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PNPLA3 gene predicts clinical recovery after sustained virological response in decompensated hepatitis C cirrhosis

BACKGROUND: Patients with decompensated hepatitis C virus (HCV) cirrhosis experience various outcomes after sustained virological response (SVR), ranging from clinical recovery to further deterioration. We hypothesised that the genetic risk for steatosis, namely the polymorphisms rs738409 of Patatin...

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Autores principales: Dunn, Winston, Vittal, Anusha, Zhao, Jie, He, Jianghua, Chakraborty, Shweta, Whitener, Melissa, Fohn, Sara, Ash, Ryan, Taylor, Ryan M, Olyaee, Mojtaba, Olson, Jody C, Todd, Nancy, Floyd, Beth N, Pandya, Prashant, Laycock, Melissa, Schmitt, Timothy, Weinman, Steven A
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BMJ Publishing Group 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6441264/
https://www.ncbi.nlm.nih.gov/pubmed/30997139
http://dx.doi.org/10.1136/bmjgast-2018-000241
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author Dunn, Winston
Vittal, Anusha
Zhao, Jie
He, Jianghua
Chakraborty, Shweta
Whitener, Melissa
Fohn, Sara
Ash, Ryan
Taylor, Ryan M
Olyaee, Mojtaba
Olson, Jody C
Todd, Nancy
Floyd, Beth N
Pandya, Prashant
Laycock, Melissa
Schmitt, Timothy
Weinman, Steven A
author_facet Dunn, Winston
Vittal, Anusha
Zhao, Jie
He, Jianghua
Chakraborty, Shweta
Whitener, Melissa
Fohn, Sara
Ash, Ryan
Taylor, Ryan M
Olyaee, Mojtaba
Olson, Jody C
Todd, Nancy
Floyd, Beth N
Pandya, Prashant
Laycock, Melissa
Schmitt, Timothy
Weinman, Steven A
author_sort Dunn, Winston
collection PubMed
description BACKGROUND: Patients with decompensated hepatitis C virus (HCV) cirrhosis experience various outcomes after sustained virological response (SVR), ranging from clinical recovery to further deterioration. We hypothesised that the genetic risk for steatosis, namely the polymorphisms rs738409 of Patatin-like Phospholipase Domain-Containing 3 (PNPLA3), rs58542926 of Transmembrane-6-Superfamily-2 (TM6SF2), and rs641738 of Membrane-bound O-acyltransferase Domain-Containing 7 (MBOAT7), is predictive of recovery. METHODS: We prospectively enrolled 56 patients with Child-Pugh (CPT) B/C cirrhosis who underwent antiviral therapy. The primary outcome was change in CPT score at 12, 24, and 48 weeks after SVR. We used a linear mixed-effects model for analysis. RESULTS: Forty-five patients (PNPLA3: 21 CC, 19 CG, 5 GG) survived to the first endpoint without liver transplantation. The mean change in CPT score at 12, 24, and 48 weeks was −1.57 (SE=0.30), –1.76 (SE=0.32), and −2.0 (SE=0.36), respectively, among the patients with the PNPLA3 CC genotype and −0.50 (SE=0.20), –0.41 (SE=0.25), and −0.24 (SE=0.27), respectively, among the other 24 patients. After adjustment for baseline characteristics, the PNPLA3 CG/GG genotypes were associated with a 1.29 (SE=0.30, p<0.0001) point higher CPT score. Most of the difference came from differences in hepatic encephalopathy and bilirubin. The results for rs58542926 and rs641738 were not significant. CONCLUSION: The PNPLA3 CG/GG genotypes could identify a subgroup of patients with decompensated HCV cirrhosis that had suboptimal clinical recovery despite SVR. An understanding of the genetic factors that influence clinical outcomes will help target patients for liver transplant based on individual genetic risk factors and provide insight leading to new therapeutic approaches.
