PNPLA3 genotype and fibrosis-4 index predict cardiovascular diseases of Japanese patients with histopathologically-confirmed NAFLD

Abstract Background Reliable noninvasive predictors of the top three causes of death [cardiovascular diseases (CVDs), malignancies, and liver-related events in patients with non-alcoholic fatty liver disease (NAFLD)] have not yet been determined. Methods We retrospectively investigated the incidence...

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Autores principales: Norio Akuta, Yusuke Kawamura, Yasuji Arase, Satoshi Saitoh, Shunichiro Fujiyama, Hitomi Sezaki, Tetsuya Hosaka, Masahiro Kobayashi, Mariko Kobayashi, Yoshiyuki Suzuki, Fumitaka Suzuki, Kenji Ikeda, Hiromitsu Kumada
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Publicado: BMC 2021
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spelling oai:doaj.org-article:28b14a49534747ce92df6ef7f9fa3ab22021-11-21T12:15:38ZPNPLA3 genotype and fibrosis-4 index predict cardiovascular diseases of Japanese patients with histopathologically-confirmed NAFLD10.1186/s12876-021-02020-z1471-230Xhttps://doaj.org/article/28b14a49534747ce92df6ef7f9fa3ab22021-11-01T00:00:00Zhttps://doi.org/10.1186/s12876-021-02020-zhttps://doaj.org/toc/1471-230XAbstract Background Reliable noninvasive predictors of the top three causes of death [cardiovascular diseases (CVDs), malignancies, and liver-related events in patients with non-alcoholic fatty liver disease (NAFLD)] have not yet been determined. Methods We retrospectively investigated the incidence of three complications [CVDs, malignancy (except for liver cancer), and liver-related events] in 477 Japanese patients with histo-pathologically confirmed NAFLD for a median follow-up of 5.9 years. In addition to histological findings, we also investigated noninvasive predictors. Results A score of ≥ 2.67 for the noninvasive diagnosis of stage 4 fibrosis based on the Fibrosis-4 (FIB-4) index indicated a high level area under the receiver operating characteristic (AUROC) curve (0.90), sensitivity (82.9%), specificity (86.4%), and negative predictive value [(NPV) of 98.5%]. The yearly incidence rates of CVDs, malignancies, and liver-related events were found to be 1.04%, 0.83%, and 0.30%, respectively. Multivariate analysis identified a FIB-4 index ≥ 2.67 score as a significant and independent, noninvasive predictor of these three complications. Furthermore, the cumulative incidence rates of CVDs were significantly different among the three genotypes of PNPLA3. PNPLA3 genotype CC, chronic kidney disease (CKD), and FIB-4 index ≥ 2.67 was could be attributed to these three significant CVD risk factors. The rates of CVDs were significantly different among the three subgroups based on the combination of risk factors. In malignancy (except for liver cancer), the incidence rate of colon cancer was 25.0%; in particular, the rate in females was 53.8%. Conclusions Our results highlighted the importance of the PNPLA3 genotype and FIB-4 index ≥ 2.67 on the incidence of complications in Japanese patients with NAFLD, especially the incidence of CVDs. Early diagnosis, based on the presence of one or more risk factors, and early treatment might improve the prognosis for NAFLD patients.Norio AkutaYusuke KawamuraYasuji AraseSatoshi SaitohShunichiro FujiyamaHitomi SezakiTetsuya HosakaMasahiro KobayashiMariko KobayashiYoshiyuki SuzukiFumitaka SuzukiKenji IkedaHiromitsu KumadaBMCarticleNonalcoholic fatty liver diseaseNonalcoholic steatohepatitisCardiovascular diseasesMalignanciesLiver-related eventsFIB-4 indexDiseases of the digestive system. GastroenterologyRC799-869ENBMC Gastroenterology, Vol 21, Iss 1, Pp 1-11 (2021)
institution DOAJ
collection DOAJ
language EN
topic Nonalcoholic fatty liver disease
Nonalcoholic steatohepatitis
Cardiovascular diseases
Malignancies
Liver-related events
FIB-4 index
Diseases of the digestive system. Gastroenterology
RC799-869
spellingShingle Nonalcoholic fatty liver disease
