Ishiba Hiroshi, Sumida Yoshio, Kamada Yoshihiro, Fujii Hideki, Iwaki Michihiro, Hayashi Hideki, Toyoda Hidenori, Oeda Satoshi, Hyogo Hideyuki, Kawanaka Miwa, Morishita Asahiro, Munekage Kensuke, Kawata Kazuhito, Tsutsumi Tsubasa, Sawada Koji, Maeshiro Tatsuji, Tobita Hiroshi, Yoshida Yuichi, Naito Masafumi, Araki Asuka, Arakaki Shingo, Kawaguchi Takumi, Noritake Hidenao, Ono Masafumi, Masaki Tsutomu, Yasuda Satoshi, Tomita Eiichi, Yoneda Masato, Tokushige Akihiro, Takahashi Hirokazu, Ueda Shinichiro, Aishima Shinichi, Nakajima Atsushi, Okanoue Takeshi
Department of Gastroenterology, Osaka General Hospital of West Japan Railway Company, Osaka, Japan.
Graduate School of Healthcare Management, International University of Healthcare and Welfare, Tokyo, Japan.
Gastro Hep Adv. 2025 Mar 28;4(7):100668. doi: 10.1016/j.gastha.2025.100668. eCollection 2025.
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.
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).
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 ( = .009) and 27.9 ( < .001) compared with COL4-7S <4.8, and the adjusted hazard ratio of AF on liver biopsy was 1.6 ( = .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.
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.
IV型胶原7S（COL4-7S）是一种用于肝纤维化的简单、非侵入性生物标志物。然而，COL4-7S能否检测晚期纤维化（AF）并预测代谢功能障碍相关脂肪性肝病（MASLD）的预后尚不清楚。我们研究了COL4-7S在诊断AF和确定MASLD预后方面的临床疗效。
共纳入881例1994年至2020年间经活检证实患有非酒精性脂肪性肝病的日本患者。采用放射免疫分析法测定血清COL4-7S水平，并将两个临界值设定为5.1 ng/mL和7.2 ng/mL。根据COL4-7S水平将患者分为3组。采用Cox回归分析评估COL4-7S对肝脏相关事件（LRE）的预测性能。
共纳入866例MASLD患者。中位随访期为4.3年。31例患者发生了LRE。AF患者中COL4-7S的曲线下面积为0.847。与COL4-7S<4.8的患者相比，4.8≤COL4-7S<6.8和COL4-7S≥6.8的患者发生LRE的调整后风险比分别为6.0（P = .009）和27.9（P < .001），肝活检时AF的调整后风险比为1.6（P = .286）。当纤维化-4指数（FIB-4）<1.30时，LRE的发生率较低。当FIB-4>1.30时，通过COL4-7S分层可以有效区分LRE风险组。FIB-4和COL4-7S联合使用比分层单独使用更有效地对未来发生LRE的风险组进行分层。
COL4-7S能准确诊断AF并预测LRE。COL4-7S以及FIB-4与COL4-7S的联合使用可能有助于医生评估未来LRE风险的预后。