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spelling pubmed-64412642019-04-17 PNPLA3 gene predicts clinical recovery after sustained virological response in decompensated hepatitis C cirrhosis Dunn, Winston Vittal, Anusha Zhao, Jie He, Jianghua Chakraborty, Shweta Whitener, Melissa Fohn, Sara Ash, Ryan Taylor, Ryan M Olyaee, Mojtaba Olson, Jody C Todd, Nancy Floyd, Beth N Pandya, Prashant Laycock, Melissa Schmitt, Timothy Weinman, Steven A BMJ Open Gastroenterol Hepatology BACKGROUND: Patients with decompensated hepatitis C virus (HCV) cirrhosis experience various outcomes after sustained virological response (SVR), ranging from clinical recovery to further deterioration. We hypothesised that the genetic risk for steatosis, namely the polymorphisms rs738409 of Patatin-like Phospholipase Domain-Containing 3 (PNPLA3), rs58542926 of Transmembrane-6-Superfamily-2 (TM6SF2), and rs641738 of Membrane-bound O-acyltransferase Domain-Containing 7 (MBOAT7), is predictive of recovery. METHODS: We prospectively enrolled 56 patients with Child-Pugh (CPT) B/C cirrhosis who underwent antiviral therapy. The primary outcome was change in CPT score at 12, 24, and 48 weeks after SVR. We used a linear mixed-effects model for analysis. RESULTS: Forty-five patients (PNPLA3: 21 CC, 19 CG, 5 GG) survived to the first endpoint without liver transplantation. The mean change in CPT score at 12, 24, and 48 weeks was −1.57 (SE=0.30), –1.76 (SE=0.32), and −2.0 (SE=0.36), respectively, among the patients with the PNPLA3 CC genotype and −0.50 (SE=0.20), –0.41 (SE=0.25), and −0.24 (SE=0.27), respectively, among the other 24 patients. After adjustment for baseline characteristics, the PNPLA3 CG/GG genotypes were associated with a 1.29 (SE=0.30, p<0.0001) point higher CPT score. Most of the difference came from differences in hepatic encephalopathy and bilirubin. The results for rs58542926 and rs641738 were not significant. CONCLUSION: The PNPLA3 CG/GG genotypes could identify a subgroup of patients with decompensated HCV cirrhosis that had suboptimal clinical recovery despite SVR. An understanding of the genetic factors that influence clinical outcomes will help target patients for liver transplant based on individual genetic risk factors and provide insight leading to new therapeutic approaches. BMJ Publishing Group 2019-03-12 /pmc/articles/PMC6441264/ /pubmed/30997139 http://dx.doi.org/10.1136/bmjgast-2018-000241 Text en © Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.
spellingShingle Hepatology
Dunn, Winston
Vittal, Anusha
Zhao, Jie
He, Jianghua
Chakraborty, Shweta
Whitener, Melissa
Fohn, Sara
Ash, Ryan
Taylor, Ryan M
Olyaee, Mojtaba
Olson, Jody C
Todd, Nancy
Floyd, Beth N
Pandya, Prashant
Laycock, Melissa
Schmitt, Timothy
Weinman, Steven A
PNPLA3 gene predicts clinical recovery after sustained virological response in decompensated hepatitis C cirrhosis
title PNPLA3 gene predicts clinical recovery after sustained virological response in decompensated hepatitis C cirrhosis
title_full PNPLA3 gene predicts clinical recovery after sustained virological response in decompensated hepatitis C cirrhosis
title_fullStr PNPLA3 gene predicts clinical recovery after sustained virological response in decompensated hepatitis C cirrhosis
title_full_unstemmed PNPLA3 gene predicts clinical recovery after sustained virological response in decompensated hepatitis C cirrhosis
title_short PNPLA3 gene predicts clinical recovery after sustained virological response in decompensated hepatitis C cirrhosis
title_sort pnpla3 gene predicts clinical recovery after sustained virological response in decompensated hepatitis c cirrhosis
topic Hepatology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6441264/
https://www.ncbi.nlm.nih.gov/pubmed/30997139
http://dx.doi.org/10.1136/bmjgast-2018-000241
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