Publication:
Development and Validation of a Clinical-Genetic Risk Score to Predict Hepatic Encephalopathy in Patients With Liver Cirrhosis.

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Date

2021

Authors

Gil-Gomez, Antonio
Ampuero, Javier
Rojas, Angela
Gallego-Duran, Rocio
Muñoz-Hernandez, Rocio
Rico, Maria C
Millan, Raquel
Garcia-Lozano, Raul
Frances, Ruben
Soriano, German

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Wolters Kluwer Health
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Abstract

We aimed to define the impact of the genetic background on overt hepatic encephalopathy (HE) in patients with liver cirrhosis by developing a combined clinical- genetic risk score . Patients suffering from liver cirrhosis from the outpatient clinics of 4 hospitals (n = 600) were included and followed up for at least 5 years until HE bouts, liver transplant , or death . Patients were genotyped for 60 candidate single nucleotide polymorphisms together with the microsatellite in the promoter region of the gene GLS. Single nucleotide polymorphisms rs601338 (FUT2), rs5743836 (TRL9), rs2562582 (SLC1A3), rs313853 (SLC1A5), and GLS microsatellite did predict independently the incidence and severity of overt HE and were included as genetic score. Competing risk analysis revealed that bilirubin (subhazard ratio [sHR] 1.30 [1.15–1.48], P < 0.001), albumin (sHR 0.90 [0.86–0.93], P < 0.001), genetic score (sHR 1.90 [1.57–2.30], P < 0.001), and previous episodes of overt HE (sHR 2.60 [1.57–4.29], P < 0.001) were independently associated to HE bouts during the follow-up with an internal (C-index 0.83) and external validation (C-index 0.74). Patients in the low- risk group had 5% and 12% risk of HE at 1 (log-rank 92.1; P < 0.001) and 5 (log-rank 124.1; P < 0.001) years, respectively, whereas 36% and 48% in the high- risk group.The genetic background influenced overt HE risk and severity. The clinical-genetic HE Risk score , which combined genetic background together with albumin , bilirubin , and previous episodes of overt HE, could be a useful tool to predict overt HE in patients with cirrhosis .

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MeSH Terms

Aged
Female
Genotype
Hepatic Encephalopathy
Humans
Incidence
Liver Cirrhosis
Male
Middle Aged
Polymorphism, Single Nucleotide
Predictive Value of Tests
Risk Assessment
Severity of Illness Index
Spain

DeCS Terms

Pacientes
Riesgo
Antecedentes genéticos
Repeticiones de Microsatélite
Polimorfismo de Nucleótido Simple
Cirrosis hepática
Bilirrubina
Albúminas
Incidencia
Encefalopatía hepática
Fibrosis

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Keywords

Variants, Promoter, glutamaninase

Citation

Gil-Gómez A, Ampuero J, Rojas Á, Gallego-Durán R, Muñoz-Hernández R, Rico MC, et al. Development and Validation of a Clinical-Genetic Risk Score to Predict Hepatic Encephalopathy in Patients With Liver Cirrhosis. Am J Gastroenterol. 2021 Jun 1;116(6):1238-1247.