Prediction of Advanced Fibrosis in Metabolic Dysfunction-Associated Steatotic Liver Disease by Type IV Collagen 7S

Background and Aims: Type IV collagen 7S (COL4-7S) is a simple, noninvasive biomarker for liver fibrosis. However, whether COL4-7S can detect advanced fibrosis (AF) and predict the prognosis of metabolic dysfunction–associated steatotic liver disease (MASLD) is unclear. We examined the clinical effi...

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Main Authors: Hiroshi Ishiba, Yoshio Sumida, Yoshihiro Kamada, Hideki Fujii, Michihiro Iwaki, Hideki Hayashi, Hidenori Toyoda, Satoshi Oeda, Hideyuki Hyogo, Miwa Kawanaka, Asahiro Morishita, Kensuke Munekage, Kazuhito Kawata, Tsubasa Tsutsumi, Koji Sawada, Tatsuji Maeshiro, Hiroshi Tobita, Yuichi Yoshida, Masafumi Naito, Asuka Araki, Shingo Arakaki, Takumi Kawaguchi, Hidenao Noritake, Masafumi Ono, Tsutomu Masaki, Satoshi Yasuda, Eiichi Tomita, Masato Yoneda, Akihiro Tokushige, Hirokazu Takahashi, Shinichiro Ueda, Shinichi Aishima, Atsushi Nakajima, Takeshi Okanoue
Format: Article
Language:English
Published: Elsevier 2025-01-01
Series:Gastro Hep Advances
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Online Access:http://www.sciencedirect.com/science/article/pii/S277257232500055X
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author Hiroshi Ishiba
Yoshio Sumida
Yoshihiro Kamada
Hideki Fujii
Michihiro Iwaki
Hideki Hayashi
Hidenori Toyoda
Satoshi Oeda
Hideyuki Hyogo
Miwa Kawanaka
Asahiro Morishita
Kensuke Munekage
Kazuhito Kawata
Tsubasa Tsutsumi
Koji Sawada
Tatsuji Maeshiro
Hiroshi Tobita
Yuichi Yoshida
Masafumi Naito
Asuka Araki
Shingo Arakaki
Takumi Kawaguchi
Hidenao Noritake
Masafumi Ono
Tsutomu Masaki
Satoshi Yasuda
Eiichi Tomita
Masato Yoneda
Akihiro Tokushige
Hirokazu Takahashi
Shinichiro Ueda
Shinichi Aishima
Atsushi Nakajima
Takeshi Okanoue
author_facet Hiroshi Ishiba
Yoshio Sumida
Yoshihiro Kamada
Hideki Fujii
Michihiro Iwaki
Hideki Hayashi
Hidenori Toyoda
Satoshi Oeda
Hideyuki Hyogo
Miwa Kawanaka
Asahiro Morishita
Kensuke Munekage
Kazuhito Kawata
Tsubasa Tsutsumi
Koji Sawada
Tatsuji Maeshiro
Hiroshi Tobita
Yuichi Yoshida
Masafumi Naito
Asuka Araki
Shingo Arakaki
Takumi Kawaguchi
Hidenao Noritake
Masafumi Ono
Tsutomu Masaki
Satoshi Yasuda
Eiichi Tomita
Masato Yoneda
Akihiro Tokushige
Hirokazu Takahashi
Shinichiro Ueda
Shinichi Aishima
Atsushi Nakajima
Takeshi Okanoue
author_sort Hiroshi Ishiba
collection DOAJ
description Background and Aims: Type IV collagen 7S (COL4-7S) is a simple, noninvasive biomarker for liver fibrosis. However, whether COL4-7S can detect advanced fibrosis (AF) and predict the prognosis of metabolic dysfunction–associated steatotic liver disease (MASLD) is unclear. We examined the clinical efficacy of COL4-7S in diagnosing AF and determining MASLD prognosis. Methods: Overall, 881 Japanese patients with biopsy-proven nonalcoholic fatty liver disease between 1994 and 2020 were enrolled. Serum COL4-7S levels were measured by radioimmunoassay, and 2 cutoff points were set as 5.1 ng/mL and 7.2 ng/mL. The patients were assigned to 3 groups based on the COL4-7S level. Cox regression analysis was used to estimate the predictive performance of COL4-7S for liver-related events (LREs). Results: Overall, 866 MASLD patients were enrolled. The median follow-up period was 4.3 years. Thirty-one patients developed LREs. The area under the curve for COL4-7S in patients with AF was 0.847. The adjusted hazard ratios for LREs in 4.8 ≤ COL4-7S < 6.8 and COL4-7S ≥6.8 patients were 6.0 (P = .009) and 27.9 (P < .001) compared with COL4-7S <4.8, and the adjusted hazard ratio of AF on liver biopsy was 1.6 (P = .286). The incidence rate of LREs was low when the Fibrosis-4 Index (FIB-4) <1.30. When the FIB-4 >1.30, effective stratification of the LRE risk group was possible by stratification of COL4-7S. A combination of FIB-4 and COL4-7S stratified risk groups for future LRE development more effectively than when used singly. Conclusion: COL4-7S accurately diagnosed AF and predicted LREs. COL4-7S and a combination of FIB-4 and COL4-7S might help physicians estimate the prognosis of future LRE risk.
