Идёт набор NCT07317193

DEFINING THE GENETIC DRIVERS OF ADULT-ONSET CHOLESTATIC LIVER DISEASE

Без фазы С лечением Cholestatic Liver Disease Progressive Familial Intrahepatic Cholestasis

Ориентир для пациента и семьи

Простыми словами

Автоматическая сводка по структурированным данным реестра. Она помогает сориентироваться, но не заменяет официальный протокол или оценку врача.

Что изучают: В протоколе указаны: Advanced Whole Genome Sequencing to Identify Rare Pathogenic Variants in Unexplained Cholestatic Liver Disease.
Кому может быть актуально: Состояния в реестре: Cholestatic Liver Disease, Progressive Familial Intrahepatic Cholestasis. Базовые параметры: 18 лет — 65 лет · Все.
Что важно проверить: Возраст, диагноз и пол — только базовые ориентиры. Предыдущее лечение, анализы и другие обязательные условия указаны ниже в критериях участия.
Где проводится: Италия
Следующий шаг: Сохраните исследование, покажите его лечащему врачу и уточните актуальный статус у исследовательского центра. Расходы, документы и поездка →

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Обзор

Cholestatic disease in adults comprises a heterogeneous group of conditions characterized by intra- or extrahepatic alterations of bile flow that can lead to fibrosis or hepatic decompensation. Due to the heterogeneity of clinical manifestation, which is sometimes very subtle, diagnosis based on clinical, histological, and radiological evaluation is often very complicated. Genetic testing can be helpful in identifying the cause of the clinical phenotype, thereby allowing for targeted follow-up adequate to the patient's specific characteristics and risk factors. Although the utility of genetic analysis has been well documented for other liver diseases or in pediatric cohorts of children with cholestatic disease, the use and benefits of genetic testing in adults with cholestatic disease are still little explored and investigated. In this context, through the use of whole-genome sequencing (WGS), the FIRST project aims to evaluate the role of rare genetic variants in the pathogenesis of cholestatic disease and the utility of WGS in defining a genetic diagnosis.

Вмешательства

Другое Advanced Whole Genome Sequencing to Identify Rare Pathogenic Variants in Unexplained Cholestatic Liver Disease
The intervention consists of advanced genetic analysis to identify the presence of rare harmful variants in genes known to be associated with cholestasis or in other genes related to liver disorders. The results from the cases will be compared with WGS data from a large group of 1025 healthy controls (previously collected within the FOGS study) to assess the enrichment of these variants. The primary objective is to establish the prevalence of pathogenic variants, while secondary objectives inclu

Первичные конечные точки

Primary Endpoint: Diagnostic Yield of Whole Genome Sequencing (WGS) in Adult Patients with Unexplained or Atypical Cholestasis [Срок оценки: 9 months]

Вторичные конечные точки (1)

Investigating New Genetic Determinants: Prevalence of Rare Variants in Liver-Related Genes [Срок оценки: 9 months]

Критерии участия

Критерии включения

Cases:

Adults, aged > 18 years with:

persistent or intermittent elevations in serum alkaline phosphatase (ALP) or gamma-glutamyltransferase (GGT) for at least six months not explained following standard diagnostic assessment adhering to the guidelines of the European Association for the Study of the Liver (EASL), or with a positive family history of unexplained cholestasis or hepato-biliary cancer, negative to previous genetic tests (targeted panel for PFIC genes or WES);
primary sclerosing cholangitis (PSC) with unusual features: small-duct PSC, non-typical radiological findings according to radiological guidelines on PSC, absence of concomitant inflammatory bowel disease, negative to previous genetic tests (targeted panel for PFIC genes or WES) or who didn't perform previous genetic test;
primary biliary cholangitis (PBC) without specific anti-mitochondrial antibodies, negative to previous genetic tests (targeted panel for PFIC genes or WES) or who didn't perform previous genetic test.
Signature of informed consent

Controls:

-Blood donors (age 18-65 years) without clinical signs of liver diseases based on the collected clinical parameters: anthropometric (BMI>18 and <25), haematological (Hb, white blood cells, platelets within the reference range), biochemical traits (albumin, bilirubin, AST, ALT, GGT, ALP within the reference range), medical history (negative for chronic or concomitant diseases, including immunological diseases)

Критерии исключения

Cases:

Patients who do not possess the above inclusion criteria or have at least one of the following exclusion criteria:
an already known genetic diagnosis explaining the clinical phenotype
affected by other causes of liver disease such as viral or autoimmune hepatitis

Controls:

-Blood donors with clinical signs of liver diseases

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да