RESUMO
Metabolic dysfunction-associated steatotic liver disease (MASLD), with its steadily increasing prevalence, represents now a major problem in public health. A proper referral could benefit from tools allowing more precise risk stratification. To this end, in recent decades, several genetic variants that may help predict and refine the risk of development and progression of MASLD have been investigated. In this review, we aim to discuss the role genetics in MASLD plays in everyday clinical practice. We performed a comprehensive literature search of PubMed for relevant publications. Available evidence highlights the emergence of genetic-based noninvasive algorithms for diagnosing fatty liver, metabolic dysfunction-associated steatohepatitis, fibrosis progression and occurrence of liver-related outcomes including hepatocellular carcinoma. Nevertheless, their accuracy is not optimal and application in everyday clinical practice remains challenging. Furthermore, susceptible genetic markers have recently become subjects of great scientific interest as therapeutic targets in precision medicine. In conclusion, decisional algorithms based on genetic testing in MASLD to facilitate the clinician decisions on management and treatment are under growing investigation and could benefit from artificial intelligence methodology.
Assuntos
Testes Genéticos , Humanos , Algoritmos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/etiologia , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/etiologia , Fígado Gorduroso/genética , Fígado Gorduroso/diagnóstico , Progressão da Doença , Predisposição Genética para Doença , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Cirrose Hepática/genética , Cirrose Hepática/diagnóstico , Cirrose Hepática/complicações , Marcadores GenéticosRESUMO
Nonalcoholic fatty liver disease (NAFLD), affecting about 25% of general population and more than 50% of dysmetabolic patients, is an emerging cause of chronic liver disease and its complications. Recently, an international consensus of experts proposed to rename this disease as 'Metabolic dysfunction-Associated Fatty Liver Disease' (MAFLD) to focus on the bidirectional interplay between fatty liver and metabolic alterations and to stress the need of assessing fatty liver independently from alcohol consumption and other coexisting causes of liver disease. The peculiarity of NAFLD/MAFLD lies in the presence of a higher risk of not only - as expected - liver-related events but also of extrahepatic events, mostly cardiovascular and cancers. Available evidence suggests that these associations are not only the expression of sharing the same risk factors but shed light about the ability of NAFLD/MAFLD and particularly of its progressive form - nonalcoholic/metabolic dysfunction-associated steatohepatitis - to act as an independent risk factor via promotion of atherogenic dyslipidemia and a proinflammatory, profibrogenic, and procoagulant systemic environment. The present review summarizes available epidemiological and clinical evidence supporting the concept of NAFLD/MAFLD as a multisystemic disease, and highlights potential explanatory mechanisms underlying the association between NAFLD/MAFLD and extrahepatic disorders.
RESUMO
BACKGROUND & AIMS: We aimed to assess the diagnostic accuracy of AGILE 3+, a recently developed score based on the combination of aspartate aminotransferase/alanine aminotransferase ratio, platelet count, diabetes status, sex, age, and liver stiffness measurement (LSM) by transient elastography, when compared with Fibrosis-4 (FIB-4) and LSM, for the diagnosis of advanced fibrosis and for the prediction of liver-related events (LREs) occurrence in patients with NAFLD. METHODS: A total of 614 consecutive patients with biopsy-proven NAFLD or clinical diagnosis of NAFLD-related compensated cirrhosis were enrolled. LREs were recorded during follow-up. FIB-4, LSM by transient elastography (FibroScan device), and AGILE 3+ were measured. The diagnostic performance of noninvasive criteria for advanced fibrosis and for the prediction of LREs was assessed using the area under the receiver operating characteristic curve (AUROC) and decision curve analysis. RESULTS: In patients with biopsy-proven NAFLD (n = 520), LSM and AGILE 3+ had higher AUROC than FIB-4 (0.88 for LSM and AGILE 3+ vs 0.78 for FIB-4; P < .001) for advanced fibrosis, and AGILE 3+ exhibited a smaller indeterminate area in the test (25.2% for FIB-4 vs 13.1% for LSM vs 8.3% for AGILE 3+). Within the entire cohort of patients, AGILE 3+ had significantly higher AUROC for predicting LREs with respect to LSM (AUROC 36 months 0.95 vs 0.93; P =.008; 60 months 0.95 vs 0.92; P = .006; 96 months 0.97 vs 0.95; P = .001). Decision curve analysis showed that all scores had modest net benefit for ruling-out advanced fibrosis at the risk threshold of 5% to 10% where advanced fibrosis was absent. At the risk threshold of 5% of false negatives or false positives in LRE at 36, 60, 96, and 120 months, AGILE 3+ outperformed both FIB-4 and LSM for ruling out LRE. CONCLUSIONS: Depending on resource availability, clinical setting, and the risk scenarios, AGILE 3+ is an accurate and valid alternative to FIB-4 and LSM for the noninvasive assessment of disease severity and prognosis in patients with NAFLD.