Organoid-guided precision hepatology for metabolic liver disease.
J Hepatol
; 80(5): 805-821, 2024 May.
Article
in En
| MEDLINE
| ID: mdl-38237864
ABSTRACT
Metabolic dysfunction-associated steatotic liver disease affects millions of people worldwide. Progress towards a definitive cure has been incremental and treatment is currently limited to lifestyle modification. Hepatocyte-specific lipid accumulation is the main trigger of lipotoxic events, driving inflammation and fibrosis. The underlying pathology is extraordinarily heterogenous, and the manifestations of steatohepatitis are markedly influenced by metabolic communications across non-hepatic organs. Synthetic human tissue models have emerged as powerful platforms to better capture the mechanistic diversity in disease progression, while preserving person-specific genetic traits. In this review, we will outline current research efforts focused on integrating multiple synthetic tissue models of key metabolic organs, with an emphasis on organoid-based systems. By combining functional genomics and population-scale en masse profiling methodologies, human tissues derived from patients can provide insights into personalised genetic, transcriptional, biochemical, and metabolic states. These collective efforts will advance our understanding of steatohepatitis and guide the development of rational solutions for mechanism-directed diagnostic and therapeutic investigation.
Key words
Full text:
1
Database:
MEDLINE
Main subject:
Digestive System Diseases
/
Fatty Liver
/
Gastroenterology
/
Liver Diseases
/
Metabolic Diseases
Limits:
Humans
Language:
En
Year:
2024
Type:
Article