
10. Storage diseases involving the liver.
11. Active malignant neoplasm undergoing treatment (excluding non-melanoma skin cancers and melanoma treated non-pharmacologically).
12. Chronic kidney disease requiring renal replacement therapy.
13. Status post organ or tissue transplantation requiring immunosuppression.
14. Pituitary, hypothalamic, or adrenal hyperfunction/hypofunction requiring hormone supplementation.
15. Addiction to psychoactive substances or drugs.
16. Other severe and incurable diseases that, in the investigator's opinion, constitute a permanent contraindication for participation in the study.
17. Lack of cooperation by the volunteer during the visit to the Research Center.

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Temporary exclusion criteria (after resolution, the volunteer may be enrolled):

1. Acute infection, low-grade fever or fever, or use of antibiotics at the time of recruitment or prior to the visit at the Research Center - inclusion possible after 6 weeks.
2. Any vaccination within the past 6 weeks.
3. Pregnancy and up to 6 months postpartum.
4. 3 months after the natural cessation of breastfeeding.
5. 3 months after surgery (does not apply to minor surgical procedures).
6. Untreated hyperthyroidism or hypothyroidism - inclusion possible 3 months after achieving euthyroidism.
7. Significant weight loss or gain in the past 3 months (>10% of initial body weight) - inclusion possible 3 months after weight stabilization.
8. 6 months after discontinuation of temporary parenteral or enteral nutrition via feeding tube.
9. 12 months after bariatric surgery.
10. Systemic treatment with steroids, chemotherapy, immunosuppressive drugs, or biological therapy known to be hepatotoxic or potentially inducing abnormalities found in MS - inclusion possible at least 3 months after completing therapy.