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spelling doaj-art-79b9e202bc9e415cb5bdf9bda1583e852025-08-20T02:25:37ZengElsevierGastro Hep Advances2772-57232025-01-014710066810.1016/j.gastha.2025.100668Prediction of Advanced Fibrosis in Metabolic Dysfunction-Associated Steatotic Liver Disease by Type IV Collagen 7SHiroshi Ishiba0Yoshio Sumida1Yoshihiro Kamada2Hideki Fujii3Michihiro Iwaki4Hideki Hayashi5Hidenori Toyoda6Satoshi Oeda7Hideyuki Hyogo8Miwa Kawanaka9Asahiro Morishita10Kensuke Munekage11Kazuhito Kawata12Tsubasa Tsutsumi13Koji Sawada14Tatsuji Maeshiro15Hiroshi Tobita16Yuichi Yoshida17Masafumi Naito18Asuka Araki19Shingo Arakaki20Takumi Kawaguchi21Hidenao Noritake22Masafumi Ono23Tsutomu Masaki24Satoshi Yasuda25Eiichi Tomita26Masato Yoneda27Akihiro Tokushige28Hirokazu Takahashi29Shinichiro Ueda30Shinichi Aishima31Atsushi Nakajima32Takeshi Okanoue33Department of Gastroenterology, Osaka General Hospital of West Japan Railway Company, Osaka, JapanGraduate School of Healthcare Management, International University of Healthcare and Welfare, Tokyo, Japan; Correspondence: Address correspondence to: Yoshio Sumida, MD, PhD, MBA, Graduate School of Healthcare Management, International University of Healthcare and Welfare, 4-1-26 Akasaka, Minato-ku, Tokyo 107-8402, Japan.Department of Advanced Metabolic Hepatology, Osaka University, Graduate School of Medicine, Suita, Osaka, JapanDepartments of Premier Preventive Medicine and Hepatology, Graduate School of Medicine, Osaka Metropolitan University, Abeno, Osaka, JapanDivision of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama, JapanDepartment of Gastroenterology and Hepatology, Gifu Municipal Hospital, Gifu, JapanDepartment of Gastroenterology, Ogaki Municipal Hospital, Ogaki, JapanDepartment of Laboratory Medicine, Liver Center, Saga University Hospital, Saga University Hospital, Saga, Japan; Department of Internal Medicine, Saga Medical School, Saga University, Saga, JapanHyogo Life Care Clinic, Minami, Hiroshima, JapanDepartment of General Internal Medicine, Kawasaki Medical Center, Kawasaki Medical School, Okayama, JapanDepartment of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Takamatsu, Kagawa, JapanDepartment of Gastroenterology and Hepatology, Kochi Medical School, Kochi, JapanHepatology Division, Department of Internal Medicine II, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, JapanDivision of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, JapanDivision of Gastroenterology, Department of Internal Medicine, Asahikawa Medical University, Asahikawa, JapanFirst Department of Internal Medicine, University of the Ryukyus Hospital, Nakagami, Okinawa, JapanDepartment of Hepatology, Shimane University Hospital, Izumo, Shimane, JapanDepartment of Gastroenterology and Hepatology, Suita Municipal Hospital, Suita, Osaka, JapanDepartment of Gastroenterology and Hepatology, Suita Municipal Hospital, Suita, Osaka, JapanPathology Unit, Shimane University Hospital, Izumo, Shimane, JapanFirst Department of Internal Medicine, University of the Ryukyus Hospital, Nakagami, Okinawa, JapanDivision of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, JapanHepatology Division, Department of Internal Medicine II, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, JapanDivision of Innovative Medicine for Hepatobiliary &amp; Pancreatology, Faculty of Medicine, Kagawa University, Takamatsu, Kagawa, JapanDepartment of Gastroenterology and Neurology, Kagawa University Faculty of Medicine, Miki, Kagawa, JapanDepartment of Gastroenterology, Ogaki Municipal Hospital, Ogaki, JapanDepartment of Gastroenterology and Hepatology, Gifu Municipal Hospital, Gifu, JapanDivision of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama, JapanDepartment of Clinical Pharmacology and Therapeutics, Graduate School of Medicine, University of the Ryukyus, Nishihara, Okinawa, JapanDepartment of Internal Medicine, Saga Medical School, Saga University, Saga, JapanDepartment of Clinical Pharmacology and