Artículo
Impact of a Loss-of-Function Variant in HSD17B13 on Hepatic Decompensation and Mortality in Cirrhotic Patients
Autor/es | Gil Gómez, Antonio
Rojas, Ángela García Lozano, María R. Muñoz Hernández, Rocío Gallego-Durán, Rocío Maya Miles, Douglas Ampuero Herrojo, Javier Romero Gómez, Manuel |
Departamento | Universidad de Sevilla. Departamento de Medicina Universidad de Sevilla. Departamento de Fisiología |
Fecha de publicación | 2022 |
Fecha de depósito | 2023-09-21 |
Publicado en |
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Resumen | Abstract: A common splice variant in HSD17B13 (rs72613567:TA) was recently found to be associated
with a reduced risk of developing chronic liver disease in NAFLD patients and a reduced risk of
progression to advanced ... Abstract: A common splice variant in HSD17B13 (rs72613567:TA) was recently found to be associated with a reduced risk of developing chronic liver disease in NAFLD patients and a reduced risk of progression to advanced fibrosis and cirrhosis. In this study, we aimed to evaluate the prognosis of cirrhotic patients harboring this variant. We performed a retrospective analysis on 483 prospectively recruited patients from four different hospitals in Spain, followed-up for at least 5 years. We collected clinical, demographic, and biochemical data, and we performed a genotyping analysis for com mon variants previously associated with liver disease risk (HSD17B13 rs72613567:TA and PNPLA3 rs738409). Patients homozygous for the TA allele showed a higher MELD score (p = 0.047), Child– Turcotte–Pugh score (p = 0.014), and INR levels (p = 0.046), as well as decreased albumin (p = 0.004) at baseline. After multivariate analysis, patients with the “protective” variant indeed had an increased risk of hepatic decompensation [aHR 2.37 (1.09–5.06); p = 0.029] and liver-related mortality [aHR 2.32 (1.20–4.46); p = 0.012]. Specifically, these patients had an increased risk of developing ascites (Log-R 11.6; p < 0.001), hepatic encephalopathy (Log-R 10.2; p < 0.01), and higher mortality (Log-R 14.1; p < 0.001) at 5 years of follow-up. Interactions with the etiology of the cirrhosis and with the variant rs738409 in PNPLA3 are also described. These findings suggest that the variant rs72613567:TA in HSD17B13 has no protective effect, but indeed increases the risk of decompensation and death in patients with advanced chronic liver disease. |
Agencias financiadoras | Consejería de Salud, Junta de Andalucía Ministerio de Ciencia e Innovación Junta de Andalucía |
Identificador del proyecto | PE-0451-2018 ,P20_01075
PI19/01404, PI19/00589 |
Cita | Gil Gómez, A., Rojas, Á., García Lozano, M.R., Muñoz Hernández, R., Gallego-Durán, R., Maya Miles, D.,...,Romero Gómez, M. (2022). Impact of a Loss-of-Function Variant in HSD17B13 on Hepatic Decompensation and Mortality in Cirrhotic Patients. International Journal of Molecular Sciences, 23 (19), 11840. https://doi.org/10.3390/ijms231911840. |
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