Nonalcoholic steatohepatitis
Cardiovascular diseases
Malignancies
Liver-related events
FIB-4 index
Diseases of the digestive system. Gastroenterology
RC799-869
Norio Akuta
Yusuke Kawamura
Yasuji Arase
Satoshi Saitoh
Shunichiro Fujiyama
Hitomi Sezaki
Tetsuya Hosaka
Masahiro Kobayashi
Mariko Kobayashi
Yoshiyuki Suzuki
Fumitaka Suzuki
Kenji Ikeda
Hiromitsu Kumada
PNPLA3 genotype and fibrosis-4 index predict cardiovascular diseases of Japanese patients with histopathologically-confirmed NAFLD
description Abstract Background Reliable noninvasive predictors of the top three causes of death [cardiovascular diseases (CVDs), malignancies, and liver-related events in patients with non-alcoholic fatty liver disease (NAFLD)] have not yet been determined. Methods We retrospectively investigated the incidence of three complications [CVDs, malignancy (except for liver cancer), and liver-related events] in 477 Japanese patients with histo-pathologically confirmed NAFLD for a median follow-up of 5.9 years. In addition to histological findings, we also investigated noninvasive predictors. Results A score of ≥ 2.67 for the noninvasive diagnosis of stage 4 fibrosis based on the Fibrosis-4 (FIB-4) index indicated a high level area under the receiver operating characteristic (AUROC) curve (0.90), sensitivity (82.9%), specificity (86.4%), and negative predictive value [(NPV) of 98.5%]. The yearly incidence rates of CVDs, malignancies, and liver-related events were found to be 1.04%, 0.83%, and 0.30%, respectively. Multivariate analysis identified a FIB-4 index ≥ 2.67 score as a significant and independent, noninvasive predictor of these three complications. Furthermore, the cumulative incidence rates of CVDs were significantly different among the three genotypes of PNPLA3. PNPLA3 genotype CC, chronic kidney disease (CKD), and FIB-4 index ≥ 2.67 was could be attributed to these three significant CVD risk factors. The rates of CVDs were significantly different among the three subgroups based on the combination of risk factors. In malignancy (except for liver cancer), the incidence rate of colon cancer was 25.0%; in particular, the rate in females was 53.8%. Conclusions Our results highlighted the importance of the PNPLA3 genotype and FIB-4 index ≥ 2.67 on the incidence of complications in Japanese patients with NAFLD, especially the incidence of CVDs. Early diagnosis, based on the presence of one or more risk factors, and early treatment might improve the prognosis for NAFLD patients.
format article
author Norio Akuta
Yusuke Kawamura
Yasuji Arase
Satoshi Saitoh
Shunichiro Fujiyama
Hitomi Sezaki
Tetsuya Hosaka
Masahiro Kobayashi
Mariko Kobayashi
Yoshiyuki Suzuki
Fumitaka Suzuki
Kenji Ikeda
Hiromitsu Kumada
author_facet Norio Akuta
Yusuke Kawamura
Yasuji Arase
Satoshi Saitoh
Shunichiro Fujiyama
Hitomi Sezaki
Tetsuya Hosaka
Masahiro Kobayashi
Mariko Kobayashi
Yoshiyuki Suzuki
Fumitaka Suzuki
Kenji Ikeda
Hiromitsu Kumada
author_sort Norio Akuta
title PNPLA3 genotype and fibrosis-4 index predict cardiovascular diseases of Japanese patients with histopathologically-confirmed NAFLD
title_short PNPLA3 genotype and fibrosis-4 index predict cardiovascular diseases of Japanese patients with histopathologically-confirmed NAFLD
title_full PNPLA3 genotype and fibrosis-4 index predict cardiovascular diseases of Japanese patients with histopathologically-confirmed NAFLD
title_fullStr PNPLA3 genotype and fibrosis-4 index predict cardiovascular diseases of Japanese patients with histopathologically-confirmed NAFLD
title_full_unstemmed PNPLA3 genotype and fibrosis-4 index predict cardiovascular diseases of Japanese patients with histopathologically-confirmed NAFLD
title_sort pnpla3 genotype and fibrosis-4 index predict cardiovascular diseases of japanese patients with histopathologically-confirmed nafld
publisher BMC
publishDate 2021
url https://doaj.org/article/28b14a49534747ce92df6ef7f9fa3ab2
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