Therapeutics, Graduate School of Medicine, University of the Ryukyus, Nishihara, Okinawa, JapanDepartment of Scientific Pathology Graduate School of Medical Sciences, Kyushu University, Fukuoka, JapanDivision of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama, JapanHepatology Center, Saiseikai Suita Hospital, Suita, Osaka, JapanBackground and Aims: Type IV collagen 7S (COL4-7S) is a simple, noninvasive biomarker for liver fibrosis. However, whether COL4-7S can detect advanced fibrosis (AF) and predict the prognosis of metabolic dysfunction–associated steatotic liver disease (MASLD) is unclear. We examined the clinical efficacy of COL4-7S in diagnosing AF and determining MASLD prognosis. Methods: Overall, 881 Japanese patients with biopsy-proven nonalcoholic fatty liver disease between 1994 and 2020 were enrolled. Serum COL4-7S levels were measured by radioimmunoassay, and 2 cutoff points were set as 5.1 ng/mL and 7.2 ng/mL. The patients were assigned to 3 groups based on the COL4-7S level. Cox regression analysis was used to estimate the predictive performance of COL4-7S for liver-related events (LREs). Results: Overall, 866 MASLD patients were enrolled. The median follow-up period was 4.3 years. Thirty-one patients developed LREs. The area under the curve for COL4-7S in patients with AF was 0.847. The adjusted hazard ratios for LREs in 4.8 ≤ COL4-7S < 6.8 and COL4-7S ≥6.8 patients were 6.0 (P = .009) and 27.9 (P < .001) compared with COL4-7S <4.8, and the adjusted hazard ratio of AF on liver biopsy was 1.6 (P = .286). The incidence rate of LREs was low when the Fibrosis-4 Index (FIB-4) <1.30. When the FIB-4 >1.30, effective stratification of the LRE risk group was possible by stratification of COL4-7S. A combination of FIB-4 and COL4-7S stratified risk groups for future LRE development more effectively than when used singly. Conclusion: COL4-7S accurately diagnosed AF and predicted LREs. COL4-7S and a combination of FIB-4 and COL4-7S might help physicians estimate the prognosis of future LRE risk.http://www.sciencedirect.com/science/article/pii/S277257232500055XType IV Collagen 7SFibrosis-4 IndexMetabolic Dysfunction–Associated Steatotic Liver DiseaseLiver-Related Event
spellingShingle Hiroshi Ishiba
Yoshio Sumida
Yoshihiro Kamada
Hideki Fujii
Michihiro Iwaki
Hideki Hayashi
Hidenori Toyoda
Satoshi Oeda
Hideyuki Hyogo
Miwa Kawanaka
Asahiro Morishita
Kensuke Munekage
Kazuhito Kawata
Tsubasa Tsutsumi
Koji Sawada
Tatsuji Maeshiro
Hiroshi Tobita
Yuichi Yoshida
Masafumi Naito
Asuka Araki
Shingo Arakaki
Takumi Kawaguchi
Hidenao Noritake
Masafumi Ono
Tsutomu Masaki
Satoshi Yasuda
Eiichi Tomita
Masato Yoneda
Akihiro Tokushige
Hirokazu Takahashi
Shinichiro Ueda
Shinichi Aishima
Atsushi Nakajima
Takeshi Okanoue
Prediction of Advanced Fibrosis in Metabolic Dysfunction-Associated Steatotic Liver Disease by Type IV Collagen 7S
Gastro Hep Advances
Type IV Collagen 7S
Fibrosis-4 Index
Metabolic Dysfunction–Associated Steatotic Liver Disease
Liver-Related Event
title Prediction of Advanced Fibrosis in Metabolic Dysfunction-Associated Steatotic Liver Disease by Type IV Collagen 7S
title_full Prediction of Advanced Fibrosis in Metabolic Dysfunction-Associated Steatotic Liver Disease by Type IV Collagen 7S
title_fullStr Prediction of Advanced Fibrosis in Metabolic Dysfunction-Associated Steatotic Liver Disease by Type IV Collagen 7S
title_full_unstemmed Prediction of Advanced Fibrosis in Metabolic Dysfunction-Associated Steatotic Liver Disease by Type IV Collagen 7S
title_short Prediction of Advanced Fibrosis in Metabolic Dysfunction-Associated Steatotic Liver Disease by Type IV Collagen 7S
title_sort prediction of advanced fibrosis in metabolic dysfunction associated steatotic liver disease by type iv collagen 7s
topic Type IV Collagen 7S
Fibrosis-4 Index
Metabolic Dysfunction–Associated Steatotic Liver Disease
Liver-Related Event
url http://www.sciencedirect.com/science/article/pii/S277257232500055X
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