Genetic testing plays an important role in the diagnosing of liver diseases, but its diagnostic performance varies across patient populations. By analyzing diagnostic yield across patient subgroups, this study aims at defining age-tailored diagnostic workflows for a more effective integration of genetic testing into clinical practice. We retrospectively analyzed 203 patients (145 children, 58 adults) with acute or subacute liver disorders of suspected genetic origin who underwent next-generation sequencing, categorized them by clinical diagnosis, and evaluated diagnostic yields to develop age-tailored testing workflows. The median age was 8 years; 65.5% were male, 84.7% White, and 27.6% had undergone liver transplantation. Cholestatic liver disorders (30%) and unexplained liver dysfunction (20.2%) were the most common indications for testing. Overall, genetic testing achieved a definitive diagnosis in 35.5% of patients, with a higher yield in children than adults (41.4% vs. 20.7%). Metabolic disorders had the highest diagnostic yield (83.3%), while PFIC/BRIC and Alagille syndrome were the most frequent genetic diagnoses. Age-specific diagnostic workflows retrospectively enriched the overall diagnostic rate by approximately 11% across age and disease categories. These findings demonstrate that tailoring genetic testing strategies to patient age and clinical presentation can improve diagnostic efficiency and support a standardized integration of genetic testing into hepatology practice.
A. Faini, Michele Pinon, Giulia Margherita Brach del Prever et al.· International Journal of Mol...· 0 citations
Introduction Genetic variants involved in lipid and glucose metabolism have been implicated in liver disease progression and hepatocellular carcinoma (HCC) development in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). However, their prognostic role in patients with established HCC remains unclear. We aimed to investigate the association between MASLD-related genetic variants and overall survival (OS) in patients with MASLD-related HCC. Methods We retrospectively evaluated 258 patients with MASLD-related HCC (median age: 73, 49–79 years; male sex: 86.8%); most patients had a diagnosis of early tumor (BCLC 0/A: n = 162; 62.8%). PNPLA3 rs738409, TM6SF2 rs58542926, MBOAT7 rs641738, GCKR rs780094, and HSD17B13 rs72613567 variants were genotyped. An independent cohort of viral-related HCC (n = 384) was analysed for exploratory comparison. Overall survival (OS) was evaluated using Kaplan-Meier analysis and multivariable Cox regression. Results Among the investigated gene variants, only the MBOAT7 rs641738 TT genotype was associated with reduced OS in patients with MASLD-related HCC compared to CC/CT carriers (19.8 vs. 32.2 months; p = 0.006). At multivariable analysis, MBOAT7 rs641738 TT genotype retained a nominal association with poorer OS after adjustment for age, sex, tumor burden, and metabolic cofactors (aHR = 1.61, 95% CI 1.05–2.46; p = 0.028). Conversely, OS did not differ according to MBOAT7 rs641738 genotype in the exploratory viral-related HCC comparison cohort (p = 0.449). Conclusions MBOAT7 rs641738 genotype was associated with poorer OS in patients with MASLD-related HCC. This finding was not observed in an exploratory viral-related HCC comparison cohort, but between-cohort differences limit etiological interpretation. These results should be considered hypothesis-generating and require external validation.
M. Guariglia, G. Caviglia, Silvia Gaia et al.· Frontiers in Oncology· 0 citations
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